Harry M Lever

Cleveland Clinic, Cleveland, Ohio, United States

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Publications (87)598.01 Total impact

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    ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a primary myopathic process in which regional left ventricular dysfunction may exist without overt global left ventricular dysfunction. In obstructive HCM patients who underwent surgical myectomy (SM), we sought to determine if there is a significant association between echocardiographic longitudinal strain, histopathology, and in vitro myocardial performance (resting tension and developed tension) of the surgical specimen.
    Journal of the American Heart Association. 10/2014; 3(6).
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    ABSTRACT: Patients with obstructive hypertrophic cardiomyopathy (HC) have various left ventricular (LV) shapes: reverse septal curvature (RSC, commonly familial), sigmoid septum (SS, common in hypertensives), and concentric hypertrophy (CH). Longitudinal (systolic and early diastolic) strain rate (SR) is sensitive in detecting regional myocardial dysfunction. We sought to determine differences in longitudinal SR of patients with obstructive HC, based on LV shapes. We studied 199 consecutive patients with HC (50% men) referred for surgical myectomy. Clinical and echocardiographic parameters were recorded. LV shapes were classified on echocardiography, using basal septal 1/3 to posterior wall ratio: RSC = ratio >1.3 (extending to mid and distal septum), SS = ratio >1.3 (extending only to basal 1/3), and concentric = ratio ≤1.3. Longitudinal systolic and early diastolic SRs were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen). Distribution of RSC, SS, and CH was 50%, 28%, and 22%, respectively. Patients with RSC were significantly younger (47 ± 12 vs 64 ± 10 and 57 ± 11, respectively) with lower hypertension (40% vs71% and 67%, respectively) than patients with SS or CH (both p <0.001). Patients with RSC had lower global systolic (-0.99 ± 0.3 vs -1.05 ± 0.3 and -1.17 ± 0.3) and early diastolic SR (0.95 ± 0.4 vs 0.98 ± 0.3 and 1.16 ± 0.4) versus patients with SS and CH (in 1/s, both p <0.01), despite being much younger and less hypertensive. RSC was associated with abnormal global LV systolic (beta 0.16) and early diastolic (beta -0.17) SR (both p <0.01). In conclusion, patients with HC with RCS have significantly abnormal LV mechanics, despite being younger and less hypertensive. A combination of LV mechanics and shapes could help differentiate between genetically mediated and other causes of obstructive HC.
    The American Journal of Cardiology 06/2014; 113(11):1879-85. · 3.43 Impact Factor
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    ABSTRACT: We sought to assess long-term outcomes in asymptomatic or minimally symptomatic patients with hypertrophic cardiomyopathy (HCM) who underwent exercise echocardiography, without invasive therapies for relief of left ventricular outflow tract (LVOT) obstruction. Many HCM patients present with LVOT obstruction, mitral regurgitation (MR), and diastolic dysfunction, often requiring invasive therapies for symptomatic relief. However, a significant proportion of truly asymptomatic patients can be closely monitored. In HCM patients, exercise echocardiography has been shown to be a useful assessment of functional capacity and risk stratification. We included 426 HCM patients (44 ± 14 years; 78% men) undergoing exercise echocardiography, excluding hypertensive heart disease of elderly, ejection fraction <50% and invasive therapy (myectomy or alcohol ablation) during follow-up. Clinical, echocardiographic (LV thickness, LVOT gradient, and MR) and exercise variables (percent of age-sex predicted metabolic equivalents [METs] and heart rate recovery [HRR] at 1 min post-exercise) were recorded. A composite endpoint of death, appropriate internal defibrillator discharge, and admission for congestive heart failure was recorded. Patients were asymptomatic or minimally symptomatic on history, but 82% of patients achieved <100% of age-sex predicted METs, and 43% had ≥II+ post-stress MR. The mean LV septal thickness, post-exercise LVOT gradient, and HRR were 2.0 ± 0.5 cm, 62 ± 47 mm Hg, and 31 ± 14 beats/min, respectively. During a mean follow-up of 8.7 ± 3 years, there were 52 events (12%). Patients achieving >100% of age-sex predicted METs had 1% event rate versus 12% in those achieving <85%. On stepwise multivariate survival analysis, percent of age-sex predicted METs (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.64 to 0.90), abnormal HRR (HR: 0.89; 95% CI: 0.82 to 0.97), and atrial fibrillation (HR: 2.73; 95% CI: 1.30 to 5.74) (overall, p < 0.001) independently predicted outcomes. In asymptomatic or minimally symptomatic HCM patients, exercise stress testing provides excellent risk stratification, with a low event rate in patients achieving >100% of predicted METs.
