Heart failure with reduced ejection fraction


  • Typical symptoms: dyspnea, orthopnea, paroxysmal nocturnal dyspnea, fatigue, reduced exercise tolerance, ankle swelling
  • Less typical symptoms: cough, abdominal distension, wheeze, abdominal bloating, early satiety, bendopnea
  • More specific signs: elevated jugular venous pressure, positive abdominojugular reflux, S3 (gallop rhythm), laterally displaced apical impulse
  • Less specific signs: weight gain, lung rales, peripheral edema, ascites, cool and/or mottled extremities, narrow proportional pulse pressure (pulse pressure: systolic blood pressure ratio ≤ 0.25), murmur of valvular regurgitation or stenosis, weight loss and cachexia (advanced heart failure)
  • Symptom severity is graded according to the New York Heart Association (NYHA) functional class designations
    • class I: no limitation in normal physical activity
    • class II: mild symptoms only during normal activity
    • class III: marked symptoms during daily activity, comfortable only at rest
    • class IV: severe limitations and symptoms even at rest
  • Patients with more signs of congestion (jugular venous distension, edema, lung rales, and S3 gallop) are at higher risk of cardiovascular death or HF hospitalization independent of symptoms, natriuretic peptides, and validated risk scores
  • As a result of compensatory upregulation in lymphatic drainage, patients with chronic HFrEF may lack lung rales or peripheral edema, even when pulmonary capillary wedge pressure is elevated
  • approximately half of HFrEF cases are of ischemic etiology


  • If a diagnosis of HFrEF is suspected, initial testing includes measurement of natriuretic peptides, electrocardiography, and chest x-ray
  • Signs of congestion on chest x-ray are sensitive (81%) for the diagnosis of acute heart failure
  • Individual signs tend to be more specific than sensitive
    • cardiomegaly is sensitive for heart failure (64%-79%)
    • peribronchial cuffing, Kerley B lines, alveolar edema, bilateral pleural effusions have 95% specificity or greater
  • 1 in 5 patients presenting with AHF has no signs of congestion on chest x-ray
  • among ambulatory patients with advanced HF with significantly elevated pulmonary capillary wedge pressure (mean [SD] 33 [6] mm Hg [normal reference level, <12 mm Hg]), 27% of patients had no radiographic evidence of pulmonary congestion, and interstitial or alveolar edema was present in only 32% of patients
  • Lab: BNP/NT-proBNP, complete blood count, basic metabolic panel, liver function tests, iron studies, thyroid function tests, hemoglobin A1c, lipid panel
  • Imaging: chest x-ray, TTE to confirm the diagnosis by identifying the presence of left ventricular systolic dysfunction with LVEF of 40% or less, coronary angiography or coronary CT angiography if low pretest probability, consider cardiac MRI, positron emission tomography scan, or 99m technetium pyrophosphate scan
  • Others: ECG, consider right heart catheterization, consider endomyocardial biopsy


  • Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020;324(5):488-504. doi:10.1001/jama.2020.10262