Hannah G. van Velzen

Long-Term Outcome of Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy in the Young and the Elderly

OBJECTIVES The aim of this study was to compare outcomes of alcohol septal ablation (ASA) in young and elderly patients with obstructive hypertrophic cardiomyopathy (HCM). BACKGROUND The American College of Cardiology Foundation/American Heart Association guidelines reserve ASA for elderly patients and patients with serious comorbidities. Information on long-term age-specific outcomes after ASA is scarce. METHODS This cohort study included 217 HCM patients (age 54 ± 12 years) who underwent ASA because of symptomatic left ventricular outflow tract obstruction. Patients were divided into young (age ≤55 years) and elderly (age >55 years) groups and matched by age in a 1:1 fashion to nonobstructive HCM patients. RESULTS Atrioventricular block following ASA was more common in elderly patients (43% vs. 21%; p = 0.001), resulting in pacemaker implantation in 13% and 5%, respectively (p = 0.06). Residual left ventricular outflow tract gradient, post-procedural New York Heart Association functional class, and necessity for additional septal reduction therapy was comparable between age groups. During a follow-up of 7.6 ± 4.6 years, 54 patients died. The 5- and 10-year survival following ASA was 95% and 90% in patients age ≤55 years and 93% and 82% in patients age >55 years, which was comparable to their control groups. The annual adverse arrhythmic event rate following ASA was 0.7%/year in young patients and 1.4%/year in elderly patients, which was comparable to their control groups. CONCLUSIONS ASA is similarly effective for reduction of symptoms in young and elderly patients; however, younger patients have a lower risk of procedure-related atrioventricular conduction disturbances. The long-term mortality rate and risk of adverse arrhythmic events following ASA are low, both in young and elderly patients, and are comparable to age-matched nonobstructive HCM patients.

Clinical Characteristics and Long-Term Outcome of Hypertrophic Cardiomyopathy in Individuals With a MYBPC3 (Myosin-Binding Protein C) Founder MutationCLINICAL PERSPECTIVE

Background— MYBPC3 (Myosin-binding protein C) founder mutations account for 35% of hypertrophic cardiomyopathy (HCM) cases in the Netherlands. We compared clinical characteristics and outcome of MYBPC3 founder mutation (FG+) HCM with nonfounder genotype-positive (G+) and genotype-negative (G−) HCM. Methods and Results— The study included 680 subjects: 271 FG+ carriers, 132 G+ probands with HCM, and 277 G− probands with HCM. FG+ carriers included 134 FG+ probands with HCM, 54 FG+ relatives diagnosed with HCM after family screening, 74 FG+/phenotype-negative relatives, and 9 with noncompaction or dilated cardiomyopathy. The clinical phenotype of FG+ and G+ probands with HCM was similar. FG+ and G+ probands were younger with less left ventricular outflow tract obstruction than G− probands, however, had more hypertrophy, and nonsustained ventricular tachycardia. FG+ relatives with HCM had less hypertrophy, smaller left atria, and less systolic and diastolic dysfunction than FG+ probands with HCM. After 8±6 years, cardiovascular mortality in FG+ probands with HCM was similar to G+ HCM (22% versus 14%; log-rank P=0.14), but higher than G− HCM (22% versus 6%; log-rank P<0.001) and FG+ relatives with HCM (22% versus 4%; P=0.009). Cardiac events were absent in FG+/phenotype-negative relatives; subtle HCM developed in 11% during 6 years of follow-up. Conclusions— Clinical phenotype and outcome of FG+ HCM was similar to G+ HCM but worse than G− HCM and FG+ HCM diagnosed in the context of family screening. These findings indicate the need for more intensive follow-up of FG+ and G+ HCM versus G− HCM and FG+ HCM in relatives.

Effect of Gender and Genetic Mutations on Outcomes in Patients With Hypertrophic Cardiomyopathy

Gender has been proposed to impact the phenotype and prognosis of hypertrophic cardiomyopathy (HC). Our aims were to study gender differences in the clinical presentation, phenotype, genotype, and outcome of HC. This retrospective single-center cohort study included 1,007 patients with HC (62% male, 80% genotyped) evaluated between 1977 and 2017. Hazard ratios (HR) were calculated using multivariable Cox proportional hazard regression models. At first evaluation, female patients presented more often with symptoms (43% vs 35%, p = 0.01), were older than male patients (56 ± 16 vs 49 ± 15 years, p <0.001), and more frequently had hypertension (38% vs 27%, p <0.001), left ventricular outflow tract obstruction (37% vs 27%, p <0.001), and impaired left ventricular systolic (17% vs 11%, p = 0.01) and diastolic (77% vs 62%, p <0.001) function. Overall, the genetic yield was similar between genders (54% vs 51%, p = 0.4); however, in patients ≥70 years, the genetic yield was less in women (15% vs 36%, p = 0.03). During 6.8-year follow-up (interquartile range 3.2 to 10.9), female gender was not independently associated with all-cause mortality (HR 1.25 [0.91 to 1.73]), cardiovascular mortality (HR 1.22 [0.83 to 1.79]), heart failure-related mortality (HR 1.77 [0.95 to 3.27]), or sudden cardiac death (SCD) and/or aborted SCD (HR 0.75 [0.44 to 1.30]). Interventions and nonfatal clinical events did not differ between the genders. In conclusion, female patients with HC present at a more advanced age with a different clinical, phenotypic, and genetic status. There is no independent association between female gender and all-cause mortality, cardiovascular mortality, heart failure-related mortality, or SCD.