What is the protocol for improving ejection fraction?

Protocol for Improving Ejection Fraction in Heart Failure with Reduced Ejection Fraction (HFrEF)

The cornerstone of improving ejection fraction in heart failure patients is implementing quadruple therapy with ARNI/RAS inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors, which can reduce mortality by up to 73% over two years and extend life expectancy by approximately 6 years in a 55-year-old patient. 1

First-Line Pharmacological Therapy

Step 1: Initiate Foundation Medications

• ACE inhibitor/ARB or ARNI:

  • Start with an ACE inhibitor (e.g., lisinopril, ramipril) or ARB 2
  • Consider switching to sacubitril/valsartan (ARNI) after clinical stability 2
  • When switching from ACE inhibitor to ARNI, observe a mandatory 36-hour washout period to avoid angioedema 1
  • No washout period required when switching from ARB to ARNI 1

• Beta-blocker (start simultaneously or in rapid sequence with ACE inhibitor/ARB/ARNI):

  • Use evidence-based beta-blockers: carvedilol, metoprolol succinate, or bisoprolol 2
  • Start at low dose and titrate gradually every 2-4 weeks as tolerated 3
  • Continue beta-blocker therapy even during hospitalization unless hemodynamically unstable 1
  • Beta-blockers improve ejection fraction by an average of 5.7-8.6 EF units across different agents 4

Step 2: Add Additional Life-Saving Therapies

• Mineralocorticoid Receptor Antagonist (MRA):

  • Add when LVEF ≤35% and/or symptoms persist (NYHA II-IV) 5
  • Monitor renal function and potassium levels closely 6
  • Only 33% of eligible patients receive MRAs despite clear mortality benefit 2

• SGLT2 Inhibitor:

  • Add dapagliflozin or empagliflozin regardless of diabetes status 2
  • High-quality evidence shows improved HRQoL with SGLT2 inhibitors (SMD 0.16,95% CI 0.08-0.23) 1

Step 3: Symptom Management

• Loop Diuretics:
  • Use for symptom management and volume control 2
  • Adjust dose to maintain euvolemia while minimizing adverse effects 1
  • When diuresis is inadequate, consider:
    1. Higher doses of loop diuretics
    2. Addition of a second diuretic (metolazone, spironolactone, or IV chlorothiazide)
    3. Continuous infusion of a loop diuretic 1

Optimization Strategy

Titration Approach

• Aim for maximum tolerated doses of all medications 5
• Consider simultaneous or rapid sequence initiation of GDMT 1
• Titrate medications every 2-4 weeks as tolerated 1
• For patients with hypotension or renal dysfunction:
  • Start with half the usual recommended dose 7
  • Prioritize reaching target doses of beta-blockers and ARNI/ACEi/ARB before maximizing MRAs 1

Monitoring Protocol

• Short-term (2-4 weeks):

  • Renal function
  • Electrolytes
  • Blood pressure
  • Assessment for medication tolerance and side effects 2

• Medium-term (3 months):

  • Reassess LVEF and symptoms
  • Optimize GDMT to target doses 2
  • Consider device therapy if appropriate

Device Therapy Considerations

• ICD: Consider for primary prevention after optimizing medical therapy for 3 months if EF remains ≤35% 2

• CRT-D: Consider if QRS ≥150 ms or LBBB with QRS ≥130 ms 2

Common Pitfalls to Avoid

1. Premature discontinuation of GDMT during hospitalization or due to mild renal function changes or asymptomatic hypotension 2

2. Discontinuing therapy if EF improves - Continue GDMT indefinitely, even if LVEF improves to >40% (HFimpEF) 2

3. Inadequate dose titration - Many patients remain on suboptimal doses of medications 1

4. Clinical inertia - Delaying addition of proven therapies or failing to titrate to target doses 1

5. Focusing only on ejection fraction - Remember that improvements in quality of life are also important outcomes 1

Special Considerations

• Hospitalized patients: Continue GDMT during hospitalization unless hemodynamically unstable 1

  • Withdrawal of ACEi/ARB during hospitalization is associated with higher mortality (HRadj 1.92; 95% CI 1.32-2.81) 8

• Patients with idiopathic cardiomyopathy may show greater EF improvement with beta-blockers (average increase 8.5 EF units) compared to those with ischemic cardiomyopathy (6.0 EF units) 4

By following this comprehensive protocol for improving ejection fraction in heart failure patients, clinicians can significantly reduce mortality, decrease hospitalizations, and improve quality of life for their patients.