What is the treatment for a patient with a reduced ejection fraction (EF) of 45%?

Treatment for Heart Failure with Ejection Fraction of 45%

For a patient with an ejection fraction of 45%, treatment should include SGLT2 inhibitors as first-line therapy, along with diuretics as needed for symptom management, and consideration of ACE inhibitors, ARBs, ARNi, MRAs, and evidence-based beta blockers to reduce heart failure hospitalizations and cardiovascular mortality. 1

Classification of Heart Failure with EF 45%

An ejection fraction of 45% falls within the category of Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF), which is defined as LVEF 41-49% according to the 2022 AHA/ACC/HFSA guidelines. 1

First-Line Treatment Recommendations

SGLT2 Inhibitors (Class 2a, Level B-R)

• SGLT2 inhibitors (like empagliflozin) have shown significant benefit in patients with HFmrEF
• They reduce the risk of heart failure hospitalization and cardiovascular death 1
• The EMPEROR-Preserved trial demonstrated a 21% reduction in the primary composite endpoint of cardiovascular death or HF hospitalization in patients with LVEF >40% 1

Diuretics (Class 1)

• Diuretics should be used as needed to manage fluid retention and symptoms 1
• In advanced heart failure, fluid restriction of 1.5-2 L/day is advised 1

Additional Treatment Options (Class 2b, Level B-NR)

For patients with HFmrEF, particularly those with LVEF on the lower end of the spectrum (closer to 41%), the following medications may be considered:

1. Evidence-based beta blockers used for HFrEF 1

   • Particularly beneficial for patients with a history of myocardial infarction
   • Meta-analysis showed reduced all-cause and cardiovascular mortality in patients with LVEF 40-49% in sinus rhythm 1

2. ACE inhibitors 1

   • Recommended as first-line therapy in patients with reduced LVEF (<40-45%)
   • Should be uptitrated to dosages shown effective in large clinical trials
   • Regular monitoring of renal function is essential

3. ARBs (Angiotensin Receptor Blockers) 1

   • Alternative for patients who cannot tolerate ACE inhibitors

4. ARNi (Angiotensin Receptor-Neprilysin Inhibitor) 1, 2

   • Sacubitril-valsartan has shown benefit in patients with LVEF 45-57% in subgroup analyses
   • Improves natriuresis and decreases NT-proBNP levels

5. MRAs (Mineralocorticoid Receptor Antagonists) 1

   • May be beneficial based on post-hoc analyses of HFrEF trials

Lifestyle Modifications

• Exercise training is encouraged in stable patients 1
• Sodium restriction is important, particularly in advanced heart failure 1
• Moderate alcohol intake is permitted (one beer or 1-2 glasses of wine/day) unless contraindicated 1

Medications to Avoid

The following medications should be used with caution or avoided in heart failure patients:

• NSAIDs and COX-2 inhibitors
• Class I antiarrhythmic agents
• Calcium antagonists (verapamil, diltiazem, and short-acting dihydropyridines)
• Tricyclic antidepressants
• Corticosteroids
• Lithium 1

Follow-up Considerations

• Patients with HFmrEF should have repeat evaluation of LVEF to determine the trajectory of their disease process 1
• If LVEF improves to >50%, it's unclear whether to treat as HFpEF or continue HFmrEF treatment 1
• If LVEF worsens to <40%, treatment should follow HFrEF guidelines

Important Caveats

• There are no prospective randomized controlled trials specifically for HFmrEF patients
• Treatment recommendations are based on post-hoc or subset analyses from previous heart failure trials
• LVEF is a spectrum, and patients with values closer to 40% may respond more similarly to HFrEF patients
• Discontinuation of therapy (particularly ARNi) after improvement has been associated with deterioration of LVEF and functional class 3