Identifying biomarker profiles within each phenogroup may suggest phenogroup-specific mechanisms that can be targeted for therapeutic purposes. However, little data exist regarding differences in underlying biologic processes or response to therapies between HFpEF phenogroups. These studies demonstrated that HFpEF phenogroups may be linked to important differences in disease prognosis ( 4, 5). Accordingly, previous studies have proposed that several different phenotypes of HFpEF exist, ( 4) encompassing relatively discrete subgroups (“phenogroups”) with distinct clinical features ( 5). Patients with HFpEF also have highly variable underlying cardiac structural and functional abnormalities ( 3). A wide range of clinical risk factors for HFpEF have been identified, including older age, female sex, history of hypertension, diabetes, obesity, atrial fibrillation (AF), and coronary artery disease, among others ( 1, 2). This heterogeneity may contribute to the difficulty identifying effective treatments for HFpEF. HFpEF likely represents a heterogeneous group of disease processes. Although several pharmacologic therapies are known to improve patient outcomes in HFrEF, no pharmacologic therapies have been clearly demonstrated to reduce adverse events in HFpEF. Heart failure with preserved ejection fraction (HFpEF), which affects approximately half of patients with heart failure, results in substantial morbidity, mortality, and impaired quality of life. Results were similar after excluding participants from Eastern Europe. Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR 0.75, 95% CI 0.59–0.95 P for interaction=0.016).
Compared to phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (HR=3.44 95% CI=2.79–4.24) phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR=2.36 95% 0=1.89–2.95 phenotype 3 HR=2.26, 95% 0=1.77–2.87). Phenogroup 3 (n=899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha-mediated inflammation, liver fibrosis, and tissue remodeling. Phenogroup 2 (n=1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 1 (n=1,214) exhibited younger age, higher smoking prevalence, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness.