Published Papers - Kusunose Kenya

Effectiveness of surveillance by echocardiography for cancer therapeutics-related cardiac dysfunction of patients with breast cancer

Okushi, Y; Saijo, Y; Yamada, H; Toba, H; Zheng, RB; Seno, H; Takahashi, T; Ise, T; Yamaguchi, K; Yagi, S; Soeki, T; Wakatsuki, T; Sata, M; Kusunose, K

JOURNAL OF CARDIOLOGY ( Journal of Cardiology )  82 ( 6 ) 467 - 472   2023.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. METHODS: We identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3 months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15 % were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. RESULTS: The mean age was 59 ± 12 years. During the follow-up period of 15 months (12-17 months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1 % vs. 5.5 %, adjusted odds ratio: 0.28, 95 % confidential intervals: 0.09-0.94; p = 0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. CONCLUSIONS: The incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.

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The Clinical Utility of Noninvasive Forrester Classification in Acute Heart Failure from PREDICT Study

Takahashi, T; Iwano, H; Shibayama, K; Kitai, T; Tanaka, H; Yamada, H; Sata, M; Kusunose, K

AMERICAN JOURNAL OF CARDIOLOGY ( American Journal of Cardiology )  207   75 - 81   2023.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The Forrester classification plays a crucial role in comprehending the underlying pathophysiology of heart failure (HF) and is employed to categorize the severity and predict the outcomes of patients with acute HF. Our objective was to assess the predictive value of the Forrester classification, based on noninvasive hemodynamic measurements obtained through Doppler echocardiography at admission, in forecasting the short-term prognosis posthospitalization of patients with acute HF. Patients were recruited for the Prospect trial to elucidate the utility of EchocarDIography-based Cardiac ouTput in acute heart failure (PREDICT) study, a multicenter, prospective study conducted in Japan. Participants were stratified into 4 profiles using cardiac index (CI) and early mitral filling velocity (E)/early-diastolic mitral annular velocity (e') ratio obtained from Doppler echocardiography upon admission (profile I: CI >2.2, E/e' ≤15, profile II: CI >2.2, E/e' >15, profile III: CI ≤2.2, E/e' ≤15, profile IV: CI ≤2.2, E/e' >15). The primary composite outcome of the study was all-cause mortality or worsening HF during the 14 days of hospitalization. Cox proportional hazards model analysis was employed to identify prognostic factors during the observation period. A total of 270 subjects, with a mean age of 74 ± 14 years and a male proportion of 60%, were enrolled in the study. During the 14-day period of hospitalization, 58 participants (22%) had a composite outcome. Patients with low CI (i.e., profiles III and IV) demonstrated an elevated risk of composite outcome after adjusting for confounding variables, as evidenced by the adjusted hazard ratios of 5.85 (95% confidence interval 1.17 to 29.09, p <0.01, vs profile III) and 6.50 (95% confidence interval 1.53 to 27.68, p <0.01, vs profile IV) in comparison with profile I, respectively. In conclusion, the Forrester classification, derived from noninvasive Doppler echocardiography at admission, may predict early deterioration in patients hospitalized with acute HF.

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Innate Immune System Regulated by Stimulator of Interferon Genes, a Cytosolic DNA Sensor, Regulates Endothelial Function.

Pham PT, Bavuu O, Kim-Kaneyama JR, Lei XF, Yamamoto T, Otsuka K, Suto K, Kusunose K, Yagi S, Yamada H, Soeki T, Shimabukuro M, Barber GN, Sata M, Fukuda D

Journal of the American Heart Association ( Journal of the American Heart Association )  12 ( 22 ) e030084   2023.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Value and challenges of lung ultrasound in stratifying ST-elevation myocardial infarction risk

Kusunose, K; Toma, Y

HEART ( Heart )  109 ( 21 ) 1580 - 1581   2023.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Correlation between energy loss index and B-type natriuretic peptide: a vector flow mapping study

Morita, S; Hirata, Y; Nishio, S; Takahashi, T; Saijo, Y; Yamada, H; Sata, M; Kusunose, K

JOURNAL OF ECHOCARDIOGRAPHY ( Journal of Echocardiography )    2023.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Vector Flow Mapping (VFM) and Energy Loss (EL) evaluation are emerging echocardiographic techniques that offer detailed insights into cardiac function. This study aimed to explore the relationship between EL parameters and B-type natriuretic peptide (BNP) levels, a well-established marker of heart failure severity. METHODS: Our study prospectively enrolled 62 patients experiencing shortness of breath and suspected heart failure, who underwent echocardiography and had BNP levels measured between January 2018 and August 2020. Patients were stratified based on BNP levels, and their clinical and echocardiographic characteristics were evaluated. Univariate and multivariate regression analyses were performed to assess the correlation between BNP levels and various echocardiographic variables, including VFM parameters. RESULTS: Patients were stratified into two groups based on their BNP levels: BNP < 200 pg/ml (n = 53) and BNP ≥ 200 pg/ml (n = 9). Patients with BNP ≥ 200 pg/ml presented significantly different clinical and echocardiographic characteristics, such as older age, larger left ventricular mass and volume indices, higher pulmonary artery systolic pressure, higher E/e' ratio, and larger EL parameters. Multivariate regression analysis demonstrated the E/e' ratio and ELA (EL during Atrial contraction phase/A wave ratio as significant determinants of logBNP. Receiver operating characteristic curve analysis showed ELA/A > 36.0 J/m2 as a significant predictor of high BNP with 89% sensitivity and 85% specificity. ELA/A demonstrated an incremental diagnostic value over elevated left atrial pressure for predicting high BNP (C statistic = 0.98 vs 0.74, P = 0.006). CONCLUSION: This study provides novel insights into the potential utility of EL parameters as auxiliary indicators of cardiac load, thereby enhancing our understanding of heart failure.

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Revolution of echocardiographic reporting: the new era of artificial intelligence and natural language processing

Kusunose, K

JOURNAL OF ECHOCARDIOGRAPHY ( Journal of Echocardiography )  21 ( 3 ) 99 - 104   2023.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Prognostic implications of pulmonary vascular resistance in transcatheter aortic valve implantation

Kusunose, K; Ikemiyagi, H

HEART ( Heart )  110 ( 1 ) 5 - 6   2023.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Olive mill wastewater and hydroxytyrosol inhibits atherogenesis in apolipoprotein E-deficient mice.

Tomoya Hara, Daiju Fukuda, Byambasuren Ganbaatar, Phuong Tran Pham, Kunduziayi Aini, Arief Rahadian, Kumiko Suto, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata

Heart and vessels   38 ( 11 ) 1386 - 1394   2023.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The Mediterranean diet, which is characterized by high consumption of olive oil, prevents cardiovascular disease. Meanwhile, olive mill wastewater (OMWW), which is obtained as a byproduct during olive oil production, contains various promising bioactive components such as water-soluble polyphenols. Hydroxytyrosol (HT), the major polyphenol in OMWW, has anti-oxidative and anti-inflammatory properties; however, the atheroprotective effects of OMWW and HT remain to be fully understood. Here, we investigated the effect of OMWW and HT on atherogenesis. Male 8-week-old apolipoprotein E-deficient mice were fed a western-type diet supplemented with OMWW (0.30%w/w) or HT (0.02%w/w) for 20 weeks. The control group was fed a non-supplemented diet. OMWW and HT attenuated the development of atherosclerosis in the aortic arch as determined by Sudan IV staining (P < 0.01, respectively) without alteration of body weight, plasma lipid levels, and blood pressure. OMWW and HT also decreased the production of oxidative stress (P < 0.01, respectively) and the expression of NADPH oxidase subunits (e.g., NOX2 and p22phox) and inflammatory molecules (e.g. IL-1β and MCP-1) in the aorta. The results of in vitro experiments demonstrated that HT inhibited the expression of these molecules that were stimulated with LPS in RAW264.7 cells, murine macrophage-like cells. OMWW and HT similarly attenuated atherogenesis. HT is a major component of water-soluble polyphenols in OMWW, and it inhibited inflammatory activation of macrophages. Therefore, our results suggest that the atheroprotective effects of OMWW are at least partially attributable to the anti-inflammatory effects of HT.

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Artificial intelligence-assisted interpretation of systolic function by echocardiogram

Yamaguchi, N; Kosaka, Y; Haga, A; Sata, M; Kusunose, K

OPEN HEART ( Open Heart )  10 ( 2 )   2023.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVE: Precise and reliable echocardiographic assessment of left ventricular ejection fraction (LVEF) is needed for clinical decision-making. Recently, artificial intelligence (AI) models have been developed to estimate LVEF accurately. The aim of this study was to evaluate whether an AI model could estimate an expert read of LVEF and reduce the interinstitutional variability of level 1 readers with the AI-LVEF displayed on the echocardiographic screen. METHODS: This prospective, multicentre echocardiographic study was conducted by five cardiologists of level 1 echocardiographic skill (minimum level of competency to interpret images) from different hospitals. Protocol 1: Visual LVEFs for the 48 cases were measured without input from the AI-LVEF. Protocol 2: the 48 cases were again shown to all readers with inclusion of AI-LVEF data. To assess the concordance and accuracy with or without AI-LVEF, each visual LVEF measurement was compared with an average of the estimates by five expert readers as a reference. RESULTS: A good correlation was found between AI-LVEF and reference LVEF (r=0.90, p<0.001) from the expert readers. For the classification LVEF, the area under the curve was 0.95 on heart failure with preserved EF and 0.96 on heart failure reduced EF. For the precision, the SD was reduced from 6.1±2.3 to 2.5±0.9 (p<0.001) with AI-LVEF. For the accuracy, the root-mean squared error was improved from 7.5±3.1 to 5.6±3.2 (p=0.004) with AI-LVEF. CONCLUSIONS: AI can assist with the interpretation of systolic function on an echocardiogram for level 1 readers from different institutions.

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Evaluation of the Accuracy of ChatGPT in Answering Clinical Questions on the Japanese Society of Hypertension Guidelines

Kusunose, K; Kashima, S; Sata, M

CIRCULATION JOURNAL ( 一般社団法人 日本循環器学会 )  87 ( 7 ) 1030 - 1033   2023.06

Type of publication: Research paper (scientific journal)

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<p><b><i>Background:</i></b> To assist healthcare providers in interpreting guidelines, clinical questions (CQ) are often included, but not always, which can make interpretation difficult for non-expert clinicians. We evaluated the ability of ChatGPT to accurately answer CQs on the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019).</p><p><b><i>Methods and Results:</i></b> We conducted an observational study using data from JSH 2019. The accuracy rate for CQs and limited evidence-based questions of the guidelines (Qs) were evaluated. ChatGPT demonstrated a higher accuracy rate for CQs than for Qs (80% vs. 36%, P value: 0.005).</p><p><b><i>Conclusions:</i></b> ChatGPT has the potential to be a valuable tool for clinicians in the management of hypertension.</p>

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Intimal Sarcoma of the Pulmonary Artery as an Embolic Cause of Sudden Death.

Shusuke Yagi, Tomoya Hara, Hirotsugu Yamada, Kenya Kusunose, Takayuki Ise, Masataka Sata

Circulation journal : official journal of the Japanese Circulation Society   87 ( 7 ) 1036 - 1036   2023.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Deep learning approach for analyzing chest x-rays to predict cardiac events in heart failure

Kenya Kusunose, Yukina Hirata, Natsumi Yamaguchi, Yoshitaka Kosaka, Takumasa Tsuji, Jun'ichi Kotoku, Masataka Sata

Frontiers in Cardiovascular Medicine ( Frontiers Media SA )  10   2023.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background A deep learning (DL) model based on a chest x-ray was reported to predict elevated pulmonary artery wedge pressure (PAWP) as heart failure (HF). Objectives The aim of this study was to (1) investigate the role of probability of elevated PAWP for the prediction of clinical outcomes in association with other parameters, and (2) to evaluate whether probability of elevated PAWP based on DL added prognostic information to other conventional clinical prognostic factors in HF. Methods We evaluated 192 patients hospitalized with HF. We used a previously developed AI model to predict HF and calculated probability of elevated PAWP. Readmission following HF and cardiac mortality were the primary endpoints. Results Probability of elevated PAWP was associated with diastolic function by echocardiography. During a median follow-up period of 58 months, 57 individuals either died or were readmitted. Probability of elevated PAWP appeared to be associated with worse clinical outcomes. After adjustment for readmission score and laboratory data in a Cox proportional-hazards model, probability of elevated PAWP at pre-discharge was associated with event free survival, independent of elevated left atrial pressure (LAP) based on echocardiographic guidelines (p &amp;lt; 0.001). In sequential Cox models, a model based on clinical data was improved by elevated LAP (p = 0.005), and increased further by probability of elevated PAWP (p &amp;lt; 0.001). In contrast, the addition of pulmonary congestion interpreted by a doctor did not statistically improve the ability of a model containing clinical variables (compared p = 0.086). Conclusions This study showed the potential of using a DL model on a chest x-ray to predict PAWP and its ability to add prognostic information to other conventional clinical prognostic factors in HF. The results may help to enhance the accuracy of prediction models used to evaluate the risk of clinical outcomes in HF, potentially resulting in more informed clinical decision-making and better care for patients.

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The Impact of Coronary Plaque Progression Stage on Coronary Neovascularization Structures in Fresh Cadavers(タイトル和訳中)

川端 豊, 若槻 哲三, 山口 浩司, 坂東 遼, 西條 良仁, 上野 理絵, 門田 宗之, 原 知也, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  87回   PJ005 - 1   2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

薬物治療可能な心筋症の非侵襲的画像診断:早期診断のための活用法(Utility of Periodic Echocardiographic Surveillance for Early Detection of Cardiac Dysfunction from Chemotherapy in Breast Cancer Patients)

西條 良仁, 大櫛 祐一郎, 楠瀬 賢也, 山田 博胤, ゼング ロバート, 高橋 智紀, 瀬野 弘光, 西尾 進, 上野 理絵, 門田 宗之, 原 知也, 川端 豊, 松浦 朋美, 伊勢 孝之, 山口 浩司, 八木 秀介, 添木 武, 若槻 哲三, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  87回   SY11 - 3   2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

未来の医療機器・デバイスのために(Novel Home-based Cardiac Telerehabilitation System Using a Wearable Device and a Web Application)

伊勢 孝之, 八木 秀介, 上野 理絵, 門田 宗之, 大谷 啓太, 根岸 佑典, 宮本 亮太, 坂東 遼, ゼング ロバート, 瀬野 弘光, 高橋 智紀, 川端 豊, 西條 良仁, 松浦 朋美, 楠瀬 賢也, 山口 浩司, 山田 博胤, 添木 武, 若槻 哲三, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  87回   SY03 - 4   2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Two-year Outcomes of Drug-coated Balloon-only Strategy for De Novo Lesions in Large Coronary Vessels(タイトル和訳中)

坂東 遼, 若槻 哲三, 山口 浩司, 川端 豊, 宮本 亮太, ゼング ロバート, 高橋 智紀, 西條 良仁, 上野 理絵, 門田 宗之, 原 知也, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 八木 秀介, 山田 博胤, 添木 武, 赤池 雅史, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  87回   OJ32 - 1   2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Benefits of guideline-directed medical therapy to loop diuretics in management of heart failure.

Kenya Kusunose, Yuichiro Okushi, Yoshihiro Okayama, Robert Zheng, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

The journal of medical investigation : JMI   70 ( 1.2 ) 41 - 53   2023 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: We sought to compare the outcomes of patients receiving combination therapy of diuretics and neurohormonal blockers, with a matched cohort with monotherapy of loop diuretics, using real-world big data. METHODS: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 78,685 patients who were first hospitalized with heart failure (HF) between April 2015 and March 2017. Propensity score (PS) was estimated with logistic regression model, with neurohormonal blockers (angiotensin-converting enzyme inhibitor : ACEi or angiotensin receptor blocker : ARB, ?-blockers and mineralocorticoid receptor antagonists : MRA) as the dependent variable and 24 clinically relevant covariates to compare the in-hospital mortality between monotherapy of loop diuretics and combination therapies. RESULTS: On PS-matched analysis, patients with ACEi?/?ARB, ?-blockers, and MRA had lower total in-hospital mortality and in-hospital mortality within 7 days, 14 days and 30 days. In the sub-group analysis, regardless of clinical characteristics including elderly people and cancer, patients treated with a combination of loop diuretics and neurohormonal blockers had significantly lower in-hospital mortality than matched patients. CONCLUSIONS: Our data indicate the benefits of guideline-directed medical therapy to loop diuretics in the management of HF. J. Med. Invest. 70 : 41-53, February, 2023.

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Isoproterenol loading transesophageal echocardiography in atrial fibrillation.

Tomonori Takahashi, Kenya Kusunose, Shuji Hayashi, Robert Zheng, Natsumi Yamaguchi, Sae Morita, Yukina Hirata, Susumu Nishio, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

The international journal of cardiovascular imaging   39 ( 3 ) 511 - 518   2022.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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In patients with sludge or severe spontaneous echo contrast (SEC) in the left atrial appendage (LAA), cases with isoproterenol loading transesophageal echocardiography (ISP-TEE) have been reported to identify the presence of thrombus in the LAA. This study aimed to assess the validity and hemodynamic changes of ISP-TEE in the LAA. We prospectively enrolled patients with atrial fibrillation (AF) who underwent ISP-TEE. The degree of sludge/SEC was categorized as being either absent (grade 0), mild SEC (grade 1), moderate SEC (grade 2), severe SEC or sludge (grade 3). The hemodynamic evaluation was performed by measuring LAA flow velocity, LAA tissue Doppler imaging (LAA-TDI) velocity, and pulmonary vein systolic forward flow velocity (PVS). In total, 35 patients (mean age 71 ± 7 years; 71% male) underwent ISP-TEE. Among 35 patients, 30 patients had grade 3 or 2 SEC, 5 patients had grade 1 SEC. After ISP loading, 23 patients (66% of all patients) showed improved sludge/SEC and one patient was diagnosed with thrombus in the LAA. There were 25 patients with grade 1 SEC, or no SEC (classified as Group1), 10 patients had residual sludge or grade 2 to 3 SEC (classified as Group2) after ISP administration. LAA flow, LAA-TDI, and PVS velocities were significantly higher in group 1 than in group 2 after ISP administration. There was no complication during the examination and after 24 h and 3 months. ISP infusion may be a potential tool to recognize LAA thrombus under the sludge/SEC during TEE in AF.

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Association of Microluminal Structures Assessed by Optical Coherence Tomography With Local Inflammation in Adjacent Epicardial Adipose Tissue and Coronary Plaque Characteristics in Fresh Cadavers.

Yutaka Kawabata, Tetsuzo Wakatsuki, Koji Yamaguchi, Daiju Fukuda, Hiroyuki Ito, Tomomi Matsuura, Kenya Kusunose, Takayuki Ise, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Yoshihiro Tsuruo, Masataka Sata

Circulation journal : official journal of the Japanese Circulation Society   87 ( 2 ) 329 - 335   2022.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Coronary intraplaque microluminal structures (MS) are associated with plaque vulnerability, and the inward progression of vascular inflammation from the adventitia towards the media and intima has also been demonstrated. Therefore, in the present study we investigated the relationships among MS, local inflammation in adjacent epicardial adipose tissue (EAT), and coronary plaque characteristics.Methods and Results: Optical coherence tomography (OCT) revealed MS in the left anterior descending coronary artery in 10 fresh cadaveric hearts. We sampled 30 lesions and subdivided them based on the presence of MS: MS (+) group (n=19) and MS (-) group (n=11). We measured inflammatory molecule levels in the adjacent EAT and percentage lipid volume assessed by integrated backscatter intravascular ultrasound in each lesion. The expression levels of vascular endothelial growth factor B and C-C motif chemokine ligand 2 were significantly higher in the MS (+) group than in the MS (-) group (0.9±0.7 vs. 0.2±0.2 arbitrary units (AU), P=0.04 and 1.5±0.5 vs. 0.6±0.7 AU, P=0.02, respectively). Percentage lipid volume was significantly higher in the MS (+) group than in the MS (-) group (38.7±16.5 vs. 23.7±10.9%, P=0.03). CONCLUSIONS: Intraplaque MS observed on OCT were associated with lipid-rich plaques and local inflammation in the adjacent EAT. Collectively, these results suggest that local inflammation in the EAT is associated with coronary plaque vulnerability via MS.

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Esaxerenone, a selective mineralocorticoid receptor blocker, improves insulin sensitivity in mice consuming high-fat diet.

Oyunbileg Bavuu, Daiju Fukuda, Byambasuren Ganbaatar, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

European journal of pharmacology   931   175190 - 175190   2022.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Esaxerenone is a novel, non-steroidal selective mineralocorticoid receptor (MR) blocker. MR activation plays a crucial role in the development of cardiovascular and metabolic diseases. In this study, we investigated the effects of esaxerenone on various metabolic parameters in mice. MATERIALS AND METHODS: Esaxerenone (3 mg/kg/day) was orally administered to high-fat diet (HFD)-fed male C57BL/6 mice. Mice fed a normal diet (ND) served as controls. Glucose and insulin tolerance, plasma lipid levels, and transaminase levels were assessed as metabolic parameters. Macrophage accumulation in the adipose tissue was evaluated using histological analysis. 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes were used for in vitro experiments. Gene expression and insulin signaling were examined using quantitative RT-PCR and western blotting, respectively. RESULTS: HFD successfully induced insulin resistance compared with that in ND. Esaxerenone ameliorated insulin resistance (P < 0.05) without altering other metabolic parameters, such as the lipid profile. Esaxerenone administration tended to decrease plasma transaminase levels compared with those in the non-treated group. In the adipose tissue, esaxerenone decreased macrophage accumulation (P < 0.05) and increased the expression levels of adiponectin and PPARγ. Aldosterone significantly decreased the expression levels of PPARγ and adiponectin in 3T3-L1 adipocytes. Furthermore, aldosterone attenuated insulin-induced Akt phosphorylation in 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes in a dose-dependent manner (P < 0.01). These effects were ameliorated by pretreatment with esaxerenone. CONCLUSION: Esaxerenone ameliorated insulin resistance in HFD-fed mice. Reduction of inflammation and improvement in insulin signaling may underlie the beneficial effects of esaxerenone.

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Clinical course and decision-making in heart failure by preload stress echocardiography: a preliminary study.

Kenya Kusunose, Hirotsugu Yamada, Yoshihito Saijo, Susumu Nishio, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

ESC heart failure   9 ( 6 ) 4020 - 4029   2022.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIMS: Abnormal left ventricular diastolic response to preload stress can be an early marker of heart failure (HF). The aim of this study was to assess clinical course in patients with HF with preserved ejection fraction (HFpEF) who underwent preload stress echocardiography. In the subgroup analysis, we assessed the prognosis of patients with unstable signs during preload stress classified by treatment strategies. METHODS AND RESULTS: We prospectively conducted preload stress echocardiographic studies between January 2006 and December 2013 in 211 patients with HFpEF. Fifty-eight patients had abnormal diastolic reserve during preload stress (unstable impaired relaxation: unstable IR). Of 58 patients with unstable IR, 19 patients were assigned to additional therapy by increased or additional therapy and 39 patients were assigned to standard therapy. Composite outcomes were prespecified as the primary endpoint of death and hospitalization for deteriorating HF. During a median period of 6.9 years, 19 patients (33%) reached the composite outcome. Unstable group with standard therapy had significantly shorter event-free survival than stable group. Patients with uptitration of therapy had longer event-free survival than those with standard therapy group after adjustment of laboratory data (hazard ratio, 0.20, 95% confidence interval, 0.05-0.90; P = 0.036); the 10 year event-free survival in patients with and without uptitration of therapy was 93% and 51%, respectively (P = 0.023). CONCLUSIONS: Patients with unstable sign had significantly shorter event-free survival than patients with stable sign. After additional therapy, the prognosis of patients with unstable signs improved. This technique may impact decision-making for improving their prognosis.

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Drug-coated balloon angioplasty for severe pulmonary vein stenosis resulting from cryoballoon ablation for atrial fibrillation.

Koji Yamaguchi, Tetsuzo Wakatsuki, Tomomi Matsuura, Kazuhisa Matsumoto, Yutaka Kawabata, Muneyuki Kadota, Kenya Kusunose, Takayuki Ise, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata

Journal of cardiology cases   26 ( 1 ) 35 - 38   2022.07 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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We performed a drug-coated balloon (DCB) angioplasty for severe pulmonary vein (PV) stenosis resulting from cryoballoon ablation for atrial fibrillation. Three and fourteen months after the angioplasty, follow-up multidetector computed tomography did not show restenosis. Lesion regression was observed at 14-month follow-up. Two years after PV angioplasty with DCB, the patient was well without any symptoms. DCB angioplasty may become an alternative effective procedure for PV stenosis. Learning objective: The usefulness and safety of drug-coated balloon angioplasty for severe pulmonary vein stenosis resulting from cryoballoon ablation for atrial fibrillation was observed at 14-month follow-up.

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A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice.

Uugantsetseg Munkhjargal, Daiju Fukuda, Byambasuren Ganbaatar, Kumiko Suto, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Journal of atherosclerosis and thrombosis   30 ( 4 ) 326 - 334   2022.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIMS: Pharmacological blockade of mineralocorticoid receptors (MRs) is a potential therapeutic approach to reduce cardiovascular complications since MRs play a crucial role in cardiovascular regulation. Recent studies suggest that MR antagonists affect several extrarenal tissues, including vessel function. We investigated the effect of a novel nonsteroidal selective MR blocker, esaxerenone, on diabetes-induced vascular dysfunction. METHODS: Diabetes was induced by a single dose of streptozotocin in 8-week-old male C57BL/6 mice. Esaxerenone (3 mg/kg/day) or a vehicle was administered by gavage to diabetic mice for 3 weeks. Metabolic parameters, plasma aldosterone levels, and parameters related to renal function were measured. Endothelium-dependent or -independent vascular responses of the aortic segments were analyzed with acetylcholine or sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study. RESULTS: Induction of diabetes elevated plasma aldosterone level (P＜0.05) and impaired endothelium-dependent vascular relaxation (P＜0.05). The administration of esaxerenone ameliorated the endothelial dysfunction (P＜0.01) without the alteration of metabolic parameters, blood pressure, and renal function. Esaxerenone improved the eNOSSer1177 phosphorylation in the aorta obtained from diabetic mice (P＜0.05) compared with that in the vehicle-treated group. Furthermore, a major MR agonist, aldosterone, decreased eNOSSer1177 phosphorylation and increased eNOSThr495 phosphorylation in HUVECs, which recovered with esaxerenone. Esaxerenone ameliorated the endothelium-dependent vascular relaxation caused by aldosterone in the aortic segments obtained from C57BL/6 mice (P＜0.001). CONCLUSION: Esaxerenone attenuates the development of diabetes-induced endothelial dysfunction in mice. These results suggest that esaxerenone has potential vascular protective effects in individuals with diabetes.

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Association between cardiovascular risk factors and left ventricular strain distribution in patients without previous cardiovascular disease.

Tomonori Takahashi, Kenya Kusunose, Robert Zheng, Natsumi Yamaguchi, Yukina Hirata, Susumu Nishio, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Journal of echocardiography   20 ( 4 ) 208 - 215   2022.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Some cardiovascular (CV) risk factors, such as hypertension and diabetes mellitus, have been reported to reduce left ventricular (LV) longitudinal strain (LS) even in patients with preserved LV ejection fraction. We hypothesized that multiple CV risk factors might cause changes in myocardial strain. Our study aimed to assess the association between multiple CV risk factors and strain in patients without previous CV disease (CVD). METHODS: We retrospectively evaluated 137 patients without CVD, who underwent echocardiography at our institution between May 2017 and February 2020. They were divided into four groups based on the number of risk factors (group 0: no risk factor, group 1: one risk factor, group 2: two risk factors, and groups 3: three or four risk factors). Risk factors were hypertension, dyslipidemia, diabetes mellitus, and chronic kidney disease. Absolute values of global LS (GLS) and relative apical LS ratio (RALSR) defined using the equation: average apical LS/(average basal LS + average mid LS) and was used as a marker of strain distribution. RESULTS: Out of 137 patients, group 0 had 35 patients, group 1 had 35 patients, group 2 had 32 patients, and group 3 had 35 patients. GLS was 22.4 ± 2.0%, 21.7 ± 2.1%, 21.3 ± 1.8%, 20.7 ± 2.2%, and RALSR was 0.64 ± 0.06, 0.66 ± 0.06, 0.68 ± 0.08, 0.69 ± 0.07 in groups 0-3, respectively. The one-way ANOVA detected significant differences between groups in GLS (p = 0.005) and RALSR (p = 0.037), respectively. Group 3 had a significantly lower GLS and higher RALSR than group 0 (p < 0.05). CONCLUSION: In patients without previous CVD, LS decreased especially from the basal segment as the number of cardiovascular risks increased. The segmental LS may be markers of occult LV dysfunction in patients with CV risk factors.

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Effects of Radiofrequency Catheter Ablation on Cardiac Reserve Using Preload Stress Echocardiography in Paroxysmal and Persistent Atrial Fibrillation.

Nao Ishii, Kenya Kusunose, Ayu Shono, Kensuke Matsumoto, Susumu Nishio, Natsumi Yamaguchi, Yukina Hirata, Tomomi Matsuura, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

The American journal of cardiology   168   71 - 77   2022.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The effects of catheter ablation on exercise tolerance and quality of life in patients with atrial fibrillation (AF) have been reported. We assessed cardiac function in more detail using the leg positive pressure (LPP) technique and found that contractile reserve is particularly important in relation to exercise tolerance and prognosis. In this study, we used the LPP technique to examine changes in contractile reserve immediately after ablation and 6 months later. We prospectively enrolled patients who underwent catheter ablation for AF at 2 institutes. We performed LPP stress echocardiography 2 to 3 days after (FU-1) and 6 months after (FU-2) ablation to examine changes in cardiac function indexes. The primary end point was improvement in contractile reserve. Ultimately, 109 patients (mean age 67.4 ± 9.6 years; 70% men) underwent 2 sessions of LPP stress echocardiography. The median CHA2DS2-VASC score was 2 (interquartile range 13). From FU-1 to FU-2, the change in the stroke volume index after the LPP maneuver increased in patients with paroxysmal and persistent AF with low CHA2DS2-VASC scores (both p <0.05). Regardless of AF subtype, contractile reserve at FU-2 improved in patients with low CHA2DS2-VASC scores compared with that at FU-1. In contrast, patients with high CHA2DS2-VASC scores had no change. In conclusion, patients with AF with a low CHA2DS2-VASC score had improved contractile reserve after ablation, whereas patients with high scores did not show any improvement. Aggressive interventions in patients with high scores may lead to better management after catheter ablation.

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Results of PRospect trial to Elucidate the utility of EchocarDiography-based Cardiac ouTput in acute heart failure (PREDICT).

Hiroyuki Iwano, Hiroto Utsunomiya, Kentaro Shibayama, Hidekazu Tanaka, Akihiro Isotani, Toshinari Onishi, Masaru Obokata, Masaki Izumo, Kenya Kusunose, Atsuko Furukawa, Masahiro Yamada, Takeshi Kitai, Tetsuari Onishi, Masayoshi Yamamoto, Shunsuke Sasaki, Kotaro Nochioka, Yoichi M Ito, Toshihisa Anzai

Journal of cardiology   80 ( 3 ) 218 - 225   2022.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The predictive value of echocardiographic parameters for early worsening heart failure (WHF), worsening of symptoms of heart failure requiring intensification of therapy during an admission for acute decompensated heart failure (ADHF), has not been elucidated. METHODS: Sixteen centers in Japan prospectively enrolled 303 ADHF hospitalized patients who did not receive positive inotropic agents as an initial therapy. Physical and Doppler echocardiographic examinations were performed before the initial therapy and the association of low output findings and occurrence of early WHF were tested. RESULTS: Early WHF occurred in 63 patients with a median duration of 6 (IQR: 2-23) hours from the administration of the initial therapy. In patients with left ventricular (LV) ejection fraction <40% (N = 153), echocardiographic stroke volume index, and cardiac index showed greater c-index [95% confidence interval, 0.71 (0.61-0.79) and 0.72 (0.63-0.80), respectively] compared to single low perfusion finding (symptomatic hypotension, reduced pulse pressure, and impaired mentation) other than cool extremities. When physical findings were combined (low perfusion score), the predictive ability improved to the similar levels of echocardiographic LV output parameters [c-index: 0.69 (0.60-0.76)]. However, addition of cardiac index significantly improved the prognostic ability when added to low perfusion score [0.82 (0.74-0.87), p < 0.001]. In contrast, in patients with LV ejection fraction ≥40% (N = 150), low perfusion score, rather than LV output parameters, was predictive of early WHF [c-index: 0.73 (0.56-0.85)]. CONCLUSIONS: We demonstrated the predictive value of echocardiographic LV output indices for early WHF in ADHF patients with LV systolic dysfunction. These data support the motivation for routine use of echocardiography for initial assessment of ADHF.

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近赤外分光法-血管内超音波法による冠動脈プラークの脆弱性と脂質コア負荷の初評価(First Assessment of Coronary Plaque Vulnerability and Lipid Core Burden Assessed by Near-Infrared Spectroscopy-Intravascular Ultrasound in a Fresh Cadaver)

川端 豊, 若槻 哲三, 山口 浩司, 福田 大受, 西條 良仁, 門田 宗之, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   CRDP4 - 1   2022.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

肺高血圧症における負荷心電図の臨床的有用性(Clinical Utility of Stress Echocardiography in Pulmonary Hypertension)

楠瀬 賢也, 山田 博胤, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   TP20 - 5   2022.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Preload Stress Echocardiography for the Assessment of Heart Failure With Preserved Ejection Fraction.

Kenya Kusunose, Hirotsugu Yamada, Yoshihito Saijo, Susumu Nishio, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

JACC. Cardiovascular imaging   15 ( 2 ) 375 - 378   2022.02 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Clinical clerkship students' preferences and satisfaction regarding online lectures during the COVID-19 pandemic.

Shusuke Yagi, Daiju Fukuda, Takayuki Ise, Koji Yamaguchi, Kenya Kusunose, Muneyuki Kadota, Yutaka Kawabata, Tomomi Matsuura, Tomohiro Soga, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinji Kawahito, Masataka Sata

BMC medical education   22 ( 1 ) 43 - 43   2022.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The COVID-19 pandemic has caused an unprecedented disruption in medical education. Students and lecturers had to adapt to online education. The current study aimed to investigate the level of satisfaction and future preference for online lectures among clinical clerkship students and elucidated the factors that affect these outcomes. METHODS: We selected a sample of 114 medical students undergoing clinical clerkship during the COVID-19 pandemic. We conducted onsite lectures before the pandemic and online lectures after the outbreak. A survey was conducted, and the sample included students and 17 lecturers. The average scores of total satisfaction and future preference related to online lectures were computed. RESULTS: Students' scores on total satisfaction with online lectures and their future preference were higher than those for onsite lectures. Scores on the ease of debating dimension were low and those on accessibility of lectures in online lectures were higher than those in onsite lectures. There was no difference between the two groups in the scores on the comprehensibility and ease of asking questions dimensions. Results of the multiple regression analysis revealed that accessibility determined total satisfaction, and future preference was determined by comprehensibility as well as accessibility. Contrary to students' future preferences, lecturers favored onsite lectures to online ones. CONCLUSION: Online lectures are an acceptable mode of teaching during the COVID-19 pandemic for students undergoing clinical clerkship. Online lectures are expected to become more pervasive to avoid the spread of COVID-19.

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Effect of febuxostat on left ventricular diastolic function in patients with asymptomatic hyperuricemia: a sub analysis of the PRIZE Study

Kusunose K.

Hypertension Research ( Hypertension Research )  45 ( 1 ) 106 - 115   2022.01 [ Peer Review Accepted ]

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Hyperuricemia is related to an increased risk of cardiovascular events from a meta-analysis and antihyperuricemia agents may influence to cardiac function. We evaluated the effect of febuxostat on echocardiographic parameters of diastolic function in patients with asymptomatic hyperuricemia as a prespecified endpoint in the subanalysis of the PRIZE study. Patients in the PRIZE study were assigned randomly to either add-on febuxostat treatment group or control group with only appropriate lifestyle modification. Of the 514 patients in the overall study, 65 patients (31 in the febuxostat group and 34 in the control group) who had complete follow-up echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e') at baseline and after 12 and 24 months were included. The primary endpoint was a comparison of the changes in the E/e' between the two groups from baseline to 24 months. Interestingly, e' was slightly decreased in the control group compared with in the febuxostat group (treatment p = 0.068, time, p = 0.337, treatment × Time, p = 0.217). As a result, there were significant increases in E/e' (treatment p = 0.045, time, p = 0.177, treatment × time, p = 0.137) after 24 months in the control group compared with the febuxostat group. There was no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive troponin I between the two groups during the study period. In conclusions, additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have a potential of preventable effects on the impaired diastolic dysfunction.

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Deep Learning for Detection of Exercise-Induced Pulmonary Hypertension Using Chest X-Ray Images.

Kenya Kusunose, Yukina Hirata, Natsumi Yamaguchi, Yoshitaka Kosaka, Takumasa Tsuji, Jun'ichi Kotoku, Masataka Sata

Frontiers in cardiovascular medicine   9   891703 - 891703   2022 [ Peer Review Accepted ]

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Background: Stress echocardiography is an emerging tool used to detect exercise-induced pulmonary hypertension (EIPH). However, facilities that can perform stress echocardiography are limited by issues such as cost and equipment. Objective: We evaluated the usefulness of a deep learning (DL) approach based on a chest X-ray (CXR) to predict EIPH in 6-min walk stress echocardiography. Methods: The study enrolled 142 patients with scleroderma or mixed connective tissue disease with scleroderma features who performed a 6-min walk stress echocardiographic test. EIPH was defined by abnormal cardiac output (CO) responses that involved an increase in mean pulmonary artery pressure (mPAP). We used the previously developed AI model to predict PH and calculated PH probability in this cohort. Results: EIPH defined as ΔmPAP/ΔCO >3.3 and exercise mPAP >25 mmHg was observed in 52 patients, while non-EIPH was observed in 90 patients. The patients with EIPH had a higher mPAP at rest than those without EIPH. The probability of PH based on the DL model was significantly higher in patients with EIPH than in those without EIPH. Multivariate analysis showed that gender, mean PAP at rest, and the probability of PH based on the DL model were independent predictors of EIPH. A model based on baseline parameters (age, gender, and mPAP at rest) was improved by adding the probability of PH predicted by the DL model (AUC: from 0.65 to 0.74; p = 0.046). Conclusion: Applying the DL model based on a CXR may have a potential for detection of EIPH in the clinical setting.

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Regression of left ventricular hypertrophy after tafamidis therapy in a patient with transthyretin amyloidosis variant.

Shusuke Yagi, Hiromu Yamazaki, Kenya Kusunose, Yusuke Osaki, Takayuki Ise, Muneyuki Kadota, Munkhtsetseg Tserensonom, Yutaka Kawabata, Tomoya Hara, Rie Ueno, Yoshihito Saijo, Tomomi Matsuura, Koji Yamaguchi, Hirotsugu Yamada, Daiju Fukuda, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

The journal of medical investigation : JMI   69 ( 3.4 ) 320 - 322   2022 [ Peer Review Accepted ]

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Transthyretin amyloidosis (ATTR) variant is a life-threatening hereditary disease predominantly affecting the peripheral nervous system and heart. Tafamidis, which prevents the deposition of amyloid by stabilizing transthyretin, is available for the treatment of neuropathy and cardiomyopathy of ATTR. However, whether tafamidis could eliminate established amyloid deposits and improve cardiac function remains unknown. We reported a case of regression of left ventricular hypertrophy after tafamidis therapy in a patient with an ATTR variant. J. Med. Invest. 69 : 320-322, August, 2022.

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Comparison of Direct Oral Anticoagulants for Acute Hospital Mortality in Venous Thromboembolism.

Yuichiro Okushi, Kenya Kusunose, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

American journal of cardiovascular drugs : drugs, devices, and other interventions   22 ( 4 ) 407 - 416   2021.12 [ Peer Review Accepted ]

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BACKGROUND: The choice of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) is at the physician's discretion; however, it is useful to know the differences in the clinical data of DOACs to help physicians choose. OBJECTIVE: We aimed to compare the mortality associated with the use of rivaroxaban, edoxaban, and apixaban in clinical practice. METHODS: We identified 38,245 patients with first hospitalization for VTE from the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). We classified patients into three groups by DOAC (rivaroxaban and edoxaban group, rivaroxaban and apixaban group, and edoxaban and apixaban group) and compared the in-hospital mortality and bleeding risk by propensity score (PS) matching in each group. RESULTS: After PS matching, patients with rivaroxaban use had significantly lower total in-hospital mortality (1.2% vs. 2.1%; odds ratio [OR] 0.55, p = 0.012) and in-hospital mortality within 21 days (0.4% vs. 1.0%; OR 0.41, p = 0.020) and 28 days (0.7% vs. 1.3%; OR 0.53, p = 0.042) than patients with apixaban use. In the subanalysis, significant differences were only observed in patients younger than 80 years of age, patients with pulmonary embolism, and patients without heart failure. There was no significant difference in in-hospital mortality in the other groups and in the rate of bleeding events among the three groups. CONCLUSION: On PS-matched analysis, there was a difference in in-hospital mortality, especially in the rivaroxaban and apixaban group. Identifying the clinical characteristics of patients associated with each DOAC, as well as prognosis, will be useful in determining treatment strategies for VTE.

