What is Heart Failure with Reduced Ejection Fraction (HFrEF)?
HFrEF is a clinical syndrome characterized by typical heart failure symptoms (dyspnea, fatigue, fluid retention) caused by structural or functional cardiac abnormalities with a left ventricular ejection fraction (LVEF) ≤40%. 1, 2
Definition and Diagnostic Criteria
HFrEF requires the presence of heart failure symptoms AND/OR signs (breathlessness, ankle swelling, fatigue, elevated jugular venous pressure, pulmonary crackles, peripheral edema) with documented LVEF ≤40% on imaging 1
Diagnosis must include elevated natriuretic peptides (BNP >35 pg/mL or NT-proBNP >125 pg/mL) AND objective evidence of cardiac dysfunction on echocardiography 2, 3
The 40% LVEF threshold distinguishes HFrEF from heart failure with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%) and heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%) 1
Clinical Presentation
Patients present primarily with dyspnea occurring at rest or with exertion, reflecting elevated left ventricular filling pressures and pulmonary congestion 2
Orthopnea and paroxysmal nocturnal dyspnea indicate advanced volume overload 2
Functional impairment due to impaired myocardial contractility of the left ventricle is the hallmark feature 2, 4
Physical examination reveals signs of congestion including elevated jugular venous pressure, pulmonary crackles, and peripheral edema 1
Pathophysiology
The underlying mechanism involves structural and/or functional cardiac abnormalities resulting in reduced cardiac output and/or elevated intracardiac pressures at rest or during stress 1
Pathological left ventricular remodeling and progressive dilatation are central to HFrEF pathogenesis, ultimately leading to adverse clinical outcomes 5
The condition involves activation of the sympathetic nervous system and renin-angiotensin-aldosterone system (RAAS), which contribute to disease progression 5
Diagnostic Imaging Findings
Echocardiography demonstrates LVEF ≤40%, ventricular dilation, and often regional wall motion abnormalities 2
Chest radiography shows cardiomegaly with pulmonary vascular congestion patterns 2
Increased left atrial volume index and increased left ventricular mass index may be present 3
Epidemiology and Burden
HFrEF represents approximately half of all heart failure cases, affecting over 64 million people globally 2, 6
The condition carries high morbidity and mortality, worse than many common cancers, with frequent hospitalizations and progressive functional decline 2
The total cost of heart failure in the US was $30.7 billion in 2012, projected to reach $69.7 billion by 2030 2, 7
Prognostic Factors
Low blood pressure in HFrEF indicates worse prognosis, though guideline-directed medical therapy attenuates this association 2
Progressive reduction in LVEF over time is a poor prognostic factor 2
Sudden death accounts for 45% of cardiovascular deaths in HFrEF patients, followed by pump failure at 26% 8
Important Clinical Distinction
HFrEF is distinguished from HFpEF not only by ejection fraction but also by treatment response—only HFrEF has therapies proven to reduce both morbidity and mortality 1
Patients with HFrEF who improve LVEF to >40% are reclassified as HFimpEF (heart failure with improved ejection fraction) but must continue HFrEF guideline-directed medical therapy to prevent relapse 3