Natriuretic peptides testing and survival prediction models for chronic heart failure: a systematic review of added prognostic value.

BACKGROUND: High natriuretic peptide levels are associated with a poor outcome in adults with chronic heart failure (CHF). However, the incremented prediction accuracy of multivariable prognostic models after adding B-type natriuretic peptide (BNP) and/or N-terminal proBNP (NT-proBNP) remains unclear. METHODS: We carried out a systematic review narrative analysis of added-value studies of BNP and NT-proBNP in CHF prognostication. Primary clinical studies investigating prognostic model development or validation in adult participants with CHF were included. Any studies of individual factors' association with patient outcomes, treatment efficacy, or those using patients with transplant/ventricular assist devices, ≥ 10% of patients with advanced HF, or significant comorbidities, HF secondary to congenital/reversible conditions, or ≥ 33% of patients with valvular HF were excluded. The databases MEDLINE, Embase, Science Citation Index, and Cochrane Prognosis Methods Group Database were searched from January 1990 to February 2024. Predictive performance was measured in terms of discrimination and calibration, the added value in terms of the c-statistic difference before and after adding BNP and/or NT-proBNP to a base model, and the risk reclassification, namely, net reclassification index (NRI) and integrated discrimination improvement (IDI). Risk of bias assessment used the Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: Fourteen added-value studies comprising a total of 50,949 individuals were included. Both BNP and NT-proBNP consistently improved mortality prediction performance, but studies only presented separately before and after c-statistics, without formally testing for statistically significant differences. Meta-analysis was impossible due to missing data on the change in predictive performance and data heterogeneity. All studies reported discrimination. Few reported calibration, NRI, and IDI. All studies except one were deemed to be at high risk of bias, whereas 50% showed high applicability to the review question, with only 14% scoring high for applicability concern, and the rest were unclear. CONCLUSIONS: Improving consistency in researching and reporting the added value of natriuretic peptide testing to predict mortality in chronic heart failure patients could facilitate summarizing and interpreting the results more meaningfully. REGISTRATION: This review is a refinement of the methods and a search update of the review of added-value biomarkers in HF prognosis (PROSPERO registration number: CRD42019086993).