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Pre-clinical medical student cardiac point-of-care ultrasound curriculum based on the American Society of Echocardiography recommendations: a pilot and feasibility study

Satoshi Jujo, Jannet J. Lee-Jayaram, Brandan I. Sakka, Atsushi Nakahira, Akihisa Kataoka, Masaki Izumo, Kenya Kusunose, Natsinee Athinartrattanapong, Sayaka Oikawa, Benjamin W. Berg

Pilot and Feasibility Studies ( Springer Science and Business Media LLC )  7 ( 1 ) 175   2021.12 [ Peer Review Accepted ]

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<title>Abstract</title><sec> <title>Background</title> Cardiac point-of-care ultrasound (POCUS) training has been integrated into medical school curricula. However, there is no standardized cardiac POCUS training method for medical students. To address this issue, the American Society of Echocardiography (ASE) proposed a framework for medical student cardiac POCUS training. The objective of this pilot study was to develop a medical student cardiac POCUS curriculum with test scoring systems and test the curriculum feasibility for a future definitive study. </sec><sec> <title>Methods</title> Based on the ASE-recommended framework, we developed a cardiac POCUS curriculum consisting of a pre-training online module and hands-on training with a hand-held ultrasound (Butterfly iQ, Butterfly Network Inc., Guilford, CT, USA). The curriculum learning effects were assessed with a 10-point maximum skill test and a 40-point maximum knowledge test at pre-, immediate post-, and 8-week post-training. To determine the curriculum feasibility, we planned to recruit 6 pre-clinical medical students. We semi-quantitatively evaluated the curriculum feasibility in terms of recruitment rate, follow-up rate 8 weeks after training, instructional design of the curriculum, the effect size (ES) of the test score improvements, and participant satisfaction. To gather validity evidence of the skill test, interrater and test-retest reliability of 3 blinded raters were assessed. </sec><sec> <title>Results</title> Six pre-clinical medical students participated in the curriculum. The recruitment rate was 100% (6/6 students) and the follow-up rate 8 weeks after training was 100% (6/6). ESs of skill and knowledge test score differences between pre- and immediate post-, and between pre- and 8-week post-training were large. The students reported high satisfaction with the curriculum. Both interrater and test-retest reliability of the skill test were excellent. </sec><sec> <title>Conclusions</title> This pilot study confirmed the curriculum design as feasible with instructional design modifications including the hands-on training group size, content of the cardiac POCUS lecture, hands-on teaching instructions, and hand-held ultrasound usage. Based on the pilot study findings, we plan to conduct the definitive study with the primary outcome of long-term skill retention 8 weeks after initial training. The definitive study has been registered in <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://clinicaltrials.gov">ClinicalTrials.gov</ext-link> (Identifier: NCT04083924). </sec>

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Impact of cancer on short-term in-hospital mortality after primary acute myocardial infarction

Robert Zheng, Kenya Kusunose, Yuichiro Okushi, Yoshihiro Okayama, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

OPEN HEART ( BMJ PUBLISHING GROUP )  8 ( 2 )   2021.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background Cardiovascular diseases are the second most common cause of mortality among cancer survivors, after death from cancer. We sought to assess the impact of cancer on the short-term outcomes of acute myocardial infarction (AMI), by analysing data obtained from a large-scale database.Methods This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination. We identified patients who were hospitalised for primary AMI between April 2012 and March 2017. Propensity Score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 21 clinically relevant covariates. The main outcome was in-hospital mortality.Results We split 1 52 208 patients into two groups with or without cancer. Patients with cancer tended to be older (cancer group 73 +/- 11 years vs non-cancer group 68 +/- 13 years) and had smaller body mass index (cancer group 22.8 +/- 3.6vs non-cancer 23.9 +/- 4.3). More patients in the non-cancer group had hypertension or dyslipidaemia than their cancer group counterparts. The non-cancer group also had a higher rate of percutaneous coronary intervention (cancer 92.6% vs non-cancer 95.2%). Patients with cancer had a higher 30-day mortality (cancer 6.0% vs non-cancer 5.3%) and total mortality (cancer 8.1% vs non-cancer 6.1%) rate, but this was statistically insignificant after PS matching.Conclusion Cancer did not significantly impact short-term in hospital mortality rates after hospitalisation for primary AMI.

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Impact of cancer on short-term in-hospital mortality after primary acute myocardial infarction.

Robert Zheng, Kenya Kusunose, Yuichiro Okushi, Yoshihiro Okayama, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Open heart   8 ( 2 )   2021.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Cardiovascular diseases are the second most common cause of mortality among cancer survivors, after death from cancer. We sought to assess the impact of cancer on the short-term outcomes of acute myocardial infarction (AMI), by analysing data obtained from a large-scale database. METHODS: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination. We identified patients who were hospitalised for primary AMI between April 2012 and March 2017. Propensity Score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 21 clinically relevant covariates. The main outcome was in-hospital mortality. RESULTS: We split 1 52 208 patients into two groups with or without cancer. Patients with cancer tended to be older (cancer group 73±11 years vs non-cancer group 68±13 years) and had smaller body mass index (cancer group 22.8±3.6 vs non-cancer 23.9±4.3). More patients in the non-cancer group had hypertension or dyslipidaemia than their cancer group counterparts. The non-cancer group also had a higher rate of percutaneous coronary intervention (cancer 92.6% vs non-cancer 95.2%). Patients with cancer had a higher 30-day mortality (cancer 6.0% vs non-cancer 5.3%) and total mortality (cancer 8.1% vs non-cancer 6.1%) rate, but this was statistically insignificant after PS matching. CONCLUSION: Cancer did not significantly impact short-term in-hospital mortality rates after hospitalisation for primary AMI.

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Use of Echocardiography and Heart Failure In-Hospital Mortality from Registry Data in Japan.

Kenya Kusunose, Yuichiro Okushi, Yoshihiro Okayama, Robert Zheng, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Journal of cardiovascular development and disease   8 ( 10 )   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Echocardiography requires a high degree of skill on the part of the examiner, and the skill may be more improved in larger volume centers. This study investigated trends and outcomes associated with the use and volume of echocardiographic exams from a real-world registry database of heart failure (HF) hospitalizations. METHODS: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). A first analysis was performed to assess the trend of echocardiographic examinations between 2012 and 2016. A secondary analysis was performed to assess whether echocardiographic use was associated with in-hospital mortality in 2015. RESULTS: During this period, the use of echocardiography grew at an average annual rate of 6%. Patients with echocardiography had declining rates of hospital mortality, and these trends were associated with high hospitalization costs. In the 2015 sample, a total of 52,832 echocardiograms were examined, corresponding to 65.6% of all HF hospital admissions for that year. We found that the use and volume of echocardiography exams were associated with significantly lower odds of all-cause hospital mortality in heart failure (adjusted odds ratio (OR): 0.48 for use of echocardiography and 0.78 for the third tertile; both p < 0.001). CONCLUSIONS: The use of echocardiography was associated with decreased odds of hospital mortality in HF. The volumes of echocardiographic examinations were also associated with hospital mortality.

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Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial.

Kenya Kusunose, Takumi Imai, Atsushi Tanaka, Kaoru Dohi, Kazuki Shiina, Takahisa Yamada, Keisuke Kida, Kazuo Eguchi, Hiroki Teragawa, Yasuchika Takeishi, Nobuyuki Ohte, Hirotsugu Yamada, Masataka Sata, Koichi Node

Cardiovascular diabetology   20 ( 1 ) 186 - 186   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. METHODS: Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. RESULTS: The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04). CONCLUSIONS: In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

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Left Atrial Strain Associated with Functional Recovery in Patients Receiving Optimal Treatment for Heart Failure.

Yuta Torii, Kenya Kusunose, Yukina Hirata, Susumu Nishio, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography   34 ( 9 ) 966 - 975   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Heart failure with recovered ejection fraction (HFrecEF) has been reported in several previous studies to have a better prognosis than heart failure with reduced ejection fraction (HFrEF). However, the factors associated with HFrecEF have not been identified. The aim of this study was to test the hypothesis that left atrial (LA) strain could help identify patients with recovered ejection fraction (EF) among those with heart failure (HF) with low EF on admission. METHODS: One hundred consecutive patients hospitalized for the first time for new-onset HF were enrolled. Patients were clinically diagnosed with HFrEF on admission (left ventricular EF < 40%) and received optimal treatment for HF. Twenty-eight patients improved to HFrecEF during 6 months of follow-up. RESULTS: Regarding clinical background, there were significantly more women and a lower rate of atrial fibrillation in the HFrecEF group than in the HFrEF group. In a multivariate logistic regression analysis, LA strain was an independent predictor of HFrecEF, even after adjustment for gender and left ventricular EF (odds ratio: 4.06; 95% CI: 2.04-8.07; P < .001). A cutoff value of 10.8% for LA strain showed high sensitivity (96%) and specificity (82%) in identifying HFrecEF in patients with HF presenting with low EF on admission. During a follow-up period of 24 ± 13 months, 31 patients (31%) had cardiovascular death or readmission for HF. Patients with reduced LA strain (<10.8%) had significantly shorter event-free survival than those with preserved LA strain (P = .02). CONCLUSIONS: LA strain is a useful indicator for predicting HFrecEF and should be considered as a routine measurement in patients with HFrEF on admission.

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Deep Learning for Detection of Elevated Pulmonary Artery Wedge Pressure Using Standard Chest X-Ray.

Yukina Hirata, Kenya Kusunose, Takumasa Tsuji, Kohei Fujimori, Jun'ichi Kotoku, Masataka Sata

The Canadian journal of cardiology   37 ( 8 ) 1198 - 1206   2021.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: To accurately diagnose and control heart failure (HF), it is important to carry out a simple assessment of elevated pulmonary arterial wedge pressure (PAWP). The aim of this study was to develop and validate an objective method for detecting elevated PAWP by applying deep learning (DL) to a chest x-ray (CXR). METHODS: We enrolled 1013 consecutive patients with a right-heart catheter between October 2009 and February 2020. We developed a convolutional neural network to identify patients with elevated PAWP (> 18 mm Hg) as the actual value of PAWP to be used in the dataset for training. In the prospective validation dataset used to detect elevated PAWP, the area under the receiver operating characteristic curve (AUC) was calculated using the DL model that evaluated the CXR. RESULTS: In the prospective validation dataset, the AUC of the DL model with CXR was not significantly different from the AUC produced by brain natriuretic peptide (BNP) and the echocardiographic left-ventricular diastolic dysfunction (DD) algorithm (DL model: 0.77 vs BNP: 0.77 vs DD algorithm: 0.70; respectively; P = NS for all comparisons); it was, however, significantly higher than the AUC of the cardiothoracic ratio (DL model vs cardiothoracic ratio [CTR]: 0.66, P = 0.044). The model based on 3 parameters (BNP, DD algorithm, and CTR) was improved by adding the DL model (AUC: from 0.80 to 0.86; P = 0.041). CONCLUSIONS: Applying the DL model based on a CXR (a classical, universal, and low-cost test) is useful for screening for elevated PAWP.

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How to standardize the measurement of left ventricular ejection fraction.

Kenya Kusunose, Robert Zheng, Hirotsugu Yamada, Masataka Sata

Journal of medical ultrasonics (2001)   49 ( 1 ) 35 - 43   2021.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Despite recent advances in imaging for myocardial deformation, left ventricular ejection fraction (LVEF) is still the most important index for systolic function in daily practice. Its role in multiple fields (e.g., valvular heart disease, myocardial infarction, cancer therapy-related cardiac dysfunction) has been a mainstay in guidelines. In addition, assessment of LVEF is vital to clinical decision-making in patients with heart failure. However, notable limitations to LVEF include poor inter-observer reproducibility dependent on observer skill, poor acoustic windows, and variations in measurement techniques. To solve these problems, methods for standardization of LVEF by sharing reference images among observers and artificial intelligence for accurate measurements have been developed. In this review, we focus on the standardization of LVEF using reference images and automated LVEF using artificial intelligence.

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Activated Factor X Signaling Pathway via Protease-Activated Receptor 2 Is a Novel Therapeutic Target for Preventing Atrial Fibrillation.

Tomomi Matsuura, Takeshi Soeki, Daiju Fukuda, Etsuko Uematsu, Takeshi Tobiume, Tomoya Hara, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masataka Sata

Circulation journal : official journal of the Japanese Circulation Society   85 ( 8 ) 1383 - 1391   2021.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF.Methods and Results:In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. CONCLUSIONS: The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.

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Evaluation of the input site and characteristics of the antegrade fast pathway based on three-dimensional bi-atrial stimulus-ventricle mapping.

Kazuhisa Matsumoto, Takeshi Tobiume, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daijyu Fukuda, Tetsuzo Wakatsuki, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata

Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing   63 ( 2 ) 417 - 424   2021.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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PURPOSE: Previous studies examined the right atrial (RA) input site of the antegrade fast pathway (AFp) (AFpI). However, the left atrial (LA) input to the atrioventricular (AV) node has not been extensively evaluated. In this study, we created three-dimensional (3-D) bi-atrial stimulus-ventricle (St-V) maps and analyzed the input site and characteristics of the AFp in both the RA and LA. METHODS: Forty-four patients diagnosed with atrial fibrillation or WPW syndrome were included in this study. Three-dimensional bi-atrial St-V mapping was performed using an electroanatomical mapping system. Sites exhibiting the minimal St-V interval (MinSt-V) were defined as AFpIs and were classified into seven segments, four in the RA (F, S, M, and I) and three in the LA (M1, M2, and M3). By combining the MinSt-V in the RA and LA, the AFpIs were classified into three types: RA, LA, and bi-atrial (BA) types. The clinical and electrophysiological characteristics were compared. RESULTS: AFpIs were most frequently observed at site S in the RA (34%) and M2 in the LA (50%), and the BA type was the most common (57%). AFpIs in the LA were recognized in 75% of the patients. There were no clinical or electrophysiological indicators for predicting AFpI sites. CONCLUSIONS: Three-dimensional bi-atrial St-V maps could classify AFpIs in both the RA and LA. AFpIs in the LA were frequently recognized. There were no significant clinical or electrophysiological indicators for predicting AFpI sites, and 3-D bi-atrial St-V mapping was the only method to reveal the precise AFp input site.

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STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases.

Phuong Tran Pham, Daiju Fukuda, Sachiko Nishimoto, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Yutaka Takahashi, Tomohito Sato, Kimie Tanaka, Kumiko Suto, Yutaka Kawabata, Koji Yamaguchi, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi, Michio Shimabukuro, Mitsutoshi Setou, Glen N Barber, Masataka Sata

European heart journal   42 ( 42 ) 4336 - 4348   2021.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIMS : Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis. METHODS AND RESULTS : Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP. CONCLUSION : Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.

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Clinical Utility of Overlap Time for Incomplete Relaxation to Predict Cardiac Events in Heart Failure.

Kenya Kusunose, Miharu Arase, Robert Zheng, Yukina Hirata, Susumu Nishio, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Journal of cardiac failure   27 ( 11 ) 1222 - 1230   2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The overlap time of transmitral flow can be a novel marker of subclinical left ventricular dysfunction for predicting adverse events in heart failure (HF). We aimed to (1) investigate the role of overlap time of the E-A wave in association with clinical parameters and (2) evaluate whether the overlap time could add prognostic information with respect to other conventional clinical prognosticators in HF. METHODS: We prospectively evaluated 153 patients hospitalized with HF (mean age 68 ± 15 years; 63% male). The primary endpoint was readmission following HF or cardiac death. RESULTS: During a median period of 25 months, 43 patients were readmitted or died. Overlap time appeared to be associated with worse outcomes. After adjustment for readmission scores and ratios of diastolic filling period and cardiac cycle length in a Cox proportional-hazards model, overlap time was associated with event-free survival, independent of elevated left atrial pressure based on guidelines. When overlap time was added to the model based on clinical variables and elevated left atrial pressure, the C-statistic significantly improved from 0.70 (95% CI: 0.63-0.77) to 0.77 (95% CI: 0.69-0.83, compared) (P = 0.035). CONCLUSION: This preliminary study suggested that prolonged overlap time may have potential for predicting readmission and cardiac mortality risk assessment in patients with HF.

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Predictive value of left atrial function for latent paroxysmal atrial fibrillation as the cause of embolic stroke of undetermined source.

Kenya Kusunose, Hironori Takahashi, Susumu Nishio, Yukina Hirata, Robert Zheng, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi, Masataka Sata

Journal of cardiology   78 ( 5 ) 355 - 361   2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission. METHODS: Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF. RESULTS: We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p-values <0.05). CONCLUSIONS: LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF.

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Inhibition of S1P Receptor 2 Attenuates Endothelial Dysfunction and Inhibits Atherogenesis in Apolipoprotein E-Deficient Mice.

Byambasuren Ganbaatar, Daiju Fukuda, Masakazu Shinohara, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Ken-Ichi Hirata, Masataka Sata

Journal of atherosclerosis and thrombosis   28 ( 6 ) 630 - 642   2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIM: The bioactive lipid, sphingosine-1-phosphate (S1P), has various roles in the physiology and pathophysiology of many diseases. There are five S1P receptors; however, the role of each S1P receptor in atherogenesis is still obscure. Here we investigated the contribution of S1P receptor 2 (S1P2) to atherogenesis by using a specific S1P2 antagonist, ONO-5430514, in apolipoprotein E-deficient (Apoe-/- ) mice. METHODS: Apoe-/- mice fed with a western-type diet (WTD) received ONO-5430514 (30 mg/kg/day) or vehicle. To examine the effect on atherogenesis, Sudan IV staining, histological analysis, qPCR, and vascular reactivity assay was performed. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments. RESULTS: WTD-fed Apoe-/- mice had significantly higher S1P2 expression in the aorta compared with wild-type mice. S1P2 antagonist treatment for 20 weeks reduced atherosclerotic lesion development (p＜0.05). S1P2 antagonist treatment for 8 weeks ameliorated endothelial dysfunction (p＜0.05) accompanied with significant reduction of lipid deposition, macrophage accumulation, and inflammatory molecule expression in the aorta compared with vehicle. S1P2 antagonist attenuated the phosphorylation of JNK in the abdominal aorta compared with vehicle (p＜0.05). In HUVEC, S1P promoted inflammatory molecule expression such as MCP-1 and VCAM-1 (p＜0.001), which was attenuated by S1P2 antagonist or a JNK inhibitor (p＜0.01). S1P2 antagonist also inhibited S1P-induced JNK phosphorylation in HUVEC (p＜0.05). CONCLUSIONS: Our results suggested that an S1P2 antagonist attenuates endothelial dysfunction and prevents atherogenesis. S1P2, which promotes inflammatory activation of endothelial cells, might be a therapeutic target for atherosclerosis.

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Acute Hospital Mortality of Venous Thromboembolism in Patients With Cancer From Registry Data.

Yuichiro Okushi, Kenya Kusunose, Yoshihiro Okayama, Robert Zheng, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Journal of the American Heart Association   10 ( 11 ) e019373   2021.06 [ Peer Review Accepted ]

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Background The prognosis of patients with cancer-venous thromboembolism (VTE) is not well known because of a lack of registry data. Moreover, there is also no knowledge on how specific types are related to prognosis. We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with a matched cohort without cancer using real-world registry data of VTE. Methods and Results This study was based on the Diagnosis Procedure Combination database in the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Of 5 106 151 total patients included in JROAD-DPC, we identified 49 580 patients who were first hospitalized with VTE from April 2012 to March 2017. Propensity score was estimated with a logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. After propensity matching, there were 25 148 patients with VTE with or without cancer. On propensity score-matched analysis with 25 148 patients with VTE, patients with cancer had higher total in-hospital mortality within 7 days (1.3% versus 1.1%, odds ratio [OR], 1.66; 95% CI, 1.31-2.11; P<0.0001), 14 days (2.5% versus 1.5%, OR, 2.07; 95% CI, 1.72-2.49; P<0.0001), and 30 days (4.8% versus 2.0%, OR, 2.85; 95% CI, 2.45-3.31; P<0.0001). On analysis for each type of cancer, in-hospital mortality in 11 types of cancer was significantly high, especially pancreas (OR, 12.96; 95% CI, 6.41-26.20), biliary tract (OR, 8.67; 95% CI, 3.00-25.03), and liver (OR, 7.31; 95% CI, 3.05-17.50). Conclusions Patients with cancer had a higher in-hospital acute mortality for VTE than those without cancer, especially in pancreatic, biliary tract, and liver cancers.

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Infective Endocarditis from Furuncle with Meningitis Complication Caused by Methicillin-resistant Staphylococcus aureus.

Shusuke Yagi, Tomoko Takahashi, Keiji Murakami, Momoyo Azuma, Mikio Sugano, Ryosuke Miyamoto, Mariko Niki, Hirotsugu Yamada, Yutaka Kawabata, Akihiro Tani, Daiju Fukuda, Muneyuki Kadota, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Tomomi Matsuura, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki, Hiroki Hata, Masataka Sata

Internal medicine (Tokyo, Japan)   60 ( 20 ) 3251 - 3255   2021.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Infective endocarditis (IE) may be acquired in the community as community-acquired (CA) IE or in the healthcare setting. In Japan, cases of CA-methicillin-resistant Staphylococcus aureus (MRSA) infection as skin infection have been increasing. CA-MRSA strains, including the USA300 clone, have higher pathogenicity and are more destructive to tissue than healthcare-associated MRSA strains because of the toxins they produce, including arginine-catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL). However, only a few IE cases induced by USA300 have been reported. We herein report a 64-year-old man who developed CA-IE from a furuncle caused by USA300 MRSA producing PVL and ACME, which resulted in complications of meningitis.

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Clinical usefulness of the HFA-PEFF diagnostic scoring system in identifying late elderly heart failure with preserved ejection fraction patients

Yoshihiro Seo, Tomoko Ishizu, Masaki Ieda, Nobuyuki Ohte, Masako Asakawa, Chikage Oshita, Masanori Takada, Mitsufumi Furuya, Fumiko Sakamaki, Hitomi Hashimoto, Takako Minami, Harutoshi Tamura, Akiko Okunaga, Yuichi Oshima, Yoshie Omori, Takuma Aoyama, Takako Iino, Makoto Saito, Tetsuya Kasuga, Taro Minagawa, Satoshi Kibira, Hidekazu Tanaka, Yoshihisa Horizoe, Hiroyoshi Yamamoto, Shintaro Beppu, Misun Pak, Miyako Nagumo, Masaki Izumo, Atsushi Kobayashi, Shohei Kikuchi, Noriaki Iwahashi, Kotaro Numaguchi, Toshinari Onishi, Yuki Izumi, Hirotsugu Yamada, Kenya Kusunose, Hideo Kawakami, Hiroyuki Iwano

Circulation Journal   85 ( 5 ) 604 - 611   2021.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in elderly. This study investigated the diagnostic ability of the HFA-PEFF scoring system in elderly patients (>75 years of age). Methods and Results: This study enrolled 286 subjects aged >75 years (130 men; mean [± SD] age 81.5±5.1 years): 95 healthy controls, 98 with hypertension (HT), and 93 with HFpEF. The HFA-PEFF score was calculated as a sum of points in functional, morphological, and biomarker domains. In the HFpEF group, 84%, 84%, and 70% of subjects met the major functional, morphological, and biomarker criteria for HFpEF, respectively. Thus, 73 subjects with HFpEF (78%) were diagnosed as having HFpEF using the HFA-PEFF scoring system. In contrast, among the healthy controls and subjects with HT, 52% and 72%, respectively, met the major functional criteria for HFpEF, 28% and 53%, respectively, met the morphological criteria, and 0% and 24%, respectively, met the biomarker criteria. As such, 32 subjects with HT (33%) were diagnosed with HFpEF. Even in the healthy control group, 72% were classified as having an intermediate probability of HFpEF, and 3 were diagnosed with HFpEF. Conclusions: In the late elderly, the HFA-PEFF scoring system diagnosed subjects with HFpEF precisely. In addition, this scoring system may be able to detect early stage HFpEF in the subclinical population.

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Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice.

Kumiko Suto, Daiju Fukuda, Masakazu Shinohara, Byambasuren Ganbaatar, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Ken-Ichi Hirata, Masataka Sata

Journal of atherosclerosis and thrombosis   28 ( 12 ) 1349 - 1360   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIMS: Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in vascular regulation. Fibrates have recently been shown to attenuate vascular complications in diabetics. Here we examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, on plasma eicosanoid levels and endothelial function in diabetic mice. METHODS: Diabetes was induced in 7-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). Pemafibrate (0.3 mg/kg/day) was administered orally for 3 weeks. Untreated mice received vehicle. Circulating levels of eicosanoids and free fatty acids were measured using both gas and liquid chromatography-mass spectrometry. Endothelium-dependent and endothelium-independent vascular responses to acetylcholine and sodium nitroprusside, respectively, were analyzed. RESULTS: Pemafibrate reduced both triglyceride and non-high-density lipoprotein -cholesterol levels (P＜0.01), without affecting body weight. It also decreased circulating levels of AA (P＜0.001), thromboxane B2 (P＜0.001), prostaglandin E2, leukotriene B4 (P＜0.05), and 5-hydroxyeicosatetraenoic acid (P＜0.001), all of which were elevated by the induction of diabetes. In contrast, the plasma levels of 15-deoxy-Δ12,14-prostaglandin J2, which declined following diabetes induction, remained unaffected by pemafibrate treatment. In diabetic mice, pemafibrate decreased palmitic acid (PA) and stearic acid concentrations (P＜0.05). Diabetes induction impaired endothelial function, whereas pemafibrate ameliorated it (P＜0.001). The results of ex vivo experiments indicated that eicosanoids or PA impaired endothelial function. CONCLUSION: Pemafibrate diminished the levels of vasoconstrictive eicosanoids and free fatty acids accompanied by a reduction of triglyceride. These effects may be associated with the improvement of endothelial function by pemafibrate in diabetic mice.

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Acute Hormonal Effect of the Angiotensin Receptor-Neprilysin Inhibitor in Patients with Chronic Heart Failure(和訳中)

門田 宗之, 八木 秀介, 伊勢 孝之, 川端 豊, 松浦 朋美, 楠瀬 賢也, 飛梅 威, 山口 浩司, 山田 博胤, 添木 武, 若槻 哲三, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ64 - 7   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Effects of Vitamin D Supplementation on Heart Failure Mortality from Japanese Registry of All Cardiac and Vascular Datasets(和訳中)

阿部 美保, 楠瀬 賢也, 大櫛 祐一郎, Zheng Robert, 伊勢 孝之, 飛梅 威, 山口 浩司, 八木 秀介, 福田 大受, 山田 博胤, 添木 武, 若槻 哲三, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ63 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Early and Chronic Phased Local Coagulative Responses Following Bioresorbable-polymer Drugeluting Stent Implantation(和訳中)

山口 浩司, 若槻 哲三, 大櫛 祐一郎, 數藤 久美子, 松本 和久, 高橋 智紀, 門田 宗之, 川端 豊, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ38 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Deep Learning for Detection of Elevated Pulmonary Artery Wedge Pressure Using Standard Chest X-Ray(和訳中)

平田 有紀奈, 楠瀬 賢也, 辻 拓将, 藤森 康平, 山口 夏美, 森田 沙瑛, 西尾 進, 大櫛 祐一郎, 瀬野 弘光, 高橋 智紀, 伊勢 孝之, 飛梅 威, 山口 浩司, 福田 大受, 八木 秀介, 山田 博胤, 添木 武, 若槻 哲三, 古徳 純一, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   SS23 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Prognostic Impact of Cancer on Venous Thromboembolism from Japanese Registry of All Cardiac and Vascular Datasets(和訳中)

大櫛 祐一郎, 楠瀬 賢也, 岡山 佳弘, 山田 博胤, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   PL01 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

癌が静脈血栓塞栓症の予後へ及ぼす影響 循環器疾患診療実態調査から(Prognostic Impact of Cancer on Venous Thromboembolism from Japanese Registry of All Cardiac and Vascular Datasets)

大櫛 祐一郎, 楠瀬 賢也, 岡山 佳弘, 山田 博胤, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   PL01 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

生体吸収性ポリマー薬剤溶出性ステント留置後の初期および慢性期の局所凝固反応(Early and Chronic Phased Local Coagulative Responses Following Bioresorbable-polymer Drugeluting Stent Implantation)

山口 浩司, 若槻 哲三, 大櫛 祐一郎, 數藤 久美子, 松本 和久, 高橋 智紀, 門田 宗之, 川端 豊, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ38 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

慢性心不全患者におけるアンジオテンシン受容体-ネプリライシン阻害剤の急性ホルモン作用(Acute Hormonal Effect of the Angiotensin Receptor-Neprilysin Inhibitor in Patients with Chronic Heart Failure)

門田 宗之, 八木 秀介, 伊勢 孝之, 川端 豊, 松浦 朋美, 楠瀬 賢也, 飛梅 威, 山口 浩司, 山田 博胤, 添木 武, 若槻 哲三, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ64 - 7   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

心不全死亡率に対するビタミンD補充の効果 循環器疾患診療実態調査より(Effects of Vitamin D Supplementation on Heart Failure Mortality from Japanese Registry of All Cardiac and Vascular Datasets)

阿部 美保, 楠瀬 賢也, 大櫛 祐一郎, Zheng Robert, 伊勢 孝之, 飛梅 威, 山口 浩司, 八木 秀介, 福田 大受, 山田 博胤, 添木 武, 若槻 哲三, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ63 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

冠動脈内微小管腔構造と心外膜脂肪組織およびプラーク形成との関連 新鮮遺体を用いた研究(Relationship between Coronary Intraplaque Microluminal Structure and Epicardial Adipose Tissue and Plaque Formation: A Fresh Cadaveric Study)

川端 豊, 若槻 哲三, 山口 浩司, 福田 大受, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ17 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

リアルワールドでの人工知能を活用した心エコー図検査およびX線検査(Utilization of Artificial Intelligence for Echocardiography and X-ray in the Real World)

楠瀬 賢也, 山田 博胤, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   MIRAI3 - 1   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Utilization of Artificial Intelligence for Echocardiography and X-ray in the Real World(和訳中)

楠瀬 賢也, 山田 博胤, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   MIRAI3 - 1   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Relationship between Coronary Intraplaque Microluminal Structure and Epicardial Adipose Tissue and Plaque Formation: A Fresh Cadaveric Study(和訳中)

川端 豊, 若槻 哲三, 山口 浩司, 福田 大受, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  85回   OJ17 - 3   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Antegrade slow pathway mapping of typical atrioventricular nodal reentrant tachycardia based on direct slow pathway capture.

Takeshi Tobiume, Ritsushi Kato, Tomomi Matsuura, Kazuhisa Matsumoto, Motoki Hara, Nobuyuki Takamori, Yoshio Taketani, Keisuke Okawa, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daijyu Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki, Takeshi Soeki, Masataka Sata, Kazuo Matsumoto

Journal of arrhythmia   37 ( 1 ) 128 - 139   2021.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Radiofrequency (RF) ablation of typical atrioventricular nodal reentrant tachycardia (tAVNRT) is performed without revealing out the location of antegrade slow pathway (ASp). In this study, we studied a new electrophysiological method of identifying the site of ASp. Methods: This study included 19 patients. Repeated series of very high-output single extrastimulations (VhoSESts) were delivered at the anatomical slow pathway region during tAVNRT. Tachycardia cycle length (TCL), coupling interval (CI), and return cycle (RC) were measured and the prematurity of VhoSESts [ΔPM (= TCL - CI)] and the prolongation of RCs [ΔPL (= RC - TCL)] were calculated. Pacing sites were classified into two categories: (i) ASp capture sites [DSPC(+) sites], where two different RCs were shown, and ASp non-capture sites [DSPC(-) sites], where only one RC was shown. RF ablation was performed at DSPC(+) sites and/or sites with catheter-induced mechanical trauma (CIMT) to ASp. Results: DSPC(+) sites were shown in 13 patients (68%). RF ablation was successful in all patients without any degree of atrioventricular block nor recurrence. Total number of RF applications was 1.8 ± 1.1. Minimal distance between successful ablation sites and DSPC(+)/CIMT sites and His bundle (HB) electrogram recording sites was 1.9 ± 0.8 mm and 19.8 ± 6.1 mm, respectively. ΔPL of more than 92.5 ms, ΔPL/TCL of more than 0.286, and ΔPL/ΔPM of more than 1.565 could identify ASp with sensitivity of 100%, 91.1%, and 88.9% and specificity of 92.9%, 97.0%, and 97.6%, respectively. Conclusions: Sites with ASp capture and CIMT were close to successful ablation sites and could be useful indicators of tAVNRT ablation.

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Cardiac reserve by 6-minute walk stress echocardiography in systemic sclerosis.

Miharu Arase, Kenya Kusunose, Sae Morita, Natsumi Yamaguchi, Yukina Hirata, Susumu Nishio, Yuichiro Okushi, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Open heart   8 ( 1 )   2021.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVES: There is a high prevalence of left ventricular diastolic dysfunction (LVDD) in systemic sclerosis (SSc) which is associated with high mortality. Thus, early detection of LVDD could be important in management of SSc. We hypothesised that exercise echocardiography in SSc patients with normal resting haemodynamics may expose early phase LVDD, which could affect its prognosis, defined as cardiovascular death and unplanned hospitalisation for heart failure. METHODS: Between January 2014 and December 2018, we prospectively enrolled 140 patients with SSc who underwent 6-minute walk (6MW) stress echocardiographic studies with normal range of estimated mean pulmonary arterial pressure (mPAP) (<25 mm Hg) and mean pulmonary artery wedge pressure (mPAWP) (<15 mm Hg) at rest. We used ΔmPAP/Δcardiac output (CO) to assess pulmonary vascular reserve and ΔmPAWP/ΔCO to assess LV cardiac reserve between resting and post-6MW. RESULTS: During a median period of 3.6 years (IQR 2.0-5.1 years), 25 patients (18%) reached the composite outcome. Both ΔmPAP/ΔCO and ΔmPAWP/ΔCO in patients with events were significantly greater than in those without events (8.9±3.8 mm Hg/L/min vs 3.0±1.7 mm Hg/L/min; p=0.002, and 2.2±0.9 mm Hg/L/min vs 0.9±0.5 mm Hg/L/min; p<0.001, respectively). Patients with both impaired LV cardiac reserve (ΔmPAWP/ΔCO>1.4 mm Hg/L/min) and impaired pulmonary vascular reserve (ΔmPAP/ΔCO>3.0 mm Hg/L/min) had worse outcomes compared with those without these abnormalities (p<0.001). CONCLUSION: The 6MW stress echocardiography revealed impaired LV cardiac reserve in SSc patients with normal resting haemodynamics. Furthermore, LV cardiac reserve independently associates with clinical worsening in SSc, providing incremental prognostic utility, in addition to pulmonary vascular parameters.

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Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals.

Kenya Kusunose, Yuichiro Okushi, Yoshihiro Okayama, Robert Zheng, Miho Abe, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Nutrients   13 ( 2 )   2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.

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Deleterious Effects of Epicardial Adipose Tissue Volume on Global Longitudinal Strain in Patients With Preserved Left Ventricular Ejection Fraction

Maimaituxun, G; Kusunose, K; Yamada, H; Fukuda, D; Yagi, S; Torii, Y; Yamada, N; Soeki, T; Masuzaki, H; Sata, M; Shimabukuro, M

FRONTIERS IN CARDIOVASCULAR MEDICINE ( Frontiers in Cardiovascular Medicine )  7   607825 - 607825   2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function. Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%. Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116-117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects. Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.

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Congenital Hypogonadotropic Hypogonadism with Early-Onset Coronary Artery Disease.

Akira Takashima, Shusuke Yagi, Koji Yamaguchi, Kiyoe Kurahashi, Yuko Kojima, Robert Zheng, Takayuki Ise, Kenya Kusunose, Sumiko Yoshida, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Ken-Ichi Aihara, Masashi Akaike, Masataka Sata

The journal of medical investigation : JMI   68 ( 1.2 ) 189 - 191   2021 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders. J. Med. Invest. 68 : 189-191, February, 2021.

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Deep Learning Analysis of Echocardiographic Images to Predict Positive Genotype in Patients With Hypertrophic Cardiomyopathy.

Sae X Morita, Kenya Kusunose, Akihiro Haga, Masataka Sata, Kohei Hasegawa, Yoshihiko Raita, Muredach P Reilly, Michael A Fifer, Mathew S Maurer, Yuichi J Shimada

Frontiers in cardiovascular medicine   8   669860 - 669860   2021 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Genetic testing provides valuable insights into family screening strategies, diagnosis, and prognosis in patients with hypertrophic cardiomyopathy (HCM). On the other hand, genetic testing carries socio-economical and psychological burdens. It is therefore important to identify patients with HCM who are more likely to have positive genotype. However, conventional prediction models based on clinical and echocardiographic parameters offer only modest accuracy and are subject to intra- and inter-observer variability. We therefore hypothesized that deep convolutional neural network (DCNN, a type of deep learning) analysis of echocardiographic images improves the predictive accuracy of positive genotype in patients with HCM. In each case, we obtained parasternal short- and long-axis as well as apical 2-, 3-, 4-, and 5-chamber views. We employed DCNN algorithm to predict positive genotype based on the input echocardiographic images. We performed 5-fold cross-validations. We used 2 reference models-the Mayo HCM Genotype Predictor score (Mayo score) and the Toronto HCM Genotype score (Toronto score). We compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus DCNN-derived probability and the reference model. We calculated the p-value by performing 1,000 bootstrapping. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we examined the net reclassification improvement. We included 99 adults with HCM who underwent genetic testing. Overall, 45 patients (45%) had positive genotype. The new model combining Mayo score and DCNN-derived probability significantly outperformed Mayo score (AUC 0.86 [95% CI 0.79-0.93] vs. 0.72 [0.61-0.82]; p < 0.001). Similarly, the new model combining Toronto score and DCNN-derived probability exhibited a higher AUC compared to Toronto score alone (AUC 0.84 [0.76-0.92] vs. 0.75 [0.65-0.85]; p = 0.03). An improvement in the sensitivity, specificity, PPV, and NPV was also achieved, along with significant net reclassification improvement. In conclusion, compared to the conventional models, our new model combining the conventional and DCNN-derived models demonstrated superior accuracy to predict positive genotype in patients with HCM.

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Deep learning to predict elevated pulmonary artery pressure in patients with suspected pulmonary hypertension using standard chest X ray

Kenya Kusunose, Yukina Hirata, Takumasa Tsuji, Jun'ichi Kotoku, Masataka Sata

Scientific Reports ( Springer Science and Business Media LLC )  10 ( 1 )   2020.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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<title>Abstract</title>Accurate diagnosis of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment. We hypothesized that application of artificial intelligence (AI) to the chest X-ray (CXR) could identify elevated pulmonary artery pressure (PAP) and stratify the risk of heart failure hospitalization with PH. We retrospectively enrolled a total of 900 consecutive patients with suspected PH. We trained a convolutional neural network to identify patients with elevated PAP (&gt; 20 mmHg) as the actual value of PAP. The endpoints in this study were admission or occurrence of heart failure with elevated PAP. In an independent evaluation set for detection of elevated PAP, the area under curve (AUC) by the AI algorithm was significantly higher than the AUC by measurements of CXR images and human observers (0.71 vs. 0.60 and vs. 0.63, all p &lt; 0.05). In patients with AI predicted PH had 2-times the risk of heart failure with PH compared with those without AI predicted PH. This preliminary work suggests that applying AI to the CXR in high risk groups has limited performance when used alone in identifying elevated PAP. We believe that this report can serve as an impetus for a future large study.

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Identifying the extent of oral fluid droplets on echocardiographic machine consoles in COVID-19 era.

Kenya Kusunose, Kosuke Matsunaga, Hirotsugu Yamada, Masataka Sata

Journal of echocardiography   18 ( 4 ) 268 - 270   2020.12 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice.

Arief Rahadian, Daiju Fukuda, Hotimah Masdan Salim, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata

Journal of atherosclerosis and thrombosis   27 ( 11 ) 1141 - 1151   2020.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIM: Recent studies have demonstrated that selective sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism. METHOD: Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE－/－) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed. RESULT: Canagliflozin decreased blood glucose (P＜0.001) and total cholesterol (P＜0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P＜0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P＜0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P＜0.05, both). Methylglyoxal also decreased the phosphorylation of eNOSSer1177 and Akt but increased the phosphorylation of eNOSThr495 and p38 MAPK in HUVECs. CONCLUSION: Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE－/－ mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.

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Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction.

Yoshihito Saijo, Kenya Kusunose, Yuichiro Okushi, Hirotsugu Yamada, Hiroaki Toba, Masataka Sata

Heart (British Cardiac Society)   106 ( 22 ) 1752 - 1758   2020.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVE: The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up. METHODS: We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up. RESULTS: LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015). CONCLUSIONS: Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.

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Association between Sarcopenia/Lower Muscle Mass and Short-Term Regression of Deep Vein Thrombosis Using Direct Oral Anticoagulants.

