Comprehensive insights into heart failure with mildly reduced ejection fraction: A critical review

This review explores the enigmatic heart failure (HF) subtype known as HF with mildly reduced ejection fraction (HFmrEF), which constitutes a significant percentage of HF cases yet remains inadequately understood. Characterized by an ejection fraction (EF) between 41% and 49%, HFmrEF poses unique challenges in diagnosis and treatment due to its intermediary nature between HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF). Epidemiological data reveal variable prevalence rates influenced by demographic and regional factors, with a higher incidence associated with aging and cardiovascular comorbidities such as hypertension and diabetes. Pathophysiological insights suggest a blend of systolic and diastolic dysfunction, myocardial fibrosis, and inflammatory processes that differentiate HFmrEF from other HF categories. Diagnostic approaches currently rely on echocardiography and biomarkers such as N-terminal pro-brain natriuretic peptide, but there is a need for more precise tools. Treatment largely extrapolates from HFrEF and HFpEF protocols, yet specific evidence for HFmrEF is sparse, underscoring the necessity for targeted clinical trials. Patient outcomes, falling between those of HFrEF and HFpEF, further highlight the need for individualized management strategies. This review underscores the urgency of dedicated research to refine diagnostic criteria, optimize therapeutic regimens, and ultimately improve patient care for those with HFmrEF. Future research must focus on tailored treatments, pathophysiological clarity, and identifying specific biomarkers to advance our understanding and management of this complex condition.