Faculty Bibliography

Background: Obesity is prevalent among patients with hypertrophic cardiomyopathy (HCM). Obese HCM patients have greater wall thickness, LV mass, worse hemodynamic function and NYHA class. Weight loss may favorably influence the HCM phenotype. Case summary: We describe six patients with hypertrophic cardiomyopathy who lost weight through diet and lifestyle changes (n = 4) or bariatric surgery (n = 2). Radiographic imaging, with cardiac MRI or CT scan, was performed before and after their weight loss. There was a mean decrease in LV mass and indexed LV mass, and a mean numerical decrease in mean wall thickness in up to 14 out of 18 LV segments. There was also NYHA class reduction in symptoms. Discussion: In this case series, we have shown that substantial weight loss in HCM patients can be associated with a decrease in LV mass, wall thickness and improvement in symptoms. These observations indicate the potential for positive remodeling of the heart by weight loss. Prospective studies of the benefits of weight loss in HCM are needed.

BACKGROUND:Apical left ventricular (LV) aneurysms in hypertrophic cardiomyopathy (HCM) are associated with adverse outcomes. The reported frequency of mid-LV obstruction has varied from 36% to 90%. OBJECTIVES/OBJECTIVE:The authors sought to ascertain the frequency of mid-LV obstruction in HCM apical aneurysms. METHODS:The authors analyzed echocardiographic and cardiac magnetic resonance examinations of patients with aneurysms from 3 dedicated programs and compared them with 63 normal controls and 47 controls with apical-mid HCM who did not have aneurysms (22 with increased LV systolic velocities). RESULTS:]; P = 0.004). Complete emptying occurs circumferentially around central PMs that contribute to obstruction. Late gadolinium enhancement was always brightest and the most transmural apical of, or at the level of, complete emptying. CONCLUSIONS:The great majority (95%) of patients in the continuum of apical aneurysms have associated mid-LV obstruction. Further research to investigate obstruction as a contributing cause to apical aneurysms is warranted.

BACKGROUND:Mitral valve (MV) elongation is a primary hypertrophic cardiomyopathy (HCM) phenotype and contributes to obstruction. The residual MV leaflet that protrudes past the coaptation point is especially susceptible to flow-drag and systolic anterior motion. Histopathological features of MVs in obstructive hypertrophic cardiomyopathy (OHCM), and of residual leaflets specifically, are unknown. OBJECTIVES/OBJECTIVE:The purpose of this study was to characterize gross, structural, and cellular histopathologic features of MV residual leaflets in OHCM. On a cellular-level, we assessed for developmental dysregulation of epicardium-derived cell (EPDC) differentiation, adaptive endocardial-to-mesenchymal transition and valvular interstitial cell proliferation, and genetically-driven persistence of cardiomyocytes in the valve. METHODS:Structural and immunohistochemical staining were performed on 22 residual leaflets excised as ancillary procedures during myectomy, and compared with 11 control leaflets from deceased patients with normal hearts. Structural components were assessed with hematoxylin and eosin, trichrome, and elastic stains. We stained for EPDCs, EPDC paracrine signaling, valvular interstitial cells, endocardial-to-mesenchymal transition, and cardiomyocytes. RESULTS:= 0.08). No markers of primary cellular processes were identified. CONCLUSIONS:MV residual leaflets in HCM were characterized by histologic findings that were likely secondary to chronic hemodynamic stress and may further increase susceptibility to systolic anterior motion.

