Treatment of Heart Failure

Staging-Based Framework (ACC/AHA)

• Goldman-Cecil Medicine, p.477

I. Lifestyle and General Measures (All Stages)

• Treat hypertension aggressively
• Smoking cessation, alcohol restriction, illicit drug avoidance
• Regular, supervised aerobic exercise (safe and improves functional capacity and quality of life)
• Dietary sodium restriction (especially severe HF)
• Daily weight monitoring (alert if weight rises >1.5-2 kg over 2 days)
• Influenza and pneumococcal vaccinations
• Enrolment in a multidisciplinary disease management program, which reduces rehospitalization
• Goldman-Cecil Medicine, p.478; p.489

II. Pharmacotherapy for HFrEF (LVEF ≤40%) - "Quadruple Therapy"

1. ARNI (Sacubitril/Valsartan) - Preferred over ACE-I or ARB

• Mechanism: Sacubitril inhibits neprilysin (which degrades natriuretic peptides), and valsartan blocks AT1 receptors. Combined, they augment vasodilation, natriuresis, and inhibit pathologic cardiac remodeling.
• Evidence: Compared with enalapril, sacubitril/valsartan reduces HF hospitalizations, cardiovascular mortality, and all-cause death (PARADIGM-HF).
• Dose: Start 49/51 mg twice daily; target 97/103 mg twice daily
• Key rules: Never combine with an ACE inhibitor (angioedema risk). Require a 36-hour washout after stopping an ACE-I before initiating. Contraindicated if SBP <95 mmHg or history of angioedema.
• If ARNI is not tolerated, use ACE inhibitor or ARB instead
• Goldman-Cecil Medicine, p.482-483

2. Beta-Blockers

• Mechanism: Counteract excess sympathetic activation - reduce heart rate, preload/afterload, myocyte hypertrophy and apoptosis.
• Approved agents for HF: Carvedilol, metoprolol succinate (bisoprolol outside the US)
• Evidence: Added to ARNI/ACE-I + MRA + SGLT2i, beta-blockers further improve LV function, reduce hospitalizations, and strikingly improve survival. Recommended for all patients with symptomatic systolic dysfunction, regardless of etiology.
• Dosing principle: Start at low dose, double at 2-week intervals, target the trial dose. Some beta-blocker is better than none.
• Caution: Do not initiate in decompensated HF. Use with care in bradycardia, reactive airway disease. Worsening congestion during up-titration can often be managed by temporarily increasing diuretics rather than stopping the beta-blocker.
• Goldman-Cecil Medicine, p.483-484

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Agents: Spironolactone, eplerenone
• Evidence: Increase survival, reduce hospitalizations, and improve NYHA class when added to standard therapy (RALES trial for spironolactone, EPHESUS for eplerenone post-MI)
• Indication: NYHA class II-IV with LVEF ≤40%
• Doses:
  • Spironolactone: start 25 mg once daily or alternate days; target 25-50 mg once daily
  • Eplerenone: start 25 mg once daily; target 50 mg once daily
• Monitoring: Check electrolytes and creatinine at 1, 4, 8, 12 weeks, then every 6 months. Stop or halve dose if K+ >5.5 mmol/L.
• Contraindications: K+ >5.0 mmol/L, creatinine >2.5 mg/dL, bilateral renal artery stenosis
• Note: Spironolactone can cause gynecomastia and breast discomfort in men (less so with eplerenone)
• Goldman-Cecil Medicine, p.484-485

4. SGLT2 Inhibitors

• Agents: Dapagliflozin, empagliflozin (approved for HFrEF independent of diabetes)
• Mechanism: Multiple beneficial effects including antifibrotic properties, augmented natriuresis and diuresis, improved myocardial metabolism and kidney perfusion.
• Evidence: Reduce HF hospitalizations and cardiovascular death in HFrEF, independent of diabetes. In HFpEF, empagliflozin reduced the composite of HF hospitalizations and cardiac death (EMPEROR-Preserved trial).
• Role: Now firmly part of the foundational four-drug regimen for HFrEF; also indicated in HFpEF.
• Guyton & Hall Physiology, p.1688; Washington Manual, p.188

III. Diuretics (Symptomatic Relief)

• Loop diuretics (furosemide, torsemide, bumetanide) are the mainstay for fluid overload - relieve dyspnea and edema but have not been shown to reduce mortality.
• Flexible dosing: patients should be taught to self-adjust the diuretic dose if weight rises >1.5 kg over 2 days.
• During acute HF, transition from IV to oral diuretic should be achieved before discharge.
• Avoid excessive diuresis (worsening renal function, electrolyte depletion).

