What is the recommended management for an adult with congestive heart failure (reduced or preserved ejection fraction)?

Management of Congestive Heart Failure

All adults with heart failure with reduced ejection fraction (HFrEF, EF ≤40%) should immediately start quadruple therapy—SGLT2 inhibitor, mineralocorticoid receptor antagonist, beta-blocker, and ARNI (or ACE inhibitor/ARB)—simultaneously at low doses, which reduces 2-year mortality by approximately 73% compared to no treatment. 1, 2

Initial Diagnostic Confirmation

Before initiating therapy, confirm the diagnosis with:

• Transthoracic echocardiography to document left ventricular ejection fraction and classify heart failure type 3, 2
• Natriuretic peptides (NT-proBNP or BNP) for risk stratification—note these may be falsely low in obesity 3
• Baseline assessment of blood pressure, heart rate, renal function (eGFR), serum potassium, and volume status (peripheral edema, jugular venous distension, pulmonary rales) 2

Approximately 31% of heart failure patients have HFrEF (EF ≤40%), 13% have mildly reduced EF (41-49%), and 56% have preserved EF (≥50%) 3

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Heart Failure with Reduced Ejection Fraction (HFrEF)

Foundational Quadruple Therapy: Start All Four Classes Simultaneously

The evidence is unequivocal: initiate all four medication classes at low doses within the first 4-6 weeks of diagnosis, then uptitrate every 1-2 weeks to target doses. 1, 2 Less than 25% of eligible patients currently receive all four medications concurrently, and only 1% reach target doses—a massive treatment gap that simultaneous initiation directly addresses 1

1. SGLT2 Inhibitors (Start Immediately)

• Empagliflozin 10 mg once daily OR dapagliflozin 10 mg once daily 2
• No dose titration required—10 mg provides maximal benefit 2
• Benefits occur within weeks of initiation 1
• Unique advantages: No blood pressure, heart rate, or potassium effects; safe in moderate kidney dysfunction (eGFR ≥30 mL/min/1.73 m² for empagliflozin, ≥20 mL/min/1.73 m² for dapagliflozin) 1

2. Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone 12.5-25 mg once daily (target 25-50 mg daily) OR eplerenone 25 mg once daily (target 50 mg daily) 2
• Provides ≥20% mortality reduction and decreases sudden cardiac death 2
• Contraindications: Serum potassium >5.0 mEq/L, creatinine >2.5 mg/dL, eGFR <30 mL/min 3, 4
• Spironolactone causes 5.7% higher rate of male gynecomastia; use eplerenone to avoid this 1

3. Beta-Blockers (Evidence-Based Only)

Use one of the three beta-blockers with proven mortality benefit (≥20% mortality reduction): 1, 2

• Carvedilol: Start 3.125 mg twice daily, target 25-50 mg twice daily 1
• Metoprolol succinate: Start 12.5-25 mg daily, target 200 mg daily 1
• Bisoprolol: Start 1.25 mg daily, target 10 mg daily 1

Choose carvedilol if refractory hypertension is present due to combined α1-β1-β2-blocking properties 1

4. ARNI (Preferred) or ACE Inhibitor/ARB

• ARNI (sacubitril/valsartan) is preferred: Start 24/26 mg or 49/51 mg twice daily, target 97/103 mg twice daily 2, 5

  • Provides ≥20% additional mortality reduction compared to ACE inhibitors 2
  • Critical: Allow strict 36-hour washout period when switching from ACE inhibitor to avoid angioedema 1, 5

• If ARNI not tolerated or unavailable:

  • Lisinopril 10 mg daily (target 40 mg daily) OR losartan 50 mg daily (target 150 mg daily) 1
  • ACE inhibitors/ARBs provide 5-16% mortality reduction 1

5. Loop Diuretics (For Volume Management Only)

• Furosemide 20-40 mg once or twice daily, torsemide 10-20 mg once daily, OR bumetanide 0.5-1.0 mg once or twice daily 2
• Titrate to achieve euvolemia—use lowest effective dose 3, 2
• No mortality benefit; used solely for symptom relief 3, 4

Uptitration Strategy

Increase one drug at a time every 1-2 weeks using small increments until target or maximally tolerated dose is achieved: 2

1. First priority: SGLT2 inhibitor and MRA (minimal blood pressure impact) 1
2. Second priority: Beta-blocker uptitration 2
3. Third priority: ARNI/ACE inhibitor/ARB uptitration 2

Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment—more frequently in elderly patients (≥65 years) and those with chronic kidney disease 1, 2

Managing Low Blood Pressure During Optimization

• Never discontinue or reduce guideline-directed medical therapy for asymptomatic hypotension with adequate perfusion 2
• Patients with adequate perfusion can tolerate systolic BP 80-100 mmHg 1
• Modest creatinine increases (up to 30% above baseline) are acceptable and should not prompt discontinuation 1
• If symptomatic hypotension occurs, address reversible non-heart failure causes first (dehydration, infection, medication interactions) 2

Additional Therapies for Specific Subgroups

• Self-identified Black patients with NYHA Class III-IV symptoms: Add hydralazine/isosorbide dinitrate to quadruple therapy 2
• Persistent symptoms despite optimal therapy with sinus rhythm and heart rate >70 bpm: Consider ivabradine 5 mg twice daily (target 7.5 mg twice daily) only after maximizing beta-blocker dose 1
• Consider potassium binders (patiromer) if hyperkalemia develops to facilitate ongoing use of MRAs 3, 2

