This secondary analysis of the Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro–Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) randomized clinical trial investigates what variables are associated with success in uptitration of guideline-directed medical therapy after hospital discharge for an acute heart failure admission. The gene discussed is NPPB; the disease is heart failure.