Defining the Phenotypes for Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) imposes a significant burden on society and healthcare. The lack in efficacious therapies is likely due to the significant heterogeneity of HFpEF. In this review, we define various phenotypes based on underlying comorbidities or etiologies, discuss phenotypes arrived at by novel methods, and explore therapeutic targets.

A few studies have used machine learning methods to uncover sub-phenotypes within HFpEF in an unbiased manner based on clinical features, echocardiographic findings, and biomarker levels. We synthesized the literature and propose three broad phenotypes: (1) young, with few comorbidities, usually obese and with low natriuretic peptide levels, (2) obese with substantive cardiometabolic burden and comorbidities and impaired ventricular relaxation, (3) old, multimorbid, with high rates of atrial fibrillation, renal and coronary artery disease, chronic obstructive pulmonary disease, and left ventricular hypertrophy. We also propose potential therapeutic strategies for these phenotypes.