What is the treatment for heart failure?

Heart Failure: Comprehensive Treatment Overview

All patients with heart failure and reduced ejection fraction (HFrEF) should receive foundational therapy with ACE inhibitors (or ARNIs), beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as this combination significantly reduces mortality and hospitalizations. 1, 2, 3

Pharmacological Treatment Algorithm

First-Line Therapy for HFrEF (LVEF ≤40%)

Foundation: Quadruple Therapy

• ACE Inhibitors are recommended as first-line therapy in all patients with reduced left ventricular systolic function 4

  • Start with low dose and titrate gradually to target maintenance doses proven effective in clinical trials 1, 5
  • Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, then every 6 months 4, 1
  • Initiation protocol: Review diuretic needs, reduce or withhold diuretics for 24 hours before starting, consider evening dosing when supine to minimize hypotension 4
  • Avoid NSAIDs during therapy 4, 5
  • Stop treatment if renal function deteriorates substantially 4

• Beta-Blockers are mandatory for all stable patients with HFrEF in NYHA class II-IV on standard treatment including diuretics and ACE inhibitors 4

  • Reduce hospitalizations, improve functional class, and prevent worsening heart failure 1
  • In post-MI patients with LV systolic dysfunction, long-term beta-blockade reduces mortality 4
  • Combination with digoxin appears superior to either agent alone 4

• Mineralocorticoid Receptor Antagonists (Spironolactone) are recommended in advanced heart failure (NYHA III-IV) in addition to ACE inhibition and diuretics to improve survival and reduce morbidity 4, 6

  • Start with low-dose administration, check serum potassium and creatinine after 5-7 days, titrate accordingly 4
  • Recheck every 5-7 days until potassium values are stable 4
  • Use extreme caution in stage 4 CKD due to hyperkalemia risk 7

• SGLT2 Inhibitors significantly reduce cardiovascular and all-cause mortality irrespective of diabetes status 2, 3, 8

  • Have class I recommendation in current guidelines 3, 8
  • Also effective in HFpEF with class I evidence 3, 8

Diuretic Management

For Symptomatic Fluid Overload

• Loop diuretics or thiazides are essential when fluid overload manifests as pulmonary congestion or peripheral edema 4

  • Provide rapid improvement of dyspnea and increased exercise tolerance 4
  • Always administer in combination with ACE inhibitors 4

• Renal function considerations: If GFR <30 ml/min, do not use thiazides as monotherapy; use only synergistically with loop diuretics 4, 7

• Insufficient response algorithm 4:

  • Increase dose of diuretic
  • Combine loop diuretics and thiazides
  • With persistent fluid retention: administer loop diuretics twice daily
  • In severe chronic heart failure: add metolazone with frequent measurement of creatinine and electrolytes

Advanced Therapies

ARNIs (Angiotensin Receptor-Neprilysin Inhibitors)

• Combined angiotensin receptor blocker neprilysin inhibitors improve hospital admissions and mortality compared with enalapril 9, 2
• Guidelines recommend substitution of ACE inhibitors or ARBs with ARNIs in appropriate patients 9, 2

Additional Agents for Specific Indications

• Ivabradine: Reduces risk of hospitalization for worsening heart failure in patients with heart rate ≥70 bpm on optimized therapy 10, 8

  • Initiate at 5 mg twice daily, titrate to maintain resting heart rate between 50-60 bpm 10

• Vericiguat: Reduces heart failure hospitalization in high-risk patients with HFrEF 2, 8

• Digoxin: Recommended in atrial fibrillation with any degree of symptomatic heart failure to slow ventricular rate 4

  • In sinus rhythm, improves clinical status in patients with persisting symptoms despite ACE inhibitor and diuretic treatment 4
  • Usual daily dose: 0.25-0.375 mg if serum creatinine normal; 0.125-0.25 mg in elderly 4
  • Recent evidence supports digitoxin in advanced HFrEF to reduce mortality and hospitalizations 8

• Hydralazine/Isosorbide Dinitrate: Has a role in certain patients with HFrEF 2

• ARBs: Consider in patients who do not tolerate ACE inhibitors for symptomatic treatment 4

  • Unclear whether ARBs are as effective as ACE inhibitors for mortality reduction 4
  • In combination with ACE inhibition, may improve symptoms and reduce hospitalizations 4

