Abstract 15391: The Natural History of Asymptomatic and Mildly Symptomatic Obstructive Hypertrophic Cardiomyopathy: Insights From the Share Registry

Abstract

Background: Contemporary studies are needed to determine the natural history of asymptomatic and mildly symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM). Methods: Patients with HCM, peak left ventricular outflow tract (LVOT) gradient ≥30 mm Hg (at rest, post-Valsalva, or exercise) and baseline NYHA I-II symptoms were identified using the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe). Patients with prior atrial fibrillation (AF) or septal reduction therapies (SRT) were excluded. Incident outcomes, including the composite of NYHA III-IV symptoms, AF or SRT, were related to LVOT using Kaplan-Meier analysis (LVOT tertiles) and Cox proportion hazard models, controlling for age, sex, race, proband status, sarcomere status, hypertension and left atrial diameter. Results: At baseline, the 1048 patients who met inclusion criteria were 52.0 ± 16.1 yrs, 48.9% female, 34.9% sarcomere mutation +, with mean LVOT gradient 72 ± 39mm Hg. Over 8.6 years follow up (IQR 2.3, 13.6), progression to the composite endpoint ocurred in 530 (50.6%) and 92 (8.8%) died. Patients in the highest tertile of LVOT gradient (>84 mm Hg) were at increased risk of the composite endpoint (Figure). Every 10 mm Hg increase in LVOT gradient was associated with increased risk of incident NYHA III-IV HF (HR 1.04, 95% CI 1.00, 1.08, p=0.04), SRT (HR 1.07, 95% CI 1.04, 1.09, p<0.001) and the composite endpoint (HR 1.03, 95% CI 1.01, 1.06, p=0.003), but not incident AF (HR 1.02, p=0.39) or death (HR 0.99, p=0.3). Older age (HR 1.01, 95% CI 1.00-1.03, p=0.03), black race (HR 1.73, 95% CI 1.11-2.69, p=0.02) and sarcomere mutations (HR 1.27, 95% CI 1.02-1.59, p=0.03) were also associated with increased risk of the composite endpoint. Conclusions: In oHCM patients with NYHA I-II symptoms, the LVOT gradient appears to predict worsening symptoms and need for SRT, but not AF or overall survival. These findings have implications for refining management strategies for oHCM.