Characterization and Prediction of Natriuretic Peptide “Nonresponse” During Heart Failure Management: Results From the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) and the NT‐proBNP–Assisted Treatment to Lessen Serial Cardiac Readmissions an

Many proven heart failure (HF) therapies decrease N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) values over time, yet some patients have an NT‐proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT‐proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT‐proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT‐proBNP over time was associated with increased cardiovascular event rates while a decreasing NT‐proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT‐proBNP–Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT‐proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT‐proBNP nonresponse to HF therapy is possible.