<h4>Background</h4>We aim to validate NT-proBNP nonresponse score (NNRS) previously derived from the PROTECT and BATTLESCARRED studies in comparison with standard health status measures in predicting natriuretic peptide responses in patients with heart failure with reduced ejection fraction.<h4>Methods</h4>Data on the GUIDE-IT trial were used to derive the NNRS based on 4 predictors including baseline NT-proBNP, heart rate, NYHA functional class, and history of atrial fibrillation. The gene discussed is NPPB; the disease is heart failure.