Yuta Torii, Kenya Kusunose, Robert Zheng, Hirotsugu Yamada, Rie Amano, Rikizo Matsumoto, Yukina Hirata, Susumu Nishio, Nao Yamada, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Yoshihiro Okayama, Masataka Sata

International heart journal   61 ( 4 ) 787 - 794   2020.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Advanced age, obesity, and muscle weakness are independent factors in the onset of deep vein thrombosis (DVT). Recently, an association between sarcopenia and DVT has been reported. We hypothesized that sarcopenia related factors, observed by ultrasonography, are associated with the regression effect on the thrombus following anticoagulation therapy. The present study focused on gastrocnemius muscle (GCM) thickness and the GCM's internal echogenic brightness. We examined the association with DVT regression following direct oral anticoagulants (DOACs) treatment.The prospective cohort study period was between October 2017 and August 2018. We enrolled 46 patients diagnosed with DVT by ultrasonography, who were aged >60 years old and treated with DOACs. Sarcopenia was evaluated using the Asian Working Group for Sarcopenia flowchart. The average DOACs treatment period was 94 days, and 29 patients exhibited thrombus regression. On univariate logistic regression analysis, sarcopenia, average GCM diameter index, and gastrocnemius integrated backscatter index were significantly associated with thrombus regression. In a multivariate model, only the average GCM diameter index correlated with thrombus regression.The average GCM diameter index is associated with DVT regression treated with DOACs. Considering the GCM diameter during DVT treatment can be a marker to make a decision for the treatment of DVT.

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循環器疾患のAI画像診断 心エコー検査における人工知能の現状と将来展望(Prospects for the Present and Future of Artificial Intelligence in Echocardiography)

楠瀬 賢也, 山田 博胤, 中谷 敏, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  84回   シンポジウム22 - 6   2020.07 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

薬剤溶出性ステント留置後の慢性的局所的な血液凝固反応に対しストラット厚の薄さとポリマー吸収の速さが及ぼす影響(The Effect of Lower Strut Thickness and Faster Polymer Resorption on Chronic Local Coagulative Response after Drug Eluting Stent Implantation)

山口 浩司, 若槻 哲三, 大櫛 祐一郎, 數藤 久美子, 松本 和久, 高橋 智紀, 門田 宗之, 上野 理絵, 川端 豊, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  84回   PJ26 - 1   2020.07 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

薬剤溶出性ステント留置後の慢性的局所的な血液凝固反応に対しストラット厚の薄さとポリマー吸収の速さが及ぼす影響(The Effect of Lower Strut Thickness and Faster Polymer Resorption on Chronic Local Coagulative Response after Drug Eluting Stent Implantation)

山口 浩司, 若槻 哲三, 大櫛 祐一郎, 數藤 久美子, 松本 和久, 高橋 智紀, 門田 宗之, 上野 理絵, 川端 豊, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  84回   PJ26 - 1   2020.07 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

循環器疾患のAI画像診断 心エコー検査における人工知能の現状と将来展望(Prospects for the Present and Future of Artificial Intelligence in Echocardiography)

楠瀬 賢也, 山田 博胤, 中谷 敏, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  84回   シンポジウム22 - 6   2020.07 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Empagliflozin ameliorates endothelial dysfunction and suppresses atherogenesis in diabetic apolipoprotein E-deficient mice.

Byambasuren Ganbaatar, Daiju Fukuda, Masakazu Shinohara, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Ken-Ichi Hirata, Masataka Sata

European journal of pharmacology   875   173040 - 173040   2020.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Recent studies reported cardioprotective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors; however, the underlying mechanisms are still obscure. Here, we investigated whether empagliflozin attenuates atherogenesis and endothelial dysfunction in diabetic apolipoprotein E-deficient (ApoE-/-) mice. Male streptozotocin (STZ) - induced diabetic ApoE-/- mice were treated with empagliflozin for 12 or 8 weeks. Empagliflozin lowered blood glucose (P < 0.001) and lipid levels in diabetic ApoE-/- mice. Empagliflozin treatment for 12 weeks significantly decreased atherosclerotic lesion size in the aortic arch (P < 0.01) along with reduction of lipid deposition (P < 0.05), macrophage accumulation (P < 0.001), and inflammatory molecule expression in plaques compared with the untreated group. Empagliflozin treatment for 8 weeks significantly ameliorated diabetes-induced endothelial dysfunction as determined by the vascular response to acetylcholine (P < 0.001). Empagliflozin reduced RNA expression of a macrophage marker, CD68, and inflammatory molecules such as MCP-1 (P < 0.05) and NADPH oxidase subunits in the aorta compared with the untreated group. Empagliflozin also reduced plasma levels of vasoconstrictive eicosanoids, prostaglandin E2 and thromboxane B2 (P < 0.001), which were elevated in diabetic condition. Furthermore, empagliflozin attenuated RNA expression of inflammatory molecules in perivascular adipose tissue (PVAT), suggesting the reduction of inflammation in PVAT. In in vitro studies, methylglyoxal (MGO), a precursor of AGEs, significantly increased the expression of inflammatory molecules such as MCP-1 and TNF-α in a murine macrophage cell line, RAW264.7. Our results indicated that empagliflozin attenuated endothelial dysfunction and atherogenesis in diabetic ApoE-/- mice. Reduction of vasoconstrictive eicosanoids and inflammation in the vasculature and PVAT may have a role as underlying mechanisms at least partially.

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Deep Learning for Assessment of Left Ventricular Ejection Fraction from Echocardiographic Images.

Kenya Kusunose, Akihiro Haga, Natsumi Yamaguchi, Takashi Abe, Daiju Fukuda, Hirotsugu Yamada, Masafumi Harada, Masataka Sata

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography   33 ( 5 ) 632 - 635   2020.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Clinically Feasible and Accurate View Classification of Echocardiographic Images Using Deep Learning.

Kenya Kusunose, Akihiro Haga, Mizuki Inoue, Daiju Fukuda, Hirotsugu Yamada, Masataka Sata

Biomolecules   10 ( 5 )   2020.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A proper echocardiographic study requires several video clips recorded from different acquisition angles for observation of the complex cardiac anatomy. However, these video clips are not necessarily labeled in a database. Identification of the acquired view becomes the first step of analyzing an echocardiogram. Currently, there is no consensus whether the mislabeled samples can be used to create a feasible clinical prediction model of ejection fraction (EF). The aim of this study was to test two types of input methods for the classification of images, and to test the accuracy of the prediction model for EF in a learning database containing mislabeled images that were not checked by observers. We enrolled 340 patients with five standard views (long axis, short axis, 3-chamber view, 4-chamber view and 2-chamber view) and 10 images in a cycle, used for training a convolutional neural network to classify views (total 17,000 labeled images). All DICOM images were rigidly registered and rescaled into a reference image to fit the size of echocardiographic images. We employed 5-fold cross validation to examine model performance. We tested models trained by two types of data, averaged images and 10 selected images. Our best model (from 10 selected images) classified video views with 98.1% overall test accuracy in the independent cohort. In our view classification model, 1.9% of the images were mislabeled. To determine if this 98.1% accuracy was acceptable for creating the clinical prediction model using echocardiographic data, we tested the prediction model for EF using learning data with a 1.9% error rate. The accuracy of the prediction model for EF was warranted, even with training data containing 1.9% mislabeled images. The CNN algorithm can classify images into five standard views in a clinical setting. Our results suggest that this approach may provide a clinically feasible accuracy level of view classification for the analysis of echocardiographic data.

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Atherosclerotic Coronary Plaque Is Associated With Adventitial Vasa Vasorum and Local Inflammation in Adjacent Epicardial Adipose Tissue in Fresh Cadavers.

Hiroyuki Ito, Tetsuzo Wakatsuki, Koji Yamaguchi, Daiju Fukuda, Yutaka Kawabata, Tomomi Matsuura, Kenya Kusunose, Takayuki Ise, Takeshi Tobiume, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Yoshihiro Tsuruo, Masataka Sata

Circulation journal : official journal of the Japanese Circulation Society   84 ( 5 ) 769 - 775   2020.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The coronary adventitia has recently attracted attention as a source of inflammation because it harbors nutrient blood vessels, termed the vasa vasorum (VV). This study assessed the link between local inflammation in adjacent epicardial adipose tissue (EAT) and coronary arterial atherosclerosis in fresh cadavers.Methods and Results:Lesion characteristics in the left anterior descending coronary artery of 10 fresh cadaveric hearts were evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), and the density of the VV and levels of inflammatory molecules from the adjacent EAT were measured for each of the assessed lesions. The lesions were divided into lipid-rich, lipid-moderate, and lipid-poor groups according to percentage lipid volume assessed by IB-IVUS. Higher expression of inflammatory molecules (i.e., vascular endothelial growth factor A [VEGFA] andVEGFB) was observed in adjacent EAT of lipid-rich (n=11) than in lipid-poor (n=11) lesions (7.99±3.37 vs. 0.45±0.85 arbitrary units [AU], respectively, forVEGFA; 0.27±0.15 vs. 0.11±0.07 AU, respectively, forVEGFB; P<0.05). The density of adventitial VV was greater in lipid-rich than lipid-poor lesions (1.50±0.58% vs. 0.88±0.23%; P<0.05). CONCLUSIONS: Lipid-rich coronary plaques are associated with adventitial VV and local inflammation in adjacent EAT in fresh cadavers. This study suggests that local inflammation of EAT is associated with coronary plaque progression via the VV.

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Study protocol for prospect trial to elucidate the utility of echocardiography-based cardiac output in acute heart failure (PREDICT).

Hiroyuki Iwano, Kentaro Shibayama, Takeshi Kitai, Kenya Kusunose, Tetsuari Onishi, Hidekazu Tanaka, Toshihisa Anzai

Journal of echocardiography   18 ( 4 ) 235 - 239   2020.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Early worsening heart failure (WHF), defined as worsening of symptoms and signs of heart failure requiring intensification of medical or mechanical therapy during an admission for acute decompensated heart failure (ADHF), has recently been recognized as a risk of morbidity or mortality after the discharge. Although echocardiographic parameters of left ventricular (LV) output has been shown to be associated with long-term outcome in heart failure patients, its predictive value for early WHF has not been elucidated. METHODS: Prospect trial to Elucidate the utility of EchocarDiography-based Cardiac output in acute heart failure (PREDICT) is a multicenter, nonrandomized, prospective observational study to test the predictive value of echocardiographic LV output parameters for early WHF in ADHF patients. We will enroll patients admitted to 16 participating hospitals due to ADHF who did not receive positive inotropic agents as an initial therapy. Primary outcome will be set at early WHF defined as need for initiation of positive inotropic agents within 7 days after the admission. Predictive accuracy will be compared between Doppler echocardiographic LV output (stroke distance, stroke volume index, and cardiac index) and low perfusion findings assessed by physical examination. RESULTS: N/A. CONCLUSIONS: The PREDICT is expected to provide large data set to test the predictive value of echocardiographic LV output for early WHF in ADHF patients.

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Diastolic Mitral Regurgitation on Color M-Mode Echocardiography in a Patient With Complete Atrioventricular Block.

Akihiro Tani, Kenya Kusunose, Kazuhisa Matsumoto, Hirotsugu Yamada, Masataka Sata

Circulation reports   2 ( 3 ) 207 - 208   2020.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction

Maimaituxun, G; Yamada, H; Fukuda, D; Yagi, S; Kusunose, K; Hirata, Y; Nishio, S; Soeki, T; Masuzaki, H; Sata, M; Shimabukuro, M

CIRCULATION JOURNAL ( 一般社団法人 日本循環器学会 )  84 ( 2 ) 203 - 216   2020.01

Type of publication: Research paper (scientific journal)

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<p><b><i>Background:</i></b>Although full-volume quantification of epicardial adipose tissue (EAT) is a predictor of LV diastolic dysfunction (LVDD), how localized EAT depots are linked to LVDD remains unclear. We evaluated the effect of local EAT depots on LV diastolic function parameters in patients with preserved LV ejection fraction (LVEF).</p><p><b><i>Methods and Results:</i></b>From 423 consecutive patients who underwent cardiac CT angiography, we recruited 252 with sinus rhythm and normal LVEF. The EAT volume index (EATV/body surface area) and the localized EAT thickness around the right coronary artery (EAT_RCA), left anterior descending artery (EAT_LAD), left circumflex artery (EAT_LCX), right ventricle (EAT_RV), left ventricle (EAT_LV), right atrium (EAT_RA), and left atrium (EAT_LA) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m², P=0.010), EAT_LCX(10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EAT_LV(2.6±1.6 vs. 2.1±1.4 mm, P=0.024) were greater than in the non-LVDD group (n=181). In contrast, EAT_LCXand EAT_LVwere markedly associated with decreased lateral e’ and increased lateral E/e’. Multiple regression analysis indicated that EAT_LCXand EAT_LVwere strongly associated with LV diastolic function parameters.</p><p><b><i>Conclusions:</i></b>Localized EAT depots are linked to altered mitral annular motion. Further study is warranted to clarify whether localized EAT depots are functionally linked to the clinical manifestations of LVDD.</p>

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Elderly Japanese Standard Data of Echocardiography; From J-LONG study

Yoshihiro Seo, Tomoko Ishizu, Masaki Ieda, Nobuyuki Ohte, Masako Asakawa, Chikage Oshita, Masanori Takada, Mitsufumi Furuya, Fumiko Sakamaki, Hitomi Hashimoto, Takako Minami, Harutoshi Tamura, Akiko Okunaga, Yuichi Oshima, Yoshie Omori, Takuma Aoyama, Takako Iino, Makoto Saito, Tetsuya Kasuga, Taro Minagawa, Satoshi Kibira, Hidekazu Tanaka, Yoshihisa Horizoe, Hiroyoshi Yamamoto, Shintaro Beppu, Misun Pak, Miyako Nagumo, Masaki Izumo, Atsushi Kobayashi, Shohei Kikuchi, Noriaki Iwahashi, Kotaro Numaguchi, Toshinari Onishi, Yuki Izumi, Hirotsugu Yamada, Kenya Kusunose, Hideo Kawakami, Hiroyuki Iwano

Journal of Echocardiography   18 ( 3 ) 175 - 182   2020 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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© 2020, Japanese Society of Echocardiography. Background: Age-related changes in cardiac morphology and function have not been unknown in the elderly. The Japanese eLderly data Of Normal echocardioGraphy (J-LONG) study is a prospective multicenter cohort study and aimed to investigate the echocardiographic data in the healthy Japanese elderly. Methods: Thirty domestic facilities participated in this study, and 130 healthy subjects (57 men, 73 women, 79.6 ± 4.7 years, range 75–98 years, interquartile range 76–82 years) were enrolled in this cohort. Echocardiographic and clinical data sets were obtained in each facility, and total analyses were performed in the University of Tsukuba. Results: Almost all cardiac morphological data were significantly larger in men than those in women. However, corrected data by body surface area (BSA) were similar or closer between genders. As a gender difference, the negative correlation between BSA and age was observed in women only (r = − 0.46, p < 0.001), showing the independent determinant of women's left ventricular end-diastolic volume (LVEDV) was age (β = − 0.29, p = 0.01), but not BSA. In men, LVEDV was significantly correlated with BSA (β = 0.42, p = 0.001), but not with age (p = 0.10). Also, women had higher LV ejection fraction (70 ± 7.1 vs. 68 ± 4.9%, p = 0.02), lower E/A (0.67 ± 0.16 vs. 0.75 ± 0.21, p = 0.02), and higher E/eʹ (10 ± 2.7 vs. 8.9 ± 2.5, p = 0.03) as compared to men. Conclusions: The J-LONG study suggested that correction by the physique was needed to interpret echocardiographic data of the elderly. Also, gender differences and age-related changes in cardiac morphology and function were observed, and further studies are needed to confirm the clinical significance.

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Effects of L-/N-Type Calcium Channel Blockers on Angiotensin II-Renin Feedback in Hypertensive Patients.

Yutaka Kawabata, Takeshi Soeki, Hiroyuki Ito, Tomomi Matsuura, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki, Mitsuhiro Kitani, Kazuhiro Kawano, Yoshio Taketani, Masataka Sata

International journal of hypertension   2020   6653851 - 6653851   2020 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Objectives: Cilnidipine, an L-/N-type calcium channel blocker (CCB), has unique organ-protective properties due to suppression of hyperactivity in the sympathetic nervous system and renin-angiotensin system (RAS). In this study, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing the RAS. Methods: A total of 25 hypertensive patients receiving a RAS inhibitor were randomly assigned to a cilnidipine (n = 12) or amlodipine (n = 13) group. The effects of cilnidipine on proteinuria and angiotensin II-renin feedback were assessed. Results: After 6 months of treatment, both systolic and diastolic blood pressures were significantly reduced to a similar extent in both groups. The urine albumin-to-creatinine ratio was significantly lower in the cilnidipine group (p < 0.05) than in the amlodipine group. Amlodipine increased plasma angiotensin I and angiotensin II levels (p < 0.05), whereas cilnidipine did not. Interestingly, the cilnidipine group had a higher ratio of angiotensin-(1-7) (Ang-(1-7)) to angiotensin II in plasma than the amlodipine group (p < 0.05). Conclusions: The L-/N-type CCB cilnidipine, but not amlodipine, decreased urinary albumin excretion in hypertensive patients. Cilnidipine also increased the ratio of Ang-(1-7) to angiotensin II in plasma, which might be one factor underlying its beneficial effects.

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Improvement of global longitudinal strain following high-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with amyloid light-chain cardiac amyloidosis: a case report

Yukina Hirata, Kenya Kusunose, Hirokazu Miki, Hirotsugu Yamada

European Heart Journal - Case Reports ( Oxford University Press (OUP) )  3 ( 4 ) 1 - 6   2019.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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<title>Abstract</title> <sec> <title>Background</title> Cardiac amyloidosis (CA) is a secondary form of cardiomyopathy where abnormal accumulation of amyloid protein in the myocardial interstitium causes cardiac hypertrophy and myocardial fibrosis. If primary CA advances to heart failure, most patients do not survive for very long after the diagnosis. </sec> <sec> <title>Case summary</title> A 40-year-old man was admitted to our hospital for dyspnoea, progressive anaemia, and decreased appetite. He has diagnosed with amyloid light-chain (AL) amyloidosis. Although BD treatment (bortezomib + dexamethasone) and medical treatment were started, there was no sign of improvement. Then, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) was initiated. Pretreatment echocardiography revealed typical findings of CA, such as ventricular wall thickening, valvular thickening, diastolic dysfunction, and pericardial effusion. Global longitudinal strain (GLS) was significantly reduced, and bull's-eye mapping showed typical apical sparing. After auto-PBSCT, GLS gradually improved and was almost normal after 2 years. Other echocardiographic parameters, functional status, and laboratory data also showed that there was significant regression of CA. </sec> <sec> <title>Discussion</title> Although the prognosis in primary CA is extremely poor, we achieved long-term survival in a patient with effective high-dose chemotherapy and auto-PBSCT. Global longitudinal strain may be a useful marker of prognosis, regression, and recovery. </sec>

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Noninvasive assessment of left-ventricular diastolic electromechanical coupling in hypertensive heart disease.

Saito Y, Yamada H, Kusunose K, Saito K, Sata M

Journal of echocardiography   17 ( 4 ) 206 - 212   2019.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: There is a need to stratify patients who may develop heart failure because of the current "heart failure pandemic". We hypothesized that noninvasive assessment of diastolic electromechanical coupling by electrocardiography and Doppler echocardiography may be clinically useful for risk stratification of hypertensive patients who may develop heart failure. METHODS: We measured the time from the peak to end of the T wave (TpTe) as an electrophysiological parameter, and peak early diastolic mitral flow (E) and lateral annular (e') velocities as mechanical parameters in 109 patients with hypertension. Relationships between these parameters and their association with the prognosis were evaluated. RESULTS: The e' was inversely correlated with TpTe (p < 0.001) and QTc (p < 0.014), whereas E/e' was positively correlated with TpTe (p < 0.001) and QTc (p < 0.001). The TpTe predicted patients with E/e' > 12. There were 24 cardiovascular events during follow-up (57 ± 20 months), and Kaplan-Meier analysis showed that outcome was worse (p = 0.003) in patients with higher E/e' than lower E/e'; however, there was no difference between patients with longer TpTe (≧72 ms) and shorter TpTe (< 72 ms). CONCLUSION: The correlation of TpTe with e' and E/e' in hypertensive patients suggests that these parameters reflect diastolic ventricular electromechanical coupling. The E/e' predicted outcome, and an elevated E/e' should be suspected when TpTe is prolonged (> 72 ms). Noninvasive evaluation of diastolic electromechanical coupling is clinically useful in patients with hypertension for predicting their outcome.

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Pulmonary Artery Hypertension-Specific Therapy Improves Exercise Tolerance and Outcomes in Exercise-Induced Pulmonary Hypertension.

Kusunose K, Yamada H, Nishio S, Hirata Y, Saijo Y, Torii Y, Yamada N, Ise T, Yamaguchi K, Fukuda D, Yagi S, Soeki T, Wakatsuki T, Sata M

JACC. Cardiovascular imaging   12 ( 12 ) 2576 - 2579   2019.12 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Association of Echocardiography Before Major Elective Non-Cardiac Surgery With Improved Postoperative Outcomes - Possible Implications for Patient Care.

Kusunose K, Torii Y, Yamada H, Nishio S, Hirata Y, Saijo Y, Ise T, Yamaguchi K, Fukuda D, Yagi S, Soeki T, Wakatsuki T, Sata M

Circulation journal : official journal of the Japanese Circulation Society   83 ( 12 ) 2512 - 2519   2019.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Whether preoperative echocardiography improves postoperative outcomes is not well established, so we examined the value of echocardiographic assessment on the onset of postoperative heart failure (HF), and determining which patients benefitted most from undergoing echocardiography prior to major elective non-cardiac surgery.Methods and Results:We identified all patients aged 50 years and older who had major elective non-cardiac surgery, and excluded patients with previously identified severe cardiovascular disease. The primary endpoint was the onset of HF during hospitalization. A total of 806 patients were included in the analysis. During hospitalization, 49 patients (6%) reached the primary endpoint. Within the matched cohort, preoperative echocardiography was associated with a statistically significant decrease in postoperative HF (hazard ratio: 0.46, P=0.01). In subgroup analyses, age, sex, body surface area, hypertension, diabetes mellitus, prior HF, surgical type, chronic kidney disease, pulmonary disease, and malignancy influenced the association of echocardiography with postoperative HF. CONCLUSIONS: The use of echocardiography in elderly patients with certain risk factors was associated with improved postoperative outcomes. The basis for this finding remains to be determined; particularly whether echocardiography is simply a marker of a population with better outcomes or whether it leads to better management that improves outcomes.

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Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice.

Aini K, Fukuda D, Tanaka K, Higashikuni Y, Hirata Y, Yagi S, Kusunose K, Yamada H, Soeki T, Sata M

International heart journal   60 ( 6 ) 1421 - 1429   2019.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Thrombin inhibition by dabigatran attenuates endothelial dysfunction in diabetic mice.

Rahadian A, Fukuda D, Salim HM, Yagi S, Kusunose K, Yamada H, Soeki T, Shimabukuro M, Sata M

Vascular pharmacology   124   106632 - 106632   2019.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Diabetic patients have coagulation abnormalities, in which thrombin plays a key role. Whereas accumulating evidence suggests that it also contributes to the development of vascular dysfunction through the activation of protease-activated receptors (PARs). Here we investigated whether the blockade of thrombin attenuates endothelial dysfunction in diabetic mice. Induction of diabetes by streptozotocin (STZ) increased the expression of PAR1, PAR3, and PAR4 in the aorta. STZ-induced diabetic mice showed impairment of endothelial function, while the administration of dabigatran etexilate, a direct thrombin inhibitor, significantly attenuated endothelial dysfunction in diabetic mice with no alteration of metabolic parameters including blood glucose level. Dabigatran did not affect endothelium-independent vasodilation. Dabigatran decreased the expression of inflammatory molecules (e.g., MCP-1 and ICAM-1) in the aorta of diabetic mice. Thrombin increased the expression of these inflammatory molecules and the phosphorylation of IκBα, and decreased the phosphorylation of eNOSSer1177 in human umbilical endothelial cells (HUVEC). Thrombin significantly impaired the endothelium-dependent vascular response of aortic rings obtained from wild-type mice. Inhibition of NF-κB attenuated thrombin-induced inflammatory molecule expression in HUVEC and ameliorated thrombin-induced endothelial dysfunction in aortic rings. Dabigatran attenuated the development of diabetes-induced endothelial dysfunction. Thrombin signaling may serve as a potential therapeutic target in diabetic condition.

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Updated Left Ventricular Diastolic Function Recommendations and Cardiovascular Events in Patients with Heart Failure Hospitalization.

Torii Y, Kusunose K, Yamada H, Nishio S, Hirata Y, Amano R, Yamao M, Zheng R, Saijo Y, Yamada N, Ise T, Yamaguchi K, Yagi S, Soeki T, Wakatsuki T, Sata M

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography   32 ( 10 ) 1286 - 1297.e2   2019.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Evaluation of diastolic dysfunction is crucial in determining elevated left atrial pressure. However, a validation of the long-term prognostic value of the newly proposed algorithm updated in 2016 has not been performed. The aim of the present study was to investigate the relative value of the updated 2016 diastolic dysfunction grading system for the incidence of readmission in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). METHODS: Two hundred thirty-two patients hospitalized with HF were retrospectively evaluated. Subjects were divided into two subgroups: those with HFrEF (n = 127) and those with HFpEF (n = 105). Readmission risk scores were calculated using the Yale Center for Outcomes Research and Evaluation HF, LACE index, and HOSPITAL scores. The primary end point was readmission following HF and cardiac death. RESULTS: Over a period of 24 months, 86 patients were either readmitted or died. Multivariate Cox analysis was performed on both the HFrEF and HFpEF groups. In the HFrEF group, both the 2009 and 2016 algorithms had superior incremental value for the association of the primary end point to several readmission risk scores. In the HFpEF group, only the 2016 algorithm led to significant improvement in association with the primary end point. The 2016 algorithm had incremental value over several readmission risk scores alone. CONCLUSIONS: The recommendations of the 2016 algorithm can be useful for readmission and cardiac mortality risk assessment in patients with HFrEF and HFpEF. The use of echocardiography to estimate elevated left atrial pressure appears to identify a higher risk group and may allow a more tailored approach to therapy.

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Association Between Right Ventricular Contractile Function and Cardiac Events in Isolated Postcapillary and Combined Pre- and Postcapillary Pulmonary Hypertension.

Kusunose K, Yamada N, Yamada H, Nishio S, Saijo Y, Hirata Y, Torii Y, Ise T, Yamaguchi K, Fukuda D, Yagi S, Soeki T, Wakatsuki T, Sata M

Journal of cardiac failure   26 ( 1 ) 43 - 51   2019.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Recent studies have shown that patients with combined pre- and postcapillary pulmonary hypertension (CpcPH) had worse outcomes than those with isolated postcapillary pulmonary hypertension (IpcPH). However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes, using echocardiography, and the association between RV longitudinal strain and cardiac events. METHODS AND RESULTS: We prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. We included 137 patients with Group 2 PH. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients experienced the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (HR: 0.84, P = 0.003; HR: 0.86, P = 0.001). CONCLUSIONS: Lower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role in PH phenotypes.

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Deterioration of biventricular strain is an early marker of cardiac involvement in confirmed sarcoidosis.

Kusunose K, Fujiwara M, Yamada H, Nishio S, Saijo Y, Yamada N, Hirata Y, Torii Y, Ise T, Yamaguchi K, Fukuda D, Yagi S, Soeki T, Wakatsuki T, Sata M

European heart journal cardiovascular Imaging   21 ( 7 ) 796 - 804   2019.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIMS: Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. METHODS AND RESULTS: LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: -18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). CONCLUSION: Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.

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Rivaroxaban, a specific FXa inhibitor, improved endothelium-dependent relaxation of aortic segments in diabetic mice.

Pham PT, Fukuda D, Yagi S, Kusunose K, Yamada H, Soeki T, Shimabukuro M, Sata M

Scientific reports   9 ( 1 ) 11206 - 11206   2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Activated factor X (FXa) plays a central role in the coagulation cascade, while it also mediates vascular function through activation of protease-activated receptors (PARs). Here, we examined whether inhibition of FXa by rivaroxaban, a direct FXa inhibitor, attenuates endothelial dysfunction in streptozotocin (STZ)-induced diabetic mice. Induction of diabetes increased the expression of a major FXa receptor, PAR2, in the aorta (P < 0.05). Administration of rivaroxaban (10 mg/kg/day) to diabetic wild-type (WT) mice for 3 weeks attenuated endothelial dysfunction as determined by acetylcholine-dependent vasodilation compared with the control (P < 0.001), without alteration of blood glucose level. Rivaroxaban promoted eNOSSer1177 phosphorylation in the aorta (P < 0.001). Induction of diabetes to PAR2-deficient (PAR2-/-) mice did not affect endothelial function and eNOSSer1177 phosphorylation in the aorta compared with non-diabetic PAR2-/- mice. FXa or a PAR2 agonist significantly impaired endothelial function in aortic rings obtained from WT mice, but not in those from PAR2-/- mice. FXa promoted JNK phosphorylation (P < 0.01) and reduced eNOSSer1177 phosphorylation (P < 0.05) in human coronary artery endothelial cells (HCAEC). FXa-induced endothelial dysfunction in aortic rings (P < 0.001) and eNOSSer1177 phosphorylation (P < 0.05) in HCAEC were partially ameliorated by a JNK inhibitor. Rivaroxaban ameliorated diabetes-induced endothelial dysfunction. Our results suggest that FXa or PAR2 is a potential therapeutic target.

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SGLT2阻害薬canagliflozinは糖尿病発症性ApoE-/-マウスにおいて内皮機能障害とアテローム性動脈硬化症を軽減する(SGLT2 inhibitor, Canagliflozin, Ameliorate Endothelial Dysfunction and Atherosclerosis in Diabetic ApoE-/- Mice)

Arief Rahadian, 福田 大受, Hotima Salim, 八木 秀介, 楠瀬 賢也, 山田 博胤, 添木 武, 佐田 政隆

日本性機能学会雑誌 ( (一社)日本性機能学会 )  34 ( 2 ) 190 - 190   2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

非糖尿病アポリポタンパク質E欠損マウスにおいてDPP-4阻害薬vildagliptinは内皮機能障害を予防する(Vildagliptin, a DPP-4 Inhibitor, prevents endothelial dysfunction in non-diabetic apolipoprotein E-deficient mice)

アイニ・クンドゥズアイ, 福田 大受, 八木 秀介, 楠瀬 賢也, 山田 博胤, 添木 武, 佐田 政隆

日本性機能学会雑誌 ( (一社)日本性機能学会 )  34 ( 2 ) 189 - 189   2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

野生型マウスにおいてFXaの直接阻害薬であるrivaroxabanは糖尿病誘発性内皮機能障害を抑制する(Rivaroxaban, a direct inhibitor of FXa, attenuated diabetes-induced endothelial dysfunction in wild-type mice)

Pham Tran Phuong, 福田 大受, 八木 秀介, 楠瀬 賢也, 山田 博胤, 添木 武, 島袋 充生, 佐田 政隆

日本性機能学会雑誌 ( (一社)日本性機能学会 )  34 ( 2 ) 191 - 191   2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Utilization of Artificial Intelligence in Echocardiography.

Kenya Kusunose, Akihiro Haga, Takashi Abe, Masataka Sata

Circulation journal : official journal of the Japanese Circulation Society   83 ( 8 ) 1623 - 1629   2019.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Echocardiography has a central role in the diagnosis and management of cardiovascular disease. Precise and reliable echocardiographic assessment is required for clinical decision-making. Even if the development of new technologies (3-dimentional echocardiography, speckle-tracking, semi-automated analysis, etc.), the final decision on analysis is strongly dependent on operator experience. Diagnostic errors are a major unresolved problem. Moreover, not only can cardiologists differ from one another in image interpretation, but also the same observer may come to different findings when a reading is repeated. Daily high workloads in clinical practice may lead to this error, and all cardiologists require precise perception in this field. Artificial intelligence (AI) has the potential to improve analysis and interpretation of medical images to a new stage compared with previous algorithms. From our comprehensive review, we believe AI has the potential to improve accuracy of diagnosis, clinical management, and patient care. Although there are several concerns about the required large dataset and "black box" algorithm, AI can provide satisfactory results in this field. In the future, it will be necessary for cardiologists to adapt their daily practice to incorporate AI in this new stage of echocardiography.

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冠動脈疾患に対する心外膜脂肪組織肥厚度の性別特異的影響(Gender specific impact of epicardial adipose tissue thickness on coronary artery disease)

マイマイチュクン・グリヌ, 福田 大受, 八木 秀介, 平田 有紀奈, 岩瀬 俊, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 山口 浩司, 山田 博胤, 添木 武, 若槻 哲三, 佐田 政隆, 島袋 充生

日本抗加齢医学会総会プログラム・抄録集 ( (一社)日本抗加齢医学会 )  19回   254 - 254   2019.06 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

A Deep Learning Approach for Assessment of Regional Wall Motion Abnormality From Echocardiographic Images.

Kusunose K, Abe T, Haga A, Fukuda D, Yamada H, Harada M, Sata M

JACC. Cardiovascular imaging   13 ( 2 Pt 1 ) 374 - 381   2019.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVES: This study investigated whether a deep convolutional neural network (DCNN) could provide improved detection of regional wall motion abnormalities (RWMAs) and differentiate among groups of coronary infarction territories from conventional 2-dimensional echocardiographic images compared with that of cardiologists, sonographers, and resident readers. BACKGROUND: An effective intervention for reduction of misreading of RWMAs is needed. The hypothesis was that a DCNN trained using echocardiographic images would provide improved detection of RWMAs in the clinical setting. METHODS: A total of 300 patients with a history of myocardial infarction were enrolled. From this cohort, 3 groups of 100 patients each had infarctions of the left anterior descending (LAD) artery, the left circumflex (LCX) branch, and the right coronary artery (RCA). A total of 100 age-matched control patients with normal wall motion were selected from a database. Each case contained cardiac ultrasonographs from short-axis views at end-diastolic, mid-systolic, and end-systolic phases. After the DCNN underwent 100 steps of training, diagnostic accuracies were calculated from the test set. Independently, 10 versions of the same model were trained, and ensemble predictions were performed using those versions. RESULTS: For detection of the presence of WMAs, the area under the receiver-operating characteristic curve (AUC) produced by the deep learning algorithm was similar to that produced by the cardiologists and sonographer readers (0.99 vs. 0.98, respectively; p = 0.15) and significantly higher than the AUC result of the resident readers (0.99 vs. 0.90, respectively; p = 0.002). For detection of territories of WMAs, the AUC by the deep learning algorithm was similar to the AUC by the cardiologist and sonographer readers (0.97 vs. 0.95, respectively; p = 0.61) and significantly higher than the AUC by resident readers (0.97 vs. 0.83, respectively; p = 0.003). From a validation group at an independent site (n = 40), the AUC by the deep learning algorithm was 0.90. CONCLUSIONS: The present results support the possibility of using DCNN for automated diagnosis of RWMAs in the field of echocardiography.

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Toll-Like Receptor 9 Plays a Pivotal Role in Angiotensin II-Induced Atherosclerosis.

Fukuda D, Nishimoto S, Aini K, Tanaka A, Nishiguchi T, Kim-Kaneyama JR, Lei XF, Masuda K, Naruto T, Tanaka K, Higashikuni Y, Hirata Y, Yagi S, Kusunose K, Yamada H, Soeki T, Imoto I, Akasaka T, Shimabukuro M, Sata M

Journal of the American Heart Association   8 ( 7 ) e010860   2019.04 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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冠動脈プラーク内微小管腔構造は心外膜の脂肪組織の質と量に関連する 新鮮遺体を用いた研究(Coronary Intraplaque Microluminal Structure are Associated with the Quality and Quantity of Epicardial Adipose Tissue: A Fresh Cadaveric Study)

川端 豊, 若槻 哲三, 山口 浩司, 伊藤 浩敬, 福田 大受, 轟 貴史, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  83回   PJ057 - 2   2019.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

冠動脈プラークと脈管の血管の微小管腔構造は冠動脈の炎症に影響を与える 未固定遺体による研究(Microluminal Structures of Coronary Plaque and Vasa Vasorums Affect Coronary Inflammation: A Fresh Cadaveric Study)

伊藤 浩敬, 若槻 哲三, 山口 浩司, 福田 大受, 川端 豊, 轟 貴史, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  83回   PJ106 - 5   2019.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Sequential speckle tracking imaging to detect early stage of cancer therapeutics-related cardiac dysfunction in a patient with breast cancer.

Saijo Y, Kusunose K, Yamada N, Yamada H, Nishio S, Hirata Y, Sata M

Journal of echocardiography   18 ( 2 ) 134 - 135   2019.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adult onset of Immunoglobulin A vasculitis - A case report.

Yagi S, Endo I, Murakami T, Hida T, Yamamoto Y, Soga T, Ise T, Kusunose K, Yamaguchi K, Fukuda D, Yamada H, Soeki T, Wakatsuki T, Kawahito S, Sata M

The journal of medical investigation : JMI   66 ( 3.4 ) 344 - 346   2019 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, primarily occurs during childhood between the ages of 3 and 15 years and is the most common form of systemic vasculitis in children ; its occurrence in adults has been rarely reported. Such low incidence could be attributable to either under-diagnosis or misdiagnosis. Thus, not only pediatricians but also physicians should be able to diagnose IgAV accurately to manage the patients appropriately and avoid its associated complications. In addition, treatment of adult onset IgAV with renal involvement has not been fully established yet. We describe here a case of adult onset IgAV complicated by proteinuria and pharyngitis, which was cured by no specific treatment. J. Med. Invest. 66 : 344-346, August, 2019.

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Osteolytic primary bone lymphoma in the multiple bones.

Shusuke Yagi, Robert Zheng, Seiichi Nishiyama, Yutaka Kawabata, Takayuki Ise, Kosuke Sugiura, Haruhiko Yoshinari, Toshihiko Nishisho, Yoshimi Bando, Kumiko Kagawa, Daiju Fukuda, Tomohiro Soga, Yoshihito Saijo, Kenya Kusunose, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinji Kawahito, Masashi Akaike, Masataka Sata

The journal of medical investigation : JMI   66 ( 3.4 ) 347 - 350   2019 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Primary non-Hodgkin bone lymphoma (PBL) can involve solitary or multiple destructive bone lesions such as those of the femur or pelvis humerus, and some cases have osteolytic lesions. PBL is a rare disease in adults. Thus, PBL is rarely considered a differential diagnosis of the osteolytic tumor. In addition, PBL can be underdiagnosed because patients do not experience symptoms or show objective abnormalities in the early stage. Here, we reported an elderly patient with PBL in multiple bones, including the cranial and femoral bones that were fractured due to falling. J. Med. Invest. 66 : 347-350, August, 2019.

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Lambda-like J wave due to acute myocardial infarction of the diagonal branch.

Yagi S, Ueno R, Sutou K, Wakatsuki T, Yamaguchi K, Saijo Y, Hara T, Ise T, Kusunose K, Bando M, Matsuura T, Tobiume T, Yamada H, Fukuda D, Soeki T, Akaike M, Sata M

The journal of medical investigation : JMI   66 ( 1.2 ) 185 - 187   2019 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The culprit lesion of acute myocardial infarction could be predicted by electrocardiogram findings. However, we experienced some cases with coronary angiographic finding in the area of ST-T elevation that was different from that predicted. The lambda-like J wave could be caused by ischemia although the mechanism has not been fully elucidated. We report a case of acute myocardial infarction that showed discrepancy between ST-T elevation with lambda-like ischemic J wave in a broad area and coronary angiographical finding of diagonal branch occlusion. J. Med. Invest. 66 : 185-187, February, 2019.

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Provocation of clinically significant left ventricular outflow tract obstruction by postural change in patients with sigmoid septum.

Hirata Y, Yamada H, Kusunose K, Nishio S, Torii Y, Horike Y, Sata M

Journal of echocardiography   16 ( 4 ) 173 - 174   2018.12 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Left atrial functional response after a marathon in healthy amateur volunteers.

Hirata Y, Kusunose K, Yamada H, Morita S, Torii Y, Nishio S, Zheng R, Saijo Y, Fukuda D, Yagi S, Soeki T, Sata M

The international journal of cardiovascular imaging   35 ( 4 ) 633 - 643   2018.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Middle-aged marathon runners have an increased risk of developing atrial fibrillation (AF). A previous study described that repetitive marathon running was associated with left atrial (LA) dysfunction. However, whether this change is common in marathon runners and which runners are at risk of LA dysfunction remain unknown. The purpose of this study was to determine which factors could predict LA dysfunction. We prospectively examined 12 healthy amateur volunteers (9 males, 31 ± 8 years old) who participated in a full marathon. All echocardiographic measurements and speckle-tracking echocardiography were performed before and after the marathon. The endpoint was defined as reduced LA reservoir strain 1 day after the marathon (non-responder group). Seven participants were in the non-responder group. Age (35 ± 9 vs. 26 ± 2 years, p = 0.020), augmentation index (76 ± 12 vs. 55 ± 8, p = 0.002), and diastolic blood pressures (83 ± 11 vs. 70 ± 7 mmHg, p = 0.021) in the non-responder group were significantly higher compared with the responder group. In multivariate linear regression analysis, only the augmentation index was an independent predictor of reduced LA reservoir function after the marathon (β = - 0.646, p = 0.023). The augmentation index was a predictive marker for reduction in LA reservoir function after a marathon in healthy amateur volunteers.

