Abstract
Contemporary clinical trials in heart failure (HF) enroll patients largely based on acuity of presentation, left ventricular ejection fraction (EF), and functional status. These trial programs variably employ certain enrichment criteria such as prior hospitalization for HF or elevated natriuretic peptide levels to reaffirm the HF diagnosis and identify patients at higher risk of clinical events. This approach has yielded heterogenous patient cohorts with distinct biological substrates and varying levels of clinical risk. Indeed, patients with HF have variable clinical trajectories that often depend on comorbidities, congestion, hemodynamics, and underlying etiology. In the past decade, progress has been made in identifying imaging- and biomarker-based signatures of HF and the development of risk scores for prognosis. Although these parameters have advanced the promise of precision-based therapeutic approaches, such tools have been variably incorporated alongside traditional eligibility criteria in contemporary trial design. Over the past 3 decades, since the initial publication of the CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) trial in 1987 (1), enrollment criteria have remained relatively stagnant and have not evolved in parallel with progress in defining HF as an entity. Similarly, patients early or late in their HF journey are loosely defined and have variable approaches to care. We explore complexities in the interpretation and application of traditional HF-related nomenclature in clinical practice and in clinical trials (Table 1).