Heart Failure With Reduced Ejection Fraction (HFrEF)

Background

• Heart failure with reduced ejection fraction (HFrEF) or systolic heart failure results in decreased heart pump function (left ventricular ejection fraction ≤ 40%) which is associated with characteristic signs and symptoms such as dyspnea, edema, fatigue, and/or impaired exercise tolerance.
• Heart failure typically classified by New York Heart Association (NYHA) I-IV functional classification or Heart Failure Society of America/European Society of Cardiology/Japanese Heart Failure Society (HFSA/ESC/JHFS) universal definition and classification of heart failure A-D staging.
• There is a higher prevalence with increasing age (2%-3% > 45 years old to about 14% at 80-86 years old) and there is an increased risk of developing heart failure among patients with coronary artery disease, diabetes, hypertension, metabolic syndrome, and impaired renal function.
• Common causes of HFrEF include coronary artery disease, dilated cardiomyopathy, valvular heart disease (both related to pressure overload and volume overload), and hypertension.
• Selected blood and imaging studies may help identify asymptomatic individuals at risk for developing symptomatic HF, and lifestyle changes and medications may help prevent progression of asymptomatic to symptomatic HF.
• Prognosis or risk of mortality due to HFrEF can be estimated using validated multivariable risk scores.

Evaluation

• Suspect heart failure in patients with a history of dyspnea with exertion or at rest, or other symptoms of heart failure including fatigue, abdominal distention, lower extremity swelling, orthopnea, or paroxysmal nocturnal dyspnea. Signs may include evidence of volume overload (elevated jugular venous pressure, peripheral edema, or rales) or diminished perfusion (cold extremities).
• Differential diagnosis for heart failure includes other causes of dyspnea such as asthma, chronic obstructive pulmonary disease, sleep apnea, pulmonary embolism, and non-cardiogenic pulmonary edema.
• Consider the use of clinical prediction rules in making the diagnosis of heart failure.
• Obtain the following initial tests in a patient with suspected heart failure (Strong recommendation):
  • 12-lead electrocardiogram (ECG)
  • chest x-ray
  • blood tests including complete blood count, serum chemistries, lipid profile, liver function tests, iron studies, and thyroid-stimulating hormone
  • B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)
  • transthoracic echocardiography (TTE) to assess systolic and diastolic function (including evaluation of left ventricular ejection fraction to confirm reduced ejection fraction), myocardial wall thickness, and valve function
• In patients for whom echocardiography is insufficient, perform additional imaging such as cardiac magnetic resonance (CMR), radionuclide imaging, or cardiac computed tomography (CT) to assess left ventricular ejection fraction (Strong recommendation).
• Other testing may include:
  • coronary angiography in patients eligible for revascularization with symptomatic ventricular arrhythmias or angina despite pharmacological therapy (Strong recommendation).
  • noninvasive stress imaging to detect myocardial ischemia and guide coronary revascularization in patients with coronary artery disease who are coronary revascularization candidates (Weak recommendation).
  • endomyocardial biopsy for selected patients where a specific cause of heart failure is suspected and diagnosis would influence therapy (such as myocarditis or amyloidosis) (Weak recommendation).
  • invasive hemodynamic monitoring for guiding management in heart failure patients with persistent or worsening diagnostic parameters, symptoms, signs, and in whom hemodynamics are uncertain (AHA/ACC/HFSA Class 2a, Level C-EO)
• Consider the use of a wireless implantable hemodynamic monitoring device in conjunction with a heart failure specialist in selected patients with HFrEF who remain symptomatic despite standard medical therapy.
• Consider performing 6-minute walk test or cardiopulmonary exercise testing (CPET) to assess functional capacity in ambulatory patients with heart failure (Weak recommendation); the New York Heart Association (NYHA) functional classification system may be used for grading degree of functional limitation from patient report of symptoms during activity and exercise testing.