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Simultaneous Pulmonary Arterial and Venous Round Structures in Pulmonary Aspergillosis.

Yagi S, Yamazaki H, Nishio S, Kusunose K, Yamada H, Sata M

Circulation journal : official journal of the Japanese Circulation Society   83 ( 6 ) 1416 - 1416   2018.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Activation of Toll-Like Receptor 9 Impairs Blood Flow Recovery After Hind-Limb Ischemia.

Nishimoto S, Aini K, Fukuda D, Higashikuni Y, Tanaka K, Hirata Y, Yagi S, Kusunose K, Yamada H, Soeki T, Shimabukuro M, Sata M

Frontiers in cardiovascular medicine   5   144 - 144   2018.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Peripheral artery disease causes significant functional disability and results in impaired quality of life. Ischemic tissue injury releases various endogenous ligands for Toll-like receptors (TLRs), suggesting the involvement of TLRs in blood flow recovery. However, the role of TLR9, which was originally known as a sensor for bacterial DNA, remains unknown. This study investigated the role of TLR9 in blood flow recovery in the ischemic limb using a mouse hind-limb ischemia model. Methods and Results: Unilateral femoral artery ligation was performed in TLR9-deficient (Tlr9 -/-) mice and wild-type mice. In wild-type mice, femoral artery ligation significantly increased mRNA expression of TLR9 in the ischemic limb (P < 0.001) and plasma levels of cell-free DNA (cfDNA) as determined by single-stranded DNA (ssDNA) (P < 0.05) and double-stranded DNA (dsDNA) (P < 0.01), which are endogenous ligands for TLR9, compared with the sham-operated group. Laser Doppler perfusion imaging demonstrated significantly improved ratio of blood flow in the ischemic to non-ischemic limb in Tlr9 -/- mice compared with wild-type mice at 2 weeks after ligation (P < 0.05). Tlr9 -/- mice showed increased capillary density and reduced macrophage infiltration in ischemic limb. Genetic deletion of TLR9 reduced the expression of TNF-α, and attenuated NF-κB activation in ischemic muscle compared with wild-type mice (P < 0.05, respectively) at 3 days after the surgery. ODN1826, a synthetic agonistic oligonucleotide for TLR9, or plasma obtained from mice with ischemic muscle promoted the expression of TNF-α in wild-type macrophages (P < 0.05), but not in Tlr9 -/- macrophages. ODN1826 also activated NF-κB signaling as determined by the degradation of IκBα in wild-type macrophages (P < 0.05), but not in Tlr9 -/- macrophages. In vitro experiments using human umbilical vein endothelial cells demonstrated that TNF-α, or conditioned medium obtained from wild-type macrophages treated with ODN1826 accelerated cell death as determined by MTS assay (P < 0.05 and P < 0.01, respectively). Conclusion: Our results suggest that ischemic muscle releases cfDNA, which activates TLR9 and enhances inflammation, leading to impairment of blood flow recovery in the ischemic limb. cfDNA-TLR9 signaling may serve as a potential therapeutic target in ischemic limb disease.

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Protease-Activated Receptor-2 Plays a Critical Role in Vascular Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice.

Hara T, Phuong PT, Fukuda D, Yamaguchi K, Murata C, Nishimoto S, Yagi S, Kusunose K, Yamada H, Soeki T, Wakatsuki T, Imoto I, Shimabukuro M, Sata M

Circulation   138 ( 16 ) 1706 - 1719   2018.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Protease-Activated Receptor-2 Plays a Critical Role in Vascular Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice.

Tomoya Hara, Pham Tran Phuong, Daiju Fukuda, Koji Yamaguchi, Chie Murata, Sachiko Nishimoto, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Issei Imoto, Michio Shimabukuro, Masataka Sata

Circulation   138 ( 16 ) 1706 - 1719   2018.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The coagulation system is closely linked with vascular inflammation, although the underlying mechanisms are still obscure. Recent studies show that protease-activated receptor (PAR)-2, a major receptor of activated factor X, is expressed in both vascular cells and leukocytes, suggesting that PAR-2 may contribute to the pathogenesis of inflammatory diseases. Here we investigated the role of PAR-2 in vascular inflammation and atherogenesis. METHODS: We generated apolipoprotein E-deficient ( ApoE-/-) mice lacking systemic PAR-2 expression ( PAR-2-/- ApoE-/-). ApoE-/- mice, which lack or express PAR-2 only in bone marrow (BM) cells, were also generated by BM transplantation. Atherosclerotic lesions were investigated after 20 weeks on a Western-type diet by histological analyses, quantitative reverse transcription polymerase chain reaction, and Western blotting. In vitro experiments using BM-derived macrophages were performed to confirm the proinflammatory roles of PAR-2. The association between plasma activated factor X level and the severity of coronary atherosclerosis was also examined in humans who underwent coronary intervention. RESULTS: PAR-2-/- ApoE-/- mice showed reduced atherosclerotic lesions in the aortic arch ( P<0.05) along with features of stabilized atherosclerotic plaques, such as less lipid deposition ( P<0.05), collagen loss ( P<0.01), macrophage accumulation ( P<0.05), and inflammatory molecule expression ( P<0.05) compared with ApoE-/- mice. Systemic PAR2 deletion in ApoE-/-mice significantly decreased the expression of inflammatory molecules in the aorta. The results of BM transplantation experiments demonstrated that PAR-2 in hematopoietic cells contributed to atherogenesis in ApoE-/- mice. PAR-2 deletion did not alter metabolic parameters. In vitro experiments demonstrated that activated factor X or a specific peptide agonist of PAR-2 significantly increased the expression of inflammatory molecules and lipid uptake in BM-derived macrophages from wild-type mice compared with those from PAR-2-deficient mice. Activation of nuclear factor-κB signaling was involved in PAR-2-associated vascular inflammation and macrophage activation. In humans who underwent coronary intervention, plasma activated factor X level independently correlated with the severity of coronary atherosclerosis as determined by Gensini score ( P<0.05) and plaque volume ( P<0.01). CONCLUSIONS: PAR-2 signaling activates macrophages and promotes vascular inflammation, increasing atherosclerosis in ApoE-/- mice. This signaling pathway may also participate in atherogenesis in humans.

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Right Ventricular Function and Beneficial Effects of Cardiac Rehabilitation in Patients With Systolic Chronic Heart Failure.

Kusunose K, Seno H, Yamada H, Nishio S, Torii Y, Hirata Y, Saijo Y, Ise T, Yamaguchi K, Fukuda D, Yagi S, Soeki T, Wakatsuki T, Sata M

The Canadian journal of cardiology   34 ( 10 ) 1307 - 1315   2018.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: It has been recognized that a comprehensive cardiac rehabilitation (CR) program improves mortality in patients with chronic heart failure. On the other hand, the magnitude of the improvement in exercise capacity after CR differs among individuals. The aim of this study was to assess the echocardiographic determinants of responders to CR using preload stress echocardiography. METHODS: We prospectively enrolled 58 chronic heart failure patients with reduced left ventricular ejection fraction (aged 62 ± 11 years; 69% male; left ventricular ejection fraction 43% ± 7%) who had received optimized medical treatment in a CR program for 5 months. We performed preload echocardiographic studies using leg positive pressure (LPP) to assess the echocardiographic parameters during preload augmentation. We defined 41 patients as a development cohort to assess the predictive value of echocardiographic variables. Next, we validated results in the remaining 17 patients as a validation cohort. RESULTS: In the development cohort, significant improvement in peak oxygen uptake (VO2) (>10%) after CR was observed in 58% patients. In a multivariable logistic regression model, the significant predictor of improvement in exercise capacity was right ventricular (RV) strain during LPP (odds ratio: 3.96 per 1 standard deviation; P = 0.01). An RV strain value of -16% during LPP had a good sensitivity of 0.79 and a specificity of 0.71 to identify patients with improvement in peak VO2. In the validation cohort, an optimal cutoff value of RV strain value was the same (area under the curve: 0.77, sensitivity: 0.78, specificity: 0.65). CONCLUSIONS: RV strain during LPP may be an echocardiographic parameter for assessing beneficial effects of CR.

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Association of Decreased Docosahexaenoic Acid Level After Statin Therapy and Low Eicosapentaenoic Acid Level with In-Stent Restenosis in Patients with Acute Coronary Syndrome

八木 秀介, D Kondo, 伊勢 孝之, 福田 大受, 山口 浩司, 若槻 哲三, 川端 豊, 伊藤 浩敬, 西條 良仁, 瀬野 弘光, 數藤 久美子, 上野 理絵, 轟 貴史, 楠瀬 賢也, 松浦 朋美, 飛梅 威, 山田 博胤, 添木 武, 島袋 充生, KI Aihara, 赤池 雅史, 佐田 政隆

Journal of Atherosclerosis and Thrombosis   26 ( 3 ) 272 - 281   2018.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIM: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited. METHODS: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography. RESULTS: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR. CONCLUSION: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

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Clinical, Electrocardiographic, and Echocardiographic Parameter Combination Predicts the Onset of Atrial Fibrillation.

Soeki T, Matsuura T, Tobiume T, Bando S, Matsumoto K, Nagano H, Uematsu E, Kusunose K, Ise T, Yamaguchi K, Yagi S, Fukuda D, Yamada H, Wakatsuki T, Shimabukuro M, Sata M

Circulation journal : official journal of the Japanese Circulation Society   82 ( 9 ) 2253 - 2258   2018.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The ability to identify risk markers for new-onset atrial fibrillation (AF) is critical to the development of preventive strategies, but it remains unknown whether a combination of clinical, electrocardiographic, and echocardiographic parameters predicts the onset of AF. In the present study, we evaluated the predictive value of a combined score that includes these parameters. Methods and Results: We retrospectively studied 1,040 patients without AF who underwent both echocardiography and 24-h Holter electrocardiography between May 2005 and December 2010. During a median follow-up period of 68.4 months (IQR, 49.9-93.3 months), we investigated the incidence of new-onset AF. Of the 1,040 patients, 103 (9.9%) developed AF. Patients who developed AF were older than patients who did not. Total heart beats, premature atrial contraction (PAC) count, maximum RR interval, and frequency of sinus pause quantified on 24-h electrocardiography were associated with new-onset AF. LA diameter (LAD) on echocardiography was also associated with the development of AF. On multivariate Cox analysis, age ≥58 years, PAC count ≥80 beats/day, maximum RR interval ≥1.64 s, and LAD ≥4.5 cm were independently associated with the development of AF. The incidence rate of new-onset AF significantly increased as the combined score (i.e., the sum of the risk score determined using hazard ratios) increased. CONCLUSIONS: A combined score that includes age, PAC count, maximum RR interval, and LAD could help characterize the risk of new-onset AF.

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A clinical application of preload stress echocardiography for predicting future hemodynamic worsening in patients with early-stage heart failure.

西條 良仁, 山田 博胤, 楠瀬 賢也, 坂東 美佳, 西尾 進, 鳥居 裕太, 平田 有紀奈, 瀬野 弘光, 松浦 朋美, 伊勢 孝之, 飛梅 威, 山口 浩司, 八木 秀介, 添木 武, 若槻 哲三, 佐田 政隆

Echocardiography   35 ( 10 ) 1587 - 1595   2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIM: To improve the prognosis of patients with heart failure, risk stratification in their early stage is important. We assessed whether the change in transmitral flow (TMF) velocity pattern during preload augmentation can predict future hemodynamic worsening in early-stage heart failure patients with impaired relaxation TMF pattern. METHODS: We designed a prospective cohort study that included 155 consecutive patients with impaired relaxation (IR) pattern at rest. Preload stress echocardiography was achieved using leg-positive pressure (LPP), and changes in TMF pattern during the LPP was observed during baseline echocardiographic examination. The patients whose TMF pattern developed to pseudonormal (PN) pattern throughout the study period were classified into the change to PN group, and patients whose TMF pattern stayed in IR pattern were classified into the stay in IR group. RESULTS: The median follow-up period was 17 months. The average age was 68 ± 11 years old, and 97 patients (63%) were male. Among 155 patients, 27 were classified into the change to PN group. A Cox proportional hazard analysis confirmed that the change in the peak atrial systolic TMF velocity during the LPP (ΔA, hazard ratio = 0.58 per 1SD; 95% CI = 0.39-0.88, P = 0.010) was the powerful independent predictor of change into PN pattern. Kaplan-Meier analysis revealed that the patients with ΔA ≤ -7 cm/s had more likely to develop into PN pattern than patients with ΔA > -7 cm/s (P = 0.001). CONCLUSIONS: Evaluation of a response in TMF during the LPP might provide an incremental diagnostic value to detect future overt heart failure in patients with early-stage heart failure.

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Novel Echocardiographic Parameters in Patients With Aortic Stenosis and Preserved Left Ventricular Systolic Function Undergoing Surgical Aortic Valve Replacement.

Huded CP, Kusunose K, Shahid F, Goodman AL, Alashi A, Grimm RA, Gillinov AM, Johnston DR, Rodriguez LL, Popovic ZB, Sato, Kimi, Svensson LG, Griffin BP, Desai MY

Am J Cardiol.     2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Reduced variability of visual left ventricular ejection fraction assessment with reference images: The Japanese Association of Young Echocardiography Fellows multicenter study.

Kenya Kusunose, Kentaro Shibayama, Hiroyuki Iwano, Masaki Izumo, Nobuyuki Kagiyama, Koji Kurosawa, Hirotsugu Mihara, Hiroki Oe, Tetsuari Onishi, Toshinari Onishi, Mitsuhiko Ota, Shunsuke Sasaki, Yumi Shiina, Hikaru Tsuruta, Hidekazu Tanaka

Journal of cardiology   72 ( 1 ) 74 - 80   2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Visual estimation of left ventricular ejection fraction (LVEF) is widely applied to confirm quantitative EF. However, visual assessment is subjective, and variability may be influenced by observer experience. We hypothesized that a learning session might reduce the misclassification rate. METHODS: Protocol 1: Visual LVEFs for 30 cases were measured by 79 readers from 13 cardiovascular tertiary care centers. Readers were divided into 3 groups by their experience: limited (1-5 years, n=28), intermediate (6-11 years, n=26), and highly experienced (12-years, n=25). Protocol 2: All readers were randomized to assess the effect of a learning session with reference images only or feedback plus reference images. After the session, 20 new cases were shown to all readers following the same methodology. To assess the concordance and accuracy pre- and post-intervention, each visual LVEF measurement was compared to overall average values as a reference. RESULTS: Experience affected the concordance in visual EF values among the readers. Groups with intermediate and high experience showed significantly better mean difference (MD), standard deviation (SD), and coefficient of variation (CV) than those with limited experience at baseline. The learning session with reference image reduced the MD, SD, and CV in readers with limited experience. The learning session with reference images plus feedback also reduced proportional bias. Importantly, the misclassification rate for mid-range EF cases was reduced regardless of experience. CONCLUSION: This large multicenter study suggested that a simple learning session with reference images can successfully reduce the misclassification rate for LVEF assessment.

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Prognostic Value of Frailty and Diastolic Dysfunction in Elderly Patients.

Kusunose K, Okushi Y, Yamada H, Nishio S, Torii Y, Hirata Y, Saijo Y, Ise T, Yamaguchi K, Yagi S, Soeki T, Wakatsuki T, Sata M

Circulation journal : official journal of the Japanese Circulation Society   82 ( 8 ) 2103 - 2110   2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: High prevalence of frailty and of diastolic dysfunction (DD) in heart failure and high mortality in frail adults have been noted. We characterized frailty by quantifying differences on echocardiography, and assessed the added prognostic utility of frailty and DD grade in an elderly population. METHODS AND RESULTS: One hundred and ninety-one patients ≥65 years who had at least 1 cardiovascular risk factor were prospectively recruited for clinically indicated echocardiography at the present institute. Weight loss, exhaustion, and deficits in physical activity, gait speed, and handgrip strength were used to categorize patients as frail (≥3 features), intermediately frail (1 or 2 features), or non-frail (0 features). DD grade ≥2 was defined as severe. Frailty was associated with larger left atrial volume, smaller stroke volume, and worse DD grade after adjustment for age. In a period of 14 months, 29 patients (15%) had cardiovascular events. The addition of frailty score and severe DD significantly improved the prognostic power of a model containing male gender (model 1, male gender, χ2=6.4; model 2, model 1 plus frailty score, χ2=16.7, P=0.004; model 3, model 2 plus severe DD, χ2=25.5, P=0.015). CONCLUSIONS: Both frailty and DD grade were significantly associated with future cardiovascular events in an elderly population with preserved ejection fraction and ≥1 risk factor of cardiovascular disease.

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Clinical, Electrocardiographic, and Echocardiographic Parameter Combination Predicts the Onset of Atrial Fibrillation.

添木 武, 松浦 朋美, 飛梅 威, 坂東 佐知子, 松本 和久, H Nagano, E Uematsu, 楠瀬 賢也, 伊勢 孝之, 山口 浩司, 八木 秀介, 福田 大受, 山田 博胤, 若槻 哲三, 島袋 充生, 佐田 政隆

Circulation Journal   82 ( 9 ) 2253 - 2258   2018.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The ability to identify risk markers for new-onset atrial fibrillation (AF) is critical to the development of preventive strategies, but it remains unknown whether a combination of clinical, electrocardiographic, and echocardiographic parameters predicts the onset of AF. In the present study, we evaluated the predictive value of a combined score that includes these parameters.Methods and Results:We retrospectively studied 1,040 patients without AF who underwent both echocardiography and 24-h Holter electrocardiography between May 2005 and December 2010. During a median follow-up period of 68.4 months (IQR, 49.9-93.3 months), we investigated the incidence of new-onset AF. Of the 1,040 patients, 103 (9.9%) developed AF. Patients who developed AF were older than patients who did not. Total heart beats, premature atrial contraction (PAC) count, maximum RR interval, and frequency of sinus pause quantified on 24-h electrocardiography were associated with new-onset AF. LA diameter (LAD) on echocardiography was also associated with the development of AF. On multivariate Cox analysis, age ?58 years, PAC count ?80 beats/day, maximum RR interval ?1.64 s, and LAD ?4.5 cm were independently associated with the development of AF. The incidence rate of new-onset AF significantly increased as the combined score (i.e., the sum of the risk score determined using hazard ratios) increased. A combined score that includes age, PAC count, maximum RR interval, and LAD could help characterize the risk of new-onset AF.

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Noninvasive Assessment of Preload Reserve Enhances Risk Stratification of Patients With Heart Failure With Reduced Ejection Fraction.

Kensuke Matsumoto, Akira Onishi, Hirotsugu Yamada, Kenya Kusunose, Makiko Suto, Yutaka Hatani, Hiroki Matsuzoe, Kazuhiro Tatsumi, Hidekazu Tanaka, Ken-Ichi Hirata

Circulation. Cardiovascular imaging   11 ( 5 ) e007160 - e007160   2018.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The leg-positive pressure maneuver can safely and noninvasively apply preload stress without increase in total body fluid volume. The purpose of this study was to determine whether preload stress could be useful for risk stratification of patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: For this study, 120 consecutive patients with heart failure with reduced ejection fraction were prospectively recruited. The stroke work index was estimated as product of stroke volume index and mean blood pressure, and the E/e' ratio was calculated to estimate ventricular filling pressure. The echocardiographic parameters were obtained both at rest and during leg-positive pressure stress. During the median follow-up period of 20 months, 30 patients developed adverse cardiovascular events. During preload stress, stroke work index increased significantly (from 3280±1371 to 3857±1581 mm Hg·mL/m2; P<0.001) along with minimal changes in ventricular filling pressure (E/e', from 16±10 to 17±9; P<0.05) in patients without cardiovascular events. However, patients with cardiovascular events showed impairment of Frank-Starling mechanism (stroke work index, from 2863±969 to 2903±1084 mm Hg·mL/m2; P=0.70) and a serious increase in E/e' ratio (from 19±11 to 25±14; P<0.001). Both the patients without contractile reserve and those without diastolic reserve exhibited worse event-free survival than the others (P<0.001). In a Cox proportional-hazards analysis, the changes in stroke work index (hazard ratio: 0.44 per 500 mm Hg·mL/m2 increase; P=0.001) and in E/e' (hazard ratio: 2.58 per 5-U increase; P<0.001) were predictors of cardiovascular events. CONCLUSION: Contractile reserve and diastolic reserve during leg-positive pressure stress are important determinants of cardiovascular outcomes for patients with heart failure with reduced ejection fraction.

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Prognostic Value of Frailty and Diastolic Dysfunction in Elderly Patients.

楠瀬 賢也, Y Okushi, 山田 博胤, 西尾 進, 鳥居 裕太, 平田 有紀奈, 西條 良仁, 伊勢 孝之, 山口 浩司, 八木 秀介, 添木 武, 若槻 哲三, 佐田 政隆

Circulation Journal   82 ( 8 ) 2103 - 2110   2018.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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High prevalence of frailty and of diastolic dysfunction (DD) in heart failure and high mortality in frail adults have been noted. We characterized frailty by quantifying differences on echocardiography, and assessed the added prognostic utility of frailty and DD grade in an elderly population. One hundred and ninety-one patients ?65 years who had at least 1 cardiovascular risk factor were prospectively recruited for clinically indicated echocardiography at the present institute. Weight loss, exhaustion, and deficits in physical activity, gait speed, and handgrip strength were used to categorize patients as frail (?3 features), intermediately frail (1 or 2 features), or non-frail (0 features). DD grade ?2 was defined as severe. Frailty was associated with larger left atrial volume, smaller stroke volume, and worse DD grade after adjustment for age. In a period of 14 months, 29 patients (15%) had cardiovascular events. The addition of frailty score and severe DD significantly improved the prognostic power of a model containing male gender (model 1, male gender, χ=6.4; model 2, model 1 plus frailty score, χ=16.7, P=0.004; model 3, model 2 plus severe DD, χ=25.5, P=0.015). Both frailty and DD grade were significantly associated with future cardiovascular events in an elderly population with preserved ejection fraction and ?1 risk factor of cardiovascular disease.

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Calcified Amorphous Tumorに対し腫瘍摘出術を行った一例

清水 郁子, 瀬野 弘光, Koji Yamaguchi, Kenya Kusunose, Hirotsugu Yamada, Tetsuzo Wakatsuki, Takeshi Soeki, Masataka Sata, Takashi Iwase, Hirotsugu Kurobe, Tetsuya Kitagawa

四国医学雑誌   74 ( 1-2 ) 84 - 84   2018.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Local Thickness of Epicardial Adipose Tissue Surrounding the Left Anterior Descending Artery Is a Simple Predictor of Coronary Artery Disease - New Prediction Model in Combination With Framingham Risk Score.

Maimaituxun G, Shimabukuro M, Fukuda D, Yagi S, Hirata Y, Iwase T, Takao S, Matsuura T, Ise T, Kusunose K, Tobiume T, Yamaguchi K, Yamada H, Soeki T, Wakatsuki T, Harada M, Sata M

Circulation journal : official journal of the Japanese Circulation Society   82 ( 5 ) 1369 - 1378   2018.04 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Paclitaxel投与を併用した冠動脈形成術後の局所凝固療法への反応の差(Differential Response of Local Coagulation after Coronary Angioplasty with Paclitaxel)

山口 浩司, 若槻 哲三, 川端 豊, 伊藤 浩敬, 轟 貴史, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  82回   PJ022 - 1   2018.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

心血管系イベント予測のための上腕収縮期血圧左右差の至適カットオフ値の設定および検証(Development and Validation of Optimal Cut-off Value in inter-armsystolic Blood Pressure Difference for Prediction of Cardiovascular Events)

廣野 明, 楠瀬 賢也, 蔭山 徳人, 藤永 裕之, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  82回   PJ033 - 2   2018.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

栄養血管の増殖は新鮮遺体において冠動脈プラーク周囲の局所炎症と関連する(Growth of Vasa Vasorum is Associated with Local Inflammation around Coronary Plaque in Fresh Cadavers)

伊藤 浩敬, 若槻 哲三, 山口 浩司, 福田 大受, 川端 豊, 轟 貴史, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山田 博胤, 添木 武, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  82回   PJ007 - 3   2018.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

高血圧患者におけるL/N型カルシウム拮抗薬が蛋白尿およびangiotensin II-reninフィードバックに及ぼす効果(Effects of L-/N-type Calcium Channel Blocker on Proteinuria and Angiotensin II-renin Feedback in Hypertensive Patients)

川端 豊, 添木 武, 伊勢 孝之, 松浦 朋美, 楠瀬 賢也, 飛梅 威, 八木 秀介, 山口 浩司, 山田 博胤, 若槻 哲三, 佐田 政隆

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  82回   PJ067 - 4   2018.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Age-related changes in morphology of left atrial appendage in patients with atrial fibrillation.

Hirata Y, Kusunose K, Yamada H, Shimizu R, Torii Y, Nishio S, Saijo Y, Takao S, Soeki T, Sata M

The international journal of cardiovascular imaging   34 ( 2 ) 321 - 328   2018.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The purpose of this study was to evaluate the relationship between age and frequency of left atrial appendage (LAA) morphology in patients with atrial fibrillation (AF) compared with sinus rhythm (SR). We enrolled 145 AF patients, and 199 SR patients for the control group without any cardiovascular disease. LAA volume index (LAAVi) and morphology were assessed by electrocardiogram-gated computed tomography angiography. LAA morphology was classified into "chicken wing" or "non-chicken wing" according to the previously described classification. There was no significant trend in frequency of non-chicken wing morphology among ages in the SR group (p = 0.36 for trend), whereas the frequency was negatively related to age in the AF group (p = 0.002 for trend). In multivariable logistic regression, age > 65 (odds ratio [OR] 0.42, p = 0.002) and duration of AF (OR 0.53, p = 0.010) and LAAVi (OR 0.62, p = 0.017) were independent factors of non-chicken wing LAA morphology in the AF group. LAA morphology is affected by age, especially in patients with AF. When we utilize non-chicken wing LAA morphology as a stroke risk factor in patients with AF, we should pay attention to their age.

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Provocation of clinically significant left ventricular outflow tract obstruction by postural change in patients with sigmoid septum

Yukina Hirata, Hirotsugu Yamada, Kenya Kusunose, Susumu Nishio, Yuta Torii, Yuki Horike, Masataka Sata

Journal of Echocardiography ( Springer Tokyo )  Vol.- ( No.- ) 1 - 2   2018.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Development and validation of optimal cut-off value in inter-arm systolic blood pressure difference for prediction of cardiovascular events

Akira Hirono, Kenya Kusunose, Norihito Kageyama, Masayuki Sumitomo, Masahiro Abe, Hiroyuki Fujinaga, Masataka Sata

Journal of Cardiology ( Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai) )  71 ( 1 ) 24 - 30   2018.01 [ Peer Review Accepted ]

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Background An inter-arm systolic blood pressure difference (IAD) is associated with cardiovascular disease. The aim of this study was to develop and validate the optimal cut-off value of IAD as a predictor of major adverse cardiac events in patients with arteriosclerosis risk factors. Methods From 2009 to 2014, 1076 patients who had at least one cardiovascular risk factor were included in the analysis. We defined 700 randomly selected patients as a development cohort to confirm that IAD was the predictor of cardiovascular events and to determine optimal cut-off value of IAD. Next, we validated outcomes in the remaining 376 patients as a validation cohort. The blood pressure (BP) of both arms measurements were done simultaneously using the ankle-brachial blood pressure index (ABI) form of automatic device. The primary endpoint was the cardiovascular event and secondary endpoint was the all-cause mortality. Results During a median period of 2.8 years, 143 patients reached the primary endpoint in the development cohort. In the multivariate Cox proportional hazards analysis, IAD was the strong predictor of cardiovascular events (hazard ratio: 1.03, 95% confidence interval: 1.01–1.05, p = 0.005). The receiver operating characteristic curve revealed that 5 mmHg was the optimal cut-off point of IAD to predict cardiovascular events (p &lt 0.001). In the validation cohort, the presence of a large IAD (IAD ≥5 mmHg) was significantly associated with the primary endpoint (p = 0.021). Conclusions IAD is significantly associated with future cardiovascular events in patients with arteriosclerosis risk factors. The optimal cut-off value of IAD is 5 mmHg.

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Predictors for the Treatment Effect of Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus

Shusuke Yagi, Ken-ichi Aihara, Takeshi Kondo, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Daiju Fukuda, Yutaka Nakaya, Kin-ichiro Suwaki, Takashi Takeji, Toshihiro Wada, Hotimah Masdan Salim, Saori Hama, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Munehide Matsuhisa, Michio Shimabukuro, Masashi Akaike, Masataka Sata

Advances in Therapy ( Springer Healthcare )  35 ( 1 ) 124 - 134   2018.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Introduction: Predictors for the effect of sodium glucose co-transporter 2 (SGLT2) inhibitors at lowering hemoglobin A1c (HbA1c) levels in type 2 diabetes mellitus patients remain unclear. We therefore aimed to elucidate these predictors in type 2 diabetes patients after 3 months of SGLT2 treatment. Methods: A total of 302 consecutive type 2 diabetes patients who had been treated with SGLT2 inhibitors as monotherapy or add-on therapy to existing antidiabetic treatments were enrolled retrospectively. After excluding 27 patients whose HbA1c levels could not be evaluated 3 months after treatment, the glucose-lowering effects of SGLT2 inhibitors were assessed in 275 patients by measuring HbA1c levels before and 3 months after treatment. The predictors for changes in HbA1c levels after 3 months of treatment were evaluated. Results: SGLT2 inhibitor treatment for 3 months decreased HbA1c levels from 7.8 ± 1.2% to 7.4 ± 1.0% (p &lt  0.0001). A multiple regression analysis showed that the independent determinants for SGLT2 inhibitor treatment effect included decreased HbA1c levels after 1 month of treatment, high baseline HbA1c levels, and a high estimated glomerular filtration rate (eGFR). Conclusion: We show that type 2 diabetes patients who received the greatest glucose-lowering effect with SGLT2 inhibitor treatment were those with preserved renal function (high baseline eGFR) and high baseline HbA1c levels. Moreover, SGLT2 inhibitor treatment efficacy could be predicted by the patients’ initial response to treatment.

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Effect of the epicardial adipose tissue volume on the prevalence of paroxysmal and persistent atrial fibrillation

Kageyuki Oba, Minetaka Maeda, Gulinu Maimaituxun, Satoshi Yamaguchi, Osamu Arasaki, Daiju Fukuda, Shusuke Yagi, Yukina Hirata, Susumu Nishio, Takashi Iwase, Shoichiro Takao, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masafumi Harada, Hiroaki Masuzaki, Masataka Sata, Michio Shimabukuro

Circulation Journal ( Japanese Circulation Society )  82 ( 7 ) 1778 - 1787   2018 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling. Methods and Results: Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m2) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m2, P&lt 0.01). Conclusions: The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

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Local thickness of epicardial adipose tissue surrounding the left anterior descending artery is a simple predictor of coronary artery disease ― new prediction model in combination with framingham risk score ―

Gulinu Maimaituxun, Michio Shimabukuro, Daiju Fukuda, Shusuke Yagi, Yukina Hirata, Takashi Iwase, Shoichiro Takao, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masafumi Harada, Masataka Sata

Circulation Journal ( Japanese Circulation Society )  82 ( 5 ) 1369 - 1378   2018 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Compared with global cardiac adiposity, the local accumulation of fat surrounding coronary arteries might have a more direct impact on coronary artery disease (CAD). Here, we compared the local epicardial adipose tissue (EAT) thickness and global cardiac adiposity volumes for predicting CAD. Methods and Results: A total of 197 consecutive subjects underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into CAD (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. EAT thickness was measured at the right coronary artery (EATRCA), the left anterior descending artery (EATLAD), and the left circumflex artery (EATLCX). Although EATRCA and EATLCX were similar between the 2 groups, EATLAD was larger in the CAD group than in the non-CAD group (5.45±2.16 mm vs. 6.86±2.19 mm, P&lt 0.001). EATLAD, after correcting for confounding factors, was strongly associated with CAD (r=0.276, P&lt 0.001) and Gensini score (r=0.239, P&lt 0.001). On multiple regression analysis, Framingham risk score combined with EATLAD was a strong predictor of CAD (adjusted R2=0.121 P&lt 0.001). Conclusions: The local fat thickness surrounding the LAD is a simple and useful surrogate marker for estimating the presence, severity, and extent of CAD, independent of classical cardiovascular risk factors.

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Left ventricular mass influences relationship between filling pressure and early-diastolic ratio of inflow velocity to mitral annular velocity (E/e′)

Masahiro Nakabachi, Satoshi Yamada, Hiroyuki Iwano, Taichi Hayashi, Kazunori Okada, Kenya Kusunose, Kiyotaka Watanabe, Tomoko Ishizu, Kazuaki Wakami, Hirotsugu Yamada, Kaoru Dohi, Yoshihiro Seo, Nobuyuki Ohte, Chikara Shimizu, Taisei Mikami

Circulation Journal ( Japanese Circulation Society )  82 ( 3 ) 732 - 738   2018 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Early-diastolic mitral annular velocity (e′) and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e′ (E/e′) have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study. Methods and Results: The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e′ only weakly correlated with τ (r=−0.35, P&lt 0.01), E/e′ modestly correlated with LVMDP (r=0.48, P&lt 0.001). Multivariable analysis revealed that hypertension (β=−0.33, P&lt 0.01) and LV ejection fraction (LVEF) (β=0.44, P&lt 0.001) were the independent determinants of e′, and LV mass index (LVMI) (β=0.37, P&lt 0.001) and LVMDP (β=0.47, P&lt 0.001) were those of E/e′. Additionally, E/e′ significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P&lt 0.001) but not in those with increased LVMI. Conclusions: The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e′, whereas LVMI altered the relationship between LV filling pressure and E/e′. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e′.

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Activated Factor X Signaling Pathway via Protease-Activated Receptor-2 is a Novel Therapeutic Target to Prevent Atrial Fibrillation

Soeki Takeshi, Matsuura Tomomi, Fukuda Daiju, Uematsu Etsuko, Tobiume Takeshi, Hara Tomoya, Kusunose Kenya, Ise Takayuki, Yamaguchi Koji, Yagi Shusuke, Yamada Hirotsugu, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   136   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Preserved Endothelial Function and Suppressed Local Coagulative and Inflammatory Response After Biodegradable Polymer SES Implantation Compared to Durable Polymer SES

Yamaguchi Koji, Wakatsuki Tetsuzo, Kawabata Yutaka, Ito Hiroyuki, Matsuura Tomomi, Ise Takayuki, Kusunose Kenya, Tobiume Takeshi, Yagi Shusuke, Yamada Hirotsugu, Soeki Takeshi, Sata Masataka

CIRCULATION   136   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Preload Stress Echocardiography Predicts Outcomes in Patients With Preserved Ejection Fraction and Low Gradient Aortic Stenosis

Kusunose Kenya, Yamada Hirotsugu, Nishio Susumu, Torii Yuta, Hirata Yukina, Seno Hiromitsu, Saijo Yoshihito, Ise Takayuki, Yamaguchi Koji, Yagi Shusuke, Soeki Takeshi, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   136   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Local Epicardial Adipose Tissue Thickness in Left Anterior Descending Artery Provides a New Prediction Model for Coronary Artery Disease

Maimaituxun Gulinu, Shimabukuro Michio, Hirata Yukina, Iwase Takashi, Takao Shoichiro, Matsuura Tomomi, Ise Takayuki, Kusunose Kenya, Tobiume Takeshi, Yamaguchi Koji, Yagi Shusuke, Fukuda Daiju, Yamada Hirotsugu, Soeki Takeshi, Wakatsuki Tetsuzo, Harada Masafumi, Sata Masataka

CIRCULATION   136   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Epicardial Adipose Tissue Produces Proinflammatory Cytokines and Influences the Pathogenesis of Atrial Fibrillation

Soeki Takeshi, Matsuura Tomomi, Uematsu Etsuko, Tobiume Takeshi, Kusunose Kenya, Ise Takayuki, Yamaguchi Koji, Yagi Shusuke, Fukuda Daiju, Yamada Hirotsugu, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   136   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Direct Slow Pathway Capture: A New Electrophysiological Method of Catheter Ablation for Atrioventricular Nodal Reentrant Tachycardia

Matsuura Tomomi, Tobiume Takeshi, Takeshi Soeki, Kato Ritsushi, Hara Motoki, Ise Takayuki, Kusunose Kenya, Yamaguchi Koji, Yagi Shusuke, Yamada Hirotsugu, Wakatsuki Tetsuzo, Sata Masataka, Matsumoto Kazuo

CIRCULATION   136   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Edoxaban improves acute venous thromboembolism while preserving protein C and protein S levels

山? 宙, 八木 秀介, Y Torii, R Amano, Y Oomichi, T Sangawa, 福田 大受, 門田 宗之, 伊勢 孝之, R Ueno, 原 知也, 楠瀬 賢也, 松浦 朋美, 飛梅 威, 山口 浩司, 山田 博胤, 添木 武, 若槻 哲三, 赤池 雅史, 佐田 政隆

Journal of Cardiology   Vol.71 ( No.3 ) 305 - 309   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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It is well known that warfarin inhibits the synthesis of vitamin K-dependent anticoagulants, including thrombin, protein C and S, and factor Xa, leading, paradoxically, to an initial hypercoagulable state. Edoxaban, a direct inhibitor of activated factor X is widely used for the treatment of acute venous thromboembolism (VTE). However, the effect of edoxaban on circulating coagulation factors, in patients with acute VTE, remains unknown. We enrolled 57 patients with acute VTE with/without pulmonary embolism treated with edoxaban (n=37) or warfarin (n=20) in a clinical setting. Before treatment and 2 weeks after treatment, we evaluated thrombotic burden using ultrasound or computed tomography angiography. We also evaluated thrombin generation, represented by prothrombin fragment F1+2; thrombus degradation, represented by D-dimer; and levels of anticoagulants, including protein C, protein S, and antithrombin III. Both edoxaban and warfarin treatment improved thrombotic burden and decreased prothrombin fragment F1+2, and D-dimer. Edoxaban treatment preserved protein C and protein S levels. In contrast, warfarin decreased protein C and protein S levels. Neither treatment affected antithrombin III. Edoxaban improves VTE while preserving protein C and protein S levels, thereby indicating that edoxaban improves thrombotic burden while maintaining levels of anticoagulants.

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Predictors of Mortality in Patients With Severe Ischemic Cardiomyopathy Undergoing Surgical Mitral Valve Intervention

Kenya Kusunose, Nancy A. Obuchowski, Marc Gillinov, Zoran B. Popovic, Scott D. Flamm, Brian P. Griffin, Deborah H. Kwon

JOURNAL OF THE AMERICAN HEART ASSOCIATION ( WILEY )  6 ( 11 ) e007163 - e007163   2017.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background-Ischemic mitral regurgitation is associated with substantial risk of death. Although surgical mitral valve intervention (MVi) may improve symptoms, it has not been shown to improve survival. The aim of this study was to identify predictors of mortality in patients with ischemic mitral regurgitation and MVi. Methods and Results-We evaluated 117 consecutive patients (age, 65 +/- 10 years) with advanced ischemic cardiomyopathy who underwent cardiac magnetic resonance and subsequent MVi between January 1, 2002 and January 1, 2012. Cardiac magnetic resonance was used to assess left ventricular remodeling and myocardial scarring. The effective regurgitant orifice area was calculated from the proximal isovelocity surface area by echocardiography. There were 43 deaths (37%) during follow-up (median, 62 months). On multivariable analysis, age &gt;= 70 years (P=0.013), diabetes mellitus (P=0.001), dyslipidemia (P=0.012), papillary muscle scar (P=0.010), incomplete revascularization (P=0.001), and total scar %xeffective regurgitant orifice area &gt;= 0.20 cm(2) (P=0.005) were each independently associated with all-cause mortality. Although patients with effective regurgitant orifice area &lt;0.2 cm(2) at baseline demonstrated an increased hazard ratio of 3.3 for every 10% increase in scar, the hazard ratio increased to 9 for every 10% increase in scar in those with baseline effective regurgitant orifice area &gt;= 0.20 cm(2). Mortality also was significantly higher in patients with incomplete revascularization compared with those with vascularized viable myocardium (61% versus 28%; P&lt;0.001). Conclusions-Increased total scar burden and the presence of incomplete revascularization are powerful predictors of mortality in patients with advanced ischemic cardiomyopathy undergoing MVi. Viability assessment with cardiac magnetic resonance imaging can identify which patients with ischemic mitral regurgitation are at highest risk for mortality after surgical MVi.