    JACC. Cardiovascular imaging 11/2013; · 14.29 Impact Factor
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    ABSTRACT: Hypertrophic cardiomyopathy (HCM) is histopathologically characterized by myocyte hypertrophy, disarray, interstitial fibrosis, and small intramural coronary arteriole dysplasia, which contribute to disease progression. Longitudinal systolic and early diastolic strain rate (SR) measurements by speckle tracking echocardiography are sensitive markers of regional myocardial function. We sought to determine the association between septal SR and histopathologic findings in symptomatic HCM patients who underwent surgical myectomy. We studied 171 HCM patients (documented on histopathology) who underwent surgical myectomy to relieve left ventricular outflow tract obstruction. Various clinical and echocardiographic parameters were recorded. Segmental longitudinal systolic and early diastolic SRs (of the septal segment removed at myectomy) were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen, Germany). Histopathologic myocyte hypertrophy, disarray, small intramural coronary arteriole dysplasia, and interstitial fibrosis were classified as none, mild (1%-25%), moderate (26%-50%), and severe (>50%). The mean age was 53 ± 14 years (52% men, ejection fraction 62% ± 5%, mean left ventricular outflow tract gradient 102 ± 39 mm Hg, and basal septal thickness of 2.2 ± 0.5 cm). Mean longitudinal systolic and early diastolic SRs were -0.91 ± 0.5 and 0.82 ± 0.5 (1/s), respectively. There was an inverse association between systolic and early diastolic septal SR and degree of myocyte hypertrophy, disarray, and interstitial fibrosis (all P < .05). There was no association between histopathologic characteristics and other echocardiography parameters. On multivariable regression analysis, myocyte disarray and echocardiographic septal hypertrophy were associated with systolic and early diastolic septal SR (P < .05). In HCM patients, there is inverse association between various histopathologic findings and septal SR. Strain rate might potentially provide further insight into HCM pathophysiology.
    American heart journal 09/2013; 166(3):503-11. · 4.56 Impact Factor
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    ABSTRACT: BACKGROUND: We report the predictors of long-term outcomes of symptomatic hypertrophic cardiomyopathy (HCM) patients undergoing surgical relief of left ventricular outflow tract (LVOT) obstruction. METHODS AND RESULTS: We studied 699 consecutive HCM patients with severe symptomatic LVOT obstruction (47±11 years, 63% male) intractable to maximal medical therapy, that were referred to a tertiary hospital between 1/1997 and 12/2007 for surgical relief of LVOT obstruction. We excluded patients < 18 years and those with ejection fraction < 50%, hypertensive heart disease of elderly and > mild aortic or mitral stenosis. Clinical, echocardiographic, and Holter data was recorded. A composite endpoint of death, appropriate internal cardioverter defibrillator discharges, resuscitated sudden death, documented stroke and admission for congestive heart failure was recorded. During a mean follow-up of 6.2 ± 3 years, 86 patients (12%) met the composite endpoint with 30-day, 1-year and 2-year event rate of 0.7%, 2.8% and 4.7%, respectively. The hard event rate (death, defibrillator discharge and resuscitated sudden death) at 30-day, 1-year and 2-years was 0%, 1.5% and 3%, respectively. Stepwise multivariable analysis identified residual postoperative AF (Hazard ratio 2.12 [1.37-3.34] p=0.001), and increasing age (Hazard ratio 1.49 [1.22-1.82] p=0.001) as independent predictors of long-term composite outcomes. CONCLUSIONS: Symptomatic adult HCM patients undergoing surgery for relief of LVOT obstruction have low event rate during long-term follow up; with worse outcomes predicted by increasing age and presence of residual AF during follow up.
