What is the recommended management for an adult patient with symptomatic systolic heart failure (HFrEF)?

Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

All adult patients with symptomatic HFrEF should receive quadruple therapy with four foundational medication classes started simultaneously as soon as possible after diagnosis: an SGLT2 inhibitor, a mineralocorticoid receptor antagonist (MRA), a beta-blocker, and an ARNI (or ACE inhibitor if ARNI not tolerated), plus loop diuretics for volume management. 1

Initial Pharmacologic Management

Foundational Quadruple Therapy

The current standard of care requires initiating all four medication classes together, which provides approximately 73% mortality reduction: 1

• SGLT2 Inhibitors (empagliflozin or dapagliflozin): Reduce cardiovascular death and HF hospitalization regardless of diabetes status, with benefits occurring within weeks 1

  • Start immediately upon diagnosis 1
  • Can be used if eGFR ≥30 mL/min/1.73 m² for empagliflozin, or ≥20 mL/min/1.73 m² for dapagliflozin 1

• Mineralocorticoid Receptor Antagonists (spironolactone or eplerenone): Provide at least 20% mortality reduction and reduce sudden cardiac death 1

  • Start with low dose (6.25-12.5 mg spironolactone daily or 12.5 mg every other day) 1
  • Can be used if eGFR >30 mL/min/1.73 m² 1
  • Requires close monitoring of potassium levels and renal function 2

• Beta-Blockers (carvedilol, metoprolol succinate, or bisoprolol): Essential for mortality reduction 2, 1

  • Target doses: carvedilol 25 mg twice daily, metoprolol succinate 200 mg daily, bisoprolol 10 mg daily 1
  • Start at low doses and uptitrate gradually 1

• ARNI (sacubitril/valsartan) or ACE Inhibitors: Reduce cardiovascular death and hospitalization 3

  • ARNI is preferred over ACE inhibitors when tolerated 2
  • Target dose for ARNI: 97/103 mg twice daily 1
  • Use ACE inhibitor if ARNI not tolerated due to cost, side effects, or if eGFR <30 mL/min/1.73 m² 1
  • If ACE inhibitor causes intolerable cough or angioedema, switch to ARB 2

Diuretics for Volume Management

• Loop diuretics are essential for symptom relief in patients with fluid overload 2
• Dose should be adjusted based on volume status, not used at fixed doses 2
• Meticulous control of fluid retention is critical 2

Titration Strategy

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

• Check serum creatinine, eGFR, and potassium at 1-2 weeks after each dose increment 1
• Modest increases in creatinine (up to 30% above baseline) are acceptable and should NOT prompt discontinuation 1
• Do not withhold therapy for asymptomatic low blood pressure if perfusion is adequate 1

Additional Therapies for Specific Situations

Second-Line or Adjunctive Agents

• Ivabradine: For patients with heart rate >70 bpm despite beta-blocker therapy, in sinus rhythm 2, 4
• Hydralazine plus isosorbide dinitrate: Particularly beneficial in African American patients or those intolerant to ACE inhibitors/ARBs/ARNI 2
• Digoxin: Can improve symptoms and reduce hospitalizations, especially in patients with atrial fibrillation 2, 5
  • Use low doses targeting serum concentration <1 ng/mL 5
• Vericiguat: Reduces heart failure hospitalization in high-risk patients with recent decompensation 4

Device Therapies

• Cardiac Resynchronization Therapy (CRT): For patients with LVEF <35% and QRS duration ≥150 ms, or 120-149 ms with mechanical dyssynchrony 2
• Implantable Cardioverter-Defibrillator (ICD): For patients with LVEF <35% and appropriate life expectancy 2

Management of Acute Decompensation

When patients present with acute HF exacerbation:

1. Immediate IV loop diuretics within 60 minutes of presentation, with initial dose equaling or exceeding chronic oral daily dose 6
2. Continue existing GDMT unless contraindications or hemodynamic instability exist 6
3. Assess volume status and perfusion simultaneously with treatment initiation 6
4. Consider IV vasodilators (nitroglycerin or nitroprusside) in patients with severe fluid overload without hypotension 2, 6
5. Avoid routine inotropes in normotensive patients without evidence of decreased organ perfusion 2

Initiating GDMT During Hospitalization

For newly diagnosed patients admitted with decompensated HF: 6

• Day 1: Start SGLT2 inhibitor and MRA once adequate perfusion confirmed and patient responding to diuretics 6
• Days 2-3: Initiate low-dose ACE inhibitor/ARB/ARNI after volume optimization, when blood pressure adequate (SBP >90-100 mmHg) 6
• Days 3-5: Start low-dose beta-blocker only after volume optimization achieved, IV vasodilators/inotropes discontinued, and clinical stability confirmed 6
• Before discharge: Ensure all four medication classes initiated and uptitration plan established 6

Transitions of Care and Follow-Up

All patients should be enrolled in multidisciplinary disease management programs coordinated by HF specialists, including HF nurses. 2, 7

Key components include: 2

• Early outpatient follow-up within 7-14 days of discharge 2
• Comprehensive written discharge instructions covering: diet, medications with emphasis on adherence and uptitration, activity level, follow-up appointments, daily weight monitoring, and symptom management 2
• Medication reconciliation and systematic monitoring of GDMT 2
• Patient education on self-care and symptom recognition 7

Critical Pitfalls to Avoid

• Do not discontinue GDMT for mild renal function decrease (up to 30% creatinine increase) or asymptomatic blood pressure reduction 1, 6
• Do not delay initiation of all four medication classes—simultaneous initiation is now standard 1
• Do not use calcium channel blockers (except amlodipine if needed for other indications) as they worsen outcomes 2, 5
• Do not use routine intermittent inotrope infusions for chronic management 2
• Do not rely on telemonitoring alone without comprehensive specialist care—it has not consistently shown benefit 7
• Do not undertitrate medications—only 73% of eligible patients receive ACE inhibitors/ARBs/ARNIs, 66% receive beta-blockers, and 33% receive MRAs, representing a major quality gap 6

Monitoring and Optimization

• Serial monitoring of natriuretic peptides can guide therapy in selected patients, particularly those with problematic uptitration or history of hospitalization 2
• Regular assessment of adherence to evidence-based therapies as a quality metric 7
• Maintain communication between cardiologists, primary care clinicians, and HF nurses 7
• Address comorbidities including renal dysfunction, diabetes, hypertension, and coronary artery disease 2

Refractory End-Stage Heart Failure

For patients with persistent severe symptoms despite optimal medical therapy: 2

• Referral to HF program with expertise in advanced therapies 2
• Consider cardiac transplantation evaluation 2
• Consider left ventricular assist device as destination therapy in highly selected patients 2
• Discuss end-of-life care options and defibrillator deactivation when appropriate 2