Conversely, the disadvantages of using NT-proBNP in CHF mortality prognostication — namely its varying normal ranges depending on patient age and gender, and its half-life — were found in a 2025 paper assessing the use of the biomarker systemic immune-inflammatory index (SII) for mortality prediction in HF with reduced ejection fraction (HFrEF). This evidence concerns the gene NPPB and hydrops fetalis.