In contrast with the PROTECT trial, the GUIDE-IT trial (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) failed to demonstrate that routine NT-proBNP-guided therapy (with a goal of < 1,000 pg/mL) was superior to usual care in high-risk patients with HFrEF with respect to the primary composite outcome of time-to-first HF hospitalization and cardiovascular mortality [31]. The gene discussed is NPPB; the disease is hydrops fetalis.