Treatment for HFpEF (Preserved Ejection Fraction)

Focus on Symptom Relief and Comorbidity Management

• Diuretics for volume overload have class I recommendation and effectively alleviate symptoms 3, 8
• SGLT2 inhibitors play a key role with class I evidence in current guidelines 3, 8
• Finerenone (non-steroidal MRA) reduces cardiovascular death and hospitalizations 8
• GLP-1 receptor agonists in obese HFpEF patients improve quality of life and reduce heart failure-related events 3, 8
• Spironolactone may improve outcomes, though no therapy has conclusively shown significant effect 9

Non-Pharmacological Management

Patient Education and Self-Management 4, 1

• Explain heart failure pathophysiology and why symptoms occur
• Teach symptom recognition and what to do when symptoms occur
• Emphasize self-weighing and daily weight monitoring 7
• Explain rationale of treatments and importance of adherence
• Discuss prognosis

Lifestyle Modifications 4, 1, 5

• Exercise: Daily physical and leisure activities in stable patients to prevent muscle deconditioning; rest not encouraged in stable conditions
• Exercise training programs recommended in stable NYHA II-III patients
• Dietary: Control sodium intake, especially in severe heart failure; avoid excessive fluids in severe HF; avoid excessive alcohol intake
• Smoking: Refrain from smoking; use nicotine replacement therapies if needed
• Travel: Advise on problems with long flights and severe heart failure, high altitudes, hot humid climates

Comorbidity Management

• Iron deficiency is common in HFrEF and associated with worse outcomes 8
• Intravenous iron supplementation improves exercise capacity and reduces hospitalization risk, especially after decompensation 8
• Vaccinations and mental health screening contribute to improved quality of life 3

Device Therapies

For Specific Subpopulations 2

• Cardiac resynchronization therapy (CRT): Beneficial in patients with interventricular dyssynchrony
• Implantable cardiac defibrillators (ICDs): For patients with more severe left ventricular dysfunction, particularly of ischemic etiology
• Transcatheter mitral valve repair: In patients with severe secondary mitral regurgitation
• Left ventricular assist devices (LVADs): Improved safety means these are becoming more commonly used in patients with severe symptoms 9

Common Pitfalls and Critical Monitoring

Medication Initiation Errors to Avoid

• Do not use potassium-sparing diuretics during initiation of ACE inhibitor therapy 4, 5
• Do not use thiazide diuretics alone in patients with GFR <30 ml/min—this is ineffective 7
• Do not initiate multiple medications simultaneously, as this increases risk of adverse effects 7
• Do not allow excessive diuresis before starting ACE inhibitors 4, 1

Monitoring Requirements

• Monitor for hypotension when starting ACE inhibitors or beta-blockers 5
• Failing to monitor renal function and electrolytes after medication changes can lead to adverse effects 7
• Regular assessment of volume status through physical examination and daily weight monitoring is essential 7

Contraindications

• Beta-blockers: Avoid in patients with asthma, severe bronchial disease, or symptomatic bradycardia/hypotension 5
• Digoxin: Contraindicated in bradycardia, second- and third-degree AV-block, sick sinus syndrome, carotid sinus syndrome, hypokalemia, and hypercalcemia 4
• Routine inotropic therapy increases mortality and should be reserved for severe episodes of heart failure 5

Treatment by NYHA Class

NYHA Class II (Mild Heart Failure) 5

• ACE inhibitor titrated to target doses
• Add beta-blocker and titrate to target dosages
• Use diuretics as needed during episodes of fluid overload

NYHA Class III-IV (Moderate to Severe Heart Failure) 5

• Diuretics plus ACE inhibitors
• Add beta-blockers
• Add spironolactone for advanced heart failure
• Consider additional agents (ivabradine, vericiguat, digoxin) based on specific clinical features

Prognosis and Outcomes

• Despite advances, disease morbidity and mortality remain high, with 5-year survival rate of 25% after hospitalization for HFrEF 2
• Rapid and comprehensive implementation of guideline-directed medical therapy substantially improves prognosis 8
• The ability to alter the natural history of HFrEF has never been better with recent developments including SGLT2 inhibitors, vericiguat, and transcatheter mitral valve repair 2