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症例検討:妊婦に発症した脳梗塞の1例

細川 忍, 戸根 沙織, Naoko Matsui, Kenya Kusunose, Kumiko Kagawa, 山上 圭, 廣島 裕也, 田村 洋人

The Journal of the Japanese Society of Internal Medicine   Vol.106 ( No.10 ) 2265 - 2272   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Echocardiographic Epicardial Adipose Tissue Thickness Is Associated with Symptomatic Coronary Vasospasm during Provocative Testing

Susumu Nishio, Kenya Kusunose, Hirotsugu Yamada, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masataka Sata

Journal of the American Society of Echocardiography ( Mosby Inc. )  30 ( 10 ) 1021 - 1027.e1   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background Epicardial adipose tissue (EAT) is the ectopic visceral fat surrounding the heart, which plays an important role in atherosclerosis of the coronary arteries via endothelial damage. Several studies have also suggested that vasospasm with angina (VSA) causes endothelial dysfunction in the coronary arteries. The aim of this study was to evaluate the thickness of EAT in the anterior interventricular groove (EAT-AIG) using echocardiography in patients who had no obstructive coronary artery disease and were suspected of having VSA. Methods Sixty-five patients who underwent intracoronary acetylcholine provocation testing for clinical indications were prospectively enrolled. VSA was diagnosed by coronary artery stenosis increase of &gt 90% and the presentation of chest pain with ischemic changes on electrocardiography. Results Subjects were divided into two groups, with and without significant coronary spasm (VSA group, 30 patients non-VSA group, 35 patients), consistent with acetylcholine provocation testing. EAT-AIG thickness was significantly greater in the VSA group than in the non-VSA group (8.2 ± 2.7 vs 6.1 ± 2.5 mm, P =.002). By receiver operating characteristic analysis, EAT-AIG thickness had a high C statistic (area under the curve = 0.81, P &lt .001) after adjustment for conventional risk factors (smoking, diabetes mellitus, and dyslipidemia). EAT-AIG thickness had incremental diagnostic value over other conventional risk factors (area under the curve = 0.81 vs 0.64, P for comparison =.020). Conclusions EAT-AIG thickness, which is noninvasively and easily measured using transthoracic echocardiography, can be one of multiple clinical variables associated with VSA.

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RV Myocardial Strain During Pre-Load Augmentation Is Associated With Exercise Capacity in Patients With Chronic HF

Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Ayumi Ishii, Yukina Hirata, Hiromitsu Seno, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

JACC: Cardiovascular Imaging ( Elsevier Inc. )  10 ( 10 ) 1240 - 1249   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Objectives The aim of this study was to assess the relationship between right ventricular (RV) function during pre-load augmentation and exercise tolerance. Background Peak oxygen uptake (VO2) is a strong predictor of mortality in chronic heart failure. Cardiac function during pre-load augmentation is an important part of the phenomenon in the evaluation of exercise capacity. Methods We prospectively performed echocardiographic studies in 68 chronic heart failure patients with cardiopulmonary exercise testing (mean age 60 ± 12 years 69% male). After resting evaluations, echocardiographic parameters were repeated during leg positive pressure (LPP). Exercise capacity was assessed by peak VO2 in all patients (left ventricular ejection fraction: 43 ± 15%). Results Patients with severely reduced exercise capacity (peak VO2 &lt 14 ml/kg/min) had significantly lower stroke volume index, left ventricular global longitudinal strain and RV strain and higher filling pressure (E/e’ and pulmonary arterial systolic pressure) than the remainder. Stroke volume index (β = 0.49), global longitudinal strain (β = −0.61), E/e’ (β = −0.32), pulmonary arterial systolic pressure (β = −0.57), and RV strain (β = −0.66) during LPP were independently correlated to peak VO2 (all p &lt 0.01). RV strain during LPP was the most powerful predictor in identifying patients with severely reduced exercise capacity (cut off value: −17% sensitivity: 81% specificity: 88% areas under the curve: 0.88 p &lt 0.001) compared with other variables including resting parameters. Conclusions RV strain during pre-load augmentation correlated independently to peak VO2 and was a powerful predictor in identifying patients with severely reduced exercise capacity.

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Preload Stress Echocardiography Predicts Outcomes in Patients with Preserved Ejection Fraction and Low-Gradient Aortic Stenosis

Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yuta Torii, Yukina Hirata, Hiromitsu Seno, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

Circulation: Cardiovascular Imaging ( Lippincott Williams and Wilkins )  10 ( 10 )   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background-The projected aortic valve area (AVAproj) at a normal transvalvular flow rate using dobutamine is helpful to determine the actual severity of aortic stenosis (AS) and to predict risk of adverse events in low-gradient AS cases with unclear surgical indication. Our study aimed to identify the independent and incremental value of preload stress echocardiography-derived AVAproj to predict outcomes in patients with preserved ejection fraction and low-gradient AS. Methods and Results-We prospectively performed echocardiographic studies in 79 patients with low-gradient AS (age, 77±7 years 30% men) with preload stress echocardiography using leg positive pressure. AVAproj was calculated using AVA and transvalvular flow rate at baseline and during leg positive pressure. The primary end point was the decision for aortic valve surgery or cardiac death. During a median period of 19 months, 23 patients had the decision for aortic valve surgery, and none died during follow-up. In a stepwise multivariable analysis, indexed AVAproj (AVAiproj hazard ratio, 2.00 per 0.1 cm2/m2 decrease 95% confidence interval, 1.36-2.96 P&lt 0.001) was associated with the primary end point. Using a receiver operating characteristic curve analysis, the best cutoff value of AVAiproj for predicting cardiac events was &lt 0.72 cm2/m2. By incorporating AVAiproj into AVAi at baseline, continuous net reclassification index for cardiac events was 0.48 (P=0.04). Conclusions-In patients with low-gradient AS, indexed AVAproj derived from preload stress echocardiography can be useful to predict risk of adverse events. The present article should be considered as a proof of concept study, and we think that larger multicenter studies are warranted.

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Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus

Shusuke Yagi, Yukina Hirata, Takayuki Ise, Kenya Kusunose, Hirotsugu Yamada, Daiju Fukuda, Hotimah Masdan Salim, Gulinu Maimaituxun, Susumu Nishio, Yuriko Takagawa, Saori Hama, Tomomi Matsuura, Koji Yamaguchi, Takeshi Tobiume, Takeshi Soeki, Tetsuzo Wakatsuki, Ken-ichi Aihara, Masashi Akaike, Michio Shimabukuro, Masataka Sata

DIABETOLOGY & METABOLIC SYNDROME ( BIOMED CENTRAL LTD )  9   78 - 78   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: It is unknown whether canagliflozin, a selective sodium glucose co-transporter 2 inhibitor, reduces epicardial adipose tissue (EAT) thickness, which is associated with insulin resistance and is a risk factor for coronary artery disease. Methods and results: We administered 100 mg of canagliflozin for 6 months to 13 patients with type 2 diabetes mellitus. We evaluated glycemic control, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area, and skeletal muscle mass by using impedance methods, and EAT thickness by using echocardiography. Canagliflozin treatment for 6 months decreased hemoglobin A1c level from 7.1 +/- 0.5% to 6.7 +/- 0.6% (P &lt; 0.05) and decreased EAT thickness from 9.3 +/- 2.5 to 7.3 +/- 2.0 mm (P &lt; 0.001), along with a trend of decreasing VAT and SAT area. No association was found between any of these changes. Conclusion: Canagliflozin reduced EAT thickness in patients with type 2 diabetes mellitus independent of its effect on lowering blood glucose, suggesting that canagliflozin may have an effect in preventing cardiovascular events in these patients (UMIN000021327).

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RV Myocardial Strain During Pre-Load Augmentation Is Associated With Exercise Capacity in Patients With Chronic HF

Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Ayumi Ishii, Yukina Hirata, Hiromitsu Seno, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

JACC-CARDIOVASCULAR IMAGING ( ELSEVIER SCIENCE INC )  10 ( 10 ) 1240 - 1249   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVES The aim of this study was to assess the relationship between right ventricular (RV) function during pre-load augmentation and exercise tolerance. BACKGROUND Peak oxygen uptake (VO2) is a strong predictor of mortality in chronic heart failure. Cardiac function during pre-load augmentation is an important part of the phenomenon in the evaluation of exercise capacity. METHODS We prospectively performed echocardiographic studies in 68 chronic heart failure patients with cardiopulmonary exercise testing (mean age 60 +/- 12 years; 69% male). After resting evaluations, echocardiographic parameters were repeated during leg positive pressure (LPP). Exercise capacity was assessed by peak VO2 in all patients (left ventricular ejection fraction: 43 +/- 15%). RESULTS Patients with severely reduced exercise capacity (peak VO2 &lt; 14 ml/kg/min) had significantly lower stroke volume index, left ventricular global longitudinal strain and RV strain and higher filling pressure (E/e' and pulmonary arterial systolic pressure) than the remainder. Stroke volume index (beta = 0.49), global longitudinal strain (beta = -0.61), E/e' (beta = -0.32), pulmonary arterial systolic pressure (beta = -0.57), and RV strain (beta = -0.66) during LPP were independently correlated to peak VO2 (all p &lt; 0.01). RV strain during LPP was the most powerful predictor in identifying patients with severely reduced exercise capacity (cut off value: -17%; sensitivity: 81%; specificity: 88%; areas under the curve: 0.88; p &lt; 0.001) compared with other variables including resting parameters. CONCLUSIONS RV strain during pre-load augmentation correlated independently to peak V(O)2 and was a powerful predictor in identifying patients with severely reduced exercise capacity. (C) 2017 by the American College of Cardiology Foundation.

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Preload Stress Echocardiography Predicts Outcomes in Patients With Preserved Ejection Fraction and Low-Gradient Aortic Stenosis.

Kusunose K, Yamada H, Nishio S, Torii Y, Hirata Y, Seno H, Saijo Y, Ise T, Yamaguchi K, Yagi S, Soeki T, Wakatsuki T, Sata M

Circulation. Cardiovascular imaging   10 ( 10 )   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Low Serum Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid are Risk Factors for Cardiogenic Syncope in Patients with Brugada Syndrome.

Yagi S, Soeki T, Aihara KI, Fukuda D, Ise T, Kadota M, Bando S, Matsuura T, Tobiume T, Yamaguchi K, Kusunose K, Yamada H, Wakatsuki T, Shimabukuro M, Akaike M, Sata M

International heart journal   58 ( 5 ) 720 - 723   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Improved Exercise Capacity After Cardiac Rehabilitation Is Associated with Reduced Visceral Fat in Patients with Chronic Heart Failure.

Takagawa Y, Yagi S, Ise T, Ishii A, Nishikawa K, Fukuda D, Kusunose K, Matsuura T, Tobiume T, Yamaguchi K, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Katoh S, Aihara KI, Akaike M, Sata M

International heart journal   58 ( 5 ) 746 - 751   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Echocardiographic Epicardial Adipose Tissue Thickness Is Associated with Symptomatic Coronary Vasospasm during Provocative Testing.

Nishio S, Kusunose K, Yamada H, Hirata Y, Ise T, Yamaguchi K, Yagi S, Soeki T, Wakatsuki T, Shimabukuro M, Sata M

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography   30 ( 10 ) 1021 - 1027.e1   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Improved exercise capacity after cardiac rehabilitation is associated with reduced visceral fat in patients with chronic heart failure

Yuriko Takagawa, Shusuke Yagi, Takayuki Ise, Ayumi Ishii, Koji Nishikawa, Daiju Fukuda, Kenya Kusunose, Tomomi Matsuura, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Shinsuke Katoh, Ken-ichi Aihara, Masashi Akaike, Masataka Sata

International Heart Journal ( International Heart Journal Association )  58 ( 5 ) 746 - 751   2017.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Participation in a comprehensive cardiac rehabilitation (CR) program has been shown to reduce mortality and improve exercise capacity and symptoms in patients with chronic heart failure (CHF). Reduced exercise capacity leads to a concomitant reduction of skeletal muscle mass and accumulation of body fat. However, it is currently unknown whether CR reduces visceral adipose tissue (VAT) and/or subcutaneous abdominal adipose tissue (SAT) in patients with CHF. In addition, the body composition associated with improved exercise capacity after CR in patients with CHF has not been previously studied. Nineteen CHF patients who were categorized as NYHA functional class II or III and had received optimal medical treatment including a CR program for 5 months were enrolled in this study. The CR program significantly increased peak VO2 and reduced B-type natriuretic peptide. In addition, fat and body composition analysis showed reductions in the visceral fat tissue (VAT) area, subcutaneous abdominal adipose tissue (SAT) area, body weight, and total fat weight after CR. There were no changes in total water weight and total muscle weight. Single regression analysis revealed that the amelioration of reduced exercise capacity seen after CR is associated with reduced VAT area but not with SAT area or body weight. In conclusion, CR reduces VAT and improves exercise capacity in patients with CHF. This suggests that reducing VAT is important for CR to be most effective in the treatment of CHF.

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Low serum levels of eicosapentaenoic acid and docosahexaenoic acid are risk factors for cardiogenic syncope in patients with brugada syndrome

Shusuke Yagi, Takeshi Soeki, Ken-ichi Aihara, Daiju Fukuda, Takayuki Ise, Muneyuki Kadota, Sachiko Bando, Tomomi Matsuura, Takeshi Tobiume, Koji Yamaguchi, Kenya Kusunose, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike, Masataka Sata

International Heart Journal ( International Heart Journal Association )  58 ( 5 ) 720 - 723   2017.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antiarrhythmic effects, possibly via modulation of the cardiac ion channels. Nevertheless, it is unknown whether low serum levels of n-3 PUFAs are risk factors for ventricular fibrillation in patients with Brugada syndrome (BrS). We retrospectively reviewed data from 62 men with BrS and evaluated their serum levels of EPA and DHA, and the risk factors for sudden cardiac death, including a history of cardiogenic syncope. Nineteen patients had a history of cardiogenic syncope, and their EPA and DHA levels were significantly lower than those of the patients without syncope. Multivariate logistic regression analysis revealed that low EPA and DHA levels were associated with the incidence of syncope. The receiver-operator characteristic curve showed the area under the curves of EPA and DHA for history of syncope were 0.84 and 0.72, respectively. In conclusion, low levels of EPA and DHA are risk factors for cardiogenic syncope in patients with BrS, which suggests that n-3 PUFAs play important roles in preventing ventricular fibrillation in BrS.

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Echocardiographic Predictors for Worsening of Six-Minute Walk Distances in Patients With Systemic Sclerosis (Scleroderma)

Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Hiromitsu Seno, Yoshihito Saijo, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

AMERICAN JOURNAL OF CARDIOLOGY ( EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC )  120 ( 2 ) 315 - 321   2017.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Change in 6-minute walk distance (6MWD) has been used as a clinical marker in pulmonary hypertension. Determinants and worsening of 6MWD remain a matter of debate because nonpulmonary factors have an impact on the 6MWD. We hypothesized that future reduction of 6MWD in patients with systemic sclerosis (SSc) was more closely associated with cardiac dysfunction. We prospectively performed standard clinical and echocardiographic evaluations in SSc patients with the 6-minute walk test at enrollment. Features associated with the 6MWD were sought in a multiple linear regression analysis and compared using standardized beta. Worsening of the 6MWD was defined as a 15% reduction and served as the primary outcome. Eighty-one patients were included. In the multivariate analysis, baseline 6MWD was related to SSc severity score (beta = -0.250, p = 0.024), left atrial volume index (beta = -0.222, p = 0.046), right ventricular fractional area change (beta = 0.252, p = 0.025), and the ratio of mean pulmonary artery pressure and cardiac output (beta = -0.31, p = 0.002). During follow-up, 20 patients reached the primary outcome. In sequential Cox models, a model based on right ventricular fractional area change at baseline (chi-square 4.8) was improved by left atrial volume index (chi-square 10.3, p = 0.007). In conclusion, determinants and worsening of 6MWD are explained by cardiac factors. When using the 6MWD as a clinical marker in pulmonary hypertension patients, their left ventricular diastolic function and right ventricular systolic function should be taken into consideration. (C) 2017 Elsevier Inc. All rights reserved.

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Plasma brain natriuretic peptide levels are elevated in patients with cancer

Sachiko Bando, Takeshi Soeki, Tomomi Matsuura, Takeshi Tobiume, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Naoki Muguruma, Tetsuji Takayama, Ichiro Kishimoto, Kenji Kangawa, Masataka Sata

PLOS ONE ( PUBLIC LIBRARY SCIENCE )  12 ( 6 ) e0178607 - e0178607   2017.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also been shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP levels in cancer patients, it remains unknown whether cancer-related inflammation affects the plasma BNP levels. We investigated the relationship between the BNP and human cancers. Methods We retrospectively studied 2,923 patients in whom the plasma BNP levels and serum Creactive protein (CRP) were measured and echocardiography was performed. Patients with clinically evident heart failure (NYHA II or higher), heart disease requiring medical treatment or surgery, renal dysfunction, and inflammatory disease were excluded. There were 234 patients in the final analysis. Blood sampling was performed before surgery and chemotherapy. In addition, we evaluated the relationship between the inflammation and plasma BNP levels in mouse models of colon cancer. Results Of the 234 patients, 80 were diagnosed with cancer. Both the plasma BNP and serum CRP levels were significantly higher in cancer patients than those without. There were no significant differences in the echocardiographic parameters. There was a significant positive correlation between the plasma BNP and serum CRP levels in cancer patients (r = 0.360, P &lt; 0.01) but not in those without. In cancer patients, only the CRP correlated with the BNP independent of the age, creatinine level, hypertension, and body mass index. In addition, in nude mice with subcutaneous colon cancer, the plasma BNP level was elevated compared with that in non-cancer mice, and there was a significant relationship between the plasma BNP and serum levels of the inflammatory markers. Conclusions In cancer patients, as well as colon cancer model mice, the plasma BNP levels were elevated, possibly due to cancer-related inflammation. The effect of cancer on the BNP levels should be considered when using BNP as an indicator of heart failure in cancer patients.

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Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study

Hirotsugu Yamada, Atsushi Tanaka, Kenya Kusunose, Rie Amano, Munehide Matsuhisa, Hiroyuki Daida, Masaaki Ito, Hiroyuki Tsutsui, Mamoru Nanasato, Haruo Kamiya, Yasuko K. Bando, Masato Odawara, Hisako Yoshida, Toyoaki Murohara, Masataka Sata, Koichi Node

CARDIOVASCULAR DIABETOLOGY ( BIOMED CENTRAL LTD )  16 ( 1 ) 63 - 63   2017.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Diabetes is associated closely with an increased risk of cardiovascular events, including diastolic dysfunction and heart failure that leads to a shortening of life expectancy. It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function. However, the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern. We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub-analysis of the PROLOGUE study. Methods: Patients in the PROLOGUE study were assigned randomly to either add-on sitagliptin treatment or conventional antidiabetic treatment. Of the 463 patients in the overall study, 115 patients ( 55 in the sitagliptin group and 60 in the conventional group) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e') at baseline and after 12 and 24 months were included in this study. The primary endpoint of this post hoc sub-analysis was a comparison of the changes in the ratio of E to e' (E/e') between the two groups from baseline to 24 months. Results: The baseline-adjusted change in E/e' during 24 months was significantly lower in the sitagliptin group than in the conventional group (-0.18 +/- 0.55 vs. 1.91 +/- 0.53, p = 0.008), irrespective of a higher E/e' value at baseline in the sitagliptin group. In analysis of covariance, sitagliptin treatment was significantly associated with change in E/e' over 24 months (beta = -9.959, p = 0.001), independent of other clinical variables at baseline such as blood pressure, HbA1c, and medications for diabetes. Changes in other clinical variables including blood pressure and glycemic parameters, and echocardiographic parameters, such as cardiac structure and systolic function, were comparable between the two groups. There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period. Conclusions: Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction (E/e') independent of other clinical variables such as blood pressure and glycemic control.

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Correlation between right ventricular T₁ mapping and right ventricular dysfunction in non-ischemic cardiomyopathy.

Jellis CL, Yingchoncharoen T, Gai N, Kusunose K, Popović ZB, Flamm S, Kwon D

The international journal of cardiovascular imaging     2017.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Clinical Utility of Longitudinal Strain to Predict Functional Recovery in Patients With Tachyarrhythmia and Reduced LVEF.

Kusunose K, Torii Y, Yamada H, Nishio S, Hirata Y, Seno H, Saijo Y, Ise T, Yamaguchi K, Tobiume T, Yagi S, Soeki T, Wakatsuki T, Sata M

JACC. Cardiovascular imaging ( ELSEVIER SCIENCE INC )  10 ( 2 ) 118 - 126   2017.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Objectives: The aim of this study was to assess the time course of presumptive TIC and the predictors of LV functional recovery in such patients.Background: Tachycardia-induced cardiomyopathy (TIC) is a potentially reversible cardiomyopathy with effective treatment of the tachyarrhythmia. However, cases without improvement of left ventricular (LV) systolic function were found occasionally. The diagnosis of TIC can be challenging, and the role of echocardiographic imaging in the prediction of LV functional recovery is limited.Methods: LV segmental longitudinal strains (LS) were evaluated by 2-dimensional speckle tracking in 71 consecutive patients (65±16 years; 61% men) with tachyarrhythmia and reduced LV ejection fraction (EF) without any other known cardiovascular disease, and 30 age and gender matched control subjects. Relative apical LS ratio (RALSR) was defined using the equation: average apical LS / (average basal LS + average mid LS) as a marker of strain distribution.Results: Compared to control subjects, patients with tachyarrhythmia had significantly lower global LS. Improvement in LVEF within 6 months after treatment of index arrhythmia was observed in 41 patients, and LVEF did not improve in 30 patients. In univariate analysis, lower LVEF at baseline (hazard ratio: HR: 0.59 per 1SD, p=0.04) and higher RALSR (HR: 11.2 per 1SD, p &lt;0.001) were associated with no recovery in LVEF during follow-up. In a multivariate logistic regression model, the significant predictor of LV systolic functional recovery was RALSR (HR: 22.9 per 1SD, p=0.001). A RALSR of 0.61 was sensitive (71%) and specific (90%) in differentiating LV systolic functional recovery (area under the curve: 0.88).Conclusions: The RALSR was associated with LV systolic functional recovery. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF.

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局所心臓周囲脂肪厚の臨床的意義 冠動脈疾患での検討

Maimaituxun Gulinu, 島袋 充生, 平田 有紀奈, 岩瀬 俊, 高尾 正一郎, 松浦 朋美, 伊勢 孝之, 楠瀬 賢也, 飛梅 威, 山口 浩司, 八木 秀介, 福田 大受, 山田 博胤, 添木 武, 若槻 哲三, 原田 雅史, 佐田 政隆

Anti-aging Science ( (株)メディカルレビュー社 )  8 ( 1 ) 61 - 61   2016.12 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Effect of Direct Oral Anticoagulants on Carotid Artery Sclerosis in Patients With Atrial Fibrillation

Torii Yuta, Yamada Hirotsugu, Kusunose Kenya, Seno Hiromitsu, Saijyo Yoshihito, Okushi Yuichiro, Nishio Susumu, Hirata Yukina, Amano Rie, Sata Masataka

CIRCULATION   134   2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Longitudinal Strain Distribution is a Powerful Predictor for Functional Recovery in Patients With Tachycardia-induced Cardiomyopathy

Kusunose Kenya, Yamada Hirotsugu, Saijo Yoshihito, Seno Hiromitsu, Hirata Yukina, Torii Yuta, Nishio Susumu, Ise Takayuki, Yamaguchi Koji, Yagi Shusuke, Soeki Takeshi, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   134   2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Longitudinal Strain Distribution is a Powerful Predictor for Functional Recovery in Patients With Tachycardia-induced Cardiomyopathy

Kusunose Kenya, Yamada Hirotsugu, Saijo Yoshihito, Seno Hiromitsu, Hirata Yukina, Torii Yuta, Nishio Susumu, Ise Takayuki, Yamaguchi Koji, Yagi Shusuke, Soeki Takeshi, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   134   2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Impact of Age on the Morphology of Left Atrial Appendage in Atrial Fibrillation

Hirata Yukia, Yamada Hirotsugu, Kusunose Kenya, Shimizu Rikuto, Torii Yuta, Nishio Susumu, Seno Hiromitsu, Saijo Yoshihito, Hayashi Shuji, Soeki Takeshi, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   134   2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Effect of Sitagliptin on Left Ventricular Function in Patients With Type 2 Diabetes a Sub Analysis of the PROLOGUE Study

Hiromitsu Seno, Yamada Hirotsugu, Kusunose Kenya, Amano Rie, Matsushita Munehide, Nanasato Mamoru, Murohara Toyoaki, Kamiya Haruo, Sata Masataka, Node Koichi

CIRCULATION   134   2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Purulent Pericarditis Accompanying Pericardial Abscess Induced by Nocardia in an Immunocompromised Patient

Akira Takashima, Shusuke Yagi, Koji Yamaguchi, Syunsuke Watanabe, Nobuaki Yamamoto, Hiroyuki Ito, Muneyuki Kadota, Tomoya Hara, Hiromu Yamazaki, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  80 ( 11 ) 2409 - 2411   2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Relationship between local production of microRNA-328 and atrial substrate remodeling in atrial fibrillation

Takeshi Soeki, Tomomi Matsuura, Sachiko Bando, Takeshi Tobiume, Etsuko Uematsu, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Masataka Sata

JOURNAL OF CARDIOLOGY ( ELSEVIER SCIENCE BV )  68 ( 5-6 ) 472 - 477   2016.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: The underlying mechanism of atrial substrate remodeling in atrial fibrillation (AF) remains unknown. In this study, we investigated whether local and systemic levels of microRNA (miR) might be associated with the presence of AF and with left atrial (LA) substrate properties. Methods: Blood from the periphery, pulmonary vein (PV), and left atrial appendage (LAA) was sampled from 30 patients with AF undergoing PV isolation, and from 10 control subjects with Wolff-Parkinson White syndrome and without AF. We measured peripheral, PV, and LAA plasma levels of miR-1,-26, -133a, -328, and -590 by reverse transcription-polymerase chain reaction. LA global contact mapping during sinus rhythm was performed before PV isolation. Results: Plasma levels of miR-328 were higher in patients with AF than in control subjects. Plasma miR-328 levels were significantly higher in the LAA than in the periphery and PV in patients with AF, but not in control subjects. Plasma miR-1 levels were also higher in the LAA than in the PV in AF patients. Interestingly, LAA plasma levels of miR-328 showed a positive correlation with the LA voltage zone index (area with voltage &lt;0.5 mV divided by total LA surface area) and a weak correlation with LA volume. Conclusion: Local production of miR-328 in the left atrium may be involved in the process of atrial remodeling in patients with AF. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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Relation of Echocardiographic Characteristics of the Right-Sided Heart With Incident Heart Failure and Mortality in Patients With Sleep-Disordered Breathing and Preserved Left Ventricular Ejection Fraction

Kenya Kusunose, Dermot Phelan, Sinziana Seicean, Andreea Seicean, Patrick Collier, Kaeleen A. Bodena, Reena Mehrad, Brian P. Griffin

AMERICAN JOURNAL OF CARDIOLOGY ( EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC )  118 ( 8 ) 1268 - 1273   2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Sleep-disordered breathing (SDB) has been associated with right-sided heart dysfunction and adverse cardiovascular outcomes. Longitudinal data are sparse in terms of understanding the prognostic implications of right ventricular remodeling in SDB on cardiovascular risk. We therefore investigated the predictive value of right-sided cardiac functional alterations on incident heart failure (HF) or death in SDB. Patients with SDB who underwent echocardiography within 1 month of index polysomnogram from January 2002 to July 2011 with normal left ventricular ejection fraction were included. Cox proportional prognostic hazard models predicting HF or death were used. Of a potential 375 subjects, 202 fulfilled the inclusion criteria (58 +/- 14 years; 50% men). Subjects were followed for 3.1 +/- 2.4 years with a total of 34 (16.8%) developing HF or death. Right ventricular end-systolic area (hazard ratio [HR] 1.3, 95% CI 1.01 to 1.6, p = 0.038), pulmonary vascular resistance (PVR; HR 1.4, 95% CI 1.1 to 1.7, p = 0.005) and also left atrial volume index (HR 1.7, 95%, CI 1.3 to 2.3, p &lt;0.001) and E/A ratio (HR 1.4, 95% CI 1.1 to 1.7; p &lt;0.001), were predictive of HF or death. Patients with increased PVR had significantly shorter event-free survival than without increased PVR (p = 0.04). In sequential Cox models, a model based on clinical data and left ventricular ejection fraction (chi(2), 5.4) was improved by left atrial volume index (chi(2), 12.7; p = 0.011) and further increased by PVR (chi(2), 19.7; p = 0.015). In conclusion, right-sided heart dysfunction provides important prognostic information in SDB and may aid in identifying those at highest risk to target for closer follow-up. (C) 2016 Elsevier Inc. All rights reserved.

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解剖学的異常を認めない膝窩動脈捕捉症候群の1例

鳥居 裕太, 西尾 進, 玉井 佑里恵, 山崎 宙, Shoichiro Takao, Kenya Kusunose, Koji Yamaguchi, Tetsuzo Wakatsuki, Hirotsugu Yamada, Masataka Sata

超音波検査技術   Vol.41 ( No.5 ) 513 - 520   2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Predictors and Prognostic Significance of Right Ventricular Ejection Fraction in Patients With Ischemic Cardiomyopathy

Marwa A. Sabe, Sharif A. Sabe, Kenya Kusunose, Scott D. Flamm, Brian P. Griffin, Deborah H. Kwon

CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  134 ( 9 ) 656 - 665   2016.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Decreased right ventricular (RV) ejection fraction (RVEF) portends poor prognosis in patients with ischemic cardiomyopathy, and previous studies have suggested an association between mitral regurgitation (MR) and RVEF. We sought to evaluate this association and whether mitral valve repair or replacement affects the relationship between RV function and mortality. METHODS: We included 588 patients (mean age, 63 +/- 11 years; 75% male) with ischemic cardiomyopathy who underwent cardiac magnetic resonance imaging between 2002 and 2008. Baseline characteristics, left ventricular ejection fraction, MR severity, treatment modality, scar burden, and RVEF were assessed. Multivariable linear regression and Cox proportional hazards models were used to assess the association between MR and RVEF and between RVEF and mortality, respectively. RESULTS: After adjustment for age, sex, left ventricular ejection fraction, right bundle-branch block, and RV scar, MR severity was found to be associated independently with RVEF. There were a total of 240 deaths during a median follow-up time of 5.7 years. After multivariable adjustment, every 10% decrease in RVEF was associated with a 17% increased risk of death (P=0.008). Although decreasing RVEF was associated with a poor prognosis in the nonrepair group (hazard ratio, 1.28; 95% confidence interval, 1.12-1.47; P&lt;0.001), it was not associated with death in the mitral valve repair or replacement group (P for interaction=0.046). CONCLUSIONS: MR severity was found to be an independent predictor of RVEF, as were right bundle-branch block, left ventricular ejection fraction, and the presence of RV scar. Decreasing RVEF is associated with increased mortality in patients with ischemic cardiomyopathy; however, this association may be mitigated in patients who undergo mitral valve repair or replacement.

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表在エコー図検査と心エコー図検査のコラボレーションにより感染性心内膜炎が迅速に診断できた僧帽弁逸脱症の1例:Staphylococcus warneriによる自己弁への感染性心内膜炎

Hirotsugu Yamada, 田中 秀和, 宮原 俊介, 尾形 竜郎, Kenya Kusunose, 西尾 進, 鳥居 裕太, 平田 有紀奈, 大北 裕, Masataka Sata

Japanese Journal of Medical Ultrasonics ( The Japan Society of Ultrasonics in Medicine )  Vol.43 ( No.4 ) 581 - 586   2016.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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症例は,46歳男性,循環器内科医師,主訴は左足関節内果部と上腕の疼痛である.僧帽弁逸脱症による僧帽弁逆流と発作性心房細動の既往がある.足関節の疼痛は蜂窩織炎を疑って,血液検査と表在エコー図検査を行った.疼痛部は皮下浮腫が著明であったが,軟部組織の血流シグナルが乏しく,後脛骨動脈の血管壁を主体とした炎症と,同動脈の閉塞が確認された.一方,左手関節近位の尺骨動脈は逆行性血流を示しており,左尺骨動脈分岐部直後で閉塞していた.これらの所見から多発性血管閉塞性動脈炎と診断し,その原因究明のために直ちに心エコー図検査を施行した.その結果,僧帽弁に可動性を有する棍棒状の異常構造物を認め,僧帽弁逆流は高度に増悪しており,感染性心内膜炎と診断された.頭部MRI検査で異常を認めなかったため,外科的加療(疣腫摘除術,僧帽弁形成術,左房縫縮術,左心耳閉鎖術,Maze手術)が行われた.血液培養は陰性であったが,摘出した疣腫の培養からStaphylococcus warneriが同定された.Staphylococcus warneriは皮膚常在菌であり,本病原体による自己弁の感染性心内膜炎は報告が少ない.術後の経過は良好であり,抗生剤を6週間静脈投与した後に社会復帰した.患者が循環器内科医であり,自身の足関節および上腕の疼痛を契機に,表在エコー図検査と心エコー図検査を用いることで,感染性心内膜炎を迅速に診断した稀有な症例であり,かつ,感染性心内膜炎の起炎菌としては稀なStaphylococcus warneriが同定されたので,文献的な考察を加えて報告する.

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Predictors and Prognostic Impact of Progressive Ischemic Mitral Regurgitation in Patients With Advanced Ischemic Cardiomyopathy A Multimodality Study

Deborah H. Kwon, Kenya Kusunose, Nancy A. Obuchowski, Joao L. Cavalcante, Zoran B. Popovic, James D. Thomas, Milind Y. Desai, Scott D. Flamm, Brian P. Griffin

Circulation-Cardiovascular Imaging ( LIPPINCOTT WILLIAMS & WILKINS )  9 ( 7 )   2016.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background-Ischemic mitral regurgitation (IMR) is associated with poor outcomes. It is unknown what factors contribute to progression of IMR and how progressive IMR affects outcomes. We sought to determine imaging predictors of IMR progression and to determine if progressive IMR is an independent predictor of survival in patients with advanced ischemic cardiomyopathy. Methods and Results-Consecutive advanced ischemic cardiomyopathy patients who underwent cardiac magnetic resonance and echocardiograms at baseline with echocardiographic follow-up were studied. Cardiac magnetic resonance was used to assess left ventricular volumes, infarct size, and mitral valve geometry. The effective regurgitant orifice area (EROA) was calculated from the proximal isovelocity surface area by echocardiography. Repeated measures mixed effects and Cox proportional hazards regression models were built to identify predictors of IMR progression and survival. We evaluated 336 patients (age, 62 +/- 11 years) over a median follow-up time of 54 months: 154 patients were subsequently revascularized, and 182 patients were medically treated. Ninety-eight patients (29%) demonstrated an increase in EROA values of &gt;= 0.1 cm(2). There were 87 adverse events (death or transplant). On multivariable analysis, infarct size (P&lt;0.001), progression in IMR (P=0.008), age (P=0.003), and baseline EROA (P=0.010) were independently associated with adverse events. Independent predictors of IMR progression were as follows: baseline EROA (P&lt;0.001), left ventricular end-systolic volume index (P=0.014), and total scar (P=0.036). Conclusions-IMR frequently increases in severity, and progression is independently associated with adverse left ventricular remodeling and infarct size, as assessed by cardiac magnetic resonance. Furthermore, IMR progression is a powerful independent predictor of adverse events, even after controlling for the severity of IMR at baseline.

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Association of Abnormal Postoperative Left Ventricular Global Longitudinal Strain With Outcomes in Severe Aortic Stenosis Following Aortic Valve Replacement

Rami Kafa, Kenya Kusunose, Andrew L. Goodman, Lars G. Svensson, Joseph F. Sabik, Brian P. Griffin, Milind Y. Desai

JAMA CARDIOLOGY ( AMER MEDICAL ASSOC )  1 ( 4 ) 494 - 496   2016.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Noninvasive Vascular Function Tests - Long Journey for Predicting Cardiovascular Events

Kenya Kusunose, Hirotsugu Yamada

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  80 ( 6 ) 1321 - 1322   2016.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Left Ventricular Global Strain for Estimating Relaxation and Filling Pressure - A Multicenter Study -

Taichi Hayashi, Satoshi Yamada, Hiroyuki Iwano, Masahiro Nakabachi, Mamoru Sakakibara, Kazunori Okada, Daisuke Murai, Hisao Nishino, Kenya Kusunose, Kiyotaka Watanabe, Tomoko Ishizu, Kazuaki Wakami, Hirotsugu Yamada, Kaoru Dohi, Yoshihiro Seo, Nobuyuki Ohte, Taisei Mikami, Hiroyuki Tsutsui

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  80 ( 5 ) 1163 - 1170   2016.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Speckle-tracking echocardiography (STE)-derived parameters may have better correlation with left ventricular (LV) relaxation and filling pressure than tissue Doppler-derived parameters. However, it has not been elucidated which parameter - strain or strain rate - and which direction of myocardial deformation - longitudinal or circumferential - is the most useful marker of LV relaxation and filling pressure. Methods and Results: We conducted a prospective multicenter study and compared the correlation of tissue Doppler-and STE-derived parameters with the time constant of LV pressure decay (tau) and LV mean diastolic pressure (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity (e') with t was weak (r=-0.32, P&lt;0.01), and that of peak longitudinal strain (LS) was the strongest (r=-0.45, P&lt;0.001) among the STE-derived parameters. There was a modest correlation between LVMDP and the ratio of early-diastolic inflow velocity (E) to e' (E/e') (r=0.50, P&lt;0.001). In contrast, the ratio of E to LS (E/LS) correlated strongly with LVMDP (r=0.70, P&lt;0.001). The correlation of E/LS with LVMDP was significantly better than that for E/e' (P&lt;0.01). Receiver-operating characteristic analysis showed that E/LS had the largest area under the curve for distinguishing elevated LVMDP (E/LS 0.86, E/e' 0.74, E/A 0.67). Conclusions: STE-derived longitudinal parameters correlated well with LV relaxation and filling pressure. In particular, E/LS could be more accurate than E/e' for estimating LV filling pressure.

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Prognostic implication of relative regional strain ratio in cardiac amyloidosis

Alpana Senapati, Brett W. Sperry, Justin L. Grodin, Kenya Kusunose, Paaladinesh Thavendiranathan, Wael Jaber, Patrick Collier, Mazen Hanna, Zoran B. Popovic, Dermot Phelan

HEART ( BMJ PUBLISHING GROUP )  102 ( 10 ) 748 - 754   2016.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Objective Cardiac amyloidosis (CA) is a rapidly progressive disease that portends poor prognosis. Our objective was to evaluate the prognostic impact of relative regional strain ratio (RRSR, a measure of the relative apical sparing of longitudinal strain (LS)) in CA. Methods This is a retrospective study evaluating 97 patients with CA from 2004 to 2013. Patients were included if they met criteria for CA based on endomyocardial biopsy or advanced imaging criteria coupled with either extracardiac biopsy or genetic analysis. Baseline clinical and imaging data were collected and compared between light-chain amyloidosis (AL) (n=59) and transthyretin amyloidosis (ATTR) (n=38) subtypes. RRSR was defined as the average apical LS divided by the sum of the average mid and basal LS values. A Cox proportional hazards model was used to assess the effects of clinical and echocardiographic characteristics, including RRSR, on the outcome of time to death or heart transplantation. Results Despite younger age, the AL subtype had a statistically significant association with the composite outcome as compared with ATTR (p=0.022). Log-transformed RRSR was independently associated with the composite outcome at 5 years (HR 2.45 (1.36 to 4.40), p=0.003). Patients with low ejection fraction and high RRSR had the worst prognosis. In multivariable analysis, RRSR remained predictive of the primary outcome (p=0.018). Addition of covariates related to systolic function (global LS and ejection fraction) to the model attenuated this effect. Conclusions High RRSR is adversely prognostic in patients with cardiac amyloid. This novel tool is both diagnostic and prognostic and may have implications in management and suitability for treatment.

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Noninvasive Quantitative Tissue Characterization of Carotid Plaques Using Color-Coded Mapping Based on Ultrasound Integrated Backscatter.