Management

• For treatment of patients with:
  • acute decompensated heart failure, see Acute Heart Failure or Cardiogenic Shock
  • diastolic heart failure, see Heart Failure With Preserved Ejection Fraction (HFpEF)
  • mildly reduced ejection fraction, see Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF)
  • refractory or end-stage heart failure, see End-stage (Refractory) Heart Failure (and refer to heart failure specialist care [Strong recommendation])
• For all patients with symptomatic HFrEF and without contraindications, prescribe the following 4 guideline-directed medical therapy (GDMT) medication classes:
  • renin-angiotensin system (RAS) inhibitor which includes an angiotensin receptor-neprilysin inhibitor (ARNI) (preferred), an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin receptor blockers (ARB) (Strong recommendation).
  • beta blocker (Strong recommendation), using bisoprolol, carvedilol, or sustained-release metoprolol succinate.
  • mineralocorticoid receptor antagonist (MRA) (Strong recommendation), using either eplerenone or spironolactone (if estimated glomerular filtration rate (eGFR) is > 30 mL/min/1.73 m² and serum potassium is < 5 mEq/L).
  • sodium-glucose cotransporter-2 (SGLT2) inhibitor (Strong recommendation), using either
    • dapagliflozin (initiation not recommended in patients with estimated glomerular filtration rate (eGFR) < 25 mL/minute/1.73 m²)
    • empagliflozin (no dosing information available for patients with estimated GFR < 20 mL/minute/1.73 m²)

Table 1. HFrEF Selected Medications and Dosing

• Continue GDMT to prevent heart failure relapse and left ventricular dysfunction in patients with heart failure with improved ejection fraction (HFimpEF) who may become asymptomatic following treatment (Strong recommendation).
  
• For patients with symptomatic heart failure and signs of volume overload, prescribe loop diuretics (Strong recommendation).
• For selected patients with HFrEF requiring further management:
  • For Black patients with New York Heart Association (NYHA) class III-IV heart failure on optimal heart failure therapy, prescribe hydralazine plus isosorbide dinitrate (Strong recommendation).
  • Consider digoxin if the patient has symptomatic HFrEF in spite of (or if unable to tolerate) guideline-directed medical therapy, with the goal to reduce heart failure-related hospitalizations (Weak recommendation).
  • Consider omega-3 polyunsaturated fatty acid (PUFA) supplementation as adjunctive therapy to decrease mortality and cardiovascular hospitalizations in patients with heart failure class II to IV symptoms (Weak recommendation).
  • Consider using ivabradine in symptomatic patients with HFrEF, in sinus rhythm, ejection fraction ≤ 35%, and heart rate ≥ 70 beats/minute who are receiving guideline-directed medical therapy (including beta blocker at maximum tolerated dose) (Weak recommendation).
  • Consider vericiguat in selected high-risk patients already on guideline-directed medical therapy with recent worsening of heart failure to reduce heart failure hospitalization and cardiovascular death (Weak recommendation).
• Consider anticoagulant therapy, statins, and IV iron supplementation as appropriate for associated comorbidities, but not as specific treatment for heart failure alone (Weak recommendation).
• Avoid nondihydropyridine calcium channel blockers, dronedarone and class IC antiarrhythmic drugs, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin and alogliptin), and nutritional supplements, hormonal therapies, and vitamins (unless to correct specific deficiencies) (Strong recommendation).
• Advise exercise training or regular physical activity to improve functional status, exercise performance, and quality of life in able patients (Strong recommendation).
• Refer patients with high-risk heart failure (especially those with recurrent hospitalizations for HFrEF) to multidisciplinary heart failure disease management programs to decrease hospitalization risk (Strong recommendation).
• Refer selected symptomatic patients with nonischemic dilated cardiomyopathy or ischemic heart disease for implantable cardioverter-defibrillator (ICD) who are at least 40 days post-myocardial infarction with left ventricular ejection fraction ≤ 35% (and taking guideline-directed medical therapy) or who have genetic arrhythmogenic cardiomyopathy with high-risk features of sudden death to reduce risk of sudden cardiac death.
• Refer selected symptomatic patients for cardiac resynchronization therapy (CRT) if the patient is in sinus rhythm with a QRS interval > 150 milliseconds. See Cardiac Resynchronization Therapy (CRT) topic for additional details.
• For patients with advanced heart failure being considered for cardiac transplantation, see Selection and Timing of Patients for Cardiac Transplantation and Mechanical Circulatory Support for Heart Failure.