What are the recommended treatments for managing heart failure?

Heart Failure Management

Foundational Quadruple Therapy for HFrEF

All patients with heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%) should be initiated on four medication classes simultaneously or sequentially to reduce mortality and hospitalizations. 1

The Four Pillars of HFrEF Treatment

1. Renin-Angiotensin System Inhibition

   • ARNi (sacubitril/valsartan) is the preferred first-line agent for NYHA class II-III symptoms to reduce morbidity and mortality 1
   • Start at 49/51 mg twice daily (or 24/26 mg twice daily in high-risk patients with severe renal impairment, moderate hepatic impairment, or age ≥75 years), titrate to target 97/103 mg twice daily every 2-4 weeks 1, 2, 3
   • If ARNi is not feasible, use ACE inhibitors as second choice 1
   • ARBs are reserved only for patients intolerant to ACE inhibitors due to cough or angioedema when ARNi cannot be used 1
   • Critical safety note: When switching from ACE inhibitor to ARNi, observe a mandatory 36-hour washout period to avoid angioedema; no washout needed when switching from ARB 2, 3

2. Beta Blockers

   • Use only one of three evidence-based beta blockers: bisoprolol, carvedilol, or metoprolol succinate (not metoprolol tartrate) 1, 4
   • Metoprolol succinate is preferred due to once-daily dosing with consistent 24-hour beta-blockade 4
   • Start metoprolol succinate at 12.5-25 mg daily, titrate to target 200 mg daily 4
   • These specific agents reduce mortality by 34% and sudden death by 41% 4
   • Continue beta blockers during acute decompensation unless severe hemodynamic instability occurs 1, 4

3. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone or eplerenone recommended for NYHA class II-IV symptoms if eGFR >30 mL/min/1.73 m² 1
   • Reduces morbidity and mortality in advanced heart failure 1
   • Monitor potassium and creatinine closely: check 5-7 days after initiation, then every 5-7 days until stable 1
   • Avoid initiating with potassium-sparing diuretics; add MRA after ACE inhibitor/ARNi stabilization 1

4. SGLT2 Inhibitors

   • Dapagliflozin or empagliflozin recommended for all HFrEF patients regardless of diabetes status 1
   • Reduces heart failure hospitalizations and cardiovascular mortality 1
   • Minimal blood pressure impact, making it ideal for patients with borderline hypotension 5

Initiation Strategy

Start all four medication classes at low doses simultaneously or sequentially without waiting to achieve target dosing before initiating the next medication. 1 Titrate each medication to target doses over weeks to months as tolerated, prioritizing getting patients on all four classes over achieving target doses of individual agents. 1

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Diuretic Management for Symptom Relief

• Loop diuretics (furosemide) or thiazides are essential for fluid retention, always administered with renin-angiotensin system inhibition 1
• Initial IV furosemide dose: 20-40 mg for diuretic-naïve patients; at least equivalent to oral dose for those on chronic therapy 1
• If eGFR <30 mL/min, avoid thiazides except when used synergistically with loop diuretics 1
• For insufficient response: increase diuretic dose, combine loop diuretics with thiazides, or administer loop diuretics twice daily 1
• In severe refractory cases, add metolazone with frequent monitoring of creatinine and electrolytes 1
• Monitor symptoms, urine output, renal function, and electrolytes regularly during IV diuretic use 1

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Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF, LVEF 41-49%)

SGLT2 inhibitors are the strongest recommendation for HFmrEF, reducing hospitalizations and cardiovascular mortality by 21% regardless of diabetes status. 5

Additional therapies to consider:

• Beta blockers, particularly for LVEF closer to 40% 5
• ACE inhibitors or ARBs for LVEF at lower end of HFmrEF spectrum 5
• MRAs may reduce hospitalizations and mortality 5

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Secondary Therapies for Persistent Symptoms

Digoxin

• Indicated for atrial fibrillation with any degree of symptomatic heart failure to control ventricular rate 1
• In sinus rhythm, improves clinical status in patients with persistent symptoms despite ACE inhibitor and diuretic therapy 1
• Usual dose: 0.25-0.375 mg daily (0.125-0.25 mg in elderly) if creatinine normal 1
• Combination with beta blocker superior to either agent alone 1

Hydralazine-Isosorbide Dinitrate

• Consider in patients with persistent symptoms on optimal therapy 1
• Particularly beneficial in African American patients 1

Ivabradine

• May be used in select patients with persistent symptoms 6, 7

Vericiguat

• Reserved for patients with worsening heart failure requiring recent hospitalization despite optimal therapy 6, 8

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Critical Medications to Avoid

• NSAIDs and COX-2 inhibitors: increase risk of heart failure worsening and hospitalization 1
• Thiazolidinediones (glitazones): increase heart failure worsening and hospitalization risk 1
• Most calcium channel blockers: should be avoided or withdrawn 9
• Most antiarrhythmic drugs: should be avoided 9
• Adaptive servo-ventilation: contraindicated in HFrEF with predominant central sleep apnea due to increased mortality 1

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Device Therapies

Implantable Cardioverter-Defibrillator (ICD)

• Indicated for LVEF ≤30%, NYHA class II-III symptoms on optimal medical therapy, at least 40 days post-MI (ischemic) or with nonischemic cardiomyopathy, with life expectancy >1 year 1, 9
• Also indicated for history of cardiac arrest, ventricular fibrillation, or hemodynamically unstable ventricular tachycardia 9

Cardiac Resynchronization Therapy (CRT)

• Indicated for LVEF ≤35%, NYHA class III-IV symptoms despite optimal therapy, and QRS duration >120 ms (particularly with left bundle branch block) 1, 9

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Acute Decompensated Heart Failure

• Continue evidence-based disease-modifying therapies unless hemodynamic instability or contraindications exist 1
• Immediate ECG and echocardiography required for suspected cardiogenic shock 1
• Transfer cardiogenic shock patients rapidly to tertiary center with 24/7 cardiac catheterization and mechanical circulatory support availability 1
• Inotropic agents are NOT recommended unless symptomatic hypotension or hypoperfusion present due to safety concerns 1

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Monitoring and Follow-up

• Check blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, then every 6 months 1
• Enroll all heart failure patients in multidisciplinary care management programs to reduce hospitalization and mortality 1
• Encourage regular aerobic exercise in stable patients to improve functional capacity, reduce symptoms, and decrease hospitalization risk 1

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Common Pitfalls to Avoid

• Using metoprolol tartrate instead of metoprolol succinate: only succinate formulation has mortality benefit evidence 4
• Inadequate beta blocker dosing: target dose for metoprolol succinate (200 mg daily) is higher than typical hypertension doses 4
• Failing to initiate all four medication classes: patients need quadruple therapy, not sequential "failure" of individual agents 1
• Discontinuing medications for asymptomatic hypotension: mortality benefit persists even with lower blood pressure 2
• Permanent dose reductions when temporary reductions would suffice: 40% of patients requiring temporary dose reduction can be restored to target doses 2
• Avoiding ARNi due to cost concerns rather than clinical contraindications: ARNi provides superior mortality benefit compared to ACE inhibitors 2
• Initiating potassium-sparing diuretics simultaneously with ACE inhibitors/ARNi: increases hyperkalemia risk 1