These newer studies, often referred to as “second-generation trials,” are characterized by enhanced design rigor, broader inclusion criteria (e.g., chronic kidney disease (CKD) and HF with preserved ejection fraction (HFpEF)), and expanded endpoints, including NT-proBNP levels, epicardial adipose tissue modulation, and HF-specific metrics. The gene discussed is NPPB; the disease is hydrops fetalis.