IV. Second-Line and Adjunctive Agents for HFrEF

Ivabradine

• Inhibits the funny channel (I-f) in the SA node - reduces heart rate without other cardiac effects (only effective in sinus rhythm)
• Indication: NYHA class II-IV, LVEF ≤35%, sinus rhythm with HR ≥70 bpm despite optimal quadruple therapy
• Improves symptoms, ejection fraction, and reduces HF hospitalization (but not mortality)
• Dose: Start 5 mg twice daily; increase to 7.5 mg twice daily after 14 days if HR >60 bpm
• Not a substitute for beta-blocker; ineffective in atrial fibrillation
• Goldman-Cecil Medicine, p.484

Hydralazine + Isosorbide Dinitrate

• Reduces mortality, hospitalizations, and symptoms when added to standard therapy in self-identified Black patients with NYHA class III-IV, LVEF ≤45%
• Target dose: 2 tablets (75 mg hydralazine / 40 mg isosorbide dinitrate) three times daily
• Also used as a substitute in patients who cannot tolerate ARNI/ACE-I/ARB due to renal dysfunction
• Main side effects: headache, dizziness; lupus-like syndrome with prolonged high-dose hydralazine
• Goldman-Cecil Medicine, p.485

Vericiguat (Soluble Guanylate Cyclase Stimulator)

• Increases cyclic GMP, causing vascular and cardiac muscle relaxation; may also prevent fibrosis and hypertrophy
• Indication: Persistent NYHA class II-IV symptoms after recent HF hospitalization or need for IV diuretics, despite full quadruple therapy
• Reduces HF hospitalizations (not mortality)
• Dose: Start 2.5 mg once daily with food; double every 2 weeks to target 10 mg once daily
• Goldman-Cecil Medicine, p.484

Digoxin

• Reduces HF hospitalizations and symptoms, but does not reduce mortality
• Used in selected patients with HFrEF who remain symptomatic despite other therapies, and in HF complicated by atrial fibrillation for rate control
• Narrow therapeutic window; monitor serum digoxin levels

Omega-3 Polyunsaturated Fatty Acids (n-3 PUFA)

• 1 gram/day led to a small reduction in cardiovascular morbidity and mortality in one trial; role remains uncertain
• Goldman-Cecil Medicine, p.486

V. Device Therapy

Implantable Cardioverter-Defibrillator (ICD)

• Reduces sudden cardiac death from ventricular arrhythmias
• Indication: LVEF ≤35% despite at least 3 months of optimal medical therapy (OMT), in patients with NYHA class I-III and expected survival >1 year
• Applicable in both ischemic and non-ischemic cardiomyopathy

Cardiac Resynchronization Therapy (CRT)

• Biventricular pacing restores synchrony in patients with dyssynchronous contraction (wide QRS)
• Indication: NYHA class II-IV, LVEF ≤35%, sinus rhythm, QRS duration ≥130 ms (especially LBBB morphology, with greatest benefit at QRS ≥150 ms)
• Benefits: improves pump function, reduces mitral regurgitation, relieves symptoms, prolongs exercise capacity, reduces mortality and HF hospitalizations
• Patients with QRS <130 ms may actually be harmed by CRT
• CRT combined with ICD is preferred in eligible patients
• Goldman-Cecil Medicine, p.488

VI. Treatment of Acute Decompensated Heart Failure (ADHF)

1. Oxygen - only if hypoxemic (SaO2 <90%); oxygen is a vasoconstrictor and reduces cardiac output in non-hypoxemic patients
2. IV Loop Diuretics - furosemide 40-80 mg IV; dose depends on prior diuretic use and renal function
3. Non-invasive ventilation - CPAP is valuable in severe pulmonary edema with hypoxemia; reduces intubation need
4. IV Vasodilators - IV nitroglycerin if SBP >100 mmHg; start 10 µg/min, titrate up
5. IV Inotropes - Dobutamine 2.5-5 µg/kg/min, titrating to response; used in cardiogenic shock or low-output state (limited by tachycardia, arrhythmias, ischemia)
6. Morphine - consider if agitated/distressed; use with caution (respiratory depression risk)
7. Mechanical support - intra-aortic balloon pump for acute mechanical complications (e.g., papillary muscle rupture, VSD)
8. Pre-discharge: Ensure near-optimal volume status achieved, transition to oral diuretics, LVEF documented, OMT initiated/optimized, follow-up scheduled within 7-10 days

• Braunwald's Heart Disease, p.1023; Goldman-Cecil Medicine, p.488

VII. Treatment of HFpEF (LVEF ≥50%)

• Washington Manual of Medical Therapeutics, p.188; Guyton & Hall, p.1689

VIII. Advanced Heart Failure (Stage D)

Left Ventricular Assist Device (LVAD)

• Used as "bridge to transplantation," "destination therapy" (permanent), or "bridge to candidacy"
• Continuous axial-flow device: ~65% 2-year survival free of repeat surgery or disabling stroke
• Newer magnetically levitated centrifugal-flow pumps may offer better outcomes
• Criteria: Persistent severe symptoms >2 months despite OMT + LVEF <25%, ≥3 HF hospitalizations in 12 months, peak VO2 <12 mL/kg/min, or dependence on IV inotropes
• Goldman-Cecil Medicine, p.489

Heart Transplantation

• Definitive treatment for eligible patients with Stage D HF
• Survival: ~85-90% at 1 year, ~70-75% at 5 years, ~20% at 20 years
• Main late complication: cardiac allograft vasculopathy (chronic rejection)
• Contraindications include: fixed pulmonary hypertension, active infection, malignancy, severe comorbidities, BMI >35, non-compliance, active substance use
• Goldman-Cecil Medicine, p.488-489

Palliative Care

• For patients who are not candidates for advanced therapies or who decline them
• Focus on symptom relief, quality of life, and end-of-life planning

Key Drug Dosing Summary

Recent Evidence Update (2025)