What is the recommended initial treatment for a patient with an ejection fraction of 35 percent?

Initial Treatment for a Patient with an Ejection Fraction of 35%

The recommended initial treatment for a patient with an ejection fraction of 35% should include a combination of an ACE inhibitor (or ARB), beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor as foundational therapy. 1

Foundational Pharmacotherapy

First-Line Medications

1. ACE inhibitor, ARB, or ARNI

   • ACE inhibitors should be started and continued indefinitely in all patients with left ventricular ejection fraction <40% 1
   • Examples include enalapril, which is indicated for treatment of symptomatic heart failure and asymptomatic left ventricular dysfunction (ejection fraction ≤35%) 2
   • ARBs are an alternative for patients who cannot tolerate ACE inhibitors 1

2. Beta-blockers

   • Should be used in all patients with left ventricular ejection fraction ≤35% 1
   • Limited to evidence-based agents: bisoprolol, carvedilol, sustained-release metoprolol succinate, or nebivolol 1
   • Beta-blockers improve left ventricular ejection fraction, all-cause mortality, and cardiovascular mortality in patients with mid-range ejection fraction (40-49%) and reduced ejection fraction 1

3. Mineralocorticoid receptor antagonists (MRAs)

   • Should be used in patients with NYHA class II-IV heart failure who have an ejection fraction ≤35% 1
   • Aldosterone receptor antagonists are recommended in post-myocardial infarction patients with ejection fraction <40% who have either diabetes or heart failure 1

4. SGLT2 inhibitors

   • Recent addition to foundational therapy for HFrEF 1
   • Should be initiated early along with other foundational therapies

Symptom Management

• Loop diuretics should be used in patients with evidence of fluid retention 1
• Diuretics should be monitored for adverse effects such as electrolyte abnormalities and dehydration 1

Implementation Strategy

The European Society of Cardiology recommends a structured approach to initiating these therapies:

1. Start all four foundational therapies as quickly as possible 3
2. Begin with low doses and titrate as tolerated
   • Even low doses of foundational therapies provide early benefits 3
   • The "target dose" in clinical trials was often not reached, and benefits were demonstrated with average doses less than target 3
3. Monitor for side effects, particularly:
   • Hyperkalemia when combining ACE inhibitors with MRAs 4
   • Renal function changes (up to 10-15% decline in eGFR with ACE inhibitors may still be associated with mortality benefit) 5

Device Therapy Considerations

For patients with ejection fraction ≤35%, consider device therapy evaluation:

• ICD (Implantable Cardioverter Defibrillator) for primary prevention in patients with NYHA class II-III on guideline-directed medical therapy 1
• CRT (Cardiac Resynchronization Therapy) for patients in sinus rhythm with NYHA class II-IV symptoms, QRS duration ≥120 ms (especially with LBBB morphology) 1

Follow-up and Monitoring

• Early follow-up (within 4 weeks) after initiating therapy 1
• Regular monitoring of:
  • Renal function and electrolytes, particularly when using ACE inhibitors with MRAs 4
  • Blood pressure and heart rate
  • Symptoms and functional capacity

Common Pitfalls to Avoid

1. Inadequate dosing: While starting with low doses is appropriate, aim to titrate to target doses as tolerated
2. Premature discontinuation of ACE inhibitors due to moderate eGFR decline (up to 35% decline may still be associated with clinical benefit) 5
3. Failure to initiate all four foundational therapies due to concerns about polypharmacy
4. Not monitoring for hyperkalemia when combining ACE inhibitors and MRAs 4
5. Overlooking device therapy evaluation in eligible patients

By implementing this comprehensive pharmacologic approach early, you can significantly improve symptoms, reduce hospitalizations, and decrease mortality in patients with an ejection fraction of 35%.