Heart Failure (HF) Treatment

HF with Reduced Ejection Fraction (HFrEF) - The "Fantastic Four"

1. ARNI (Angiotensin Receptor - Neprilysin Inhibitor) - Preferred over ACE inhibitor/ARB

• Drug: Sacubitril/valsartan (Entresto)
• Indication: NYHA Class II-III (preferred); ACEi or ARB used for Class II-IV if ARNI not tolerated
• Key rule: Never combine with ACEi (risk of angioedema); must have 36-hour washout from ACEi before starting
• Reduces mortality, hospitalizations, and symptoms more than enalapril (PARADIGM-HF trial)
• Goldman-Cecil Medicine, p. 479

2. Beta-Blockers

• Drugs with proven benefit: Carvedilol, bisoprolol, metoprolol succinate (extended-release)
• Mechanism: Counteract chronic sympathetic overdrive; reduce heart rate, prevent hypertrophy and myocyte apoptosis
• Beta-blockers reduced all-cause mortality by ~27% in patients in sinus rhythm in pooled trial analysis
• "Start low, go slow" - titrate up every 2 weeks; avoid initiation during acute decompensation
• Contraindications: Asthma, 2nd/3rd degree AV block
• Goldman-Cecil Medicine, p. 483

3. Mineralocorticoid Receptor Antagonist (MRA)

• Reduce morbidity and mortality in moderate-severe HF; aldosterone causes myocardial/vascular fibrosis beyond its renal effects
• Monitor: K+ at 1, 4, 8, 12 weeks; stop if K+ >6.0 mmol/L or creatinine >310 µmol/L
• Eplerenone causes less gynecomastia than spironolactone
• Goldman-Cecil Medicine, p. 485; Katzung's Basic and Clinical Pharmacology, 16e

4. SGLT2 Inhibitors

• Drugs: Dapagliflozin (Farxiga) or Empagliflozin (Jardiance)
• Indication: NYHA Class II-IV with LVEF ≤40%; first-line regardless of diabetes status
• Benefits: Improve survival, reduce hospitalizations, slow eGFR decline, reduce serum uric acid
• Contraindications: Prior DKA, eGFR <20 mL/min/1.73m²; use caution if eGFR <30
• Goldman-Cecil Medicine, p. 485

Diuretics - For Symptom Relief

• Loop diuretics (furosemide) are first choice for fluid overload - reduce preload and pulmonary congestion
• No mortality benefit on their own; used alongside the "fantastic four"
• Thiazides for mild failure only; loop agents for moderate-severe
• Monitor K+ (supplement if needed or add K+-sparing agent)
• Katzung's Basic and Clinical Pharmacology, 16e, p. 345

Additional Pharmacologic Options

Device Therapy (HFrEF)

• LVEF ≤35%, NYHA Class I-III, >1 year expected survival on optimal GDMT
• Prevents sudden cardiac death from ventricular arrhythmia

• LVEF ≤35%, sinus rhythm, LBBB with QRS ≥150 ms, NYHA Class II-III (or ambulatory IV)
• Improves LV function, symptoms, and reduces mortality
• His-bundle and left bundle branch pacing may match or exceed biventricular pacing outcomes

HF with Preserved Ejection Fraction (HFpEF)

• Diuretics: Symptom control (use cautiously - these patients are preload-dependent)
• SGLT2 inhibitors: Now recommended; EMPEROR-Preserved and DELIVER trials show reduced HF hospitalizations
• MRAs: May be useful
• ARNI: Reduces NT-proBNP and symptoms
• Beta-blockers / CCBs: Useful to control heart rate and blood pressure
• Treat underlying causes: Hypertension, obesity, AF, coronary disease
• Digoxin has little or no role in HFpEF - Katzung's Basic and Clinical Pharmacology, 16e, Table 13-4

Acute / Decompensated HF

• IV loop diuretics (furosemide) - cornerstone
• IV vasodilators (nitroprusside, nitroglycerin) - reduce preload/afterload in hypertensive AHF
• Avoid initiating beta-blockers until stabilized
• Inotropes (dobutamine, milrinone) for cardiogenic shock or low-output state
• Positive pressure ventilation (CPAP/BiPAP) for respiratory failure
• Avoid adaptive servo-ventilation (ASV) in patients with central sleep apnea + systolic HF (increased mortality in SERVE-HF trial)

Non-Pharmacologic Measures (All HF)

• Sodium restriction (<2 g/day) and fluid restriction in severe cases
• Daily weight monitoring - alert for >2 kg gain in 2 days
• Exercise rehabilitation - improves functional capacity and quality of life
• Treat precipitating/comorbid conditions: AF, hypertension, anemia, sleep apnea, diabetes
• Vaccination: Influenza, pneumococcal, COVID-19

GDMT Dosing Reference (HFrEF)