The combined ceramide heart failure score (CHFS) was independently associated with adverse outcomes [Hazard Ratio, 2.80 (95% CI: 1.78–4.40; P < 0.001); 2.68 995% CI: 1.12–6.46; P = 0.028)] and improved the predictive value of Acute Decompensated Heart Failure National Registry score and BNP [net reclassification index, 0.34 (95% confidence interval, CI: 0.19–0.50); 0.42 (95% CI: 0.13–0.70)] in the discovery and validation set, respectively. This evidence concerns the gene NPPB and heart failure.