Surgical myectomy remains the time-honored primary treatment for hypertrophic cardiomyopathy patients with drug refractory limiting symptoms due to LV outflow obstruction. Based on >50 years experience, surgery reliably reverses disabling heart failure by permanently abolishing mechanical outflow impedance and mitral regurgitation, with normalization of LV pressures and preserved systolic function. A consortium of 10 international currently active myectomy centers report about 11,000 operations, increasing significantly in number over the most recent 15 years. Performed in experienced multidisciplinary institutions, perioperative mortality for myectomy has declined to 0.6%, becoming one of the safest currently performed open-heart procedures. Extended myectomy relieves symptoms in >90% of patients by ≥ 1 NYHA functional class, returning most to normal daily activity, and also with a long-term survival benefit; concomitant Cox-Maze procedure can reduce the number of atrial fibrillation episodes. Surgery, preferably performed in high volume clinical environments, continues to flourish as a guideline-based and preferred high benefit: low treatment risk option for adults and children with drug refractory disabling symptoms from obstruction, despite prior challenges: higher operative mortality/skepticism in 1960s/1970s; dual-chamber pacing in 1990s, alcohol ablation in 2000s, and now introduction of strong negative inotropic drugs potentially useful for symptom management.

BACKGROUND:Hypertrophic cardiomyopathy (HCM) is a common and clinically heterogeneous inherited cardiac disease. Quality of life (QOL) and physical functioning are important clinically but are underexplored in diverse populations with HCM. OBJECTIVES/OBJECTIVE:To examine predictors for and compare QOL and physical functioning in Black and White adults with HCM. METHODS:We analyzed a sub-sample from a longitudinal prospective study on HCM. Eligibility criteria included self-identified Black and White adults (≥18 years) with clinical HCM. QOL was measured with the Minnesota Living with Heart Failure Questionnaire (MLWHF);physical functioning included age-adjusted exercise capacity and NYHA class. Covariates included HCM structural characteristics and common comorbidities. We analyzed data from 434 individuals, 57 (13.1%) of whom self-identified as Black/African American. RESULTS:In this sample, the Black cohort had higher MLWHF scores, 31.2 (27.2) v. 23.9 (22.1), p=0.042, signifying worse QOL, but there were no intergroup differences when QOL was dichotomized. Mean metabolic equivalents (METs) on symptom-limited stress testing were similar, though the Black cohort was younger, 54.6 (13.4) v.62.5 (14.8) years, p=0.001. No one from the Black cohort achieved an "excellent-for-age" exercise capacity, and 64.1% had a "below-average-for-age" exercise capacity vs 47% in the White cohort, though this was not statistically significant, p=0.058. There was no difference between groups in advanced NYHA class. Female gender was associated with worse QOL and physical functioning irrespective of covariates. CONCLUSIONS:This study is a starting point that underscores the need for a more comprehensive examination of well-being and physical functioning in Black populations with HCM.

BACKGROUND:Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy. Implantable Cardioverter Defibrillator (ICD) is important for prevention of sudden cardiac death (SCD) in patients at high risk. In recent years the subcutaneous ICD (S-ICD) has emerged as a viable alternative to the transvenous ICD (TV-ICD). The S-ICD does not require intravascular access, but cannot provide antitachycardia pacing therapy (ATP). OBJECTIVE:To assess the real world incidence of ICD therapy in patients with HCM implanted with TV-ICD versus S-ICD. METHODS:We compared the incidence of ATP and shock therapies between all HCM patients with S-ICD and TV-ICD enrolled in the Boston Scientific ALTITUDE database. Cumulative Kaplan Meier incidence was used to compare therapy free survival and Cox proportional hazard ratios were calculated. We performed an unmatched as well as propensity match analysis. RESULTS:We included 2047 patients with TV-ICD and 626 patients with S-ICD followed for an average of 1650.5±1038.5 and 933.4±550.6 days, respectively. Patients with HCM and TV-ICD had significantly higher rate of device therapy as compared to those with S-ICD (32.7 vs. 14.5 therapies /100 patient year; p<0.001), driven by a high incidence of ATP therapy in the TV-ICD group which accounted for more than 67% of therapies delivered. Shock incidence was similar between groups, both in the general and in the matched cohorts. CONCLUSIONS:Patients with HCM and S-ICD had significantly lower therapy rate than patients with TV-ICD without difference in shock therapy, suggesting potentially unnecessary ATP therapy. Empiric ATP programing in patients with HCM may be unbeneficial.