Bando M, Yamada H, Kusunose K, Fukuda D, Amano R, Tamai R, Torii Y, Hirata Y, Nishio S, Satomi J, Nagahiro S, Sata M

JACC. Cardiovascular imaging ( ELSEVIER SCIENCE INC )  9 ( 5 ) 625 - 627   2016.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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COMPARISON OF RIGHT VENTRICULAR GLOBAL LONGITUDINAL STRAIN BETWEEN VENDER-DEPENDENT AND VENDER-INDEPENDENT TWO-DIMENSIONAL SPECKLE TRACKING SOFTWARE

Seno Hiromitsu, Kusunose Kenya, Yamada Hirotsugu, Saijo Yoshihito, Nishio Susumu, Hirata Yukina, Ise Takayuki, Yamaguchi Koji, Yagi Shusuke, Soeki Takeshi, Wakatsuki Tetsuzo, Masataka Sata

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   67 ( 13 ) 1781   2016.04 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Effects of Transthoracic Echocardiographic Simulator Training on Performance and Satisfaction in Medical Students

Kenya Kusunose, Hirotsugu Yamada, Rino Suzukawa, Yukina Hirata, Masami Yamao, Takayuki Ise, Shusuke Yagi, Masashi Akaike, Masataka Sata

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY ( MOSBY-ELSEVIER )  29 ( 4 ) 375 - 377   2016.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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m Prognostic Implications of Non-Invasive Vascular Function Tests in High-Risk Atherosclerosis Patients

Kenya Kusunose, Mitsuyo Sato, Hirotsugu Yamada, Yoshihito Saijo, Mika Bando, Yukina Hirata, Susumu Nishio, Shuji Hayashi, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  80 ( 4 ) 1034 - 1040   2016.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: The aim of this study was to assess the role of clinically available vascular function tests as predictors of cardiovascular events and decline in kidney function. Methods and Results: One hundred and fourteen patients who had at least 2 cardiovascular risk factors were recruited for vascular function assessment including ankle-brachial blood pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI) and flow-mediated vasodilatation (%FMD). During a median period of 51 months, 35 patients reached the primary endpoint (29 cardiovascular events and 6 cardiac deaths), and 30 patients reached the secondary endpoint (decline in kidney function: defined as a 5% per year decline of estimated glomerular filtration rate). In sequential Cox models, a model on the basis of the Framingham risk score, hemoglobin, and high-sensitivity C-reactive protein (chi-squared, 16.6) was improved by the ABI (chisquared: 21.5; P=0.047). The baPWV (hazard ratio: 1.42 per 1 SD increase; P=0.025) and the CAVI (hazard ratio: 1.52 per 1 SD increase; P=0.040) were associated with the secondary endpoint. The %FMD was only slightly associated with the primary and secondary endpoints. Conclusions: Both ABI and baPWV are significantly associated with future cardiovascular events in high-risk patients with cardiovascular disease. The predictive capabilities of these parameters are greater than that of other parameters in this cohort.

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Erratum: Relationship between right ventricular longitudinal strain, invasive hemodynamics, and functional assessment in pulmonary arterial hypertension (Korean Circulation Journal (2015) 45 (398-407) DOI: 10.4070/kcj.2015.45.5.398)

Jae-Hyeong Park, Kenya Kusunose, Deborah H. Kwon, Margaret M. Park, James D. Thomas, Richard A. Grimm, Brian P. Griffin, Thomas H. Marwick, Zoran B. Popovic

Korean Circulation Journal ( Korean Society of Circulation )  46 ( 2 ) 273   2016.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Rest and exercise echocardiography for early detection of pulmonary hypertension

Kenya Kusunose, Hirotsugu Yamada

Journal of Echocardiography ( Springer Tokyo )  14 ( 1 ) 2 - 12   2016.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Early detection of pulmonary hypertension (PH) is essential to ensure that patients receive timely and appropriate treatment for this progressive disease. Rest and exercise echocardiography has been used to screen patients in an attempt to identify early stage PH. However, current PH guidelines recommend against exercise tests because of the lack of evidence. We reviewed previous studies to discuss the current standpoint concerning rest and exercise echocardiography in PH. Around 20 exercise echocardiography studies were included to assess the cutoff value for exercise-induced pulmonary hypertension (EIPH). Approximately 40 exercise echocardiography studies were also included to evaluate the pulmonary artery pressure-flow relationship as assessed by the slope of the mean pulmonary artery pressure and cardiac output (ΔmPAP/ΔQ). There were several EIPH and ΔmPAP/ΔQ reference values in individuals with pulmonary vascular disease. We believed that assessing the ΔmPAP/ΔQ makes sense from a physiological standpoint, and the clinical value should be confirmed in future studies. Exercise echocardiography is an appealing alternative in PH. Further studies are needed to assess the prognostic value of the pulmonary artery pressure-flow relationship in high-risk subjects.

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Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension (vol 45, pg 398, 2015)

Jae-Hyeong Park, Kenya Kusunose, Deborah H. Kwon, Margaret M. Park, James D. Thomas, Richard A. Grimm, Brian P. Griffin, Thomas H. Marwick, Zoran B. Popovic

KOREAN CIRCULATION JOURNAL ( KOREAN SOC CARDIOLOGY )  46 ( 2 ) 273 - 273   2016.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Vegetation in the coronary sinus that concealed the presence of a coronary arteriovenous fistula in a patient with infectious endocarditis

Akira Takashima, Shusuke Yagi, Koji Yamaguchi, Eri Takagi, Tamotsu Kanbara, Hirohisa Ogawa, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Tetsuya Kitagawa, Masataka Sata

INTERNATIONAL JOURNAL OF CARDIOLOGY ( ELSEVIER IRELAND LTD )  207   266 - 268   2016.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Effects of the Addition of Eicosapentaenoic Acid to Strong Statin Therapy on Inflammatory Cytokines and Coronary Plaque Components Assessed by Integrated Backscatter Intravascular Ultrasound

Toshiyuki Niki, Tetsuzo Wakatsuki, Koji Yamaguchi, Yoshio Taketani, Hiroyasu Oeduka, Kenya Kusunose, Takayuki Ise, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  80 ( 2 ) 450 - 460   2016.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: The effects of eicosapentaenoic acid (EPA) on coronary artery disease have been previously reported; however, those of the addition of EPA to strong statins on coronary plaque components and local inflammatory cytokines are not known. Methods and Results: A total of 95 patients who had been treated with strong statin for at least 6 months were randomized into 2 groups: an EPA group (additional treatment with EPA at 1,800 mg/day, n=48) or a control group (no additional treatment, n=47), for 6 months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein. A significant reduction in lipid volume (18.5+/-1.3 to 15.0+/-1.5 mm(3), P=0.007) and a significant increase in fibrous volume (22.9+/-0.8 to 25.6+/-1.1 mm(3), P=0.01) were observed in IB-IVUS image analyses in the EPA group, but no significant changes in the plaque components in the control group. CS levels of pentraxin 3 and monocyte chemoattractant protein-1 were lower after than before treatment with EPA (3.3+/-2.1 to 2.6+/-1.2 ng/ml, 120.4+/-26.2 to 110.2+/-26.8 pg/ml, P=0.015 and P=0.008, respectively); however, there were no significant changes in those inflammatory cytokines between pre-and post-treatment in the control group. Conclusions: The addition of EPA was associated with reduced lipid volume in coronary plaques and decreased inflammatory cytokines.

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Left Ventricular Lipomatous Hamartoma Mimicking a Calcified Amorphous Tumor

Yuta Torii, Hirotsugu Yamada, Susumu Matsukuma, Susumu Nishio, Kenya Kusunose, Miho Abe, Masataka Sata

CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  133 ( 8 ) E408 - E410   2016.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Supplemental Digital Content is available in the text.

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Comparison of Tricuspid Annular Plane Systolic Excursion in Patients With Atrial Fibrillation Versus Sinus Rhythm

Yuta Torii, Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Rie Amano, Masami Yamao, Mika Bando, Shuji Hayashi, Masataka Sata

AMERICAN JOURNAL OF CARDIOLOGY ( EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC )  117 ( 2 ) 226 - 232   2016.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Echocardiography now plays a central guiding role in the management of patients with atrial fibrillation (AF). However, the current guidelines mention little about the presence AF during the assessment of echocardiographic variables in the clinical setting. AF itself may impact on tricuspid annular plane systolic excursion (TAPSE) as a right ventricular systolic function compared with sinus rhythm (SR). The aim of this study was to compare and assess the echocardiographic parameters including TAPSE in patients with AF and SR. From January 1, 2013, to September 30, 2014, patients with AF without any cardiovascular disease were retrospectively evaluated using echocardiography. Age-, gender-, and left ventricular ejection fraction matched patients with SR were selected from our database on the basis of a comprehensive history, physical examination, and echocardiographic findings. During the study period, we identified 239 patients with AF (74 +/- 9 years; 65% men) and without any cardiac disease who underwent echocardiography. We also included 281 patients in the SR group (74 +/- 8 years; 67% men). In all study subjects, TAPSE in AF was smaller than in SR regardless of age (17 +/- 3 vs 20 +/- 3 mm, p &lt;0.001). In the stepwise multiple regression model, TAPSE was strongly associated with the presence of AF (standardized beta = -0.362, p &lt;0.001) and stroke volume index (standardized beta = 0.173, p &lt;0.001) after adjustment for age, gender, heart rate, left ventricular ejection fraction, and tricuspid regurgitant grade. In conclusions, patients with AF had lower TAPSE than those with SR regardless of age. When we assess TAPSE in the clinical setting, we must pay attention to the presence of AF. (C) 2016 Elsevier Inc. All rights reserved.

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Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Strain in Patients With Significant Aortic Stenosis

Andrew Goodman, Kenya Kusunose, Zoran B. Popovic, Roosha Parikh, Tyler Barr, Joseph F. Sabik, L. Leonardo Rodriguez, Lars G. Svensson, Brian P. Griffin, Milind Y. Desai

JOURNAL OF THE AMERICAN HEART ASSOCIATION ( WILEY-BLACKWELL )  5 ( 1 )   2016.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background-In aortic stenosis (AS), symptoms and left ventricular (LV) dysfunction represent a later disease state, and objective parameters that identify incipient LV dysfunction are needed. We sought to determine prognostic utility of brain natriuretic peptide (BNP) and left ventricular global longitudinal strain (LV-GLS) in patients with aortic valve area &lt; 1.3 cm(2). Methods and Results-Five-hundred and thirty-one patients between January 2007 and December 2008 with aortic valve area &lt; 1.3 cm(2) (86% with aortic valve area &lt;= 1.1 cm(2)) and left ventricular ejection fraction = 50% who had BNP drawn = 90 days from initial echo were included. Society of Thoracic Surgeons (STS) score and mortality were recorded. Mean STS score, glomerular filtration rate, and median BNP were 11 +/- 5, 73 +/- 35 mL/min per 1.73 m, and 141 (60-313) pg/mL, respectively; 78% were in New York Heart Association class &gt;= II. Mean LV-stroke volume index (LV-SVI) and LV-GLS were 39 +/- 10 mL/m(2) and -13.9 +/- 3%. At 4.7 +/- 2 years, 405 patients (76%) underwent aortic valve replacement; 161 died (30%). On multivariable survival analysis, age (hazard ratio [HR] 1.46), New York Heart Association class (HR 1.27), coronary artery disease (HR 1.72), decreasing glomerular filtration rate (HR 1.15), increasing BNP (HR 1.16), worsening LV-GLS (HR 1.13) and aortic valve replacement (time dependent) (HR 0.34) predicted survival (all P&lt; 0.01). For mortality, the c-statistic incrementally increased as follows (all P&lt; 0.01): STS score (0.60 [0.58-0.64]), STS score+ BNP (0.67 [0.62-0.70]), and STS score+ BNP+ LV-GLS (0.74 [0.68-0.78]). Conclusions-In normal LVEF patients with significant aortic stenosis, BNP and LV-GLS provide incremental (additive not duplicative) prognostic information over established predictors, suggesting that both play a synergistic role in defining outcomes.

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Left Atrial Size and Function in a Canine Model of Chronic Atrial Fibrillation and Heart Failure

Adam Goldberg, Kenya Kusunose, Salima Qamruddin, L. Leonardo Rodriguez, Todor N. Mazgalev, Brian P. Griffin, David R. Van Wagoner, Youhua Zhang, Zoran B. Popovic

PLOS ONE ( PUBLIC LIBRARY SCIENCE )  11 ( 1 ) e0147015 - e0147015   2016.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS). Methods HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 mu s, 20 Hz, 3-7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms. Results RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p&lt;0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p&lt;0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals. Conclusions In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration.

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Pulmonary embolism due to right atrial free-floating thrombus during echocardiographic examination: a case of a pulmonary saddle thrombus

Mika Bando, Hirotsugu Yamada, Kenya Kusunose, Shuji Hayashi, Yuriko Takagawa, Yoshihito Saijo, Susumu Nishio, Kozue Ogasawara, Masataka Sata

Journal of Echocardiography ( Springer Tokyo )  13 ( 4 ) 145 - 147   2015.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 69-year-old female with polymyositis was referred to our hospital with a chief complaint of dyspnea. Transthoracic echocardiography showed right ventricular overloading. In addition to two-dimensional echocardiography, observation of the abnormal free-floating string-like mass by three-dimensional echocardiography provided superior visualization of the features of the mass which protruded into the right ventricle across the tricuspid valve during diastole. These findings enabled us to confirm the diagnosis of venous thrombus. The thrombus disappeared during the echocardiographic examination. Multidetector-row computed tomography showed a string-like thrombus across the bifurcation of the main pulmonary artery. Anticoagulation therapy was initiated with heparin and warfarin, and fondaparinux was started on the fourth day. Three-dimensional echocardiography was useful in characterizing the motion and extent of the thrombus.

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Reduced ratio of eicosapentaenoic acid and docosahexaenoic acid to arachidonic acid is associated with early onset of acute coronary syndrome (vol 14, 111, 2015)

Shusuke Yagi, Ken-ichi Aihara, Daiju Fukuda, Akira Takashima, Mika Bando, Tomoya Hara, Sachiko Nishimoto, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike, Masataka Sata

NUTRITION JOURNAL ( BIOMED CENTRAL LTD )  14   121   2015.12 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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: Combination of Clinical, Electrocardiographic and Echocardiographic Parameters Predict the Onset of Atrial Fibrillation

Soeki Takeshi, Bando Sachiko, Matsuura Tomomi, Tobiume Takeshi, Uematsu Etsuko, Kusunose Kenya, Ise Takayuki, Yamaguchi Koji, Yagi Shusuke, Fukuda Daiju, Yamada Hirotsugu, Wakatsuki Tetsuzo, Shimabukuro Michio, Sata Masataka

CIRCULATION   132   2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Clinical Utility of Echocardiographic Epicardial Adipose Tissue Thickness Measured Using a High-frequency Linear Probe in Patients With Coronary Artery Disease

Hirata Yukia, Yamada Hirotsugu, Kusunose Kenya, Nishio Susumu, Bando Mika, Yamaguchi Koji, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   132   2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Atrial Late Potentials and Atrial Substrate Remodeling in Patients With Atrial Fibrillation

Bando Sachiko, Soeki Takeshi, Matsuura Tomomi, Tobiume Takeshi, Ise Takayuki, Kusunose Kenya, Yamaguchi Koji, Yagi Shusuke, Yamada Hirotsugu, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   132   2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

3D Transthoracic Echocardiography Provides Accurate Cross-Sectional Area of the RV Outflow Tract

Naoko Sawada, Hirotsugu Yamada, Kenya Kusunose, Shuji Hayashi, Takashi Lwase, Masataka Sata

JACC-CARDIOVASCULAR IMAGING ( ELSEVIER SCIENCE INC )  8 ( 11 ) 1343 - 1345   2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Characteristics and Outcomes of Patients With Severe Bioprosthetic Aortic Valve Stenosis Undergoing Redo Surgical Aortic Valve Replacement

Peyman Naji, Brian P. Griffin, Joseph F. Sabik, Kenya Kusunose, Fadi Asfahan, Zoran B. Popovic, L. Leonardo Rodriguez, Bruce W. Lytle, Richard A. Grimm, Lars G. Svensson, Milind Y. Desai

CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  132 ( 21 ) 1953 - 1960   2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background With improved event-free survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. We sought to (1) identify of the characteristics of patients with severe bioprosthetic PAS undergoing redo AVR, and (2) assess the outcomes of these patients, along with factors associated with adverse outcomes. Methods and Results We studied 276 patients with severe bioprosthetic PAS (6416 years, 58% men) who underwent redo-AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease, and transcatheter AVR). Society of Thoracic Surgeons score was calculated. Severe PAS was defined as AV area &lt;0.8 cm(2), mean AV gradient 40 mmHg, or dimensionless index &lt;0.25. A composite outcome of death and congestive heart failure admission was recorded. Mean Society of Thoracic Surgeons score and mean AV gradients were 8 +/- 8 and 53 +/- 17 mmHg, whereas 28% had &gt;II+ aortic regurgitation. Only 39% had an isolated redo AVR, the rest were combination surgeries (coronary bypass and/or aortic surgeries). At 4.2 +/- 3 years, 64 (23%) patients met the composite end point (48 deaths and 19 congestive heart failure admissions, 2.5% 30-day deaths). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio, 1.35), higher grades of aortic regurgitation (hazard ratio, 1.29), and higher right ventricular systolic pressure (hazard ratio, 1.3) were associated with worse longer-term outcomes (all P&lt;0.01). Conclusions At an experienced center, in patients with severe bioprosthetic PAS undergoing redo AVR, the majority undergo combination surgeries but have excellent outcomes.

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Clinical Utility of Measuring Epicardial Adipose Tissue Thickness with Echocardiography Using a High-Frequency Linear Probe in Patients with Coronary Artery Disease

Yukina Hirata, Hirotsugu Yamada, Kenya Kusunose, Takashi Iwase, Susumu Nishio, Shuji Hayashi, Mika Bando, Rie Amano, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY ( MOSBY-ELSEVIER )  28 ( 10 ) 1240 - +   2015.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: The relationship between epicardial adipose tissue (EAT) and coronary artery disease (CAD) has recently attracted a great deal of attention in the medical community. The objective of this study was to determine whether measuring EAT thickness in the anterior interventricular groove (AIG) using echocardiography is feasible and whether this index can be a marker of CAD. Methods: A total of 311 patients (mean age, 676 11 years; 208 men) who underwent coronary angiography between December 2011 and December 2013 were prospectively enrolled. EAT-AIG thickness and EAT thickness on the free wall of the right ventricle (RV) were measured in systole using a high-frequency linear probe. Seventy-one patients who underwent multidetector-row computed tomography were enrolled to validate the method for measuring EAT thickness using echocardiography. Subjects were divided into two groups, those with and without significant coronary stenosis, on the basis of findings on coronary angiography (&gt;= 75% luminal narrowing). Results: EAT-AIG thickness measured using echocardiography was validated by computed tomography. EAT-AIG thickness was strongly correlated with EAT volume (r = 0.714, P &lt; .001). The CAD group had thicker EAT-AIG than the non-CAD group (8.3 +/- 3.0 vs 6.3 +/- 2.5 mm, P &lt; .001). EAT-RV thickness was greater in the CAD group than in the non-CAD group (5.0 +/- 2.1 vs 4.4 +/- 2.3 mm, P = .009) as well. The area under the curve on receiver operating characteristic curve analysis of EAT-AIG thickness for predicting CAD was 0.704, which was higher than the EAT-RV thickness. Conclusions: Measuring EAT thickness using echocardiography with a high-frequency linear probe was validated with computed tomography. EAT-AIG was thicker in the CAD group than in the non-CAD group, as was EAT-RV thickness. This noninvasive index may have potential as a diagnostic marker for predicting coronary atherosclerosis.

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Successful Surgical Repair of Aged Sinus Venosus Atrial Septal Defect with Partial Anomalous Pulmonary Venous Connection: A Case Report

Kadota Muneyuki, Ise Takayuki, Yagi Shusuke, Kusunose Kenya, Kinoshita Hajime, Kurobe Hirotsugu, Yamada Hirotsugu, Soeki Takeshi, Wakatsuki Tetsuzo, Sata Masataka

JOURNAL OF CARDIAC FAILURE   21 ( 10 ) S185   2015.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Reduced ratio of eicosapentaenoic acid and docosahexaenoic acid to arachidonic acid is associated with early onset of acute coronary syndrome

Shusuke Yagi, Ken-ichi Aihara, Daiju Fukuda, Akira Takashima, Mika Bando, Tomoya Hara, Sachiko Nishimoto, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike, Masataka Sata

NUTRITION JOURNAL ( BIOMED CENTRAL LTD )  14 ( No.1 ) 111 - 111   2015.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: The hospitalization rate for acute coronary syndrome (ACS) for people aged &lt;= 50 has remained stable over the past decade. Increased serum levels of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a decreased incidence of cardiovascular events and mortality in older patients; however, it is currently unknown whether reduced serum levels of n-3 PUFAs is also a risk factor for ACS in patients aged &lt;= 50 years. Methods and results: We retrospectively reviewed 102 (male/female 73/29) Japanese ACS patients whose serum levels of EPA/arachidonic acid (AA) and DHA/AA were evaluated on admission. The EPA/AA ratio was the lowest in patients aged &lt;= 50 compared to patients aged 51-74 and &gt;= 75. Pearson correlation analysis showed that early ACS onset was associated with low EPA/AA and DHA/AA ratios, and multiple regression analysis determined that decreased ratios of EPA/AA and DHA/AA, and male sex, current smoker status, increased body mass index and triglyceride levels, independently correlated with early ACS onset. Conversely, low-density and high-density lipoproteins, glycated hemoglobin, and hypertension did not correlate with early ACS onset. Subgroup analyses of male patients revealed that decreased ratios of EPA/AA and DHA/AA independently correlated with early ACS onset. Conclusion: Decreased EPA/AA and DHA/AA ratios may be risk factors for early onset of ACS, suggesting that reduced EPA/AA and DHA/AA may represent targets for preventing ACS in Japanese young people.

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Echocardiographic screening for congenital heart disease in 8819 children: A report from local community events for children's healthcare

Susumu Nishio, Kenya Kusunose, Hirotsugu Yamada, Masami Yamao, Yukina Hirata, Kazuhiro Mori, Suguru Matsuoka, Masataka Sata

JOURNAL OF CARDIOLOGY ( ELSEVIER SCIENCE BV )  66 ( 3-4 ) 315 - 319   2015.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: We had the opportunity to perform echocardiographic screening of children at local community events for children's healthcare sponsored by the prefectural government. The aim of this study was to assess the utility of echocardiographic screening by measuring the prevalence of congenital heart disease (CHD) and abnormal findings in children without history of diagnosed CHD. Methods: Subjects consisted of 8819 infants and preschool children (1 month to 6 years) who underwent echocardiographic examination at public events from 2001 to 2013. Children with known CHD were excluded. Results: We performed echocardiographic screening on 752 (range: 464-993) children at each event. At a total of 12 events, subjects consisted of 3175 infants less than one year (36%), 2292 one-year-olds (26%), 1058 two-year-olds (12%), 794 three-year-olds (9%), and other children up to age six years. We identified echocardiographic abnormalities in 137 children (15.5/1000 subjects), and 89 children (10.1/1000 subjects) were diagnosed with CHD. The prevalence of an echocardiographic abnormality did not change over the 12-year period (Kendall's tau = -0.272, p = 0.19). Conclusions: CHD which could not be identified by prenatal echocardiography and neonatal auscultation could be detected in a substantial number of young children by echocardiographic screening. Echocardiographic screening may be useful for early diagnosis of CHD. However, our study is based on cross-sectional data without follow-up. Larger prospective studies are needed to verify the utility of echocardiographic screening with follow-up data in this cohort. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension

Jae-Hyeong Park, Kenya Kusunose, Deborah H. Kwon, Margaret M. Park, Serpil C. Erzurum, James D. Thomas, Richard A. Grimm, Brian P. Griffin, Thomas H. Marwick, Zoran B. Popovic

KOREAN CIRCULATION JOURNAL ( KOREAN SOC CARDIOLOGY )  45 ( 5 ) 398 - 407   2015.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background and Objectives: Right ventricular longitudinal strain (RVLS) is a new parameter of RV function. We evaluated the relationship of RVLS by speckle-tracking echocardiography with functional and invasive parameters in pulmonary arterial hypertension (PAH) patients. Subjects and Methods: Thirty four patients with World Health Organization group 1 PAH (29 females, mean age 45 +/- 13 years old). RVLS were analyzed with velocity vector imaging. Results: Patients with advanced symptoms {New York Heart Association (NYHA) functional class III/IV} had impaired RVLS in global RV (RVLSglobal, -17 +/- 5 vs. -12 +/- 3%, p&lt;0.01) and RV free wall (RVLSFW, -19 +/- 5 vs. -14 +/- 4%, p&lt;0.01 to NYHA class I/II). Baseline RVLSglobal and RVLSFW showed significant correlation with 6-minute walking distance (r=-0.54 and r=-0.57, p&lt;0.01 respectively) and logarithmic transformation of brain natriuretic peptide concentration (r=0.65 and r=0.65, p&lt;.01, respectively). These revealed significant correlations with cardiac index (r=-0.50 and r=-0.47, p&lt;0.01, respectively) and pulmonary vascular resistance (PVR, r=0.45 and r=0.45, p=0.01, respectively). During a median follow-up of 33 months, 25 patients (74%) had follow-up examinations. Mean pulmonary arterial pressure (mPAP, 54 +/- 13 to 46 +/- 16 mmHg, p=0.03) and PVR (11 +/- 5 to 6 +/- 2 wood units, p&lt;0.01) were significantly decreased with pulmonary vasodilator treatment. RVLSglobal (-12 +/- 5 to -16 +/- 5%, p&lt;0.01) and RVLSFW (-14 +/- 5 to -18 +/- 5%, p&lt;0.01) were significantly improved. The decrease of mPAP was significantly correlated with improvement of RVLSglobal (r=0.45, p&lt;0.01) and RVLSFW (r=0.43, p&lt;0.01). The PVR change demonstrated significant correlation with improvement of RVLSglobal (r=0.40, p&lt;0.01). Conclusion: RVLS correlates with functional and invasive hemodynamic parameters in PAH patients. Decrease of mPAP and PVR as a result of treatment was associated with improvement of RVLS.

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Impact of Indoxyl Sulfate, a Uremic Toxin, on Non-Culprit Coronary Plaque Composition Assessed on Integrated Backscatter Intravascular Ultrasound

Hiromu Yamazaki, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki, Toshiyuki Niki, Yoshio Taketani, Atsunori Kitaoka, Kenya Kusunose, Takayuki Ise, Takeshi Tobiume, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  79 ( 8 ) 1773 - 1779   2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Uremic toxin has emerged as an important determinant of cardiovascular risk. The aim of this study was to examine the relationship between serum uremic toxin and coronary plaque composition on integrated backscatter intravascular ultrasound (IB-IVUS). Methods and Results: IB-IVUS was performed in 47 patients with planned treatment for angina pectoris. Non-culprit intermediate plaque analyzed in this study had to be &gt;5mm apart from the intervention site. 3-D IB-IVUS analysis was performed to determine percent lipid volume (LV) and fibrous volume (FV). We also measured serum uremic toxins (indoxyl sulfate [IS], asymmetric dimethylarginine [ADMA], and p-cresol [PC]). Glomerular filtration rate correlated with IS (r=-0.329, P=0.04), but did not correlate with ADMA or PC. Percent LV correlated with IS ( r=0.365, P=0.02), but did not correlate with ADMA or PC. Percent FV also correlated with IS (r=-0.356, P=0.03), but did not correlate with ADMA or PC. On multivariate regression, only IS was associated with percent LV (r=0.359, P=0.04) and percent FV (r=-0.305, P=0.04) independently of potentially confounding coronary risk factors. Conclusions: Among the uremic toxins, serum IS might be a novel useful biomarker to detect and monitor lipid-rich coronary plaque on IB imaging.

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Comparison of carotid plaque tissue characteristics in patients with acute coronary syndrome or stable angina pectoris: assessment by iPlaque, transcutaneous carotid ultrasonography with integrated backscatter analysis

Mika Bando, Hirotsugu Yamada, Kenya Kusunose, Daiju Fukuda, Rie Amano, Rina Tamai, Yuta Torii, Yukina Hirata, Susumu Nishio, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

CARDIOVASCULAR ULTRASOUND ( BIOMED CENTRAL LTD )  13 ( No.1 ) 34 - 34   2015.07 [ Peer Review Accepted ]

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Background: The association of the tissue characteristics of carotid plaques with coronary artery disease has attracted interest. The present study compared the tissue characteristics of carotid plaques in patients with acute coronary syndrome (ACS) with those in patients with stable angina pectoris (SAP) using the iPlaque system, which is based on ultrasound integrated backscatter. Methods and results: Carotid ultrasound examinations were performed in 26 patients with ACS, and 38 age- and gender-matched patients with SAP. Neither plaque area nor maximal intima-media thickness differed significantly between the two groups. However, the average integrated backscatter value within the plaque was greater in the ACS patients than in the SAP patients. iPlaque analysis revealed that the percentage blue area (lipid pool) was greater in the ACS patients than in the SAP patients (43.4 +/- 11.2 vs 18.3 +/- 10.3 %, p &lt; 0.0001), and that the percentage green area (fibrosis) was lower in the ACS than in the SAP patients (7.5 +/- 7.5 % vs 20.7 +/- 11.7 %, p &lt; 0.0001). Conclusions: The lipid component of carotid plaques is greater in ACS patients than in SAP patients. Our iPlaque system provides a useful and feasible method for the tissue characterization of carotid plaques in the clinical setting.

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Prediction of Future Overt Pulmonary Hypertension by 6-Min Walk Stress Echocardiography in Patients With Connective Tissue Disease

Kenya Kusunose, Hirotsugu Yamada, Junko Hotchi, Mika Bando, Susumu Nishio, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Jun Kishi, Masataka Sata

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY ( ELSEVIER SCIENCE INC )  66 ( 4 ) 376 - 384   2015.07 [ Peer Review Accepted ]

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BACKGROUND Early detection of pulmonary hypertension (PH) in connective tissue disease (CTD) is crucial to ensuring that patients receive timely treatment for this progressive disease. Exercise stress tests have been used to screen patients in an attempt to identify early-stage PH. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (Q) responses as having the potential to assess the disease state. OBJECTIVES This study hypothesized that pulmonary circulation pressure-flow relationships obtained by 6-min walk (6MW) stress echocardiography would better delineate differential progression of PH and predict development of PH during follow-up. METHODS We prospectively performed 6MW stress echocardiographic studies in 78 CTD patients (age 58 +/- 12 years; 9% male) at baseline and follow-up. All patients underwent yearly echocardiographic follow-up studies for up to 5 years. RESULTS During a median period of 32 months (range: 15 to 62 months), 16 patients reached the clinical endpoint of development of PH and none died during follow-up. PH was confirmed by right heart catheterization in all 16 patients (mPAP &gt;= 25 mm Hg and pulmonary capillary wedge pressure &lt;= 15 mm Hg). In a Cox proportional-hazards survival model, 6MW distance (hazard ratio [HR]: 0.99; p = 0.010), early diastolic tricuspid annulus motion velocity (HR: 0.79; p = 0.025), and Delta mPAP/Delta Q by 6MW stress (HR: 1.10; p = 0.005) were associated with development of PH. In sequential Cox models, a model on the basis of 6MW distance (chi-square, 6.6) was improved by Delta mPAP/Delta Q (chi-square: 14.4; p = 0.019). Using a receiver-operating characteristic curve, we found that the best cutoff value of Delta mPAP/Delta Q for predicting development of pulmonary hypertension was &gt; 3.3 mm Hg/l/min. CONCLUSIONS The 6MW stress echocardiography noninvasively provides an incremental prognostic value of PH development in CTD. This is a single-center prospective cohort study. Larger multicenter studies are warranted to confirm this result. (C) 2015 by the American College of Cardiology Foundation.

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[Case Report; Successful treatment with methotrexate and low-dose corticosteroids for recurrent cardiac sarcoidosis].

Ise T, Takagi E, Iwase T, Kusunose K, Yamaguchi K, Yagi S, Yamada H, Soeki T, Wakatsuki T, Sata M

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   104 ( 6 ) 1175 - 1179   2015.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Assessment of Right Ventricular Longitudinal Strain in Patients with Ischemic Cardiomyopathy: Head-to-Head Comparison between Two-Dimensional Speckle-Based Strain and Velocity Vector Imaging Using Volumetric Assessment by Cardiac Magnetic Resonance as a "Gold Standard"

Jae-Hyeong Park, Kenya Kusunose, Hirohiko Motoki, Deborah H. Kwon, Richard A. Grimm, Brian P. Griffin, Thomas H. Marwick, Zoran B. Popovic

ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES ( WILEY )  32 ( 6 ) 956 - 965   2015.06 [ Peer Review Accepted ]

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BackgroundLongitudinal strain of right ventricle (RV) can be used to determine RV systolic function. This study compared RV longitudinal strain values of two different speckle tracking software technologies, velocity vector imaging (VVI) and two-dimensional speckle tracking echocardiography (2DSTE), and longitudinal strain by cardiac magnetic resonance (CMR). MethodsWe studied 36 patients (28 men, 6311years) with ischemic cardiomyopathy (ICM) who underwent echocardiography with GE machines and CMR. Longitudinal strain of RV analyzed with 2DSTE and VVI in same DICOM files. Longitudinal RV strain analyzed with 2DSTE and VVI in same raw data. These values were compared with RVEF and longitudinal strain by CMR. ResultsVVI strain showed significant correlations with RVEF by CMR (global RV: r=-0.56, P&lt;0.01, free wall: r=-0.52, P&lt;0.01, and septum: r=-0.49, P&lt;0.01). 2DSTE strain also revealed significant correlations (global RV: r=-0.40, P=0.02, and septum: r=-0.35, P=0.04). 2DSTE strain had significant bias with wide limits of agreement in global RV and septum compared with CMR strain. 2DSTE strain had significantly lower intra-observer variability than VVI (P=0.03) or CMR strain (P=0.04) in RV-free wall. ConclusionsRV longitudinal strains by VVI and 2SDTE demonstrated relatively good correlations with RVEF and longitudinal strain by CMR. However, when compared to CMR-derived strain, 2DSTE-derived strain underestimates longitudinal strain of RV septum and of global right ventricle. 2DSTE strain had significantly lower intra-observer variability compared with VVI or CMR strain analysis.

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Serial Imaging Changes During Treatment of Immunoglobulin G4-Related Disease With Multiple Pseudotumors

Kenya Kusunose, Junko Hotchi, Yuriko Takagawa, Susumu Nishio, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  131 ( 21 ) 1882 - 1883   2015.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Cardiac MR imaging in constrictive pericarditis: multiparametric assessment in patients with surgically proven constriction

Michael A. Bolen, Prabhakar Rajiah, Kenya Kusunose, Patrick Collier, Allan Klein, Zoran B. Popovic, Scott D. Flamm

INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING ( SPRINGER )  31 ( 4 ) 859 - 866   2015.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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To assess the utility of cardiac magnetic resonance (MR) imaging in the diagnosis of constrictive pericarditis (CP). This study was approved by the institutional review board, with a waiver of informed consent. A total of 42 consecutive patients (mean age, 55 +/- A 16 years; 3 women, 39 men) with CP treated with pericardiectomy who had undergone cardiac MR before surgery were evaluated retrospectively. An additional 21 patients were evaluated as a control group; of these, 10 consecutive patients received cardiac MR for reasons other than suspected pericardial disease, and 11 consecutive patients had a history of pericarditis but no clinical suspicion of pericardial constriction. MR imaging parameters were analyzed independently and with a decision tree algorithm for usefulness in the prediction of CP. Catheterization data were also reviewed when available. A model combining pericardial thickness and relative interventricular septal (IVS) excursion provided the best overall performance in prediction of CP (C statistic, 0.98, 100 % sensitivity, 90 % specificity). Several individual parameters also showed strong predictive value in the assessment of constriction, including relative IVS excursion (sensitivity, 93 %; specificity, 95 %), pericardial thickness (sensitivity, 83 %; specificity, 100 %), qualitative assessment of pathologic coupling (sensitivity, 88 %; specificity, 100 %), diastolic IVS bounce (sensitivity, 90 %; specificity, 85 %), left ventricle area change (sensitivity, 86 %; specificity, 100 %), and eccentricity index (sensitivity, 86 %; specificity, 90 %; all P &lt; 0.001). Strong agreement was observed between catheterization and surgical findings of constriction (97 %). Cardiac MR provides robust quantitative and qualitative analysis for the diagnosis of CP.

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Right Ventricular Echocardiographic Parameters Are Associated with Mortality after Acute Pulmonary Embolism

Danai Khemasuwan, Teerapat Yingchoncharoen, Pichapong Tunsupon, Kenya Kusunose, Ajit Moghekar, Allan Klein, Adriano R. Tonelli

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY ( MOSBY-ELSEVIER )  28 ( 3 ) 355 - 362   2015.03 [ Peer Review Accepted ]

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Background: There is limited information on the utility of certain echocardiographic measurements, such as right ventricular RV) strain analysis, in predicting mortality in patients with acute pulmonary embolism PE). Methods: A total of 211 patients with acute PE admitted to a medical intensive care unit (ICU) were retrospectively identified. Echocardiographic variables were prospectively measured in this cohort. The focus was on ICU, hospital, and long-term mortality. Results: The mean age was 61 6 15 years. Median Acute Physiology and Chronic Health Evaluation IV and simplified Pulmonary Embolism Severity Index scores were 60 (interquartile range, 40-71) and 2 interquartile range, 1-2), respectively. Thirty-eight patients (18%) died during the sentinel hospitalization (13% died in the ICU). A total of 61 patients (28.9%) died during a median follow-up period of 15 months interquartile range, 526 months). The echocardiographic variables associated with long-term mortality from PE diagnosis) were ratio of RV to left ventricular end-diastolic diameter hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2-4.8), tricuspid annular plane systolic excursion HR, 0.53; 95% CI, 0.31-0.92), and RV-right atrial gradient HR, 1.02; 95% CI, 1.01-1.4). ICU mortality was associated with ratio of RV to LV end-diastolic diameter HR, 4.4; 95% CI, 1.3-15), RV systolic pressure HR, 1.03; 95% CI, 1.01-1.05), tricuspid annular plane systolic excursion HR, 0.4; 95% CI, 0.18-0.9), and inferior vena cava collapsibility &lt; 50% HR, 4.3; 95% CI, 1.7-11). These variables remain significantly associated with mortality after adjusting by Acute Physiology and Chronic Health Evaluation IV score, Pulmonary Embolism Severity Index score, or the use of thrombolytic agents. RV strain parameters were not correlated with hospital or long-term mortality. Conclusions: Four simple parameters that measure different aspects of the right ventricle ratio of RV to left ventricular end-diastolic diameter, RV systolic pressure, tricuspid annular plane systolic excursion, and inferior vena cava collapsibility) were independently associated with mortality in patients presenting with acute PE who were admitted to the ICU.

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Plasma MicroRNA-100 Is Associated With Coronary Plaque Vulnerability

Takeshi Soeki, Koji Yamaguchi, Toshiyuki Niki, Etsuko Uematsu, Sachiko Bando, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Junko Hotchi, Takeshi Tobiume, Shusuke Yagi, Daiju Fukuda, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  79 ( 2 ) 413 - 418   2015.02 [ Peer Review Accepted ]

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Background: Although numerous studies have reported altered plasma levels of various microRNAs (miRNAs) in patients with cardiovascular disease, there are no data on the relationship between plasma miRNAs and vulnerable coronary plaque. In this study, we investigated whether plasma miRNAs might be a sensitive marker of coronary plaque vulnerability. Methods and Results: Integrated backscatter intravascular ultrasound (IB-IVUS) was performed in 32 consecutive patients with angina pectoris who underwent percutaneous coronary intervention. Three-dimensional analysis of IB-IVUS was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Circulating miRNAs were measured in EDTA-plasma simultaneously obtained from the aorta and the coronary sinus (CS). Muscle-enriched (miR-133a, miR-208a, miR-499), vascular-enriched (miR-92a, miR-100, miR-126, miR-127, miR145), and myeloid cell-enriched miRNAs (miR-155, miR-223) were measured. Plasma miR-100 was higher in the CS than in the aorta, but there were no significant differences in the levels of other miRNAs between the aorta and CS. Plasma miR-100 in the aorta was positively correlated with %LV (r=0.48, P&lt;0.01) and negatively correlated with % FV (r=-0.41, P&lt;0.05). Importantly, transcoronary concentration gradient of circulating miR-100 was more strongly correlated with % LV (r=0.53, P&lt;0.01) and % FV (r=-0.56, P&lt;0.01). Conclusions: miR-100 might be released into the coronary circulation from vulnerable coronary plaques. This study provides insights into the role of miRNAs in coronary atherosclerotic disease.

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Regurgitant Volume Informs Rate of Progressive Cardiac Dysfunction in Asymptomatic Patients With Chronic Aortic or Mitral Regurgitation

Kenya Kusunose, Paul C. Cremer, Rayji S. Tsutsui, Richard A. Grimm, James D. Thomas, Brian P. Griffin, Zoran B. Popovic

JACC-CARDIOVASCULAR IMAGING ( ELSEVIER SCIENCE INC )  8 ( 1 ) 14 - 23   2015.01 [ Peer Review Accepted ]

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OBJECTIVES This study hypothesized that regurgitation severity, as determined by using the regurgitant volume index, would better delineate differential cardiac dysfunction in asymptomatic patients with moderate to severe aortic regurgitation (AR) and mitral regurgitation (MR). BACKGROUND Frequent surveillance echocardiography is considered appropriate in asymptomatic patients with moderate to severe AR and MR. However, the evidence to support this practice and to define the appropriate frequency is Limited. METHODS This was an observational cohort study of consecutive patients with moderate to severe asymptomatic AR or MR who underwent exercise echocardiography. Our cohort included 130 patients with moderate to severe asymptomatic MR and 130 patients with moderate to severe asymptomatic AR who were matched according to age and regurgitant volume index. All patients underwent yearly echocardiographic follow-up studies. Regurgitation severity was determined according to regurgitant volume index, with a Level &gt;= 30 ml/m(2) considered a marker of severe regurgitation. RESULTS During follow-up, regardless of etiology, patients with severe regurgitation demonstrated increasing left ventricular volume indexes (4.2 +/- 1.5 ml/m(2) per year; p = 0.01) and decreasing left ventricular ejection fractions (1.3 +/- 0.4% per year; p = 0.002). In patients with moderate regurgitation, left ventricular volumes and ejection fractions did not significantly change. In addition, patients with severe regurgitation experienced a similar drop in contractility (end-systolic pressure/end-systolic volume ratio and single-beat pre-Load recruitable stroke work) during follow-up independent of regurgitation etiology. Contractility parameters did not change in patients with moderate regurgitation. CONCLUSIONS These asymptomatic patients with moderate AR or MR had stable cardiac function during 3 years of follow-up; thus, frequent echocardiography without a change in clinical status may not be necessary. In the setting of severe regurgitation, further cardiac deterioration occurred at a similar rate and manner irrespective of whether the dysfunction was related to AR or MR. (C) 2015 by the American College of Cardiology Foundation.

