What is the best treatment approach for a patient with decompensated heart failure, particularly one with a history of heart failure with reduced ejection fraction?

Decompensated Heart Failure Management in HFrEF

For a patient with decompensated heart failure and reduced ejection fraction, immediate treatment focuses on achieving euvolemia with intravenous loop diuretics, followed by rapid initiation or optimization of all four foundational guideline-directed medical therapies (SGLT2 inhibitor, ARNI/ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist) once hemodynamically stable, ideally before hospital discharge. 1, 2, 3

Immediate Stabilization Phase (First 24-48 Hours)

Volume Management

• Administer intravenous loop diuretics as the cornerstone of acute therapy to relieve pulmonary congestion and peripheral edema 1, 3
• Target clinical euvolemia: no peripheral edema, no jugular venous distension, no orthopnea, and resolution of pulmonary rales 2
• Consider vasodilators (nitroglycerin, nitroprusside) if systolic blood pressure >110 mmHg with severe pulmonary edema 3, 4
• For severe circulatory failure with hypoperfusion, inotropic support (dobutamine, milrinone) or mechanical circulatory support may be necessary 3

Hemodynamic Assessment

• Identify the patient's hemodynamic profile: fluid overload (wet) vs. adequate perfusion (warm) vs. low cardiac output (cold) 4
• Monitor for signs of inadequate perfusion: cool extremities, narrow pulse pressure, altered mental status, rising creatinine 2

Transition to Guideline-Directed Medical Therapy (Days 2-5)

Critical Timing Principle

Begin GDMT initiation as soon as the patient is hemodynamically stable—defined as no intravenous vasodilators or increase in IV loop diuretics in 6 hours, and no IV inotropes in 24 hours. 1, 2

The Four Foundational Medications

Start all four medication classes simultaneously or in rapid sequence before discharge: 1, 2, 5

1. SGLT2 Inhibitor (Dapagliflozin 10 mg or Empagliflozin 10 mg once daily)

   • Initiate immediately—no titration required 2, 5
   • Benefits occur within weeks of initiation 2
   • Minimal blood pressure effect makes it ideal as first agent 2, 5
   • Can be used if eGFR ≥20 ml/min/1.73 m² (dapagliflozin) or ≥30 ml/min/1.73 m² (empagliflozin) 2
   • Emerging evidence supports in-hospital initiation during acute decompensation, with studies showing enhanced diuresis and improved outcomes 1, 6

2. Mineralocorticoid Receptor Antagonist (Spironolactone 12.5-25 mg or Eplerenone 25 mg once daily)

   • Start early as it has minimal blood pressure effect 2, 5
   • Provides at least 20% mortality reduction and reduces sudden cardiac death 1, 2
   • Requires potassium <5.0 mEq/L and eGFR >30 ml/min/1.73 m² 2, 5

3. ARNI (Sacubitril/Valsartan) or ACE Inhibitor

   • Sacubitril/valsartan 24/26 mg or 49/51 mg twice daily is preferred over ACE inhibitors 2, 7
   • Provides superior mortality reduction (at least 20% better than ACE inhibitors) 1, 2
   • Must wait 36 hours after last ACE inhibitor dose before starting ARNI to avoid angioedema 7
   • If ARNI not tolerated, use ACE inhibitor (enalapril 2.5 mg twice daily) 1, 5
   • Reduce starting dose by half if patient not previously on ACE inhibitor/ARB or on low doses 7

4. Evidence-Based Beta-Blocker (Carvedilol, Metoprolol Succinate, or Bisoprolol)

   • Start at low dose: carvedilol 3.125 mg twice daily, metoprolol succinate 12.5-25 mg daily, or bisoprolol 1.25 mg daily 2, 5
   • Continue beta-blocker during hospitalization unless cardiogenic shock or requiring IV inotropes 3
   • Provides at least 20% mortality reduction and decreases sudden cardiac death 1, 2

Sequencing Strategy for Low Blood Pressure Patients

If systolic blood pressure 90-110 mmHg but adequate perfusion (warm extremities, normal mentation): 2, 5

• Start SGLT2 inhibitor and MRA first (minimal BP effects)
• Add low-dose beta-blocker if heart rate >70 bpm
• Add very low-dose ARNI/ACE inhibitor last
• Never withhold GDMT for asymptomatic hypotension with adequate perfusion 2

Post-Discharge Optimization (Weeks 1-12)

Uptitration Protocol

• Increase one medication at a time every 1-2 weeks using small increments until target doses achieved 1, 2, 5
• Target doses proven in trials: sacubitril/valsartan 97/103 mg twice daily, carvedilol 25-50 mg twice daily, bisoprolol 10 mg daily, metoprolol succinate 200 mg daily, spironolactone 25-50 mg daily 2, 5
• Prioritize SGLT2 inhibitor and MRA first, then beta-blocker, then ARNI 2

Monitoring Requirements

• Check blood pressure, heart rate, renal function (BUN, creatinine), and electrolytes (potassium) at 1-2 weeks after each dose increment 1, 2, 5
• Modest increases in creatinine (up to 30% above baseline) are acceptable and should not prompt discontinuation 2
• If potassium rises to 5.5-6.0 mEq/L, consider potassium binders (patiromer) rather than stopping MRA 2

Critical Contraindications and Medications to Avoid

• Never combine ACE inhibitor with ARNI (risk of angioedema) 1, 2, 7
• Avoid triple combination of ACE inhibitor + ARB + MRA (hyperkalemia and renal dysfunction risk) 1, 2
• Discontinue or avoid NSAIDs as they interfere with RAAS inhibitor efficacy and worsen renal function 1, 5
• Avoid diltiazem or verapamil which increase risk of worsening heart failure 1, 2
• Stop alpha-blockers (tamsulosin, doxazosin) if blood pressure is limiting GDMT optimization 2

Common Pitfalls to Avoid

• Delaying GDMT initiation until after discharge—delayed initiation is associated with never initiating GDMT 1
• Accepting suboptimal doses—only 1% of eligible patients achieve target doses of all medications in real-world practice 2
• Stopping medications for asymptomatic hypotension—discontinuing RAAS inhibitors after hypotension is associated with 2-4 fold higher risk of adverse events 2
• Excessive diuresis before starting ACE inhibitors/ARNI—can precipitate symptomatic hypotension 1, 5
• Using non-evidence-based beta-blockers—only carvedilol, metoprolol succinate, and bisoprolol have proven mortality benefit 2, 5

When to Refer to Advanced Heart Failure Specialist

Use the I-NEED-HELP mnemonic: 1

• IV inotropes required
• NYHA class IIIB/IV or persistently elevated natriuretic peptides
• Ejection fraction ≤35% despite 3-6 months optimal therapy
• Defibrillator shocks
• Hospitalizations >1 in past year
• Edema despite escalating diuretics
• Low blood pressure with high heart rate
• Prognostic medication intolerance or down-titration of GDMT

Special Considerations for SGLT2 Inhibitors in Acute Decompensation

Emerging evidence supports in-hospital initiation of SGLT2 inhibitors during acute decompensated heart failure: 1, 6

• Multiple ongoing trials (EMPULSE, DAPA-ACT-HF-TIMI 68, DICTATE-AHF) are evaluating safety and efficacy of starting SGLT2 inhibitors during hospitalization 1
• One study showed dapagliflozin added to furosemide resulted in significantly greater weight loss, improved diuresis parameters, and better dyspnea scores without affecting potassium or kidney function 6
• Current practice: initiate once patient stabilized (day 2-5 of hospitalization) rather than waiting until outpatient follow-up 1, 2