What are the management strategies for Heart Failure with Reduced Ejection Fraction (HFrEF)?

From the Guidelines

Heart failure with reduced ejection fraction (HFrEF) management should prioritize guideline-directed medical therapy (GDMT) with four medication classes: ACE inhibitors/ARNIs, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors, as recommended by the 2022 AHA/ACC/HFSA guideline 1. The cornerstone of HFrEF treatment includes these four medication classes, which work synergistically to reduce mortality, hospitalizations, and symptoms by addressing neurohormonal activation, reducing cardiac remodeling, and improving hemodynamics.

• Start with an ACE inhibitor like lisinopril (10-40 mg daily) or consider an ARNI such as sacubitril/valsartan (24/26 mg to 97/103 mg twice daily) for patients with persistent symptoms, as recommended by the 2016 ESC guidelines 1.
• Beta-blockers such as carvedilol (3.125-25 mg twice daily), metoprolol succinate (12.5-200 mg daily), or bisoprolol (1.25-10 mg daily) should be initiated at low doses and gradually uptitrated, as recommended by the 2009 ACC/AHA guidelines 1.
• Add an MRA like spironolactone (25-50 mg daily) or eplerenone (25-50 mg daily) for patients with LVEF ≤35% and NYHA class II-IV symptoms.
• SGLT2 inhibitors such as dapagliflozin (10 mg daily) or empagliflozin (10 mg daily) should be added regardless of diabetes status, as recommended by the 2022 AHA/ACC/HFSA guideline 1.
• Loop diuretics like furosemide (20-80 mg daily or twice daily) should be used for volume management. Lifestyle modifications including sodium restriction (<2-3g daily), fluid restriction if needed, regular physical activity, smoking cessation, and limiting alcohol consumption are essential components of management.
• Regular monitoring of renal function, electrolytes, and symptoms is necessary to optimize therapy and prevent complications, as recommended by the 2022 AHA/ACC/HFSA guideline 1.

From the FDA Drug Label

Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction.

In trials in patients treated with digitalis and diuretics, treatment with enalapril resulted in decreased systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure and heart size, and increased cardiac output and exercise tolerance.

HFrEF Management:

• Sacubitril and valsartan tablets are indicated for adult patients with chronic heart failure and reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure 2.
• Enalapril has been shown to decrease systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure, and heart size, and increase cardiac output and exercise tolerance in patients with heart failure 3.
• The use of enalapril was associated with an 11 percent reduction in all-cause mortality and a 30 percent reduction in hospitalization for heart failure in a multicenter, placebo-controlled clinical trial 3.

From the Research

HFrEF Management Overview

• Heart failure with reduced ejection fraction (HFrEF) is a complex and progressive clinical condition characterized by dyspnea and functional impairment 4.
• Basic treatment strategies for HFrEF include diuretics for symptom relief and quadruple therapy (Angiotensin receptor blocker/neprilysin inhibitors, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors) for reduction in hospitalizations, all-cause mortality, and cardiovascular mortality 4.

Medication Management

• The initiation or optimization of the four pillars of HFrEF therapy (beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 inhibitors) during hospitalization for acute decompensation is feasible and well-tolerated 5.
• Sacubitril-valsartan was associated with lower risks of all-cause mortality or all-cause hospitalization compared with ACE/ARB in a heterogeneous cohort of patients with systolic HF 6.
• ACE inhibitors are part of first-line treatment for reduced ejection fraction heart failure (HFrEF) and have been shown to reduce all-cause mortality, with a number needed to treat (NNT) to avoid one death at 6 months of 50 (33-107) 7.

Device Therapies

• Specific groups of patients with HFrEF may be candidates for various device therapies such as implanted cardioverter defibrillators, cardiac resynchronization therapy, and trans catheter mitral valve repair 4.
• The use of implantable cardioverter-defibrillator therapy in patients with heart failure with improved ejection fraction (HFimpEF) is a topic of ongoing research, with questions remaining about the safety of discontinuing this therapy in select patients 8.

Special Considerations

• Renal function should be carefully considered when optimizing HFrEF therapy, as changes in serum creatinine levels can occur 5.
• The use of certain medications, such as MRAs and SGLT2 inhibitors, may need to be adjusted in specific patient subgroups 5.
• Emerging clinical experience suggests that heart failure arising from acute etiologies that fully resolve along with complete LVEF recovery may have a favorable prognosis with lower risk of relapse 8.