Durable Remission After Triple Therapy in New-Onset HFrEF

BACKGROUND: Although quadruple guideline-directed medical therapy (GDMT) improves outcomes in heart failure with reduced ejection fraction (HFrEF), the optimal method to initiate and sequence quadruple therapy remains uncertain. CASE SUMMARY: Two patients with new-onset HFrEF achieved remission with symptom resolution and near-normalization of left ventricular ejection fraction and elevated N-terminal-pro-B-type natriuretic peptide levels after administration of angiotensin-converting enzyme inhibitor, beta-blocker, and mineralocorticoid receptor antagonist, without angiotensin receptor-neprilysin inhibitor or sodium glucose cotransporter-2 inhibitor. One patient received cardiac resynchronization therapy, and the other patient stopped using alcohol and prescription amphetamine/dextroamphetamine (Adderall). Remission has lasted ≥12 years in both patients. DISCUSSION: Methods are needed to identify which patients with new-onset HFrEF can achieve remission with fewer drugs than quadruple therapy. This personalized GDMT strategy would reduce costs and the risks of drug-related side effects. TAKE-HOME MESSAGE: Durable remission from new-onset HFrEF can be achieved with fewer drugs than quadruple GDMT. Diagnostic tools are needed to identify such patients.