Published Papers - Kusunose Kenya

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 ]

Type of publication: Research paper (scientific journal)

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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 ]

Type of publication: Research paper (scientific journal)

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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 < .001), reduced LAA emptying velocity (odds ratio, 12.7; 95% CI, 6.11-26.44; P < .001), and reduced left ventricular ejection fraction (odds ratio, 2.11; 95% CI, 1.03-4.32; P < .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 <1.3 cm(2) evaluated between January to June 2008 (excluding severe other valve disease and LV ejection fraction <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, <= 1 cm2; mean gradient >= 40 mm Hg), and (c) paradoxical severe (n=141; aortic valve area, <= 1 cm2 and mean gradient <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<0.001), New York Heart Association class (hazard ratio, 1.44; 1.11-1.87; P<0.001), AV surgery with time-dependent covariate analysis (hazard ratio, 0.29; 0.19-0.45; P<0.001), and LV-GLS (hazard ratio, 1.05; 1.03-1.07; P<0.001) were independent predictors of mortality. LV-GLS <-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<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 >70% stenosis in >= 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<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 < 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 < 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 < 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 < 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 < 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 <= 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 < .0001). Worse RV strain was associated with reduced LVEF (r = -0.45, P < .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 < .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 > -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 >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 < 0.001). In 400 LA images with 20 patients, an excellent correlation was obtained between LAVs using echocardiography and MDCT (R = 0.98, P < 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 > 50%, LV end-diastolic dimension <= 70 mm, LV end-systolic dimension <= 50 mm or <= 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 < 0.001), and further increased by exercise TAPSE (chi(2), 64.4; P < 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 < 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 < 0.001). Finally, transmitral flow showed decreased atrial contribution to left ventricular filling in the control group (P < 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<0.15 (mean value-SD) nmol/l, n = 21] and hypercoagulative [Delta frF1 + 2>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<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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