Pharmacotherapy

Initial Management:

• Assess volume status and perfusion
• Initiate IV diuretics for congestion ( loop diuretics – furosemide, bumetanide, torsemide)
• Vasodilators for hypertension or hypoperfusion (nitroglycerin, nitroprusside)
• Inotropes for refractory hypotension (dobutamine, milrinone)
• Anticoagulation if atrial fibrillation, LV thrombus, or embolic risk
• Treat precipitating factors (e.g. ACS, arrhythmia, infection)
• Avoid potential nephrotoxins (NSAIDs, contrast dye, aminoglycosides)
• Monitor renal function, electrolytes, fluid status

Oral Guideline-Directed Medical Therapy for HFrEF:

Angiotensin Converting Enzyme (ACE) Inhibitors

• First-line for all HFrEF patients
• Block conversion of angiotensin I → angiotensin II
• Reduce ventricular remodeling, improve LVEF
• Decrease mortality, hospitalization
• Start at low doses, titrate to target over weeks
• Monitor BP, renal function, potassium
• Adverse effects: Cough, angioedema, hyperkalemia, renal dysfunction, hypotension
• Avoid if history of angioedema
• Contraindicated in pregnancy

Angiotensin II Receptor Blockers (ARBs)

• Alternative if ACE inhibitor not tolerated
• Block angiotensin II receptor
• Similar benefits as ACE inhibitors
• Candesartan, valsartan or losartan specifically studied in HF trials
• Like ACE inhibitors, start low and titrate slowly
• Monitor BP, renal function, potassium
• Lower risk of cough/angioedema than ACE inhibitors

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

• Sacubitril/valsartan – preferred over ACEI or ARB in HFrEF
• Reduces mortality, hospitalizations
• Initiate at 49/51 mg twice daily
• Uptitrate to 97/103 mg twice daily
• If on low-dose ACEI/ARB at baseline, start 24/26 mg twice daily
• Monitor BP, renal function, potassium closely
• Avoid if history of angioedema with ACEI or ARB

Beta-Blockers

• Standard therapy for all stable HFrEF patients
• Carvedilol, metoprolol succinate, or bisoprolol
• Decrease mortality, hospitalization, improve LVEF
• Start at low doses, titrate gradually over weeks-months
• Target doses from clinical trials
• Monitor HR, BP, fluid status, glycemic control
• May initially worsen HF symptoms before improving

Aldosterone Antagonists

• Spironolactone or eplerenone in all HFrEF patients
• Block aldosterone receptor → decrease mortality
• Start at low doses (12.5-25 mg daily)
• Monitor potassium, renal function closely
• Hyperkalemia risk with renal dysfunction

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

• Empagliflozin or dapagliflozin reduce mortality and hospitalization
• Benefits demonstrated in HFrEF patients with and without diabetes
• Monitor volume status, renal function
• Avoid in severe renal impairment per package inserts
• Advise patients to monitor for UTIs and genital infections

Hydralazine and Isosorbide Dinitrate

• Reduces mortality in African American patients taking GDMT
• Consider if ACEI/ARB/ARNI not tolerated
• Headache, tachycardia, hypotension common
• 3 times daily dosing

Ivabradine

• If HR >70 bpm on maximally tolerated β-blocker dose
• Reduces risk of hospitalization
• Bradycardia and visual disturbances common
• Avoid use if HR <60 bpm

Digoxin

• Reduce hospitalizations but no effect on mortality
• Consider if symptomatic on GDMT
• Target serum concentration 0.5-0.9 ng/mL
• Toxicity risk with renal dysfunction

Diuretics

• Loop diuretics first-line
• Thiazides for mild fluid retention
• Adjust doses based on volume status
• Monitor renal function, electrolytes, weight

Vericiguat

• Reduce hospitalization but no effect on mortality
• Hypotension, anemia noted in trial
• Role still being determined

Oral Therapy for HFpEF:

• Treat comorbidities like hypertension, CAD
• Diuretics for congestion
• Consider sacubitril/valsartan
• Spironolactone to reduce hospitalization

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Non-Pharmacologic Management:

• Sodium and fluid restriction
• Close monitoring of symptoms and weight
• Exercise training and cardiac rehabilitation
• Implantable cardioverter-defibrillator (ICD)
• Cardiac resynchronization therapy (CRT)
• Education on lifestyle, medications, self-care
• Palliative care discussions in advanced HF

Combination pharmacotherapy is key for HFrEF. Frequent monitoring and uptitration are required to achieve optimal benefits. Multidisciplinary HF disease management programs improve outcomes. Treatment of HFpEF remains challenging with limited proven options.