Diastolic Dysfunction Predicts Cardiorespiratory Fitness and Clinical Outcomes in Hypertrophic Cardiomyopathy

Background. Echocardiographic indices of diastolic dysfunction are routinely obtained in hypertrophic cardiomyopathy (HCM), but their relationships with cardiorespiratory fitness and long-term clinical outcomes remain poorly defined. Objectives. This study therefore sought to determine the extent to which E/e', left atrial volume index (LAVi), and peak tricuspid regurgitation velocity (TRVmax) relate to peak oxygen uptake, ventilatory efficiency, their longitudinal trajectories, and clinical outcomes in HCM. Methods. We retrospectively studied patients with HCM who completed cardiopulmonary exercise testing within 7 days of resting echocardiography. Each diastolic index was related to percent-predicted peak oxygen uptake (VO2), ventilatory efficiency (VE/VCO2 slope), their serial trajectories, and a composite of heart failure hospitalization, transplantation, or death. Results. Among 441 patients with HCM (mean age 49 +/- 16 years; 66% men), each SD higher E/e', LAVi, and TRVmax was independently associated with lower peak VO2 (-6.0, -3.6, and -6.3 percentage points of predicted) and higher VE/VCO2 slope (+0.9, +1.0, and +2.5; all P <= 0.045), nonlinearly for E/e' with peak VO2 and LAVi with VE/VCO2 slope. On serial testing, only LAVi predicted progressively worsening VE/VCO2 slope (+0.4/yr/SD; 95% CI: 0.13-0.68; P = 0.005). Over a median of 4.8 years, 118 of 436 patients (27.1%) reached the composite endpoint, for which LAVi was the strongest echocardiographic predictor (adjusted HR: 1.68/SD; 95% CI: 1.40-2.03). Conclusions. In HCM, resting diastolic indices were associated with cardiorespiratory fitness, and higher LAVi was independently associated with a steeper rise in VE/VCO2 slope and heart failure events. Resting diastolic phenotyping may complement exercise testing.