    Circulation 06/2013; · 14.95 Impact Factor
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    ABSTRACT: Diastolic dysfunction (DD) is often incriminated in the symptomatology of patients with hypertrophic cardiomyopathy (HCM), but with limited supporting data. This study sought to assess the relationship between baseline diastolic function and exercise capacity in patients with HCM. Retrospective study. Tertiary referral centre from Cleveland, Ohio, USA. 695 consecutive patients with a diagnosis of HCM who underwent exercise stress echocardiography between 1996 and 2011. PRIMARY AND SECONDARY OUTCOME MEASURES: Diastolic function was reassessed from the resting echocardiograms by two blinded board-certified cardiologists. Maximal metabolic equivalents (MET) were extracted from the records. Multivariate regression analysis was performed to determine independent predictors of METs achieved. Of 695 patients, 130 were excluded because of inability to assess diastolic function. There was no significant difference in maximal METs achieved between those excluded and included in the analysis (p=0.80). There were 495 remaining patients with a mean age (SD) of 50 (15) years, and 32% women among whom 102 (21%) had normal diastolic function, 243 (49%) stage 1 DD; 131 (26%) stage 2 DD and 19 (4%) stage 3 DD. Patients with advanced DD had lower maximal METs achieved compared with those with normal diastolic function (OR 3.18(1.96 to 5.14) for stage 1 versus normal, and 3.21(1.89 to 5.43) for stage ≥2 versus normal, p<0.0001 for both). After adjustment for demographics, comorbidities, echocardiographic parameters and haemodynamics, baseline DD was not an independent predictor of maximal METs achieved. Although baseline DD is common in patients with HCM, it does not predict maximal METs achieved beyond traditional risk factors.
    BMJ Open 10/2012; 2(6). · 2.06 Impact Factor
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    ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a complex and common genetic disease. The left ventricular outflow tract obstruction is an important determinant of symptoms and outcomes. Its pathophysiology is determined by the complex interaction of the mitral valve, papillary muscles, chordae tendinea, and interventricular septum. The knowledge and importance of the mitral valve apparatus in the physiology of the HCM are expanding with the new imaging modalities, in particular, cardiac magnetic resonance. Several abnormalities of the mitral apparatus have been described in patients with HCM including abnormal papillary muscles, leaflets' lengths, and mitral regurgitation. Ignoring these variables can lead to unnecessary or incomplete surgical treatments and worse outcomes. This review discusses the role of the mitral apparatus in HCM with a focus on a multimodality imaging approach and the clinical importance of each abnormality.
    Progress in cardiovascular diseases 05/2012; 54(6):517-22. · 4.25 Impact Factor
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    Andrew C Y To, Harry M Lever, Milind Y Desai
    Journal of the American College of Cardiology 03/2012; 59(13):1197. · 15.34 Impact Factor
  • Circulation Cardiovascular Imaging 03/2011; 4(2):156-68. · 5.80 Impact Factor
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    ABSTRACT: Exercise capacity in patients with hypertrophic cardiomyopathy (HCM) varies despite similar diastolic dysfunction, left ventricular outflow tract (LVOT) obstruction and mitral regurgitation (MR). Pulse wave velocity (PWV), determined by cardiac magnetic resonance (CMR), measures aortic stiffness and is abnormal in patients with HCM in comparison with controls. To determine potential clinical and imaging predictors of peak oxygen consumption (pVO(2)) in patients with HCM. Fifty newly referred patients with HCM (62% men, 44+/-13 years, 90% receiving optimal drugs, 18% hypertensive) underwent Doppler echocardiography (transthoracic echocardiography (TTE)), cardiopulmonary exercise testing and CMR for symptom evaluation. TTE variables (diastology, post exercise MR and LVOT gradient (mmHg)), pVO(2) (ml/kg/min) and CMR variables (PWV (aortic path length between mid- and descending aorta/time delay between arrival of the foot of the pulse wave between two points, m/s), and LV volumetric indices) were measured. After exercise LVOT gradient, MR, deceleration time and pVO(2) were 104+/-52, 1+/-1, 240+/-79 ms, and 25+/-6, respectively. Mean basal septal thickness (cm), PWV, EF, ESV index (ml/m(2)), EDV index (ml/m(2)) and LV mass index (g/m(2)) were 1.9+/-0.5, 9.3+/-7, 64%+/-7, 32+/-9, 87+/-17 and 112+36, respectively. Multiple regression analyses showed that only age (beta=-0.38, p=0.004) and PWV (beta=-0.33, p=0.01) predicted pVO(2). In patients with HCM, age and PWV are predictors of pVO(2), independent of LV thickness, LVOT gradient and diastolic indices. Aortic stiffness potentially has a role in evaluation of symptoms of patients with HCM.
