Association of duration and intensity of exercise with phenotypic expression in hypertrophic cardiomyopathy.

OBJECTIVES: There is limited data regarding the impact of exercise on phenotypic expression in hypertrophic cardiomyopathy (HCM). We aimed to investigate whether such an association exists in a cohort of genotype-positive HCM patients. METHODS: In this cross-sectional study of genotype-positive HCM families, we used structured questionnaires to obtain data regarding intensity and duration of exercise of participants starting at the age of 10, as well as data regarding exercise recommendations and their impact on quality of life (QOL). The association of cumulative metabolic-equivalent hours of exercise at different ages with different measures of phenotypic expression (maximal wall thickness, left atrial diameter, extent of late gadolinium enhancement) was analyzed. RESULTS: The study included 109 patients from 55 families, including 43 male (39%) and 90 (83%) phenotype-positive. No association was identified between exercise duration or intensity with any of the phenotypic markers with the exception of greater cumulative exercise associated with younger age at presentation. Similar results were obtained when analysis was limited to exercise until the age of 20, until the age of 30 or only after 30. Among phenotype-positive patients, 89% recalled receiving recommendations regarding exercise restriction, 29% noted reduction in exercise level following such recommendations and 25% noted this having a significant impact on their QOL. CONCLUSION: We found no association between exercise intensity or duration and phenotypic expression in genotype-positive HCM patients. These findings are important for physician-patient discussions and support the recent trend towards more permissive exercise restrictions in HCM.

Markers of responsiveness to disopyramide in patients with hypertrophic cardiomyopathy.

BACKGROUND: Significant left-ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) may result in symptoms and is associated with adverse outcomes. Although disopyramide can reduce resting gradients, nearly 30% of HCM patients do not respond. We sought to study the clinical and echocardiographic variables associated with disopyramide-induced LVOT-gradient reduction. METHODS: Forty-one disopyramide-treated HCM patients (average daily-dose 305 mg) were subdivided into two groups: (1) nineteen responders, with a reduction of LVOT-gradients of at least 30% from baseline, and (2) twenty-two non-responders, in whom LVOT-gradients did not change or increased following treatment. All patients had a thorough clinical and echocardiographic assessment pre- and post-treatment initiation. RESULTS: Patients who responded to disopyramide had better pretreatment left ventricular (LV) systolic function (LV ejection fraction of 67.9 ±â€¯5.6% vs. 59.7 ±â€¯5.8%, p = 0.0001), better LV global longitudinal strain (-17.9 ±â€¯2.3% vs. -16.1 ±â€¯2.5%, p = 0.048), less mitral regurgitation, smaller LV size (indexed LV end-systolic volume of 16.2 ±â€¯5.1 ml/m2 vs. 23.2 ±â€¯6.8 ml/m2, p = 0.001), and lower LV maximal wall thickness (17.2±3 mm vs.19.2 ±â€¯3.4 mm, p = 0.046). Baseline left atrial (LA) volumes were significantly lower in the responders, with higher indices of LA ejection fraction (62 ±â€¯11.2% vs. 50.5 ±â€¯12.2%, p = 0.005), systolic LA strain (34 ±â€¯12.4% vs. 25.8 ±â€¯10.6%, p = 0.04), and LA strain-rate (1.34 ±â€¯0.49%/sec vs. 0.99 ±â€¯0.24%/sec, p = 0.012). In multivariable analysis, the presence of reduced LV systolic function and systolic LA strain-rate remained independently associated with poor response to disopyramide. CONCLUSIONS: Obstructive HCM patients with more severe disease at baseline tend to respond less to disopyramide treatment. In those patients, early referral for alcohol septal ablation or myectomy surgery should be considered.

Velocity vector imaging in the measurement of left ventricular myocardial mechanics on cardiac magnetic resonance imaging: correlations with echocardiographically derived strain values.

BACKGROUND: Regional and global function can be measured by echocardiography using speckle-tracking, a technique that has previously been validated against crystal sonomicrometry. However, the application of Velocity Vector Imaging (VVI) to images obtained from cardiac magnetic resonance (CMR) imaging has never been validated against those values derived from VVI applied to two-dimensional echocardiographic images in the same patient group. The aim of this study was to validate for the first time the application of VVI to retrospectively acquired CMR data sets for the assessment of left ventricular strain and rotation, using echocardiographic strain assessment by VVI as the reference technique. METHODS: Cine steady-state free precession CMR data sets and two-dimensional echocardiographic images obtained on the same day in 36 adult patients with hypertrophic cardiomyopathy were analyzed retrospectively using VVI to quantify global longitudinal and circumferential strain and rotation parameters. RESULTS: The absolute differences in longitudinal strain between the two imaging modalities were -1.1 ± 3.3% (endocardial) and -2.2 ± 3.6% (full thickness). The absolute differences in circumferential strain were -4.7 ± 5.3% (endocardial) and -3.4 ± 3.8% (full thickness). CMR consistently resulted in higher strain values than echocardiography. The absolute differences in twist were -0.2 ± 5.6% (endocardial) and 0.1 ± 5.8% (full thickness). CONCLUSIONS: The application of VVI to CMR data sets allows a feasible and reproducible method for strain analysis in HCM, demonstrating excellent agreement with two-dimensional echocardiography-derived values. Given the superior image quality obtained with CMR in a significant proportion of patients, this technique provides a method for strain assessment without the need for dedicated CMR acquisition and analytic techniques.

Myocardial mechanical remodeling after septal myectomy for severe obstructive hypertrophic cardiomyopathy.

BACKGROUND: Septal myectomy for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) is a well-established procedure for symptomatic relief. Myocardial mechanics are abnormal in patients with HOCM, demonstrating low longitudinal strain, high circumferential strain, and high apical rotation compared with healthy subjects. The aim of this study was to determine whether functional improvement after myectomy is associated with improved myocardial mechanics. METHODS: Clinical data and paired echocardiographic studies before and after myectomy (6-18 months) were retrospectively analyzed and compared in 66 patients (mean age, 54 ± 13 years; 64% men) with HOCM. Myocardial mechanics including longitudinal and circumferential strain and rotation were assessed using two-dimensional strain software (Velocity Vector Imaging). RESULTS: Patients had significant symptomatic alleviation (mean New York Heart Association class, 2.8 ± 0.4 at baseline and 1.3 ± 0.5 after myectomy; P < .05). Left ventricular outflow gradient decreased dramatically (from 93 ± 26 to 17 ± 12 mm Hg; P < .05), and left atrial volume index decreased (from 48 ± 16 to 37 ± 13 cm(3)/m(2); P < .05). Low longitudinal strain decreased at the myectomy site, increased in the lateral segments, and remained unchanged globally (-16 ± 4). High circumferential strain decreased (from -31 ± 5 to -25 ± 6, P < .05). High left ventricular twist normalized (from -15.5 ± 6.2° to 12.8 ± 4.2°, P < .05). Independent predictors of symptomatic response included younger age before myectomy, thinner posterior wall, and higher lateral early diastolic velocity (e'). CONCLUSION: In patients with HOCM, surgical myectomy alleviated symptoms, relieved obstruction, and decreased left atrial volume index. Longitudinal strain remained unchanged, but circumferential strain and rotation decreased, demonstrating different mechanical adaptations to chronic elevated afterload seen in patients with severe aortic stenosis undergoing valve replacement. Disease extent (age, posterior wall involvement) and the presence of diastolic dysfunction seem to be related to partial symptomatic response to myectomy.