What is the management approach for a patient with a severely reduced ejection fraction (EF) of 25%?

Management of Heart Failure with Ejection Fraction of 25%

For a patient with severely reduced ejection fraction of 25%, initiate all four core medication classes of guideline-directed medical therapy (GDMT) simultaneously at low doses: SGLT2 inhibitor, mineralocorticoid receptor antagonist (MRA), beta-blocker, and ARNI (or ACE inhibitor/ARB if ARNI unavailable), with gradual titration to target doses. 1

Immediate Pharmacological Management

First-Line Therapy: Four Pillars of GDMT

Start these medications together, not sequentially, as each provides independent mortality benefit 1:

1. SGLT2 Inhibitor (Start First)

• Initiate empagliflozin 10 mg daily or dapagliflozin 10 mg daily immediately 1
• Provides rapid benefits with minimal blood pressure effects 1
• Effective even with moderate kidney dysfunction (eGFR ≥30 mL/min/1.73 m² for empagliflozin, ≥20 mL/min/1.73 m² for dapagliflozin) 1
• No diabetes required for indication 2

2. Mineralocorticoid Receptor Antagonist (Start Early)

• Begin spironolactone 25 mg daily (or eplerenone 25 mg daily) 1, 3
• In the landmark RALES trial, spironolactone reduced all-cause mortality by 30% in patients with EF ≤35% and NYHA class III-IV symptoms 3
• Minimal blood pressure effects make early initiation feasible 1
• Monitor potassium and creatinine closely; exclude if baseline K+ >5.0 mEq/L or creatinine >2.5 mg/dL 3

3. Beta-Blocker

• Initiate evidence-based beta-blocker (carvedilol, metoprolol succinate, or bisoprolol) at low dose 1
• Start if heart rate >70 bpm 1
• Selective β₁ receptor blockers may have lesser blood pressure-lowering effects 1
• Titrate every 2-4 weeks to target doses 1

4. ARNI (Angiotensin Receptor-Neprilysin Inhibitor)

• Sacubitril/valsartan is preferred over ACE inhibitors or ARBs for NYHA class II-III symptoms 1, 4
• Start with low dose (24/26 mg or 49/51 mg twice daily) 1, 4
• If ARNI not feasible, use ACE inhibitor or ARB 1
• Critical pitfall: Must wait 36 hours after stopping ACE inhibitor before starting ARNI to avoid angioedema 4

Titration Strategy

• Start all medications at low doses simultaneously, beginning with SGLT2i and MRA due to minimal blood pressure impact 1
• Titrate gradually every 2-4 weeks as tolerated 1
• Target doses shown to improve outcomes in clinical trials:
  • Spironolactone: 25-50 mg daily 3
  • Sacubitril/valsartan: 97/103 mg twice daily 4
  • Beta-blockers: carvedilol 25 mg twice daily, metoprolol succinate 200 mg daily, or bisoprolol 10 mg daily 2

Additional Symptomatic Management

Diuretics (Loop Diuretics)

• Use as needed for volume management and symptom control 2
• Not proven to reduce mortality but essential for congestion management 2
• Adjust dose based on daily weights and clinical signs of fluid retention 1

Digoxin

• Consider for persistent symptoms despite optimal GDMT 2
• May reduce hospitalizations but does not improve mortality 2

Monitoring Protocol

Initial Phase (First 12 Weeks)

• Check serum potassium, creatinine, and eGFR every 2-4 weeks during titration 1, 3
• Monitor blood pressure and heart rate at each visit 1
• Daily weight monitoring by patient 1
• Follow-up visits every 2-4 weeks during active titration 1

Maintenance Phase

• Laboratory monitoring every 3 months for first year, then every 6 months 3
• Assess symptoms, vital signs, fluid status at each visit 1
• Monitor for signs of hypoperfusion or worsening congestion 1

Device Therapy Considerations

Implantable Cardioverter-Defibrillator (ICD)

• Consider for primary prevention if EF ≤35% persists after ≥3 months of optimal GDMT 2
• NYHA class II-III symptoms required 2
• Expected survival >1 year with good functional status 2

Cardiac Resynchronization Therapy (CRT)

• Evaluate if QRS duration ≥150 ms with left bundle branch block morphology 2
• Particularly beneficial in patients with EF ≤35% and NYHA class II-IV despite optimal GDMT 2

Revascularization Assessment

Coronary Evaluation

• CABG or percutaneous intervention indicated if angina present with suitable coronary anatomy, especially left main stenosis >50% 2
• CABG reasonable to improve survival with significant multivessel CAD when viable myocardium present 2
• Consider CABG even without proven viability in severe LV dysfunction (EF <35%) with operable coronary anatomy 2

Critical Pitfalls to Avoid

1. Sequential Rather Than Simultaneous Initiation

• Do not wait to start one medication before adding another 1
• Each medication class provides independent benefit 1

2. Inadequate Dosing

• Aim for target doses proven in clinical trials, not just "some dose" 5
• Underdosing is a common reason for suboptimal outcomes 5

3. Premature Discontinuation for Asymptomatic Hypotension

• Low blood pressure without symptoms or hypoperfusion is not an indication to reduce GDMT 2
• Systolic BP 80-90 mmHg is often well-tolerated if patient asymptomatic 2

4. Stopping GDMT During Hospitalization

• Continue GDMT during acute decompensation unless hemodynamic instability or contraindications present 1
• Discontinuation associated with worse outcomes than the side effects themselves 2

5. Delaying SGLT2 Inhibitor Initiation

• Strong evidence supports early use regardless of diabetes status 5, 1
• Provides benefits within weeks of initiation 1

Special Considerations for Low Blood Pressure

If systolic BP <90 mmHg but patient asymptomatic:

• Prioritize SGLT2i and MRA first (minimal BP effects) 2
• Add beta-blocker and ARNI more gradually 2
• Evaluate for non-cardiac causes of hypotension 2

If symptomatic hypotension or evidence of hypoperfusion:

• Review and discontinue non-essential BP-lowering medications 2
• Consider reducing or temporarily holding ARNI or beta-blocker before stopping SGLT2i or MRA 2
• Refer to heart failure specialist for management optimization 2

Prognosis Context

With EF of 25%, this patient faces significantly elevated cardiovascular risk—each 10% reduction in EF below 45% increases mortality hazard by 39% 6. However, approximately 1 in 4 patients with HFrEF show recovery of systolic function with optimal GDMT, and these recovered patients have dramatically improved outcomes compared to those with persistent reduced EF 7. This underscores the critical importance of aggressive, comprehensive GDMT implementation.