    Heart (British Cardiac Society) 08/2010; 96(16):1303-10. · 6.02 Impact Factor
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    ABSTRACT: In patients with hypertrophic cardiomyopathy with bifid hypermobile papillary muscles and a dynamic left ventricular outflow tract gradient, we performed surgical papillary muscle reorientation, fixing the mobile papillary muscle to the posterior left ventricle to reduce mobility. We report the outcomes of patients with hypertrophic cardiomyopathy undergoing surgical papillary muscle reorientation versus those of patients undergoing standard surgical procedures. We studied 204 consecutive patients with hypertrophic cardiomyopathy undergoing surgical intervention (after consensus decision) for symptomatic left ventricular outflow tract gradient. Preoperative and postoperative maximal (resting/provocable) left ventricular outflow tract gradients were recorded by using echocardiographic analysis. The population was divided into 3 groups: (1) isolated myectomy (n = 143; age, 54 +/- 14 years; 48% men), (2) myectomy plus mitral valve repair/replacement (n = 39; age, 54 +/- 13 years; 54% men), and (3) papillary muscle reorientation with or without myectomy (n = 22; age, 50 +/- 14 years; 59% men). The mean preoperative (103 +/- 32, 103 +/- 32, and 114 +/- 36 mm Hg; P = .3) and predischarge (15 +/- 18, 14 +/- 14, and 16 +/- 21 mm Hg; P = .9) maximal left ventricular outflow tract gradients were similar. There were no deaths either in the hospital or at 30 days. At a median follow-up of 166 days (interquartile range, 74-343 days), 21 of 22 patients in group 3 were asymptomatic. One patient in group 3 had a symptomatic left ventricular outflow tract gradient (87 mm Hg) requiring mitral valve replacement. In patients with hypertrophic cardiomyopathy with bifid hypermobile papillary muscles (even with a basal septal thickness <1.5 cm), papillary muscle reorientation reduces the symptomatic left ventricular outflow tract gradient. Long-term outcomes need to be ascertained.
    The Journal of thoracic and cardiovascular surgery 08/2010; 140(2):317-24. · 3.41 Impact Factor
  • Article: Reply.
    Journal of the American College of Cardiology 02/2010; 55(5):505-6. · 15.34 Impact Factor
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    ABSTRACT: The purpose of this study was to perform a systematic review and meta-analysis of comparative studies to compare outcomes of septal ablation (SA) with septal myectomy (SM) for treatment of hypertrophic obstructive cardiomyopathy (HOCM). SM is considered the gold standard for treatment of HOCM. However, SA has emerged as an attractive therapeutic alternative. A Medline search using standard terms was conducted to determine eligible studies. Due to a lack of randomized control trials, we included observational studies for review. Twelve studies were found eligible for review. No significant differences between short-term (risk difference [RD]: 0.01; 95% confidence interval [CI]: -0.01 to 0.03) and long-term mortality (RD: 0.02; 95% CI: -0.05 to 0.09) were found between the SA and SM groups. In addition, no significant differences could be found in terms of post-intervention functional status as well as improvement in New York Heart Association functional class, ventricular arrhythmia occurrence, re-interventions performed, and post-procedure mitral regurgitation. However, SA was found to increase the risk of right bundle branch block (RBBB) (pooled odds ratio [OR]: 56.3; 95% CI: 11.6 to 273.9) along with need for permanent pacemaker implantation post-procedure (pooled OR: 2.6; 95% CI: 1.7 to 3.9). Although the efficacy of both SA and SM in left ventricular outflow tract gradient (LVOTG) reduction seems comparable, there is a small yet significantly higher residual LVOTG amongst the SA group patients as compared with the SM group patients. SA does seem to show promise in treatment of HOCM owing to similar mortality rates as well as functional status compared with SM; however, the caveat is increased conduction abnormalities and a higher post-intervention LVOTG. The choice of treatment strategy should be made after a thorough discussion of the procedures with the individual patient.
