Heart Failure Management

Staging Framework (2022 ACC/AHA)

• Stage A - At risk (hypertension, diabetes, obesity, family history of cardiomyopathy, cardiotoxin exposure) but no structural disease or symptoms
• Stage B - Pre-HF: structural heart disease, elevated filling pressures, or elevated natriuretic peptides - but no symptoms yet
• Stage C - Symptomatic HF (current or prior symptoms with structural heart disease)
• Stage D - Advanced HF: marked symptoms interfering with daily life, recurrent hospitalizations despite optimized GDMT

Therapies of Proven Benefit (Goldman-Cecil Medicine, Table 46-1)

Chronic HFrEF (EF < 40%) - Quadruple GDMT

1. Diuretics

• Loop diuretics (furosemide, torsemide, bumetanide) are the cornerstone for congestive symptoms
• Thiazides for mild failure; loop agents required for moderate-severe disease
• Sodium removal by dietary salt restriction + diuretics remains the foundational symptomatic approach
• Torsemide and bumetanide have superior oral bioavailability compared to furosemide
• Add spironolactone/eplerenone to counter potassium loss and gain mortality benefit
• SGLT2 inhibitors also exert natriuresis and partly work via this mechanism

2. ACE Inhibitors / ARBs

• First drug for patients with LV dysfunction but no edema
• Multiple large RCTs confirm ACEIs are superior to placebo and to vasodilators alone
• ARBs (losartan, valsartan, candesartan) are reserved for ACEI-intolerant patients (usually cough)
• Benefits include reduced mortality and HF hospitalization
• Monitor potassium, renal function, and blood pressure closely - especially in older patients

3. ARNI: Sacubitril-Valsartan (Entresto)

• Recommended over ACEI in patients who can tolerate it (PARADIGM-HF trial)
• PARADIGM-HF (2014, n=8,442): reduced total mortality by 16%, CV death by 20%, HF hospitalization by 21% vs. enalapril
• Benefits were consistent across age groups including patients > 75 years
• Do not co-administer with an ACEI (risk of angioedema); washout period of 36 hours required when switching

4. Beta-Blockers

• Not a class effect - only carvedilol, bisoprolol, and metoprolol succinate (extended release) have RCT evidence for mortality reduction
• Nebivolol and bucindolol also shown to reduce mortality but are not approved for HF in the US
• Must be started at low doses; several months may be needed before symptomatic improvement
• Mechanism: counter the adverse effects of chronically elevated catecholamines and cardiac remodeling
• Carvedilol preferred in hypertensive HFrEF patients due to its vasodilating properties

5. Mineralocorticoid Receptor Antagonists (MRA)

• Spironolactone and eplerenone reduce morbidity and mortality in moderate-severe HFrEF
• Should be considered in all patients with moderate-to-severe HF
• Careful monitoring of potassium and renal function required - especially in elderly patients
• Starting doses: spironolactone 12.5-25 mg/day; eplerenone 25 mg/day

6. SGLT2 Inhibitors (Dapagliflozin, Empagliflozin)

• Now first-line therapy for both HFrEF and HFpEF
• Reduce all-cause mortality and HF hospitalizations - benefit appears independent of glycemic control
• A 2025 meta-analysis (PMID 40884036, DAPA ACT HF-TIMI 68, Circulation) confirmed benefit of dapagliflozin even in patients hospitalized for HF, regardless of ejection fraction
• Mechanism in HF not fully elucidated but includes natriuresis, reduced preload/afterload, metabolic and direct cardiorenal effects

Additional Pharmacotherapy

Ivabradine

• I(f) channel blocker that slows heart rate without affecting contractility
• Indicated in sinus rhythm with resting HR ≥ 70 bpm, on maximally tolerated beta-blocker
• Reduces HF hospitalizations; may be useful in diastolic HF to improve filling time

Hydralazine + Isosorbide Dinitrate (BiDil)

