A 50-year-old man with HFrEF (LVEF 28%) is on optimal guideline-directed medical therapy: ACE inhibitor, beta-blocker, MRA, and dapagliflozin. He remains NYHA Class III despite 3 months of optimization. QRS duration is 148 ms with LBBB morphology. LVEF remains <35%. What is the next recommended therapy?

• A Add digoxin for symptom control
• B Cardiac resynchronization therapy (CRT-D) — Class I indication
• C Intravenous milrinone as bridge to transplant
• D Switch ACE inhibitor to sacubitril-valsartan (ARNI) ✓

Explanation

In this scenario, all four pillars of HFrEF therapy (ACE inhibitor, beta-blocker, MRA, SGLT2i) are in place. CRT is a Class I indication when QRS ≥150 ms with LBBB AND LVEF ≤35% despite GDMT — his QRS of 148 ms falls just below the threshold (marginal zone 130-149 ms with LBBB is Class IIa). However, the question specifies ACE inhibitor rather than sacubitril-valsartan — the PARADIGM-HF trial showed ARNI (sacubitril-valsartan) reduces cardiovascular mortality by 20% vs. enalapril in HFrEF. Switching to ARNI is the recommended pharmacological upgrade at this stage per 2021 ESC HF guidelines. CRT remains a concurrent consideration but ARNI switch is the immediate next pharmacological step.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.