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Effect of ghrelin on autonomic activity in healthy volunteers

Takeshi Soeki, Kunihiko Koshiba, Toshiyuki Niki, Kenya Kusunose, Koji Yamaguchi, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Kazuo Minakuchi, Ichiro Kishimoto, Kenji Kangawa, Masataka Sata

PEPTIDES ( ELSEVIER SCIENCE INC )  62   1 - 5   2014.12 [ Peer Review Accepted ]

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Ghrelin is a novel growth hormone (GH)-releasing peptide originally isolated from the stomach. Recently, we have shown that ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. In the present study, we evaluated the effect of ghrelin on autonomic nerve activity in healthy human subjects. An intravenous bolus of human synthetic ghrelin (10 mu g/kg) was administered to 10 healthy men (mean age, 33 years). Holter monitoring assessment was performed before and during 2 h after the ghrelin therapy. The standard deviation of normal RR intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent RR intervals (rMSSD), high-frequency power (HF), and low-frequency power (LF) were analyzed. Blood samples were also obtained before and after the therapy. A single administration of ghrelin decreased both heart rate and blood pressure. Interestingly, ghrelin significantly decreased the LF and LF/HF ratio of heart rate variability and increased the SDNN, rMSSD, and HF. Ghrelin also elicited a marked increase in circulating GH, but not insulin-like growth factor-1. These data suggest that ghrelin might suppress cardiac sympathetic nerve activity and stimulate cardiac parasympathetic nerve activity. (C) 2014 Elsevier Inc. All rights reserved.

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Global Left Atrial Strain in the Prediction of Sinus Rhythm Maintenance after Catheter Ablation for Atrial Fibrillation

Hirohiko Motoki, Kazuaki Negishi, Kenya Kusunose, Zoran B. Popovic, Mandeep Bhargava, Oussama M. Wazni, Walid I. Saliba, Mina K. Chung, Thomas H. Marwick, Allan L. Klein

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY ( MOSBY-ELSEVIER )  27 ( 11 ) 1184 - 1192   2014.11 [ Peer Review Accepted ]

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Background: Left atrial (LA) strain is a sensitive measure of LA mechanics. However, its relationship with rhythm outcomes after catheter ablation in patients with atrial fibrillation (AF) is not well established. The aim of this study was to evaluate whether baseline LA global longitudinal strain (LA epsilon) predicts rhythm outcomes in patients who undergo catheter ablation for AF. Methods: In 256 patients with AF (paroxysmal, 204; persistent, 52), comprehensive echocardiography was performed with assessment of LA epsilon by using Velocity Vector Imaging to calculate average strain values from apical four- and two-chamber views before ablation (median, 41 days; interquartile range, 1-95 days). Results: After a median of 8.0 months (interquartile range, 4.0-23.3 months) of follow-up, 149 patients (58%) had maintained sinus rhythm and 107 patients (42%) had recurrence of AF. In our study cohort (mean age 59 +/- 11 years; mean left ventricular ejection fraction, 58 +/- 10%), impaired total LA epsilon (LA epsilon(total)) was associated with greater left ventricular mass index (r = -0.245, P &lt; .001) and worsening left ventricular diastolic function (ratio of transmitral flow peak early diastolic velocity to peak early diastolic velocity of the mitral annulus: r = -0.357, P &lt; .001; maximal LA volume index: r = -0.393, P &lt; .001). Patients with LA epsilon(total) &lt; 23.2% showed a higher incidence of AF recurrence compared with patients with LA epsilon(total) &gt;= 23.2% (log-rank P &lt; .001). In multivariate Cox proportional-hazards analysis, LA epsilon(total) was independently related to rhythm outcomes (hazard ratio, 0.944; 95% confidence interval, 0.915-0.975; P &lt; .001) after AF ablation. Moreover, LA epsilon(total) provided incremental predictive value for rhythm outcomes over clinical features (increment in global chi(2) = 14.63, P &lt; .001). Conclusions: In patients with AF, baseline LA epsilon(total) was associated with rhythm outcome after catheter ablation.

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Prognostic Value of RV Function Before and After Lung Transplantation

K. Kusunose, Michael A. Bolen

JACC-CARDIOVASCULAR IMAGING ( ELSEVIER SCIENCE INC )  7 ( 11 ) 1085 - 1094   2014.11 [ Peer Review Accepted ]

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OBJECTIVES We investigated the effects of lung transplantation on right ventricular (RV) function as well as the prognostic value of pre-and post-transplantation RV function. BACKGROUND Although lung transplantation success has improved over recent decades, outcomes remain a challenge. Identifying predictors of mortality in lung transplant recipients may Lead to improved long-term outcomes after lung transplantation. METHODS Eighty-nine (age 60 +/- 6 years, 58 men) consecutive patients who underwent single or double lung transplantation and had pre-and post-transplantation echocardiograms between July 2001 and August 2012 were evaluated. Echocardiographic measurements were performed before and after lung transplantation. Left ventricular (LV) and RV longitudinal strains were analyzed using velocity vector imaging. Cox proportional prognostic hazard models predicting all-cause death were built. RESULTS There were 46 all-cause (52%) and 17 cardiac (19%) deaths during 43 +/- 33 months of follow-up. After lung transplantation, echocardiography showed improved systolic pulmonary artery pressure (SPAP) (50 +/- 19 mm Hg to 40 +/- 13 mm Ng) and RV strain (-17 5% to - 18 +/- 4%). No pre-transplantation RV parameter predicted all-cause mortality. After adjustment for age, sex, surgery type, and etiology of lung disease in a Cox proportional hazards model, both posttransplantation RV strain (hazard ratio: 1.13, 95% confidence interval: 1.04 to 1.23, p = 0.005), and post-transplantation SPAP (hazard ratio: 1.03,95% confidence interval: 1.01 to 1.05, p = 0.011) were independent predictors of all-cause mortality. When post-transplantation RV strain and post-transplantation SPAP were added the clinical predictive model based on age, sex, surgery type, and etiology, the C-statistic improves from 0.60 to 0.80 (p = 0.002). CONCLUSIONS Alterations of RV function and pulmonary artery pressure normalize, and post-transplantation RV function may provide prognostic data in patients after lung transplantation. Our study is based on a highly and retrospectively selected group. We believe that larger prospective studies are warranted to confirm this result. (C) 2014 by the American College of Cardiology Foundation.

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Prognostic Significance of Left Atrial Appendage "Sludge'' in Patients with Atrial Fibrillation: A New Transesophageal Echocardiographic Thromboembolic Risk Factor

Boris S. Lowe, Kenya Kusunose, Hirohiko Motoki, Brandon Varr, Kevin Shrestha, Christine Whitman, W. H. Wilson Tang, James D. Thomas, Allan L. Klein

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY ( MOSBY-ELSEVIER )  27 ( 11 ) 1176 - 1183   2014.11 [ Peer Review Accepted ]

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Background: When stratifying thromboembolic risk to patients with atrial fibrillation (AF), left atrial appendage (LAA) thrombus is currently the only echocardiographic index that absolutely contraindicates cardioversion. The aim of this study was to identify the predictors of LAA "sludge'' and its impact on subsequent thromboembolism and survival in patients with AF. Methods: A total of 340 patients (mean age, 66 +/- 12 years; 75% men) who underwent transesophageal echocardiography to exclude LAA thrombus before electrical cardioversion or radiofrequency pulmonary vein isolation) for AF were retrospectively studied. LAA sludge was defined as a dynamic, viscid, layered echodensity without a discrete mass, visualized throughout the cardiac cycle. Follow-up was obtained after a mean of 6.7 +/- 3.7 years, and patients were analyzed according to LAA thrombus (n = 62 [18%]), sludge (n = 47 [14%]), or spontaneous echocardiographic contrast (n = 84 [25%]). Patients without these transesophageal echocardiographic characteristics served as controls (n = 147 [43%]). Results: LAA sludge was independently predicted by enlarged left atrial area (odds ratio, 4.54; 95% confidence interval [CI], 2.38-8.67; P &lt; .001), reduced LAA emptying velocity (odds ratio, 12.7; 95% CI, 6.11-26.44; P &lt; .001), and reduced left ventricular ejection fraction (odds ratio, 2.11; 95% CI, 1.03-4.32; P &lt; .001). Thromboembolic event and all-cause mortality rates in patients with sludge were 23% and 57%, respectively. Multiple logistic regression analyses identified the presence of LAA sludge to be independently associated with thromboembolic complications (adjusted hazard ratio, 3.43; 95% CI, 1.42-8.28; P = .006) and all-cause mortality (adjusted hazard ratio, 2.02; 95% CI, 1.22-3.36; P = .007). Conclusion: Sludge within the LAA is independently associated with subsequent thromboembolic events and all-cause mortality in patients with AF.

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Incremental Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients With Aortic Stenosis and Preserved Ejection Fraction

Kenya Kusunose, Andrew Goodman, Roosha Parikh, Tyler Barr, Shikhar Agarwal, Zoran B. Popovic, Richard A. Grimm, Brian P. Griffin, Milind Y. Desai

CIRCULATION-CARDIOVASCULAR IMAGING ( LIPPINCOTT WILLIAMS & WILKINS )  7 ( 6 ) 938 - +   2014.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background-We sought to assess the utility of left ventricular global longitudinal strain (LV-GLS) in predicting mortality in moderate to severe and paradoxical severe aortic stenosis (AS) patients with preserved ejection fraction. Methods and Results-We studied 395 AS patients (70 +/- 14 years, 57% men) with aortic valve area &lt;1.3 cm(2) evaluated between January to June 2008 (excluding severe other valve disease and LV ejection fraction &lt;50%). Clinical and echocardiographic data were recorded. LV-GLS was analyzed using Velocity Vector Imaging. AS patients were classified as (a) moderate-severe (n=93; aortic valve area, 1.1-1.3 cm(2)), (b) standard severe (n=161; aortic valve area, &lt;= 1 cm2; mean gradient &gt;= 40 mm Hg), and (c) paradoxical severe (n=141; aortic valve area, &lt;= 1 cm2 and mean gradient &lt;40 mm Hg). Additive Euroscore was 7 +/- 3. The association of LV-GLS with all-cause mortality was assessed after risk-adjustment using Cox proportional hazards models. Median LV-GLS was -14.8% (interquartile range, -17.2%, -12.1%). At 4.4 +/- 1.4 years, there were 92 (23%) deaths. On multivariable Cox analysis, additive Euroscore (hazard ratio, 1.19; 1.13-1.27; P&lt;0.001), New York Heart Association class (hazard ratio, 1.44; 1.11-1.87; P&lt;0.001), AV surgery with time-dependent covariate analysis (hazard ratio, 0.29; 0.19-0.45; P&lt;0.001), and LV-GLS (hazard ratio, 1.05; 1.03-1.07; P&lt;0.001) were independent predictors of mortality. LV-GLS &lt;-12.1% (4th quartile) was associated with significantly reduced survival. Addition of LV-GLS to clinical parameters (additive Euroscore+New York Heart Association class) led to significant improvement in prediction of mortality (chi(2) increased from 48 to 58; P&lt;0.01). Conclusions-LV-GLS independently predicts mortality in moderate-severe and severe AS patients with preserved LV ejection fraction, providing incremental prognostic utility, in addition to standard clinical and echocardiographic parameters.

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Targeting Sleep Disordered Breathing to Prevent Heart Failure: What is the Evidence?

Kusunose K, Mehra R

Current cardiovascular risk reports   8 ( 10 ) 403   2014.10 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Infarct Characterization and Quantification by Delayed Enhancement Cardiac Magnetic Resonance Imaging Is a Powerful Independent and Incremental Predictor of Mortality in Patients With Advanced Ischemic Cardiomyopathy

Deborah H. Kwon, Lisa Asamoto, Zoran B. Popovic, Kenya Kusunose, Monique Robinson, Milind Desai, Thomas H. Marwick, Scott D. Flamm

CIRCULATION-CARDIOVASCULAR IMAGING ( LIPPINCOTT WILLIAMS & WILKINS )  7 ( 5 ) 796 - U79   2014.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background-Infarct heterogeneity has been shown to be independently associated with adverse outcomes in previous smaller studies. However, it is unknown whether infarct characterization is an independent predictor of all-cause mortality in patients with advanced ischemic cardiomyopathy, after adjusting for clinical risk factors, severity of ischemic mitral regurgitation, incomplete revascularization, and device therapy. Methods and Results-A total of 362 patients with ischemic cardiomyopathy (left ventricular dysfunction with &gt;70% stenosis in &gt;= 1 epicardial coronary artery) underwent delayed hyperenhancement-magnetic resonance imaging and coronary angiography between 2002 and 2006. Total myocardial scar and peri-infarct (PI) area were measured using various threshold techniques. Multivariate survival analysis (primary end point of all-cause mortality) was conducted. One hundred fifty-seven deaths occurred during a mean 5.4-year follow-up (mean left ventricular ejection fraction, 23 +/- 9%; mean end-systolic volume index, 113 +/- 48 mL; mean total myocardial scar %, 25.5 +/- 16.0%; mean PI%, 5.7 +/- 2.9%). PI% (beta=2.07; P&lt;0.001) was an independent predictor of survival, independent of age, end-systolic volume, sex, mitral regurgitation, diabetes mellitus, dyslipidemia, coronary artery disease severity, implantable cardioverter defibrillator, and incomplete revascularization. PI% using 2 to 3 SD technique yielded the highest incremental prognostic power (chi(2) score 149). Conclusions-In advanced ischemic cardiomyopathy, PI% is a powerful independent and incremental predictor of all-cause mortality. Infarct heterogeneity offers substantial further risk stratification when compared with quantification of total myocardial scar % alone even after adjusting for clinical risk factors, end-systolic volume index, mitral regurgitation, incomplete revascularization, and implantable cardioverter defibrillator implantation.

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Pentraxin 3 is a local inflammatory marker in atrial fibrillation

Takeshi Soeki, Sachiko Bando, Etsuko Uematsu, Tomomi Matsuura, Toshiyuki Niki, Takayuki Ise, Kenya Kusunose, Junko Hotchi, Yuka Ueda, Noriko Tomita, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Masataka Sata

HEART AND VESSELS ( SPRINGER )  29 ( 5 ) 653 - 658   2014.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 +/- 1.4 vs 3.3 +/- 1.2 ng/ml, P &lt; 0.01), but not in control subjects (2.4 +/- 0.5 vs 2.4 +/- 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-alpha concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P &lt; 0.01). These data demonstrate that Local PTX3 production in the left atrium might reflect the local inflammation of AF.

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Pre-Load Stress Echocardiography for Predicting the Prognosis in Mild Heart Failure

Hirotsugu Yamada, Kenya Kusunose, Susumu Nishio, Mika Bando, Junko Hotchi, Shuji Hayashi, Takayuki Ise, Shusuke Yagi, Koji Yamaguchi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

JACC-CARDIOVASCULAR IMAGING ( ELSEVIER SCIENCE INC )  7 ( 7 ) 641 - 649   2014.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVES This study sought to introduce and confirm the efficacy of pre-load stress echocardiography with Leg-positive pressure (LPP) for improving risk stratification of patients with mild stable heart failure. BACKGROUND Heart failure patients with mild symptoms and a poor prognosis should be identified and treated aggressively to improve clinical outcome. METHODS We performed transthoracic echocardiography with LPP in 202 patients with chronic cardiac disease. Twenty-two of these patients also underwent cardiac catheterization, and left ventricular pressure was measured during LPP along with simultaneous Doppler recordings. Patients were classified into 3 groups on the basis of their left ventricular (LV) diastolic dysfunction as assessed by transmitral flow velocity: restrictive or pseudonormal (PN) at rest, impaired relaxation (IR) at rest and during LPP (stable IR), and IR at rest and PN during LPP (unstable IR). Clinical outcome was compared among these groups. RESULTS The LPP increased LV end-diastolic pressure from 15.8 +/- 4.7 mm Hg to 20.5 +/- 5.0 mm Hg in the unstable IR group and from 10.5 +/- 2.6 mm Hg to 14.7 +/- 3.8 mm Hg in the stable IR group (both p &lt; 0.001). During an average follow-up of 548 +/- 407 days, 5 patients had cardiac death, 37 had acute heart failure, 4 had an acute myocardial infarction, and 7 had a stroke. The all-cause cardiac event rate in unstable IR was higher than in stable IR (p &lt; 0.001), and was similar in the PN group (p = 0.81). Event-free survival was significantly lower in unstable IR than in stable IR (p = 0.003). In a Cox proportional hazards model, unstable IR was an independent predictor of all-cause cardiac events (hazard ratio: 8.0; p &lt; 0.001). CONCLUSIONS The left LV end-diastolic pressure-volume relationship can be estimated by changes in transmitral flow velocity during LPP. Thus, pre-load stress echocardiography using LPP provides additional prognostic information in mild heart failure beyond that provided by conventional Doppler echocardiography at rest. (C) 2014 by the American College of Cardiology Foundation.

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Right Ventricular Global Longitudinal Strain Provides Prognostic Value Incremental to Left Ventricular Ejection Fraction in Patients with Heart Failure

Hirohiko Motoki, Allen G. Borowski, Kevin Shrestha, Bo Hu, Kenya Kusunose, Richard W. Troughton, W. H. Wilson Tang, Allan L. Klein

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY ( MOSBY-ELSEVIER )  27 ( 7 ) 726 - 732   2014.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Right ventricular (RV) global longitudinal strain (RV strain) is a sensitive measure of RV mechanics. Its relationship with standard clinical markers and long-term events in chronic systolic heart failure is not well established. The aim of this study was to examine the ability of RV strain to provide incremental prognostic value to left ventricular (LV) ejection fraction (LVEF) in patients with chronic systolic heart failure. Methods: In 171 patients with chronic systolic heart failure (LVEF &lt;= 35%), a retrospective substudy of RV strain was performed using Velocity Vector Imaging to analyze previously recorded, comprehensive echocardiographic images. Death, cardiac transplantation, and heart failure hospitalization were tracked for 5 years. Results: In this study cohort (mean age, 57 +/- 14 years; mean LVEF, 25 +/- 6%), mean RV strain was -11.6 +/- 5.4%. More impaired RV strain was associated with increasing New York Heart Association class (rank-sums P = .0001) and greater LV volume (LV end-systolic volume index: r = 0.35, P &lt; .0001). Worse RV strain was associated with reduced LVEF (r = -0.45, P &lt; .0001), worse LV diastolic dysfunction (E/e' septal: r = 0.19, P = .017; left atrial volume index: r = 0.18, P = .031), and standard indices of RV systolic and diastolic dysfunction (RV s': r = -0.43, P &lt; .0001; RV e'/a': r = 0.16, P = .0040; right atrial volume index: r = 0.20, P =.015). RV strain predicted long-term adverse events (hazard ratio, 1.30; 95% confidence interval, 1.02-1.70; P = .037). Furthermore, RV strain &gt; -14.8% predicted adverse events after adjustment for age, LVEF, RV s', E/e' septal, and right atrial volume index. Conclusion: In patients with chronic systolic heart failure, worse RV strain provides prognostic value incremental to LV function.

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Relation Between Echocardiographically Estimated and Invasively Measured Filling Pressures in Constrictive Pericarditis

M. Chadi Alraies, Kenya Kusunose, Kazuaki Negishi, Hirad Yarmohammadi, Hirohiko Motoki, Wael AlJaroudi, Zoran B. Popovic, Allan L. Klein

AMERICAN JOURNAL OF CARDIOLOGY ( EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC )  113 ( 11 ) 1911 - 1916   2014.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The ratio of early transmitral flow velocity (E) to mitral annular velocity (E') is considered a predictor of pulmonary capillary wedge pressure (PCWP). In a previous small study, the paradoxical relation between PCWP and E/E' ratio has been described in patients with constrictive pericarditis (CP). We sought to test this paradoxical relation in a larger cohort. We retrospectively identified 49 patients with surgically confirmed CP (40 men; mean age 61 10 years) who underwent right-sided cardiac catheterization with PCWP measurement, preceded by an echocardiographic study. Of these, 48 patients underwent either computed tomography or magnetic resonance imaging to measure pericardial thickness on the lateral side of the left ventricular wall. Mean interval time between echocardiogram and right-sided cardiac catheterization was 1.5 +/- 3.8 days. There were no significant correlations between mean, medial, or lateral E/E' and PCWP (r = -0.17, 95% confidence interval [CI] -0.43 to -0.12; r = -0.17, 95% CI -0.43 to -0.12; and r = -0.12, 95% CI -0.39 to -0.17, respectively). Similarly, there was no correlation between mean E/E' and brain natriuretic peptide (Spearman r = -0.17, p = NS). Patients with increased pericardial thickness (defined as &gt;4 mm) had both lower lateral peak systolic annular velocity (S') and lower lateral S' integral (7.8 +/- 2.4 vs 9.6 +/- 2.4, p = 0.02 and 13.2 +/- 4.2 vs 15.9 +/- 4.7, p = 0.04, respectively). In patients with CP, there were no correlations between septal, lateral, or mean E/E' and PCWP. In conclusion, E/E' is not predictive of filling pressures in patients with CP, and perhaps the "annulus paradoxus" phenomenon should be revisited. The relation between the mitral annular velocity and thickness of the parietal pericardium may affect this phenomenon. (C) 2014 Elsevier Inc. All rights reserved.

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Report of the American College of Cardiology (ACC) Scientific Sessions 2014, Washington, DC

Kenya Kusunose

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  78 ( 6 ) 1311 - 1316   2014.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The American College of Cardiology (ACC) Scientific Session was held at the Walter E. Washington Convention Center in Washington, DC from March 29-31, 2014. The ACC Scientific Session is one of 3 major scientific cardiology meetings in the world, with over 20,000 attendees from 109 countries. There were over 2,200 oral and poster abstracts, and 22 late-breaking clinical trials (LBCTs), which are the focus of this report. Interestingly, in the CoreValve trials, transcatheter aortic valve replacement with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a higher survival rate at 1 year than surgical aortic valve replacement. Long-term results in a further study are needed. I hope the present report will encourage others to attend the ACC Scientific Session 2015 to be held in San Diego on March 14-16, 2015.

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Echocardiographic image tracker with a speckle adaptive noise reduction filter for the automatic measurement of the left atrial volume curve

Kenya Kusunose, Tomoaki Chono, Tomotsugu Tabata, Hirotsugu Yamada, Masataka Sata

EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING ( OXFORD UNIV PRESS )  15 ( 5 ) 509 - 514   2014.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Aims Since tracking accuracy in left atrial (LA) images decreases due to low image quality around the LA in the apical view, a practical tracking method for LA images has not yet been proposed. The aim of this study was to assess an accurate and high-speed LA volume tracking (LAVT) method for the automatic measurement of LA volume (LAV) curves. Methods and results We used three approved protocols in this study: (i) LAV curves were measured by LAVT on computer-simulated images; (ii) in 20 healthy volunteers, we assessed the feasibility and accuracy of this method compared with experts measurements; and (iii) echocardiography and multi-detector row computed tomography (MDCT) imaging were performed on the same day in 20 patients with suspected coronary artery disease. On computer-simulated images, mean absolute percentage LAVT error in one cardiac cycle was 3 in filtered images and 16 in original images. In 20 healthy volunteers, there are strong correlations between LAVT and the experts LA measurements (LA maximum volume; R = 0.93, P &lt; 0.001). In 400 LA images with 20 patients, an excellent correlation was obtained between LAVs using echocardiography and MDCT (R = 0.98, P &lt; 0.001), with a small bias (14 of the mean) and narrow limits of agreement (15 of the mean). The mean time required for the LAVT analysis was 1.8 min, for the MDCT analysis was 35.8 min, and for the manual echocardiographic analysis was 14.0 min. Conclusion This LAVT method is fast, valid, accurate, and reproducible for determining LAV in both simulated images and the clinical setting.

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Decision Making in Asymptomatic Aortic Regurgitation in the Era of Guidelines Incremental Values of Resting and Exercise Cardiac Dysfunction

Kenya Kusunose, Shikhar Agarwal, Thomas H. Marwick, Brian P. Griffin, Zoran B. Popovic

CIRCULATION-CARDIOVASCULAR IMAGING ( LIPPINCOTT WILLIAMS & WILKINS )  7 ( 2 ) 352 - 362   2014.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background- The decision-making role of exercise echocardiography in the surgical timing for aortic regurgitation remains a matter of debate because of limited data on its link with outcome. The aim of this study was to assess the role of echocardiographic measurements at rest and during exercise as predictors of valve surgery in asymptomatic aortic regurgitation. Methods and Results- Comprehensive resting and exercise echocardiography was performed in 159 consecutive patients (50 +/- 15 years; 80% male) with isolated moderately severe to severe aortic regurgitation and preserved left ventricular (LV) function (LV ejection fraction &gt; 50%, LV end-diastolic dimension &lt;= 70 mm, LV end-systolic dimension &lt;= 50 mm or &lt;= 25 mm/m(2)) in whom initial management was expectant. Echocardiographic measurements were performed at rest and during exercise. LV and right ventricular (RV) longitudinal strain was analyzed at rest using velocity vector imaging. Valve surgery was performed in 50 patients (31%) during 30 +/- 21 months. After adjustment for age and sex in a multivariable Cox proportional-hazards model, exercise tricuspid annular plane systolic excursion (TAPSE; hazards ratio [HR], 0.48; P=0.001) was associated with valve surgery-free, independent of resting LV strain (HR, 1.63; P=0.005), exercise LV end-diastolic volume (HR, 1.38; P=0.048), and resting RV strain (HR, 1.69; P=0.002). In sequential Cox models, a model based on clinical data (chi(2), 20.4) was improved by resting LV strain (chi(2), 30.1; P=0.001), resting RV strain (chi(2), 49.7; P &lt; 0.001), and further increased by exercise TAPSE (chi(2), 64.4; P &lt; 0.001). Conclusions- In asymptomatic aortic regurgitation, resting LV strain, resting RV strain, and exercise TAPSE were independently associated with the need for earlier aortic surgery.

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Impact of Vagal Nerve Stimulation on Left Atrial Structure and Function in a Canine High-Rate Pacing Model

Kenya Kusunose, Youhua Zhang, Todor N. Mazgalev, David R. Van Wagoner, James D. Thomas, Zoran B. Popovic

CIRCULATION-HEART FAILURE ( LIPPINCOTT WILLIAMS & WILKINS )  7 ( 2 ) 320 - 326   2014.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background- Cervical vagal nerve stimulation (VNS) can improve left ventricular dysfunction in the setting of heart failure (HF). However, little is known about the impact of VNS on left atrial (LA) function. The aim of this study was to compare LA mechanics and histology between control and VNS-treated animals during HF development. Methods and Results- Fifteen mongrel dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 beats per minute for the first 4 weeks to develop HF and another 4 weeks at 180 beats per minute to maintain HF). LA contractile function (LA negative peak strain), conduit function (LA positive peak strain), and reservoir function (LA total strain) were measured from speckle tracking in 2 groups. At the end of the terminal study, the LA appendage was obtained. Baseline LA strains were comparable in the control and VNS-treated dogs. At 4 and 8 weeks of ventricular pacing, all LA strains were decreased and LA volumes were increased in the control group compared with the VNS group (P &lt; 0.05). Histological evaluation of the left atrium revealed that percent fibrosis was significantly lower in the VNS versus the control group (8 +/- 1% versus 13 +/- 1%; P &lt; 0.001). Finally, transmitral flow showed decreased atrial contribution to left ventricular filling in the control group (P &lt; 0.05). Conclusions- VNS improved LA function and volumes and suppressed LA fibrosis in the canine high-rate ventricular pacing model. VNS is a novel and potentially useful therapy for improving LA function during HF.

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Effects of Telmisartan on Inflammatory Cytokines and Coronary Plaque Component as Assessed on Integrated Backscatter Intravascular Ultrasound in Hypertensive Patients

Koji Yamaguchi, Tetsuzo Wakatsuki, Takeshi Soeki, Toshiyuki Niki, Yoshio Taketani, Hiroyasu Oeduka, Kenya Kusunose, Takayuki Ise, Takashi Iwase, Hirotsugu Yamada, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  78 ( 1 ) 240 - 247   2014.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Telmisartan has unique pleiotropic effects in addition to renin-angiotensin system (RAS)-inhibition effects. The aim of this study was to evaluate the effects of telmisartan on the coronary plaque component and local inflammatory cytokines. Methods and Results: A total of 50 patients with hypertension were randomized to 2 groups: the telmisartan group (additional treatment with telmisartan 80 mg/day, n=25) or the control group (additional treatment with other anti-hypertensive drugs except RAS blockers, n=25) for 6 months. Tissue characteristics of target coronary plaque were analyzed using integrated backscatter intravascular ultrasound (IB-IVUS) before and after treatment. Plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein were also measured. Significant increases in fibrous volume (51.2 +/- 10.4 to 58.3 +/- 7.7%, P=0.03) and reductions in lipid volume (38.4 +/- 12.4 to 32.8 +/- 9.7%, P=0.03) were observed on IB in the telmisartan group, while there were no significant changes in the plaque component in the control group. CS levels of inflammatory cytokines (matrix metalloproteinase [MMP]3, tumor necrosis factor-alpha, high-sensitivity C-reactive protein and MMP9) were lower after than before treatment in the only telmisartan group (7.7 +/- 6.1 to 5.5 +/- 4.9 ng/ml, 3.1 +/- 1.9 to 2.3 +/- 2.0 pg/ml, 5.6 +/- 6.0 to 2.2 +/- 2.4 mg/L, 36.1 +/- 39.3 to 19.9 +/- 27.5 ng/ml, P=0.02, P=0.03, P=0.04, P=0.07, respectively). Conclusions: Decreased local inflammatory response and plaque stabilization on IB imaging were observed after 6 months of telmisartan treatment. These findings might be associated with local anti-inflammatory and anti-arteriosclerotic effects of telmisartan.

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Left Main Coronary Artery Compression Syndrome with an Incomplete Atrioventricular Septal Defect Presenting as Angina Induced by Hyperthyroidism

Kenya Kusunose, Noriko Tomita, Susumu Nishio, Mika Bando, Shuji Hayashi, Junko Hotchi, Takashi Iwase, Hirotsugu Yamada, Masataka Sata

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  53 ( 18 ) 2083 - 2085   2014 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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We herein report the case of a 29-year-old woman who was diagnosed with incomplete atrioventricular septal defect and extrinsic compression of the left main coronary artery (LMCA) with chest pain due to postpartum thyroiditis. She exhibited chest pain with ST elevation, and coronary computed tomography showed that the LMCA was compressed between the dilated pulmonary artery and aorta. After her hyperthyroidism was treated, her chest pain resolved. Surgical repair of endocardiosis and coronary bypass grafting were performed. On the one-year follow-up visit, the dilation of the pulmonary artery and right heart was decreased. It is important to consider the possibility of compression of the LMCA in patients presenting with pulmonary hypertension and chest pain.

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Multimodality imaging of biatrial myxomas in an asymptomatic patient

Susumu Nishio, Kenya Kusunose, Hirotsugu Yamada, Junko Hotchi, Shuji Hayashi, Mika Bando, Yoshihiko Saijo, Yukina Hirata, Miho Abe, Masataka Sata

Journal of Cardiology Cases ( Elsevier Ltd )  10 ( 3 ) 85 - 87   2014 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Myxomas are located in the left atrium in 75-80% of cases and almost always present with signs and symptoms of a thromboembolic event. Biatrial myxomas are rare, and their incidence is generally less than 2.5% of all myxomas. We herein present a case of biatrial myxomas as an incidental finding by echocardiography where the patient underwent surgery. Echocardiography continues to be the initial imaging modality for intracardiac masses. Cardiac magnetic resonance provides superior tissue characterization, particularly important in differentiating a myxoma from a thrombus. Appropriate use of these non-invasive imaging modalities may lead to a correct diagnosis and good outcome.&lt . Learning objective: In this report we present a rare case of cardiac biatrial myxomas. Multimodality imaging, especially delayed enhancement cardiac magnetic resonance imaging, provided specific findings for the diagnosis.&gt . © 2014 Japanese College of Cardiology.

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Local persistent hypercoagulability after sirolimus-eluting stent implantation in patients with stable angina

Koji Yamaguchi, Tetsuzo Wakatsuki, Toshiyuki Niki, Kenya Kusunose, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike, Masataka Sata

INTERNATIONAL JOURNAL OF CARDIOLOGY ( ELSEVIER IRELAND LTD )  153 ( 3 ) 272 - 276   2011.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Late stent thrombosis (LST) after sirolimus-eluting stent (SES) implantation has been demonstrated previously. Although incomplete neointimal coverage after SES implantation has been reported, local long-term hypercoagulability remains unknown. Methods: We evaluated the local persistent coagulative response in eighty-three consecutive patients with stable angina, treated with either SES (n = 51) or BMS (n = 32) implantation for isolated de novo left anterior descending (LAD) stenosis. We measured prothrombin fragment F1+ 2 (frF1 + 2) and D-dimer levels sampled in the coronary sinus (CS) and sinus of Valsalva (V). The transcardiac gradient (Delta) was defined as the CS level minus V level. Results: The Delta frF1 + 2 and Delta D-dimer were significantly greater in the SES group than in the BMS group (0.50 +/- 0.35 vs -0.14 +/- 0.15 nmol/l, p = 0.009 and 0.24 +/- 0.21 vs -0.05 +/- 0.16 mu g/ml, p = 0.041, respectively). We selected the hypocoagulative [Delta frF1 + 2&lt;0.15 (mean value-SD) nmol/l, n = 21] and hypercoagulative [Delta frF1 + 2&gt;0.85 (mean value + SD) nmol/l, n = 14] groups out of the SES patients. Multivariate analysis was performed to identify independent predictors of local hypercoagulability. Total SES length was the only independent predictor of local hypercoagulability. There was a significant positive correlation between the Delta frF1 + 2 and total stent length in the SES group (r = 0.57, p&lt;0.05). Conclusions: An increased local coagulative response was observed in the convalescent phase after SES implantation as compared to BMS. Careful long-term follow-up of patients after longer SES implantation is recommended in order to avoid LST. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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Detection of Cardiac Involvement in Patients with Sarcoidosis Using Cardiac Magnetic Resonance

Iwase Takashi, Takao Shoichiro, Akaike Masashi, Ise Takayuki, Niki Toshiyuki, Kusunose Kenya, Sumitomo-Ueda Yuka, Tomita Noriko, Yamaguchi Koji, Taketani Yoshio, Yamada Hirotsugu, Soeki Takeshi, Aihara Ken-ichi, Wakatsuki Tetsuzo, Harada Masafumi, Sata Masataka

CIRCULATION   124 ( 21 )   2011.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Ultrasonic Tissue Characterization of Carotid Artery Plaque using High-resolution Integrated Backscatter Imaging: Validation Study with Histological Correlation

Bando Mika, Yamada Hirotsugu, Nishio Susumu, Uematsu Etsuko, Hayashi Shuji, Hotchi Junko, Kusunose Kenya, Tomita Noriko, Tamai Rina, Hirata Yukina, Hirota Daichi, Nakagawa Maya, Niki Toshiyuki, Yamaguchi Koji, Taketani Yoshio, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Shimabukuro Michio, Sata Masataka

CIRCULATION   124 ( 21 )   2011.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Single-Beat Assessment of Left Ventricular Systolic and Diastolic Function During Atrial Fibrillation using Myocardial Strain and Strain Rate

Kusunose Kenya, Yamada Hirotsugu, Nishio Susumu, Tomita Noriko, Hayashi Shuji, Hotchi Junko, Tamai Rina, Hirota Daichi, Hirata Yukina, Bando Mika, Ogasawara Kozue, Takashima Akira, Yamazaki Hiromu, Bando Sachiko, Ise Takayuki, Niki Toshiyuki, Yamaguchi Koji, Taketani Yoshio, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Sata Masataka

CIRCULATION   124 ( 21 )   2011.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Effects of Telmisartan on Inflammatory Cytokines and Coronary Plaque Component Assessed by Integrated Backscatter Intravascular Ultrasound in Hypertensive Patients

Yamaguchi Koji, Wakatsuki Tetsuzo, Soeki Takeshi, Niki Toshiyuki, Taketani Yoshio, Oezuka Hiroyasu, Bando Sachiko, Tomita Noriko, Kusunose Kenya, Iwase Takashi, Yamada Hirotsugu, Sata Masataka

CIRCULATION   124 ( 21 )   2011.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

A patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite

Hiromu Yamazaki, Koji Yamaguchi, Takashi Iwase, Toshiyuki Niki, Kenya Kusunose, Noriko Tomita, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Yutaka Fukunaga, Hideki Nakanishi, Haruhiko Maruyama, Hiroyuki Matsuoka, Masataka Sata

Journal of Cardiology Cases   4 ( 2 ) e106 - e109   2011.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 71-year-old female had worked on a farm in the mountains and noticed itching of the left 3rd toe. She visited a local hospital due to a color change to purple in this area. Attachment of a tick was observed between the left 2nd and 3rd toes, and it was extracted. However, due to persistent pain, she was referred to our department of cardiovascular medicine for close examination and treatment. Lower extremity angiography showed that vascular visualization was poor in the area supplied by the arteries distal to the tick bite site, but the other blood vessels of the toe were clearly visualized. Toe amputation was performed and pathological examination of a surgical specimen revealed that most blood vessels near the necrosis were occluded by thrombi. We speculated that tick bite reactions were associated with thrombogenic vasculopathy. This report shows a patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite. © 2011 Japanese College of Cardiology.

