Furthermore, in the context of advanced age and common comorbidities (including impaired renal function, alterations in body composition, and arrhythmias), the use of readily available biomarkers of cardiac overload, such as NT-proBNP, maintains a discriminative role in the diagnostic work-up of HF only at extreme values (rule-out or rule-in) [13]. This evidence concerns the gene NPPB and hydrops fetalis.