Guideline-Directed Medical Therapy for Left Ventricular Ejection Fraction 40-45%

Classification and Treatment

The American College of Cardiology and the American Heart Association recommend that patients with LVEF 40-45% be 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, and should continue or be started on full HFrEF treatment 1, 2
Patients with LVEF 40-45% fall into one of two categories: HFimpEF, previously had HFrEF (LVEF <40%) but improved to >40%, or HFmrEF, newly diagnosed with LVEF 41-49% 1, 2

For HFimpEF, the American College of Cardiology recommends continuing full HFrEF treatment regimen even if symptoms improve or resolve, which is a Class I recommendation with Level of Evidence B-R 1, 2
For HFmrEF, treatment should follow HFrEF guidelines, though evidence is less robust, and the four cornerstone medication classes should be considered 1, 2

The European Society of Cardiology recommends beta-blockers for heart rate control in patients with LVEF ≥40%, with evidence-based beta-blockers (bisoprolol, carvedilol, long-acting metoprolol, or nebivolol) being preferred 4
The American College of Cardiology recommends ACE inhibitors or ARBs for all patients with previous or current HFrEF, which provides high economic value 3, 2
Mineralocorticoid Receptor Antagonists (MRAs) should be considered, particularly for patients with LVEF closer to 40%, and provides high economic value in HFrEF 2
SGLT2 inhibitors should be considered for patients with HFmrEF, and provides intermediate economic value 2
ARNi (Angiotensin Receptor-Neprilysin Inhibitor) should be considered, especially for patients with LVEF closer to 40%, and provides high economic value when used instead of ACEi 2
Diuretics should be used for relief of symptoms due to volume overload 5, 6

Combination therapy should be considered if a single agent does not achieve necessary heart rate target 4
Device therapy considerations, such as ICD and/or CRT, should be considered for patients with LVEF ≤40% and appropriate indications, but is generally not indicated for patients with LVEF 41-45% unless other criteria are met 7

The American College of Cardiology recommends initiating and optimizing the four cornerstone medications, starting with lower doses and titrating up as tolerated, and aiming for at least a GDMT score of 5 for improved outcomes 1, 2
Regular reassessment of LVEF is recommended to guide therapy adjustments 2

Inappropriate medication discontinuation should be avoided, as it increases risk of relapse of HF and LV dysfunction 1, 2
Harmful medications, such as most antiarrhythmic drugs, most calcium channel blockers (except amlodipine), NSAIDs, and thiazolidinediones, should be avoided 3