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Elevated concentrations of pentraxin 3 are associated with coronary plaque vulnerability

Takeshi Soeki, Toshiyuki Niki, Kenya Kusunose, Sachiko Bando, Yoichiro Hirata, Noriko Tomita, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masashi Akaike, Masataka Sata

JOURNAL OF CARDIOLOGY ( ELSEVIER IRELAND LTD )  58 ( 2 ) 151 - 157   2011.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Inflammation is a critical contributing factor to the development and progression of atherosclerosis. Pentraxin 3 (PTX3) is produced abundantly in atherosclerotic lesions while C-reactive protein (CRP) is mainly produced in the liver. In this study, we investigated whether plasma levels of PTX3 might be a sensitive marker both for the severity of coronary artery disease and vulnerable plaques. Next, we determined whether assays for inflammatory molecules can be used to monitor the therapeutic effects of telmisartan on stabilization of vulnerable atherosclerotic plaques. Methods and results: We measured PTX3 concentrations in the peripheral and coronary sinus plasma of 40 patients with angina pectoris (AP) and 20 control subjects. Next, in 28 patients with AP, we determined the correlation between levels of inflammatory molecules and the computed tomography (CT) density of plaques as a quantitative index of plaque vulnerability. There was no significant difference in peripheral plasma PTX3 concentrations between patients with AP and control subjects, while coronary sinus plasma PTX3 concentrations were significantly higher in AP patients than control subjects. The concentrations of PTX3 in coronary sinus and peripheral plasma correlated with Gensini scores as an index of severity of coronary atherosclerosis. Interestingly, there was a significantly negative correlation between plasma PTX3 concentrations and CT density (r= 0.67, p &lt; 0.01). On the other hand, CT density did not correlate with the peripheral plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) or high-sensitivity CRP (hsCRP). Furthermore, telmisartan treatment for 6 months decreased plasma concentrations of PTX3 but not those of MCP-1 or hsCRP in 12 patients with essential hypertension. Multivariate regression analysis revealed that changes in PTX3 levels were independent of blood pressure changes. Conclusions: PTX3 is likely more specific than hsCRP as an indicator of coronary plaque vulnerability that could lead to plaque rupture. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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Comparison of chronic-stage histopathological findings among 3 coronary stents implanted in the same patient

Toshiyuki Niki, Tetsuzo Wakatsuki, Koji Yamaguchi, Kenya Kusunose, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike, Masataka Sata

INTERNATIONAL JOURNAL OF CARDIOLOGY ( ELSEVIER IRELAND LTD )  150 ( 1 ) E25 - E27   2011.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 73-year-old woman suffering from anterior thoracic pain on exertion presented to our hospital. We performed coronary angiography and noted three stenotic legions in each coronary artery. For each angiographic finding, we implanted a bare metal stent (BMS), sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) into the right coronary artery, left anterior descending and left circumflex coronary arteries, respectively. Nine months later, she died of lung disease, and we could compare the histopathological findings among the three coronary stents. In the drug-eluting stents, very thin intima, infiltration of inflammatory cells, and fibrin deposition were observed, while thick intima and no inflammatory findings were observed in the BMS. Fibrin deposition was more marked in the PES than in the SES. This report shows marked differences in the subsequent pathological course among three stents in the same patient. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

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Effect of Low-Dose (1 mg/day) Pitavastatin on Left Ventricular Diastolic Function and Albuminuria in Patients With Hyperlipidemia

Shusuke Yagi, Masashi Akaike, Ken-Ichi Aihara, Takashi Iwase, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

AMERICAN JOURNAL OF CARDIOLOGY ( EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC )  107 ( 11 ) 1644 - 1649   2011.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The aim of the present study was to evaluate the factors that modulate the protective action of statins on cardiorenal function, regardless of the lipid-lowering effect. To treat abnormal serum lipid profiles, low-dose pitavastatin (1.0 mg/day) was administered to 65 hyperlipidemic patients. The exclusion criteria included left ventricular ejection fraction &lt;40% and apparent renal disease. Age- and gender-matched patients with hyperlipidemia (n = 40) served as the controls. After 12 to 16 weeks of pitavastatin treatment, pitavastatin had decreased low-density lipoprotein cholesterol (from 143.5 +/- 31.4 to 98.2 +/- 19.4 mg/dl, p &lt;0.01), triglycerides (from 157.7 +/- 57.2 to 140.5 +/- 60.7 mg/dl, p &lt;0.01), E/e' (from 10.8 +/- 6.2 to 9.0 +/- 4.5, p &lt;0.05), a parameter of left ventricular diastolic function, and albuminuria (from 47.6 +/- 55.9 to 28.5 +/- 40.0 mg/g creatinine, p &lt;0.01). Furthermore, pitavastatin decreased serum transforming growth factor-beta 1 (from 709 +/- 242 to 550 +/- 299 pg/ml, p &lt;0.01), urinary 8-hydroxy-2'-deoxyguanosine (from 6.6 +/- 4.1 to 5.0 +/- 3.1 mu g/g creatinine, p &lt;0.01), an oxidative stress marker, and increased urinary nitrate and nitrite (from 22.5 +/- 14.6 to 29.4 +/- 27.6 nmol/g creatinine, p &lt;0.05). No such changes were observed in the controls. Multiple regression analysis in the pitavastatin group revealed the effect of pitavastatin on cardiorenal function was associated with suppression of oxidative stress, but not on low-density lipoprotein cholesterol reduction. In conclusion, pitavastatin decreases E/e' and albuminuria, which is associated with suppression of oxidative stress. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1644-1649)

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Observation of short-term atorvastatin-induced changes in coronary arterial plaque properties using integrated backscatter intravascular ultrasound in a patient

Koji Yamaguchi, Tetsuzo Wakatsuki, Toshiyuki Niki, Yoshio Taketani, Hiroyasu Oezuka, Kenya Kusunose, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata

Journal of Cardiology Cases   3 ( 3 ) e111 - e114   2011.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Integrated backscatter intravascular ultrasound (IB-IVUS) capable of assessing plaque properties has recently become clinically applicable. We observed short-term atorvastatin-induced changes in coronary arterial plaque properties using IB-IVUS. The patient was a 57-year-old man who underwent coronary angiography when admitted to our hospital for cerebrovascular surgery, and lesions were observed in 2 branches: 99% and 90% stenoses in the proximal anterior descending branch (LAD) and middle region of the circumflex, respectively. Stenting was performed for the LAD on November 4, 2009 and for the circumflex on December 9. Oral atorvastatin administration at 10. mg/day was initiated on November 5 because the LDL-cholesterol level was high (160. mg/dl). A region about 5. mm in length proximal to the stent placed in the LAD was analyzed using IB-IVUS. Atorvastatin lowered the LDL cholesterol level from 160 to 79. mg/dl. On IB image analysis, although the period was as short as about 1 month, a marked decrease in the fatty component (44% → 26%) and an increase in the fibrous component (53% → 66%) were observed in the plaque. It was suggested that atorvastatin changes the tissue properties of coronary arterial plaques from a very early phase. It might be associated with the stabilization of coronary plaque. © 2011 Japanese College of Cardiology.

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Serial imaging changes during treatment of Takayasu arteritis with pulmonary artery stenosis

Kenya Kusunose, Hirotsugu Yamada, Noriko Tomita, Susumu Nishio, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Masataka Sata

INTERNATIONAL JOURNAL OF CARDIOLOGY ( ELSEVIER IRELAND LTD )  148 ( 3 ) E47 - E50   2011.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Most cases of chronic stenosis or occlusive lesions of the pulmonary arteries are attributed to thromboembolism, and pulmonary arteritis is extremely rare as the primary cause of these entities. We report a case of pulmonary stenosis and occlusion caused by Takayasu arteritis. The patient was a 54-year-old woman who presented with dyspnea. Total occlusion of the left pulmonary artery and significant stenosis of the right pulmonary artery caused by Takayasu arteritis were confirmed by various imaging modalities including pulmonary angiography, 18fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging and real-time three-dimensional transesophageal echocardiography. After 6 weeks of steroid therapy, follow-up imaging studies showed that the stenotic lesion had resolved. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

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RELATIONSHIP BETWEEN CAROTID ARTERY STIFFNESS PARAMETER ? AND BRACHIAL ARTERY FLOW-MEDIATED DILATION IN CORONARY ARTERY DISEASE

Nishio Susumu, Yamada Hirotsugu, Tamai Rina, Endo Keisuke, Hayashi Shuji, Kusunose Kenya, Tomita Noriko, Miki Junko, Bando Sachiko, Hisaoka Sahika, Niki Toshiyuki, Yamaguchi Koji, Taketani Yoshio, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Akaike Masashi, Sata Masataka

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   57 ( 14 ) E1569   2011.04 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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Acute hemodynamic effects of adaptive servo ventilation in patients with pulmonary hypertension

Shusuke Yagi, Masashi Akaike, Takashi Iwase, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata

INTERNATIONAL JOURNAL OF CARDIOLOGY ( ELSEVIER IRELAND LTD )  148 ( 1 ) 125 - 127   2011.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia.

Shusuke Yagi, Masashi Akaike, Ken-ichi Aihara, Takashi Iwase, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

The American Journal of Cardiology   Vol.107 ( No.11 ) 1644 - 1649   2011.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The aim of the present study was to evaluate the factors that modulate the protective action of statins on cardiorenal function, regardless of the lipid-lowering effect. To treat abnormal serum lipid profiles, low-dose pitavastatin (1.0 mg/day) was administered to 65 hyperlipidemic patients. The exclusion criteria included left ventricular ejection fraction &lt;40% and apparent renal disease. Age- and gender-matched patients with hyperlipidemia (n = 40) served as the controls. After 12 to 16 weeks of pitavastatin treatment, pitavastatin had decreased low-density lipoprotein cholesterol (from 143.5 ± 31.4 to 98.2 ± 19.4 mg/dl, p &lt;0.01), triglycerides (from 157.7 ± 57.2 to 140.5 ± 60.7 mg/dl, p &lt;0.01), E/e&amp;apos; (from 10.8 ± 6.2 to 9.0 ± 4.5, p &lt;0.05), a parameter of left ventricular diastolic function, and albuminuria (from 47.6 ± 55.9 to 28.5 ± 40.0 mg/g creatinine, p &lt;0.01). Furthermore, pitavastatin decreased serum transforming growth factor-1 (from 709 ± 242 to 550 ± 299 pg/ml, p &lt;0.01), urinary 8-hydroxy-2&amp;apos;-deoxyguanosine (from 6.6 ± 4.1 to 5.0 ± 3.1 g/g creatinine, p &lt;0.01), an oxidative stress marker, and increased urinary nitrate and nitrite (from 22.5 ± 14.6 to 29.4 ± 27.6 nmol/g creatinine, p &lt;0.05). No such changes were observed in the controls. Multiple regression analysis in the pitavastatin group revealed the effect of pitavastatin on cardiorenal function was associated with suppression of oxidative stress, but not on low-density lipoprotein cholesterol reduction. In conclusion, pitavastatin decreases E/e&amp;apos; and albuminuria, which is associated with suppression of oxidative stress.

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Validation of Longitudinal Peak Systolic Strain by Speckle Tracking Echocardiography With Visual Assessment and Myocardial Perfusion SPECT in Patients With Regional Asynergy

Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukio Mizuguchi, Masahito Choraku, Yasuhiro Maeda, Shinobu Hosokawa, Nobuo Yamazaki, Noriko Tomita, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  75 ( 1 ) 141 - 147   2011.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Automated function imaging (AFI) is a recently developed method of calculating the longitudinal peak systolic strains (LS) of the regional left ventricular (LV) wall using speckle tracking echocardiography and displaying them on a single bull&apos;s-eye map. The feasibility of AFI in patients with regional LV wall motion abnormalities caused by myocardial infarction (MI) was evaluated by comparison with visual assessment and myocardial perfusion single-photon emission computed tomography (SPECT). Methods and Results: Segmental LS was measured by AFI in 60 patients with MI (67 +/- 11 years) and 58 controls (71 +/- 9 years). Wall thickening (WT) was measured by SPECT in 20 patients with MI. There was a strong positive linear relationship between the wall motion score index by expert visual assessment and global LS. The receiver-operating characteristic analysis revealed the best cutoff value of -11% &lt;LS to identify hypokinetic segments. The overall accuracy of wall motion scoring by LS in the 2,006 segments was 96.8% (kappa=0.90) compared with visual assessment. The correlation coefficient between LS and WT was R(2)=0.65 in the 340 segments. Conclusions: Assessment of LV regional asynergy by AFI showed good agreement with visual and SPECT assessments. AFI is clinically useful for quantitative assessment of LV regional wall motion abnormalities. (Circ J 2011;75: 141-147)

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A case of renal artery stenosis in an elderly patient after nephrectomy diagnosed by ultrasound sonography, showing improvement of blood pressure and renal dysfunction after renal artery stenting

Kojiro Nagai, Kenya Kusunose, Susumu Nishio, Yoshio Taketani, Hirotsugu Yamada, Masataka Sata, Naoki Kondo, Fumi Kishi, Seiji Kishi, Toshikazu Araoka, Motokazu Matsuura, Akira Mima, Hideharu Abe, Taichi Murakami, Masayuki Nakamura, Toshio Doi

Japanese Journal of Nephrology   53 ( 1 ) 68 - 74   2011 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Arteriosclerotic renal artery stenosis is one of the increasingly common diseases that affects many aged patients. There are various non-invasive methods to diagnose renal artery stenosis, such as contrast enhanced CT or MRI. However, these methods are not appropriate for patients with renal dysfunction. Ultrasound sonography is becoming one of the promising methods to diagnose artery stenosis because of photographic improvements. In this case, a 72-year-old woman was hospitalized 7 months after nephrectomy because of severe hypertension, heart failure and kidney dysfunction. The heart failure was quite uncontrollable in spite of massive administration of diuretics, and finally, hemodialysis was started to control her volume status. In consideration of her past history and abdominal bruit, we evaluated the renal artery stenosis by ultrasound sonography and confirmed the diagnosis by renal angiography. To improve hypertension control, we performed renal artery stenting, which resulted in an impressive improvement of her blood pressure and renal function. We recognized the importance of careful causal evaluation of renal dysfunction, even though it is difficult to apply invasive therapy to patients after nephrectomy.

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Ventricular Tachycardia in Cardiac Sarcoidosis Controlled by Radiofrequency Catheter Ablation

Mika Bando, Takeshi Soeki, Toshiyuki Niki, Kenya Kusunose, Noriko Tomita, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masashi Akaike, Masataka Sata

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  50 ( 11 ) 1201 - 1206   2011 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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We report a case of a 78-year-old woman with cardiac sarcoidosis with a history of syncope and palpitation. Further assessment with echocardiography, gadolinium-enhanced cardiovascular magnetic resonance (CMR) and histology led to a diagnosis of cardiac sarcoidosis. As the patient suffered from ventricular tachycardia (VT) despite active corticosteroid therapy, an implantable cardioverter-defibrillator (ICD) was positioned. She was also administered a beta blocker, but an electrical storm appeared every several days requiring ICD therapy. The drug-refractory VT was finally controlled with a catheter ablation session, during which we could detect the VT focus in the right ventricular outflow tract next to the aneurysm by using an electroanatomic mapping system (CARTO). Referring to echocardiographic and CMR images proved very useful in detecting the aneurysm using the CARTO system.

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Removal of a pinched off central venous catheter.

Kusunose K, Wakatsuki T, Sata M

Heart Asia   3 ( 1 ) 32 - 32   2011 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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PJ3-044 Congenital Long QT Syndrome with Compound Mutations in KCNH2 Gene

Sachiko Bando, Takeshi Soeki, Toshivuki Niki, Kenya kusunose, Koji Yamaguchi, Yoshio Taketani, Iwase Takashi, Hirotsugu Yamada, Tetsuzo Wakatsuki, Wataru Simizu, Masataka Sata

Journal of Arrhythmia   27   2011 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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We report a case with long QT syndrome caused by compound mutations in KCNH2 gene.A 20-year-old man was referred to our hospital for evaluation of syncope. When he was a high school student, he experienced syncope. In electrocardiogram, the QT interval was prolonged to 498ms (QTc=479ms). His 22-year-old elder brother, who had syncopal episodes twice and the prolonged QT interval in electrocardiogram, suffered from ventricular fibrillation and became vegetative state on May 26, 2009. Genetic testing revealed the frameshift mutation by the insertion of 25 nucleotides causing both an altered amino acid sequence from codon 302 and a premature termination codon (i.e., TAG) at codon 339 and the missense mutation of c.1474 C&gt T (p.H492Y) in KCNH2 gene in both brothers. These mutations have not been reported previously. Family genetic screening found that their father had the same fameshift mutation and their mother and sister had the same missense mutation in KCNH2 gene. However the family members without two brothers experienced no symptoms and had no prolonged QT interval in electrocardiogram. These results suggest that the compound mutations in KCNH2 gene inherited independently from the parents made the phenotype of their sons more severe. Then we planted the implantable cardioverter defibrillator into him on March 17, 2010. © 2011, Japanese Heart Rhythm Society. All rights reserved.

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繰り返す心不全と維持透析導入から離脱しえた腎動脈狭窄症の一例

門田 宗之, Yoshio Taketani, Tetsuzo Wakatsuki, Koji Yamaguchi, Kenya Kusunose, Toshiyuki Niki, 坂東 左知子, 久岡 白陽花, Yuka Ueda, 冨田 紀子, 竹内 秀和, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike, Masataka Sata, Kojiro Nagai, Toshio Doi

Shikoku Acta Medica   Vol.66 ( No.5, 6 ) 175 - 180   2010.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Ghrelin Attenuates Myocardial Ischemia/Reperfusion Injury via the Extracellular Signal-Regulated Kinase 1/2 and Phosphatidylinositol 3-Kinase/Akt Pathway

Soeki Takeshi, Niki Toshiyuki, Bando Sachiko, Hisaoka Sahika, Takeuchi Hidekazu, Kusunose Kenya, Yamaguchi Koji, Hirata Yoichiro, Tomita Noriko, Taketani Yoshio, Iwase Takashi, Yamada Hirotsugu, Wakatsuki Tetsuzo, Akaike Masashi, Kangawa Kenji, Sata Masataka

CIRCULATION   122 ( 21 )   2010.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Time-Dependent Changes of Local Coagulative Response up to Five Years After Sirolimus-Eluting Stent Implantation

Yamaguchi Koji, Wakatsuki Tetsuzo, Niki Toshiyuki, Taketani Yoshio, Bando Sachiko, Hisaoka Sahika, Kusunose Kenya, Ueta Yuka, Takeuchi Hidekazu, Iwase Takashi, Tomita Noriko, Yamada Hirotsugu, Soeki Takeshi, Akaike Masashi, Sata Masataka

CIRCULATION   122 ( 21 )   2010.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Time Difference between Onset of Mitral Inflow and Onset of Early Diastolic Mitral Annulus Velocity predicts Left Ventricular End-diastolic Pressure: Assessment by Dual Doppler Echocardiography

Kusunose Kenya, Yamada Hirotsugu, Nishio Susumu, Tomita Noriko, Hayashi Shuji, Bando Sachiko, Hisaoka Sahika, Niki Toshiyuki, Yamaguchi Koji, Taketani Yoshio, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Akaike Masashi, Sata Masataka

CIRCULATION   122 ( 21 )   2010.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Left Ventricular Dyssynchrony during Lower Leg Positive Pressure Assessed by Real-time 3-dimensional Echocardiography

Kusunose Kenya, Yamada Hirotsugu, Nishio Susumu, Tomita Noriko, Hayashi Shuji, Bando Sachiko, Hisaoka Sahika, Niki Toshiyuki, Yamaguchi Koji, Taketani Yoshio, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Akaike Masashi, Sata Masataka

CIRCULATION   122 ( 21 )   2010.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Ghrelin Protects Heart Against Ischemia-Induced Arrhythmias by Preserving Connexin43 Protein

Soeki Takeshi, Niki Toshiyuki, Bando Sachiko, Hisaoka Sahika, Takeuchi Hidekazu, Kusunose Kenya, Yamaguchi Koji, Hirata Yoichiro, Tomita Noriko, Taketani Yoshio, Iwase Takashi, Yamada Hirotsugu, Wakatsuki Tetsuzo, Akaike Masashi, Kangawa Kenji, Sata Masataka

CIRCULATION   122 ( 21 )   2010.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Bosentan ameliorated exercise-induced pulmonary arterial hypertension complicated with systemic sclerosis.

Shusuke Yagi, Masashi Akaike, Takashi Iwase, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Sumiko Yoshida, Yuka Sumitomo-Ueda, Ken-ichi Aihara, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

Internal Medicine   Vol.49 ( No.21 ) 2309 - 2312   2010.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Pulmonary arterial hypertension (PAH) is a frequent complication in patients with systemic sclerosis. Bosentan is used in patients with symptomatic PAH; however, it has not been established whether or not bosentan ameliorates the progression of PAH in patients with no PAH-related symptoms. We present a case of systemic sclerosis with no PAH-related symptoms in which bosentan ameliorated exercise-induced PAH evaluated by 6-minute walk stress echocardiography, brachial flow-mediated dilation, and skin temperature of hands and feet. The results suggest that administration of bosentan in patients with early-stage PAH ameliorates pulmonary arterial vasodilatation through improvement of endothelial function.

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Cardiac Magnetic Resonance Imaging and 2-Dimensional Speckle Tracking Echocardiography in Secondary Cardiac Amyloidosis

Kenya Kusunose, Hirotsugu Yamada, Takashi Iwase, Susumu Nishio, Noriko Tomita, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Takao Shoichiro, Masafumi Harada, Noriko Kagawa, Eiji Kudo, Masataka Sata

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC )  74 ( 7 ) 1494 - 1496   2010.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Effects of Additional Administration of Low-Dose Indapamide on Patients With Hypertension Treated With Angiotensin II Receptor Blocker

Hirotsugu Yamada, Yuichiro Mishiro, Kenya Kusunose, Masataka Sata

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS ( SAGE PUBLICATIONS INC )  15 ( 2 ) 145 - 150   2010.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Low-dose thiazide or thiazide-like diuretics have proven useful for the management of blood pressure in patients older than 65 years (elderly group). However, there are few reports about the antihypertensive effects of antihypertensive diuretic agents in patients younger than 65 years (middle-aged group). So, we evaluated the efficacy of low-dose indapamide on blood pressure. Methods: Indapamide(1 mg) was given daily for 3 months and was then given every other day for 3 months to patients whose hypertension was poorly controlled with angiotensin II receptor blocker (ARB)-based treatment. Results: After daily administration of indapamide, blood pressure was significantly decreased in both the middle-aged and elderly groups. Blood pressure was not significantly changed by every-other-day administration compared with that observed after daily administration in either group. The rate of attainment of the target blood pressure was 90.3% and 85.7% in the middle-aged and elderly groups, respectively. The serum uric acid levels were reduced after every-other-day administration compared to daily administration but tended to be higher than the levels at the baseline in both groups. Conclusions: The addition of low-dose indapamide is a useful strategy for the management of hypertension, as it reduced blood pressure without marked side effects.

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Congenital ventricular aneurysm as an unexpected complication of monomorphic premature ventricular contractions.

Shusuke Yagi, Masashi Akaike, Mitsunori Fujimura, Takehiko Kimura, Takeshi Nishiuchi, Takashi Iwase, Ken-ichi Aihara, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

Internal Medicine   Vol.49 ( No.10 ) 907 - 912   2010.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Congenital ventricular diverticulum (CVD) in adults is a rare cardiac malformation, which includes fibrous type congenital ventricular aneurysm (CVA). CVA is often clinically asymptomatic and shows no abnormality in the electrocardiogram or chest X-ray. However, some cases of sudden death resulting from ventricular tachycardia, cardiac embolism or ventricular rupture have been reported. Therefore, physicians should perform further cardiac imaging studies to detect a CVA if ventricular arrhythmia originating from the left ventricle is observed. Here, we report two successfully followed cases of CVA which were diagnosed from premature ventricular contractions.

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Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.

Shusuke Yagi, Masashi Akaike, Ken-ichi Aihara, Takashi Iwase, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

Journal of Atherosclerosis and Thrombosis   Vol.17 ( No.2 ) 173 - 180   2010.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIM: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment. RESULTS: Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2&amp;apos;-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels. CONCLUSION: Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.

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Bosentan Ameliorated Exercise-Induced Pulmonary Arterial Hypertension Complicated with Systemic Sclerosis

Shusuke Yagi, Masashi Akaike, Takashi Iwase, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Sumiko Yoshida, Yuka Sumitomo-Ueda, Ken-ichi Aihara, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  49 ( 21 ) 2309 - 2312   2010 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Pulmonary arterial hypertension (PAH) is a frequent complication in patients with systemic sclerosis. Bosentan is used in patients with symptomatic PAH; however, it has not been established whether or not bosentan ameliorates the progression of PAH in patients with no PAH-related symptoms. We present a case of systemic sclerosis with no PAH-related symptoms in which bosentan ameliorated exercise-induced PAH evaluated by 6-minute walk stress echocardiography, brachial flow-mediated dilation, and skin temperature of hands and feet. The results suggest that administration of bosentan in patients with early-stage PAH ameliorates pulmonary arterial vasodilatation through improvement of endothelial function.

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Ezetimibe Ameliorates Metabolic Disorders and Microalbuminuria in Patients with Hypercholesterolemia

Shusuke Yagi, Masashi Akaike, Ken-ichi Aihara, Takashi Iwase, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS ( JAPAN ATHEROSCLEROSIS SOC )  17 ( 2 ) 173 - 180   2010 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Aim: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia. Methods: Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age-and sex-matched patients with hypercholesterolemia (n = 38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment. Results: Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels. Conclusion: Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.

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Diagnostic utility of cardiac magnetic resonance for detection of cardiac involvement in female carriers of Duchenne muscular dystrophy.

Iwase T, Takao S, Akaike M, Adachi K, Sumitomo-Ueda Y, Yagi S, Niki T, Kusunose K, Tomita N, Hirata Y, Yamaguchi K, Koshiba K, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Aihara K, Harada M, Nishitani H, Sata M

Heart Asia   2 ( 1 ) 52 - 55   2010 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Congenital Ventricular Aneurysm as an Unexpected Complication of Monomorphic Premature Ventricular Contractions

Shusuke Yagi, Masashi Akaike, Mitsunori Fujimura, Takehiko Kimura, Takeshi Nishiuchi, Takashi Iwase, Ken-ichi Aihara, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  49 ( 10 ) 907 - 912   2010 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

　View Summary

Congenital ventricular diverticulum (CVD) in adults is a rare cardiac malformation, which includes fibrous type congenital ventricular aneurysm (CVA). CVA is often clinically asymptomatic and shows no abnormality in the electrocardiogram or chest X-ray. However, some cases of sudden death resulting from ventricular tachycardia, cardiac embolism or ventricular rupture have been reported. Therefore, physicians should perform further cardiac imaging studies to detect a CVA if ventricular arrhythmia originating from the left ventricle is observed. Here, we report two successfully followed cases of CVA which were diagnosed from premature ventricular contractions.

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Long-Term Local Inflammatory Response After Coronary Artery Stenting: Bare Metal vs Sirolimus-Eluting vs Paclitaxel-Eluting Stent

Wakatsuki Tetsuzo, Niki Toshiyuki, Kusunose Kenya, Yamaguchi Koji, Koshiba Kunihiko, Yagi Shusuke, Tomita Noriko, Taketani Yoshio, Iwase Takashi, Yamada Hirotsugu, Soeki Takeshi, Akaike Masashi, Sata Masataka

CIRCULATION   120 ( 18 ) S994   2009.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Prognostic Value of Changes in Transmitral Flow Velocity Pattern During Leg Positive Pressure in Mild Heart Failure: A Clinical Application of "Preload Stress Echocardiography"

Yamada Hirotsugu, Kusunose Kenya, Nishio Susumu, Tomita Noriko, Endo Keisuke, Takashima Hiromitsu, Mimura Chihiro, Niki Toshiyuki, Yamaguchi Koji, Koshiba Kunihiko, Taketani Yoshio, Yagi Shusuke, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Akaike Masashi, Sata Masataka

CIRCULATION   120 ( 18 ) S728   2009.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Long-Term Local Inflammatory Response After Coronary Artery Stenting With Drug-Eluting Stent

Tetsuzo Wakatsuki, Toshiyuki Niki, Kenya Kusunose, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Noriko Tomita, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike, Masataka Sata

CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  120 ( 18 ) S914 - S914   2009.11 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Clinical Utility of Single-Beat E/e &apos; Obtained by Simultaneous Recording of Flow and Tissue Doppler Velocities in Atrial Fibrillation With Preserved Systolic Function

Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Noriko Tomita, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Masataka Sata

JACC-CARDIOVASCULAR IMAGING ( ELSEVIER SCIENCE INC )  2 ( 10 ) 1147 - 1156   2009.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVES We evaluated the usefulness of the ratio of the early diastolic transmitral flow velocity (E) to the mitral annular velocity (e&apos;) calculated from simultaneously recorded E and e&apos; in atrial fibrillation (AF). BACKGROUND The ratio of the E to the e&apos; (E/e&apos;) has been reported as a useful index even in AF patients. However, E and e&apos; were measured during different beats in the previous studies. METHODS Fifty-six AF patients with preserved systolic function (mean age 66 +/- 11 years) underwent routine echocardiographic study. The E/e&apos; was calculated from the E and e&apos; simultaneously recorded by the dual Doppler echocardiography. A single-beat E/e&apos; was calculated from simultaneously recorded E and e&apos; when the preceding RR interval/pre-preceding RR interval = 1. Brain natriuretic peptide (BNP) levels were also examined. Twenty-one patients underwent simultaneous pulmonary artery catheterization. RESULTS The single-beat lateral E/e&apos; correlated with pulmonary capillary wedge pressure (PCWP) (r = 0.74, p &lt; 0.001). The single-beat lateral E/e&apos; of &gt;= 11 could predict elevated PCWP (&gt;= 15 mm Hg) with a sensitivity of 90% and a specificity of 90%. The single-beat lateral E/e&apos; also correlated well with the log BNP concentration. The single-beat lateral E/e&apos; of &gt;= 9.2 predicted a plasma BNP level of &gt;= 200 pg/ml with 88% sensitivity and 84% specificity. CONCLUSIONS The single-beat lateral E/e&apos; correlated with plasma BNP level and PCWP in AF patients with preserved systolic function. In addition, the single-beat lateral E/e&apos; (&gt;= 11) was a good predictor of elevated PCWP (&gt;= 15 mm Hg). Dual Doppler echocardiography offers an advantage of providing the single-beat lateral E/e&apos; correctly even in AF patients, for the evaluation of left ventricular diastolic function. (J Am Coll Cardiol Img 2009; 2: 1147-56) (C) 2009 by the American College of Cardiology Foundation

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Bosentan, an Endothelin Receptor Antagonist, Improves Systemic Sclerosis-Related Peripheral Circulation Insufficiency Through Regulation of Oxidative Stress, Inflammation, and Nitric Oxide Bioavailability

Yagi Shusuke, Akaike Masashi, Iwase Takashi, Aihara Ken-ichi, Yoshida Sumiko, Sumitomo-Ueda Yuka, Kusunose Kenya, Niki Toshiyuki, Yamaguchi Koji, Koshiba Kunihiko, Taketani Yoshio, Tomita Noriko, Yamada Hirotsugu, Soeki Takeshi, Wakatsuki Tetsuzo, Matsumoto Toshio, Sata Masataka

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   29 ( 7 ) E49 - E50   2009.07 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Change of Tricuspid Annular Velocity Pro. le by the Treatment of Left-sided Heart Failure With Secondary Pulmonary Hypertension Determined by Pulsed Tissue Doppler Imaging

Nishio Susumu, Yamada Hirotsugu, Kusunose Kenya, Tomita Noriko, Niki Toshiyuki, Yamaguchi Koji, Koshiba Kunihiko, Yagi Shusuke, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Akaike Masashi, Sata Masataka

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   53 ( 10 ) A236   2009.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

The Mitral L-Wave Predicts Adverse Response to Volume Overloading in Patients With Atrial Fibrillation

Yamada Hirotsugu, Kusunose Kenya, Nishio Susumu, Tomita Noriko, Niki Toshiyuki, Yamaguchi Koji, Koshiba Kunihiko, Yagi Shusuke, Iwase Takashi, Soeki Takeshi, Wakatsuki Tetsuzo, Akaike Masashi, Sata Masataka

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   53 ( 10 ) A235   2009.03 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Platypnea-Orthodeoxia Syndrome Associated with Patent Foramen Ovale and Aortic Ectasia

Kenya Kusunose, Hirotsugu Yamada, Takashi Todoroki, Susumu Nishio, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Tetsuya Kitagawa, Masataka Sata

ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES ( WILEY-BLACKWELL PUBLISHING, INC )  26 ( 1 ) 114 - 117   2009.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 59-year-old man was admitted for dyspnea on exertion and edema. The patient did not have any pulmonary diseases that could cause dyspnea. Transesophageal echocardiography on the tilting bed with contrast infusion revealed a right-to-left shunt through the patent foramen ovale. Therefore, he was diagosed as platypnea-orthodeoxia syndrome due to the patent foramen ovale. Surgical closure was done and all of his symptoms had improved. (ECHOCARDIOGRAPHY, Volume 26, January 2009).

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ENHANCED MACROPHAGE INFILTRATION IN EPICARDIAL ADIPOSE TISSUE IN PATIENTS WITH CORONARY ARTERY DISEASE.

Hirata Yoichiro, Niki Toshiyuki, Kusunose Kenya, Yamaguchi Koji, Yagi Shusuke, Koshiba Kunihiko, Iwase Takashi, Yamada Hirotsugu, Soeki Takeshi, Wakatsuki Tetsuzo, Akaike Masashi, Kurobe Hirotsugu, Chikugo Humio, Hori Takaki, Kitagawa Tetsuya, Sata Masataka

JOURNAL OF VASCULAR RESEARCH   46   166   2009 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

Local Hypercoagulability and Endothelial Dysfunction after Sirolimus-Eluting Stent Implantation: Implication for Late Stent Thrombosis

Koji Yamaguchi, Tetsuzo Wakatsuki, Toshlyuki Niki, Kenya Kusunose, Kunihiko Koshiba, Syusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike, Masataka Sata

CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  118 ( 18 ) S651 - S651   2008.10 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Long-Term Endothelial Dysfunction after Coronary Artery Slanting with Drug-Eluting Stent Associated with Local Inflammatory Response

Tatsuzo Wakatsuki, Koji Yamaguchi, Toshiyuki Niki, Kenya Kusunose, Kunihiko Koshiba, Hirotsugu Yamada, Takeshi Soeki, Syusuke Yagi, Takashi Iwase, Masashi Akaike, Masataka Sata

CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  118 ( 18 ) S749 - S749   2008.10 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

C-type natriuretic peptide ameliorates the progression of experimental autoimmune myocarditis

K. Koshiba, T. Soeki, T. Niki, K. Kusunose, K. Yamaguchi, H. Yamada, T. Wakatsuki

EUROPEAN HEART JOURNAL ( OXFORD UNIV PRESS )  29   898 - 898   2008.09 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Long-term local inflammatory response after coronary artery stenting with drug-eluting stent

T. Wakatsuki, K. Yamaguchi, T. Niki, K. Kusunose, K. Koshiba, H. Yamada, T. Soeki, M. Akaike

EUROPEAN HEART JOURNAL ( OXFORD UNIV PRESS )  29   464 - 465   2008.09 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Elevated concentration of Pentraxin 3 is associated with coronary plaque vulnerability

T. Soeki, T. Niki, K. Koshiba, K. Kusunose, K. Yamaguchi, H. Yamada, T. Wakatsuki

EUROPEAN HEART JOURNAL ( OXFORD UNIV PRESS )  29   612 - 612   2008.09 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

A case of neurogenic myocardial stunning presenting transient left ventricular mid-portion ballooning simulating atypical takotsubo cardiomyopathy

Koji Yamaguchi, Tetsuzo Wakatsuki, Kenya Kusunose, Toshiyuki Niki, Kunihiko Koshiba, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike

JOURNAL OF CARDIOLOGY ( ELSEVIER IRELAND LTD )  52 ( 1 ) 53 - 58   2008.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 57-year-old female patient, who was initially suspected to have subarachnoid hemorrhage, was admitted to our hospital. She experienced severe dyspnea and chest pain owing to pneumonia on the fourth admission day. Electrocardiography showed ST-segment elevation in leads V(2) through V(5), and echocardiography revealed hypokinetic left ventricular watt motion. No stenosis was found in the coronary arteries by urgent coronary angiography. However, left ventriculography revealed that the basal and apical areas were hyperkinetic and the mid portion was akinetic. After a month, left ventricular watt motion was improved and coronary artery spasm provocation tests were negative. Although the clinical course of this patient was similar to that of neurogenic myocardial stunning, the shape of her left ventricle was not typical. (C) 2008 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

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Usefulness of TEI Index in Atrial Fibrillation : Assessment by Dual Doppler Echocardiography

KUSUNOSE Kenya, YAMADA Hirotsugu, KAWANO Hiromi, NISHIO Susumu, HIRAOKA Hazuki, SATO Mitsuyo, TADATSU Yoko, SOEKI Takeshi, AKAIKE Masashi

Jpn J Med Ultrasonics ( The Japan Society of Ultrasonics in Medicine )  35   S315   2008.04 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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E/e' as a Predictor of the Cardiac Response to Increment of Preload in Patients with Atrial Fibrillation.

Hirotsugu Yamada, Kenya Kusunose, A Iga, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki

Circulation Journal   Vol.72 ( No.0 ) S_749 - S_749   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Predictors of Local Hypercoagulability after Sirolimus-Eluting Stent Implantation: Implication for Correlates of Late Stent Thrombosis.

K Yamaguchi, Tetsuzo Wakatsuki, Kenya Kusunose, T Niki, K Koshiba, Tomohito Kawano, Hirotsugu Yamada, Takeshi Soeki

Circulation Journal   Vol.72 ( No.0 ) 249_FRS022 - 249_FRS022   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Long-Term Local Inflammatory Response after Coronary Artery Stenting with Drug-Eluting Stent.

Tetsuzo Wakatsuki, K Yamaguchi, T Niki, Kenya Kusunose, K Koshiba, Takeshi Soeki, Hirotsugu Yamada

Circulation Journal   Vol.72   421_PJ456 - 421_PJ456   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Left Atrial Volume does not reflect Brain Natriuretic Peptide Levels in Patients with Atrial Fibrillation.

Kenya Kusunose, Hirotsugu Yamada, A Iga, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki

Circulation Journal   Vol.72   508_PE367 - 508_PE367   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Importance of Left Atrial Function for the Pseudonormalization of Transmitral Flow Velocity Pattern in Patients with Hypertrophic Cardiomyopathy.

Kenya Kusunose, Hirotsugu Yamada, A Iga, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki

Circulation Journal   Vol.72   426_PJ492 - 426_PJ492   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Ghrelin Attenuates Myocardial Ischemia/Reperfusion Injury via the Extracellular Signal-Regulated Kinase 1/2 and Phosphatidylinositol.

Takeshi Soeki, K Koshiba, T Niki, Kenya Kusunose, K Yamaguchi, Tomohito Kawano, Hirotsugu Yamada, Tetsuzo Wakatsuki, Kenji Kangawa

Circulation Journal   Vol.72 ( No.0 ) 145_OE022 - 145_OE022   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Elevated Concentration of Pentraxin 3 is Associated with Coronary Plaque Vulnerability.

Takeshi Soeki, T Niki, K Koshiba, Kenya Kusunose, K Yamaguchi, Tomohito Kawano, Hirotsugu Yamada, Tetsuzo Wakatsuki

Circulation Journal   Vol.72 ( No.0 ) 632_PE499 - 632_PE499   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Elevated Concentration of Interferon-Inducible Protein of 10kd (IP-10) is Associated with Coronary Atherosclerosis.

T Niki, Takeshi Soeki, Kenya Kusunose, K Yamaguchi, K Koshiba, Tomohito Kawano, Hirotsugu Yamada, Tetsuzo Wakatsuki, Kenji Kangawa

Circulation Journal   Vol.72 ( No.0 ) 715_OJ233 - 715_OJ233   2008.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Assessment of Left Atrial Ejection Force in Patients with Hypertensive Heart Disease.

S Nishio, Hirotsugu Yamada, H Motonari, H Okada, Kenya Kusunose, Y Tadatsu, M Sato, H Hiraoka, H Kawano, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike

Journal of the American Society of Echocardiography   Vol.21   552 - 552   2008 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Usefulness of Tei Index in Atrial Fibrillation: Assessment by Dual Doppler Echocardiography.

S Nishio, Hirotsugu Yamada, H Motonari, Kenya Kusunose, Y Tadatsu, M Sato, H Hiraoka, H Kawano, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike

Journal of the American Society of Echocardiography   Vol.21   543 - 543   2008 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

The Mitral L-Wave Predicts the Cardiac Response to Preload Increment in Atrial Fibrillation.

Hirotsugu Yamada, Kenya Kusunose, S Nishio, Y Tadatsu, M Sato, H Hiraoka, H Kawano, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike

Journal of the American Society of Echocardiography   Vol.21   545 - 545   2008 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Role of Left Atrial Function for Pseudonormalization of Transmitral Flow Velocity Pattern in Patients with Hypertrophic Cardiomyopathy.

Kenya Kusunose, Hirotsugu Yamada, S Nishio, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike

Journal of the American Society of Echocardiography   Vol.21   524 - 524   2008 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Multicenter Trial for the Validation of Automated Function Imaging in Patients with Local Left Ventricular Asynergy (VANILLA Study).

Kenya Kusunose, K Takechi, Hirotsugu Yamada, S Nishio, Y Tadatsu, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, M Choraku, Y Maeda

Journal of the American Society of Echocardiography   Vol.21   538 - 538   2008 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Importance of Left Atrial Function in Cardiac Response to Increment of Preload in Patients with Old Myocardial Infarction: Assessment by Automated Left Atrial Volume Tracking Method.

Kenya Kusunose, Hirotsugu Yamada, S Nishio, M Sato, H Hiraoka, H Kawano, Y Tadatsu, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike

Journal of the American Society of Echocardiography   Vol.21   552 - 552   2008 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Beat-To-Beat Variation of Mitral Annular Velocities in Atrial Fibrillation.

S Nishio, Hirotsugu Yamada, H Motonari, Kenya Kusunose, Y Tadatsu, M Sato, H Hiraoka, H Kawano, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike

Journal of the American Society of Echocardiography   Vol.21   550 - 550   2008 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Relationship between the ratio of peak early diastolic transmitral flow and mitral annular velocities and the plasma B-Type natriuretic peptide (BNP) concentration in patients with atrial fibrillation: Assessment by simultaneous recording of transmitral flow and mitral annular velocity

Kenya Kusunose, Hirotsugu Yamada, Hiroyuki Niki, Tomohiro Nakajima, Koji Yamaguchi, Kunihiko Koshiba, Tomohito Kawano, Takeshi Soeki, Tetsuzo Wakatsuki, Susumu Ito

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY ( ELSEVIER SCIENCE INC )  49 ( 9 ) 137A - 137A   2007.03 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Assessment of the cardiac response to increment of preload in patients with atrial fibrillation using dual pulsed Doppler echocardiography.

Hirotsugu Yamada, Kenya Kusunose, Y Uzuuchi, H Niki, T Nakajima, K Yamaguchi, K Koshiba, Tomohito Kawano, Takeshi Soeki, Tetsuzo Wakatsuki

Journal of the American Society of Echocardiography   Vol.20   594 - 594   2007 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)

Measurement of left atrial volume curve by advanced 2D tissue tracking technique: validation by contrast multidetector computed tomography.

Kenya Kusunose, Hirotsugu Yamada, T Chono, H Niki, T Nakajima, K Yamaguchi, K Koshiba, Tomohito Kawano, Takeshi Soeki, Tetsuzo Wakatsuki, K Aihara, Hiromu Nishitani

Journal of the American Society of Echocardiography   Vol.20   603 - 603   2007 [ Peer Review Accepted ]

Type of publication: Research paper (bulletin of university, research institution)