In the Irbesartan in Patients with Heart Failure and Preserved Systolic Function Study (I-PRESERVE), which enrolled 4128 patients with HF and an LVEF ≥ 45% for a mean follow-up of 49.5 months, NT-proBNP above the median value of 339 ng/L was independently associated with an increased risk of the primary composite endpoint of all-cause death and cardiovascular hospitalization in patients with LVEF ≥ 45% [35]. This evidence concerns the gene NPPB and hydrops fetalis.