Device Therapy

• Implantable cardioverter-defibrillator (ICD): Indicated for primary prevention in patients with LVEF ≤35%, NYHA Class II-III symptoms, and expected survival >1 year with good functional status 2
• Cardiac resynchronization therapy (CRT): Indicated for patients with LVEF ≤35%, NYHA Class II-IV symptoms, sinus rhythm, and QRS ≥150 msec with left bundle branch block morphology 2

Critical Contraindications

• Never combine ACE inhibitor with ARNI (36-hour washout required) 1, 5
• Avoid in HFrEF: Non-dihydropyridine calcium channel blockers, alpha-blockers, moxonidine 1, 2

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Heart Failure with Preserved Ejection Fraction (HFpEF, EF ≥50%)

SGLT2 inhibitors are the cornerstone of HFpEF pharmacotherapy, with the strongest evidence for reducing heart failure hospitalizations and cardiovascular death. 3, 4, 1

First-Line Therapy

1. SGLT2 Inhibitors (Class 2a Recommendation)

• Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily 3, 4
• Reduces heart failure hospitalizations (HR 0.77-0.82) based on DELIVER and EMPEROR-PRESERVED trials 4
• Should be considered in all patients with HFpEF regardless of diabetes status 3, 6

2. Blood Pressure Control (Class I Recommendation)

• Target systolic/diastolic BP <130/80 mmHg; less stringent target <140/90 mmHg acceptable for individuals ≥65 years 4
• ACE inhibitors or ARBs are preferred first-line antihypertensive agents 4
  • Start lisinopril 10 mg daily or losartan 50 mg daily, titrate upward until BP target achieved 4
  • Effectively lower blood pressure but do not confer robust mortality benefit seen in HFrEF 4

3. Loop Diuretics (For Symptom Relief)

• Use at lowest effective dose to relieve fluid retention symptoms 3, 4
• Monitor for volume depletion, electrolyte disturbances, and worsening renal function 4
• No prognostic benefit—purely symptomatic management 4, 7

Additional Therapies to Consider

Mineralocorticoid Receptor Antagonists (Class 2b Recommendation)

• Spironolactone 12.5-25 mg daily may be added in appropriately selected patients 4
• Selection criteria: Serum potassium <5.0 mmol/L, creatinine <2.5 mg/dL, eGFR >30 mL/min 4
• TOPCAT trial showed modest reduction in heart failure hospitalizations (HR 0.83), though primary endpoint did not reach statistical significance 4
• Close monitoring of potassium and renal function required when combined with ACE inhibitors/ARBs 4

ARNI (Angiotensin Receptor-Neprilysin Inhibitor)

• May be considered for EF up to 55-60% 3
• Weaker evidence in HFpEF compared to HFrEF 3

Beta-Blockers

• Metoprolol succinate 100 mg daily is reasonable but may be insufficient if BP remains above target 4
• Can be titrated up to 200 mg daily for additional BP and heart rate control 4
• Evidence for mortality benefit in HFpEF is limited 3, 4

Comorbidity Management

• Diabetes: SGLT2 inhibitors as first-line therapy 3
• Obesity (BMI ≥30 kg/m²): Consider GLP-1 receptor agonists 3
• Atrial fibrillation: Rate control for symptom management (Class 2a recommendation) 1

Acute Decompensated HFpEF

• Intravenous loop diuretics as first-line for acute fluid overload 4
• Initial parenteral dose should be greater than or equal to chronic oral daily dose 4
• Monitor electrolytes, renal function, and blood pressure during diuresis to avoid excessive diuresis leading to renal dysfunction 4

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Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF, EF 41-49%)

Treat similarly to HFrEF with quadruple therapy: 3

• Diuretic (if congested) + SGLT2 inhibitor + ARNI or ACE inhibitor or ARB + beta-blocker + MRA 3
• GLP-1 receptor agonist if BMI ≥30 kg/m² and EF ≥45% 3

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Implementation Strategies

• Refer newly diagnosed HFrEF patients to heart failure specialty care to maximize guideline-directed medical therapy optimization 2
• Nurse-led titration programs reduce all-cause mortality (OR 0.66,95% CI 0.48-0.92) 1
• Pharmacist involvement improves guideline-directed medical therapy adherence and dosing 1
• Early follow-up within 7-14 days after medication changes to monitor volume status, blood pressure, renal function, and electrolytes 1

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Common Pitfalls to Avoid

• Do not wait to achieve target dosing of one medication before initiating the next—simultaneous initiation is superior 1, 2
• Do not discontinue guideline-directed medical therapy for asymptomatic laboratory changes (modest creatinine elevation up to 30% above baseline is acceptable) 1
• Do not use beta-blockers alone as sufficient therapy for HFpEF—mortality benefit is weak 3, 4
• Do not overreact to temporary symptoms of fatigue and weakness with dose increases—these usually resolve within days 1
• Do not use non-dihydropyridine calcium channel blockers in HFrEF—they may worsen outcomes 1

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Expected Outcomes

In HFrEF, combined quadruple therapy reduces all-cause mortality by 61% (HR 0.39,95% CI 0.32-0.49), and transitioning from traditional dual therapy to quadruple therapy can extend life expectancy by approximately 6 years. 2