Published Papers - Kusunose Kenya

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 <0.8 cm(2), mean AV gradient 40 mmHg, or dimensionless index <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 >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<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 (>= 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 < .001). The CAD group had thicker EAT-AIG than the non-CAD group (8.3 +/- 3.0 vs 6.3 +/- 2.5 mm, P < .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 <= 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 <= 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 <= 50 compared to patients aged 51-74 and >= 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<0.01) and RV free wall (RVLSFW, -19 +/- 5 vs. -14 +/- 4%, p<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<0.01 respectively) and logarithmic transformation of brain natriuretic peptide concentration (r=0.65 and r=0.65, p<.01, respectively). These revealed significant correlations with cardiac index (r=-0.50 and r=-0.47, p<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<0.01) were significantly decreased with pulmonary vasodilator treatment. RVLSglobal (-12 +/- 5 to -16 +/- 5%, p<0.01) and RVLSFW (-14 +/- 5 to -18 +/- 5%, p<0.01) were significantly improved. The decrease of mPAP was significantly correlated with improvement of RVLSglobal (r=0.45, p<0.01) and RVLSFW (r=0.43, p<0.01). The PVR change demonstrated significant correlation with improvement of RVLSglobal (r=0.40, p<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 >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 ]

Type of publication: Research paper (scientific journal)

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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 < 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 < 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 ]

Type of publication: Research paper (scientific journal)

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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 >= 25 mm Hg and pulmonary capillary wedge pressure <= 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 > 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 ]

Type of publication: Research paper (scientific journal)

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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<0.01, free wall: r=-0.52, P<0.01, and septum: r=-0.49, P<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 < 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 ]

Type of publication: Research paper (scientific journal)

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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 < 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 ]

Type of publication: Research paper (scientific journal)

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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<0.01) and negatively correlated with % FV (r=-0.41, P<0.05). Importantly, transcoronary concentration gradient of circulating miR-100 was more strongly correlated with % LV (r=0.53, P<0.01) and % FV (r=-0.56, P<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 ]

Type of publication: Research paper (scientific journal)

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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 >= 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 ]

Type of publication: Research paper (scientific journal)

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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 ]

Type of publication: Research paper (scientific journal)

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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 < .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 < .001; maximal LA volume index: r = -0.393, P < .001). Patients with LA epsilon(total) < 23.2% showed a higher incidence of AF recurrence compared with patients with LA epsilon(total) >= 23.2% (log-rank P < .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 < .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 < .001). Conclusions: In patients with AF, baseline LA epsilon(total) was associated with rhythm outcome after catheter ablation.

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