    Journal of the American College of Cardiology 02/2010; 55(8):823-34. · 15.34 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2010; · 4.44 Impact Factor
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    Barry J Maron, Harry Lever
    Journal of the American College of Cardiology 12/2009; 54(24):2339-40; author reply 2340. · 15.34 Impact Factor
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    ABSTRACT: The aim of the study was to determine if patients with hypertrophic cardiomyopathy (HCM), both with and without myocardial fibrosis, have altered aortic stiffness as assessed by magnetic resonance imaging (MRI) pulse wave velocity (PWV) measurements. Abnormal aortic stiffness implies an unfavorable prognosis and has been established in a variety of aortic diseases and ischemic cardiomyopathy. However, the relationship between aortic stiffness and HCM has not been studied previously. The study was institutional review board approved and Health Insurance Portability and Accountability Act of 1996 compliant. Velocity-encoded MRI was performed in 100 HCM and 35 normal control subjects. PWV was determined between the mid-ascending and -descending thoracic aorta. Delayed-enhancement MRI was acquired for identification of myocardial fibrosis. Mean age was 52.4 years in HCM and 45.3 years in control subjects. The prevalence of myocardial fibrosis in HCM was 70%. PWV was significantly higher in HCM patients compared with control subjects (8.72 +/- 5.83 m/s vs. 3.74 +/- 0.86 m/s, p < 0.0001). PWV was higher (i.e., increased aortic stiffness) in HCM patients with myocardial fibrosis than in those without (9.66 +/- 6.43 m/s vs. 6.51 +/- 3.25 m/s, p = 0.005). Increased aortic stiffness, as indicated by increased PWV, is evident in HCM patients, and is more pronounced in those with myocardial fibrosis. Further, aortic stiffening may adversely affect left ventricular performance. In addition, increased aortic stiffness correlates with myocardial fibrosis, and may represent another potentially important parameter for risk stratification in HCM, warranting further study.
    Journal of the American College of Cardiology 07/2009; 54(3):255-62. · 15.34 Impact Factor
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    ABSTRACT: In hypertrophic cardiomyopathy (HCM) patients undergoing surgical myectomy, we sought to determine the association between pre-operative cardiac magnetic resonance (CMR) findings, small intramural coronary arteriole dysplasia (SICAD) on histopathology, and ventricular tachycardia (VT). Myocardial scarring (fibrosis) and SICAD are frequently observed on histopathology in HCM patients. CMR measures wall thickness and detects scar. Sixty symptomatic HCM patients (62% men; mean age 51 +/- 14 years), with preserved ejection fraction (mean 64 +/- 5%) and no angiographic coronary disease underwent CMR (cine and delayed post-contrast) using a Siemens 1.5 T scanner, followed by septal myectomy. Maximal basal septal thickness was recorded on cine CMR. Scar was determined (percentage of total myocardium) on delayed post-contrast CMR images and quantified as none, mild (0% to 25%), moderate (26% to 50%), or severe (>50%). VT was assessed using Holter monitoring. Degree of SICAD was determined (normal, mild, moderate, and severe) on histopathology of surgical specimen. SICAD and scar were seen in 45 (75%) and 38 (63%) patients, respectively. In 15 patients without SICAD, 12 (80%) had no scar; 23 (70%) patients with mild SICAD had mild scar on CMR. On multivariate analysis, degree of SICAD was independently associated with scar on CMR (Wald chi-square statistic: 6.8, p < 0.01). Patients with basal septal scar on CMR had higher VT frequency compared with those without (27% vs. 5%, p = 0.03). A strong association exists between degree of SICAD and myocardial scarring seen on CMR.
