The PROVE-HF study [5] (Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure) found that the magnitude of improvement in indices of cardiac structure and function was consistent across subgroups that were not represented in the PARADIGM-HF trial [2] (namely those with NT-proBNP levels lower than those determined by the entry criteria for PARADIGM-HF [2], those not achieving the target S/V dose, and those with new-onset HF or naïve to ACE inhibitor and ARB). The gene discussed is ACE; the disease is hydrops fetalis.