What is the initial treatment for a patient with Heart Failure with Reduced Ejection Fraction (HFrEF) and a Left Ventricular Ejection Fraction (LVEF) of 35, according to American Heart Association (AHA) guidelines?

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Last updated: September 24, 2025View editorial policy

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Initial Treatment for HFrEF with LVEF of 35% According to AHA Guidelines

For patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and LVEF of 35%, the initial treatment should include triple neurohormonal blockade with an ACE inhibitor (or ARB if ACE inhibitor intolerant), beta-blocker, and mineralocorticoid receptor antagonist, along with diuretics for symptom relief. 1

First-Line Medications

1. ACE Inhibitors

  • Class I, Level A recommendation 1
  • Start with low dose and titrate up as tolerated
  • Examples: lisinopril, enalapril, ramipril
  • Contraindications: history of angioedema, bilateral renal artery stenosis, pregnancy
  • Monitor: renal function, potassium levels 1-2 weeks after initiation

2. Beta Blockers

  • Class I, Level A recommendation 1
  • Use only the three beta blockers proven to reduce mortality:
    • Bisoprolol
    • Carvedilol
    • Sustained-release metoprolol succinate
  • Start at low dose and titrate gradually every 2 weeks as tolerated
  • Target: maximum tolerated dose shown effective in clinical trials
  • Can be safely initiated before hospital discharge if patient is clinically stable 1

3. Mineralocorticoid Receptor Antagonists (MRAs)

  • Class I, Level A recommendation for NYHA class II-IV with LVEF ≤35% 1
  • Options: spironolactone (12.5-25 mg daily) or eplerenone
  • Monitoring requirements:
    • Serum creatinine should be ≤2.5 mg/dL in men or ≤2.0 mg/dL in women
    • Potassium should be <5.0 mEq/L
    • Regular monitoring of renal function and electrolytes

4. Diuretics

  • Class I, Level C recommendation for symptom relief in patients with fluid retention 1
  • Loop diuretics (furosemide, torsemide, bumetanide) are first-line
  • Initial dosing:
    • Furosemide: 20-40 mg once or twice daily
    • Bumetanide: 0.5-1.0 mg once or twice daily
    • Torsemide: 10-20 mg once daily
  • Adjust dose based on symptoms and volume status

Additional Therapies to Consider

1. Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

  • Consider as replacement for ACE inhibitor in patients who remain symptomatic despite optimal therapy 2
  • Requires 36-hour washout period when switching from ACE inhibitor
  • Contraindicated in patients with history of angioedema

2. Ivabradine

  • Consider for persistently symptomatic patients with:
    • Sinus rhythm
    • Heart rate ≥70 beats/min despite maximally tolerated beta-blocker dose
    • LVEF ≤35% 1

3. Device Therapy

  • ICD for primary prevention is indicated for patients with:

    • LVEF ≤35%
    • NYHA class II-III symptoms on guideline-directed medical therapy 1
    • Expected survival >1 year
  • Cardiac Resynchronization Therapy (CRT) is indicated for patients with:

    • NYHA class II-IV symptoms
    • LVEF ≤35%
    • Left bundle branch block with QRS ≥150 ms 1

Treatment Algorithm

  1. Initial Visit:

    • Start ACE inhibitor (or ARB if intolerant) and beta-blocker simultaneously
    • Add diuretics if fluid retention is present
    • Educate patient on salt restriction and self-monitoring
  2. Follow-up at 2 weeks:

    • Check renal function and electrolytes
    • Titrate medications as tolerated
    • Add MRA if patient has LVEF ≤35% and remains symptomatic
  3. Subsequent visits (every 2-4 weeks):

    • Continue uptitration of medications to target doses
    • Reassess symptoms and volume status
    • Adjust diuretics based on symptoms and weight changes
  4. After optimal medical therapy:

    • Evaluate for device therapy (ICD, CRT) based on criteria
    • Consider ARNI in patients who remain symptomatic

Common Pitfalls and Caveats

  • Avoid calcium channel blockers with negative inotropic effects in HFrEF patients 1
  • Avoid NSAIDs as they can worsen renal function and cause fluid retention
  • Do not combine ACE inhibitors, ARBs, and aldosterone antagonists due to risk of hyperkalemia 1
  • Do not abruptly withdraw beta-blocker therapy as it can lead to clinical deterioration 1
  • Monitor potassium and renal function closely when using MRAs, especially in patients with diabetes or renal impairment

By following this comprehensive approach to HFrEF management with LVEF of 35%, clinicians can significantly reduce mortality, hospitalizations, and improve quality of life in these patients.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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