    Journal of the American College of Cardiology 07/2009; 54(3):242-9. · 15.34 Impact Factor
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    ABSTRACT: Patients with hypertrophic cardiomyopathy (HCM) exhibit a difference in left ventricular outflow tract (LVOT) obstruction, independently of basal septal thickness (BST). Some patients with HCM have a steeper left ventricle to aortic root angle than controls. To test the predictors of the LV-aortic root angle and the association between LV-aortic root angle and LVOT obstruction using three-dimensional imaging. 153 consecutive patients with HCM (mean (SD) age 46 (14) years, 68% men) and 62 patients with hypertensive heart disease of the elderly (all >65 years of age, 73 (6) years, 34% men) who underwent whole-heart three-dimensional cardiac magnetic resonance (CMR) angiography (1.5 T) and Doppler echocardiography. Forty-two controls (age 43 (11) years, 38% men) who underwent contrast-enhanced multidetector computed tomography and were free of cardiovascular pathology were also studied. LV-aortic root angle, BST and maximal non-exercise LVOT gradient were measured in patients with HCM and in hypertensive-elderly patients. Additionally, LV-aortic root angle and BST were measured in controls. The mean (SD) LV-aortic root angle was significantly different (p<0.001) in the three groups: HCM (134 (10) degrees ), hypertensive-elderly (128 (10) degrees ), control (140 (7) degrees ). There was an inverse correlation between age and LV-aortic root angle in the three groups (all p<0.001): HCM (r = -0.56), hypertensive-elderly (r = -0.35), control (r = -0.48). On univariate analysis, in the HCM group, LV-aortic root angle (beta = -0.34, p<0.001), age (beta = 0.23, p = 0.01) and end-systolic volume index (beta = -0.20, p = 0.02), but not BST (beta = 0.02, p = 0.8), were associated with LVOT gradient. On multivariate analysis, only LV-aortic root angle was associated with LVOT gradient. Patients with HCM have a steeper LV-aortic root angle than controls. In patients with HCM, a steeper LV-aortic root angle predicts dynamic LVOT obstruction, independently of BST.
    Heart (British Cardiac Society) 06/2009; 95(21):1784-91. · 6.02 Impact Factor
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    ABSTRACT: Prosthetic valve obstruction by pannus or thrombus represents a rare but potentially serious cause of prosthetic valve dysfunction. We report a case in which the diagnosis of prosthetic valve obstruction was made in the catheterization laboratory utilizing cineradiography, left ventriculography and intracardiac echocardiography. The findings in this case suggest that in patients with a prosthetic aortic valve and increased left ventricular outflow tract gradient, evaluation in the catheterization laboratory may provide useful diagnostic information in addition to that obtained by noninvasive studies.
    The Journal of invasive cardiology 05/2009; 21(4):190-2. · 1.57 Impact Factor
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    ABSTRACT: To assess the impact of left ventricular (LV) volume/mass ratio on diastolic function parameters in subjects with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) and healthy controls. We performed echocardiography in 44 healthy controls, 35 HCM subjects, 29 DCM subjects with narrow QRS complex (DCM-n), and 27 DCM subjects with wide QRS complex (DCM-w). Mitral annulus velocity (E(a)) and transmitral E-wave velocity were used to estimate time constant of isovolumic pressure decay (tau). LV flow propagation velocity (V(p)) and early intraventricular pressure gradient (IVPG) were derived from colour M-mode of LV inflow. We calculated LV twist and peak untwisting rate (UntwR) by speckle tracking. Mean LV volume/mass ratio was 0.34 +/- 0.09 mL/g in healthy controls, 0.15 +/- 0.06 mL/g in HCM, 0.6 +/- 0.2 mL/g in DCM-n, and 0.8 +/- 0.3 mL/g in DCM-w patients (P < 0.001 for all groups). Resting LV ejection fractions were 63 +/- 7, 64 +/- 8, 31 +/- 8, and 26 +/- 8%, respectively (P < 0.01 vs. controls for DCM groups). In a multivariate analysis, LV volume/mass ratio remained a strong independent predictor of V(p) (P < 0.001), IVPG (P = 0.009), and UntwR (P < 0.001) but not for E(a) (P = 0.25). LV volume/mass ratio had influences on diastolic function parameters independent of intrinsic diastolic function and filling pressures. It should be considered when assessing patients suspected of LV diastolic dysfunction.
    European Heart Journal 04/2009; 30(10):1213-21. · 14.72 Impact Factor