What is the recommended Guideline-Directed Medical Therapy (GDMT) for a patient with a Left Ventricular Ejection Fraction (LVEF) of 40-45%?

Guideline-Directed Medical Therapy (GDMT) for LVEF 40-45%

For patients with LVEF 40-45%, they should continue or be started on full HFrEF treatment as they are classified as having HFimpEF (Heart Failure with improved Ejection Fraction) if previously diagnosed with HFrEF, or HFmrEF (Heart Failure with mildly reduced Ejection Fraction) if newly diagnosed. 1

Classification Based on LVEF

• Patients with LVEF 40-45% fall into one of two categories:
  • HFimpEF: Previously had HFrEF (LVEF <40%) but improved to >40% 1
  • HFmrEF: Newly diagnosed with LVEF 41-49% 1

GDMT for Patients with LVEF 40-45%

First-Line Therapies

• For HFimpEF (previously HFrEF now improved to 40-45%):

  • Continue full HFrEF treatment regimen even if symptoms improve or resolve 1
  • This is a Class I recommendation with Level of Evidence B-R 1

• For HFmrEF (newly diagnosed with LVEF 41-49%):

  • Treatment should follow HFrEF guidelines, though evidence is less robust 1
  • The four cornerstone medication classes should be considered: 2
    1. Renin-angiotensin system inhibitors (ACEi/ARB/ARNi)
    2. Evidence-based beta-blockers
    3. Mineralocorticoid receptor antagonists (MRAs)
    4. Sodium-glucose cotransporter-2 inhibitors (SGLT2i)

Specific Medication Recommendations

1. Beta-blockers:

   • Recommended for heart rate control in patients with LVEF ≥40% 1
   • Evidence-based beta-blockers (bisoprolol, carvedilol, long-acting metoprolol, or nebivolol) are preferred 1, 3

2. ACE inhibitors or ARBs:

   • Recommended for all patients with previous or current HFrEF 1
   • Provides high economic value 1

3. Mineralocorticoid Receptor Antagonists (MRAs):

   • Should be considered, particularly for patients with LVEF closer to 40% 1
   • Provides high economic value in HFrEF 1

4. SGLT2 inhibitors:

   • Should be considered for patients with HFmrEF 1
   • Provides intermediate economic value 1

5. ARNi (Angiotensin Receptor-Neprilysin Inhibitor):

   • Should be considered, especially for patients with LVEF closer to 40% 1
   • Provides high economic value when used instead of ACEi 1

6. Diuretics:

   • Should be used for relief of symptoms due to volume overload 1

Additional Considerations

• Combination therapy should be considered if a single agent does not achieve necessary heart rate target 1

• Device therapy considerations:

  • For patients with LVEF ≤40% and appropriate indications, ICD and/or CRT should be considered 1
  • For patients with LVEF 41-45%, device therapy is generally not indicated unless other criteria are met 1

Implementation Strategy

1. Initiate and optimize the four cornerstone medications:

   • Start with lower doses and titrate up as tolerated 2, 4
   • Aim for at least a GDMT score of 5 (based on combination and dosage of medications) for improved outcomes 4

2. Monitor for improvement in LVEF:

   • Patients who improve from HFrEF to LVEF >40% should continue their HFrEF treatment 1
   • Regular reassessment of LVEF is recommended to guide therapy adjustments 1

3. Specialized care:

   • Referral to a heart failure clinic is associated with higher rates of GDMT initiation and optimization 3

Common Pitfalls and Caveats

• Avoid inappropriate medication discontinuation:

  • Do not discontinue HFrEF therapies even if LVEF improves to >40% and symptoms resolve 1
  • Discontinuation increases risk of relapse of HF and LV dysfunction 1

• Avoid harmful medications:

  • Most antiarrhythmic drugs, most calcium channel blockers (except amlodipine), NSAIDs, and thiazolidinediones should be avoided 1
  • Long-term use of infused positive inotropic drugs is potentially harmful 1

• Medication optimization at discharge:

  • Optimizing GDMT before discharge for hospitalized patients is associated with lower 1-year mortality 5

• Consider impact on secondary mitral regurgitation:

  • GDMT titration is associated with a three-fold increased chance of reducing secondary mitral regurgitation severity 6
  • ARNi and combinations of RASi+MRA, BB+MRA, or all three together significantly improve secondary mitral regurgitation 6

By following these guidelines, patients with LVEF 40-45% can receive appropriate therapy that reduces mortality, hospitalization, and improves quality of life.