Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry. Circulation Marstrand, P., Han, L., Day, S. M., Olivotto, I., Ashley, E. A., Michels, M., Pereira, A. C., Wittekind, S. G., Helms, A., Saberi, S., Jacoby, D., Ware, J. S., Colan, S. D., Semsarian, C., Ingles, J., Lakdawala, N. K., Ho, C. Y., SHaRe Investigators 2020


Background: The terminology "end-stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (herein referred to as HCM-LVSD), defined when left ventricular ejection fraction (LVEF) <50% is present. The prognosis of HCM-LVSD has reportedly been poor, but due to its relative rarity, natural history remains incompletely characterized. Methods: Data from eleven high-volume HCM specialty centers comprising the international Sarcomeric Human Cardiomyopathy Registry (SHaRe) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development. Results: From a cohort of 6,793 HCM patients, 553 (8%) met criteria for HCM-LVSD. Overall, 75% of HCM-LVSD patients experienced clinically relevant events and 35% met the composite outcome (all-cause death (n=128), cardiac transplantation (n=55) or left ventricular assist device implantation (n=9). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (Hazard Ratio (HR) 5.6 [95% Confidence Interval 2.3-13.5]), atrial fibrillation (HR 2.6 [1.7, 3.5]), LVEF <35% (HR 2.0 [1.3, 2.8]). The incidence of new HCM-LVSD was ~7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater LV cavity size (HR 1.1 [1.0-1.3] and wall thickness (HR 1.3 [1.1, 1.4]), LVEF 50-60% (HR 1.8 [1.2, 2.8]-2.8 [1.8, 4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR 2.3 [1.0, 4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR 1.5 [1.0, 2.1] and 2.5 [1.2, 5.1], respectively). Conclusions: HCM-LVSD affects approximately 8% of HCM patients. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death-equivalent with an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and in the risk for incident development of HCM-LVSD (thin filament variants).

View details for DOI 10.1161/CIRCULATIONAHA.119.044366

View details for PubMedID 32228044