Abstract 16910: Complex Heart Failure Phenotypes Differ in Response to Medical Therapy and Exercise Training

Abstract

Background: Patients with heart failure (HF) are heterogeneous with multiple complex phenotypes across the ejection fraction (EF) spectrum. Phenotype-specific response to various treatments have not been well-described. Hypothesis: Clinical response to specific interventions will vary according to HF phenotype. Methods: Using latent class analysis, six cluster-based HF phenotypes across the EF spectrum were previously identified using patient data from 2130 patients enrolled in HF-ACTION (LVEF ≤ 35%) and 1767 patients enrolled from the Americas in TOPCAT (LVEF ≥ 45%) based on age, sex, race, CAD, BMI, hyperlipidemia, hypertension, diabetes mellitus, atrial fibrillation, COPD, anemia, and renal function, but not LVEF. Response to aerobic exercise training vs. usual care (HF-ACTION) and spironolactone vs. placebo (TOPCAT) were quantified by phenotype. The primary outcome was a composite of cardiovascular mortality (CVM) or HF hospitalization (HFH). Secondary outcomes included CVM, HFH, and all-cause mortality (ACM). Change in peak VO2 at 3 and 12 months were also analyzed in HF-ACTION. Results: Of the established phenotypes, the phenotype composed of elderly non-ischemic patients as well as the non-white/non-ischemic/hypertensive phenotype experienced improvement in combined CVM and HFH, ACM and exercise capacity (28% vs 38%, HR: 0.66 [0.46-0.94], 8% vs 16% HR: 0.49 [0.27-0.91], change in VO2: 1.06±3.01 vs 0.04±3.14, p<0.05). Elderly patients with non-ischemic HFrEF enrolled in HF-ACTION randomized to therapeutic exercise program demonstrated significantly improved exercise capacity compared to usual care (change in VO2: 1.45±2.82 vs -0.09±2.49 and 1.25±3.18 vs 0.66±3.64 respectively, p<0.05). Elderly non-ischemic patients treated with spironolactone in TOPCAT had a lower risk of the primary outcome CVM and HFH (20% vs 27%, HR: 0.67 [0.48-0.95]), driven mostly by reduced CVM (9% vs 17%, HR: 0.52 [0.32-0.84]). Conclusions: Response to varied treatments such as exercise training and spironolactone varies among complex HF phenotypes in both HFpEF and HFrEF. Additional investigation which further characterizes phenotype-specific treatments may help select specific interventions most likely to benefit specific phenotypes.