BACKGROUND: 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. METHODS: 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 discriminative capacity of the NNRS and health status measures for having NT-proBNP >
1,000 pg/mL at 12 months was assessed and compared with baseline or follow-up health status measures including Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), Duke Activity Status Index (DASI), and 6-minute walk distance. Multivariable logistic regression analysis was used to determine the predictive value of the score and health status measures greater than the median values for NT-proBNP response with adjustment for age, sex, body mass index, comorbidities, baseline creatinine and NT-proBNP levels. RESULTS: Among 877 patients, 252 (28.7%) patients had NT-proBNP >
1,000 pg/mL at 12 months. The discriminative capacity of the NT-proBNP nonresponse score was 0.72 (95% CI, 0.67-0.77). After adjusting for covariates, only NNRS (P = .044) and KCCQ-OSS (P = .002) remained predictive for NT-proBNP nonresponse at 12 months. CONCLUSION: NT-proBNP nonresponse score and KCCQ-OSS was associated with persistently elevated NT-proBNP 12 months independently of baseline NT-proBNP levels.