• Fixed combination (arteriolar + venous dilation)
• Specifically recommended for Black patients with HFrEF who cannot tolerate ACEI/ARB
• Used in patients with high filling pressures (nitrates) or low output (hydralazine) predominantly

Vericiguat

• Soluble guanylate cyclase stimulator
• Approved for high-risk, worsening chronic HFrEF (recent decompensation); reduces CV death and HF hospitalization

Digoxin

• Indicated mainly when HF coexists with atrial fibrillation
• Used when diuretics and ACEIs have failed to control symptoms
• Target plasma level ≤ 1 ng/mL to minimize toxicity
• Reduces hospitalizations and progressive HF deaths but at the expense of increased sudden cardiac death; net mortality effect is neutral

Diastolic HF / HFpEF (EF ≥ 50%)

• SGLT2 inhibitors are now first-line for HFpEF (Katzung 16e)
• Control of hypertension is particularly important
• ACEIs/ARBs: may help reduce LVH and are used adjunctively
• Rate control for atrial fibrillation is critical - tachycardia severely limits diastolic filling time
• Bradycardic agents (ivabradine) may help maintain adequate filling time even in sinus rhythm
• Treat hyperlipidemia and consider revascularization if CAD is present
• Diuretics should be used with caution - these patients are preload-dependent

Acute / Decompensated Heart Failure

• IV therapy is standard
• Furosemide IV at high dose is the workhorse diuretic; adding acetazolamide to high-dose furosemide shows important additive benefit
• Dopamine or dobutamine for acute failure with severe hypotension (positive inotropes, short-acting)
• Levosimendan: approved in Europe; non-inferior to dobutamine in trials
• IV vasodilators: nitroprusside (arteriolar + venous), nitroglycerin (venous), nesiritide (BNP analog) - reduce afterload and pulmonary congestion
• Conivaptan / Tolvaptan (vasopressin antagonists): for HF with dilutional hyponatremia; do not reduce mortality but correct hyponatremia

Acute precipitants to address:

• Non-adherence to medications or diet
• Acute myocardial infarction (emergency revascularization with PCI or thrombolytics)
• Infection/fever, anemia, arrhythmias (AF)
• Uncontrolled hypertension

Device Therapy

Implantable Cardioverter-Defibrillator (ICD)

• LVEF < 40%, Stage B: post-MI > 40 days with expected survival > 1 year
• LVEF < 35%, Stage C with expected survival > 1 year

Cardiac Resynchronization Therapy (CRT)

• For patients with LVEF ≤ 35%, LBBB, QRS ≥ 150 ms, NYHA Class II-IV on optimal GDMT
• Improves symptoms, reduces hospitalization, and reduces mortality

Ventricular Assist Devices (VAD)

• Bridge to transplantation or destination therapy in Stage D
• Left ventricular assist devices (LVADs) improve survival in advanced HF

Heart Transplantation

• Definitive therapy for Stage D HF refractory to all other measures
• 1-year survival > 85%; median survival ~12-13 years

Non-Pharmacological / Lifestyle Measures

• Sodium restriction: dietary salt restriction is foundational alongside diuretics
• Exercise training: proven benefit (Goldman-Cecil, Table 46-1); improves functional capacity and quality of life
• Fluid restriction in advanced HF with hyponatremia
• Monitor daily weight: early detection of fluid retention
• Vaccinations: influenza, pneumococcal (prevent HF exacerbations)
• Avoid NSAIDs, non-DHP calcium channel blockers (in HFrEF), and thiazolidinediones

Stages A & B - Prevention Focus

• Treat hypertension aggressively
• SGLT2 inhibitors for all Type 2 diabetes patients with CVD risk
• Control hyperlipidemia (statins)
• Correct arrhythmias, especially atrial fibrillation
• ACEIs/ARBs for patients with LVEF < 40% even before symptoms develop (Stage B)
• ICD implantation for eligible Stage B post-MI patients