Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry

Background: The term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized. Methods: Data from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) 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 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD 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% CI, 2.3-13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7-3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 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 left ventricular cavity size (HR, 1.1 [95% CI, 1.0-1.3] and wall thickness (HR, 1.3 [95% CI, 1.1-1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]-2.8 [95% CI, 1.8-4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0-4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0-2.1] and 2.5 [95% CI, 1.2-5.1], respectively). Conclusions: HCM-LVSD affects ≈8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent 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 the risk for incident development of HCM-LVSD (thin filament variants)

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. Methods: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy 70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679