A prospective study (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment, GUIDE-IT) to determine the impact of NT-proBNP-guided therapy on time to CV death or HF hospitalization at 12 months in ∼1100 patients with HFrEF when compared with usual care was recently terminated due to futility, with no difference in the primary outcome observed between treatment groups [34–36]. This evidence concerns the gene NPPB and hydrops fetalis.