What are the management parameters for patients with heart failure and an ejection fraction (EF) of 40% or less?

Management of Heart Failure with Ejection Fraction ≤40%

Patients with heart failure and an ejection fraction (EF) of 40% or less should be treated with a comprehensive medication regimen including beta-blockers, ACE inhibitors/ARBs, mineralocorticoid receptor antagonists, SGLT2 inhibitors, and diuretics as needed, along with consideration for device therapy based on specific criteria. 1

Pharmacological Management

First-Line Medications

• Beta-blockers should be considered for all patients with LVEF <50% to improve symptoms and reduce the risks of heart failure hospitalization and premature death 1
• ACE inhibitors (or ARBs if ACE inhibitors not tolerated) should be considered for patients without left ventricular outflow tract obstruction (LVOTO) who have LVEF <50% to reduce the risks of heart failure hospitalization and premature death 1, 2
• Low-dose loop diuretics should be considered for symptomatic patients in NYHA functional Class II–IV with LVEF <50% to improve symptoms and reduce the risk of heart failure hospitalization 1
• Mineralocorticoid receptor antagonists (MRAs) should be considered for all patients with persisting symptoms (NYHA functional Class II–IV) and LVEF <50% despite treatment with an ACE inhibitor and a beta-blocker, to reduce the risks of heart failure hospitalization and premature death 1
• SGLT2 inhibitors can be beneficial in decreasing heart failure hospitalizations and cardiovascular mortality in patients with reduced ejection fraction 1

Advanced Therapy Options

• Angiotensin receptor-neprilysin inhibitors (ARNi) like sacubitril/valsartan should be considered instead of ACE inhibitors in patients with chronic symptomatic HFrEF, as they provide high economic value and improved outcomes 1, 3
• Low-dose digoxin may be considered for patients without LVOTO who are in NYHA functional Class II–IV with EF <50% and permanent atrial fibrillation to control heart rate response 1
• For patients self-identified as African American with NYHA class III to IV HFrEF receiving optimal medical therapy, the combination of hydralazine and isosorbide dinitrate provides high economic value 1

Device Therapy

• Implantable cardioverter-defibrillator (ICD) provides high economic value in the primary prevention of sudden cardiac death, particularly when the patient's risk of ventricular arrhythmia is high and risk of non-arrhythmic death is low 1
• Cardiac resynchronization therapy (CRT) implantation provides high economic value for patients with LVEF ≤35%, sinus rhythm, left bundle branch block with QRS duration ≥150 ms, and NYHA class II-IV symptoms on guideline-directed medical therapy 1

Medications to Avoid

• Calcium channel blockers, specifically verapamil, diltiazem, and short-acting dihydropyridines should be avoided due to their negative inotropic effects 4
• Class I antiarrhythmic agents should be avoided as they can worsen heart failure 4
• NSAIDs and COX-2 inhibitors should be avoided as they cause sodium and water retention 4
• Tricyclic antidepressants should be used with caution or avoided due to potential cardiac effects 4

Lifestyle Modifications

• Moderate alcohol intake is generally permitted unless the patient has alcoholic cardiomyopathy 4
• Fluid restriction of 1.5-2 L/day is advised for patients with advanced heart failure 4
• Sodium restriction is more important in advanced heart failure than in mild cases 4
• Exercise training programs are encouraged for stable patients in NYHA class II-III 4

Special Considerations

Heart Failure with Improved EF (HFimpEF)

• Patients with HFrEF who improve their LVEF to >40% are considered to have HFimpEF 1
• In patients with HFimpEF after treatment, guideline-directed medical therapy should be continued to prevent relapse of heart failure and left ventricular dysfunction, even in patients who may become asymptomatic 1

Monitoring and Follow-up

• Regular monitoring of renal function is essential when taking ACE inhibitors, particularly when dose is increased or when other medications affecting renal function are added 4
• Withdrawal of ACE inhibitors/ARBs during heart failure hospitalization is associated with higher rates of post-discharge mortality and readmission, even after adjustment for severity of illness 5

Important Caveats

• The threshold for considering therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors is an EF of <50% because of the preservation of cavity size in patients with advanced systolic failure 1
• Relatively small left ventricular volumes mean that some patients may be unable to tolerate high doses of vasodilators and diuretics 1
• Combination of ACE inhibitors and ARBs is not recommended as it has not been associated with additional benefit over either one alone and may potentially be harmful 2