What is the management of heart failure with reduced ejection fraction?

Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

Guideline-directed medical therapy (GDMT) for HFrEF should include four medication classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. 1

First-Line Pharmacological Therapy

Core Quadruple Therapy

1. Renin-Angiotensin System Inhibitors

   • First choice: Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
     • Sacubitril/valsartan: Starting dose 49/51 mg twice daily, target dose 97/103 mg twice daily 2
     • Improves mortality, reduces hospitalizations, and enhances quality of life 1
   • Alternative: ACE inhibitors or ARBs if ARNI not tolerated or contraindicated

2. Beta-Blockers

   • Evidence-based options: carvedilol, metoprolol succinate, or bisoprolol
   • Start at low dose and titrate gradually every 2 weeks
   • Target heart rate 50-70 bpm

3. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone: Indicated for NYHA Class III-IV HFrEF 3
   • Starting dose 12.5-25 mg daily
   • Monitor potassium and renal function

4. Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i)

   • Add regardless of diabetes status
   • High-quality evidence shows improved quality of life and reduced hospitalizations 1
   • Can be initiated at any point in treatment sequence

Sequencing and Titration Strategy

1. Initiation Phase

   • Start with low doses of multiple agents rather than maximum dose of one agent
   • Begin with ACEi/ARB/ARNI and beta-blocker simultaneously or within 1-2 weeks
   • Add MRA and SGLT2i within 4-6 weeks

2. Titration Phase

   • Titrate one drug at a time every 2-4 weeks 1
   • Prioritize reaching target doses of all four medication classes
   • Monitor blood pressure, heart rate, renal function, and potassium

3. Management of Low Blood Pressure

   • If systolic BP <90 mmHg with symptoms, adjust medications based on clinical profile:
     • With HR <60 bpm: Reduce beta-blocker first
     • With eGFR <30 ml/min: Reduce RAS inhibitor first
     • With K >5.0 mEq/L: Reduce MRA first 1
   • SGLT2i typically have minimal impact on blood pressure and should be continued if possible 1

Additional Therapies for Persistent Symptoms

1. Loop Diuretics

   • Essential for symptom management and volume control
   • Adjust to maintain euvolemia using lowest effective dose
   • Monitor renal function, electrolytes, and orthostatic blood pressure 1

2. Ivabradine

   • For patients in sinus rhythm with HR ≥70 bpm despite maximum tolerated beta-blocker
   • Reduces hospitalizations and improves quality of life 4

3. Hydralazine and Isosorbide Dinitrate

   • Particularly beneficial in Black patients
   • Consider for those who cannot tolerate RAS inhibitors 1

4. Intravenous Iron

   • For patients with iron deficiency
   • Improves quality of life and functional status 1

Device Therapy Considerations

1. Implantable Cardioverter-Defibrillator (ICD)

   • For primary prevention in patients with LVEF ≤35% despite optimal medical therapy
   • After at least 3 months of GDMT

2. Cardiac Resynchronization Therapy (CRT)

   • For patients with LVEF ≤35%, QRS duration ≥130 ms, and LBBB pattern
   • Improves symptoms, reduces hospitalizations, and decreases mortality

Monitoring and Follow-up

1. Regular Assessment

   • Monitor weight, symptoms, volume status
   • Check renal function and electrolytes 1-2 weeks after medication initiation or dose changes
   • Assess for medication side effects: hypotension, hyperkalemia, worsening renal function

2. Laboratory Monitoring

   • Baseline and follow-up: electrolytes, BUN/creatinine, natriuretic peptides
   • Monitor potassium closely when using MRAs

Special Considerations

1. Improved LVEF

   • Patients whose LVEF improves to >40% should continue their HFrEF treatment 1

2. Low Blood Pressure Management

   • Space out medications to reduce synergistic hypotensive effects
   • Consider physical training and compression stockings for orthostatic hypotension 1

3. Advanced HF

   • Refer to specialized HF team for patients with persistent symptoms despite optimal therapy
   • Consider advanced therapies (LVAD, transplant) for appropriate candidates 1

Common Pitfalls to Avoid

1. Underutilization of GDMT

   • Many patients receive suboptimal doses or incomplete GDMT regimens
   • Aim for target doses of all four medication classes

2. Inappropriate Medication Discontinuation

   • Continue GDMT even when symptoms improve or LVEF normalizes
   • Temporary dose reduction is preferable to discontinuation

3. Medication Interactions

   • Avoid NSAIDs due to risk of renal dysfunction and fluid retention
   • Avoid potassium supplements with MRAs unless carefully monitored

4. Neglecting Non-pharmacological Interventions

   • Sodium restriction (2-3g/day)
   • Regular exercise training
   • Weight reduction in overweight/obese patients

By implementing this comprehensive approach to HFrEF management with quadruple therapy as the cornerstone, clinicians can significantly improve mortality, reduce hospitalizations, and enhance quality of life for patients with HFrEF.