Gray zone NT-proBNP values and long-term outcomes in emergency department patients without prior heart failure

The clinical significance of gray zone N-terminal pro-B-type natriuretic peptide (NT-proBNP) values in the emergency department (ED) remains poorly defined in patients without prior heart failure (HF). We aimed to determine whether, among ED patients without prior HF who did not meet age-adjusted rule-in criteria, gray zone NT-proBNP values were associated with worse long-term outcomes compared with rule-out values.

This retrospective, observational study included consecutive patients presenting to a tertiary care ED between March and August 2022 who underwent NT-proBNP testing. Patients with prior HF or NT-proBNP values above age-adjusted rule-in thresholds were excluded. First HF hospitalization and all-cause mortality were analyzed as 2 separate, independent outcomes.

A total of 454 patients were included, of whom 228 (50.2%) had gray zone NT-proBNP values and 226 (49.8%) had rule-out values. During a median follow-up of 2.7 years, patients with gray zone values had significantly higher rates of first HF hospitalization (24.1% vs 2.2%) and mortality (36.4% vs 5.3%). After multivariable adjustment, gray zone NT-proBNP values were associated with first HF hospitalization (subdistribution hazard ratio [HR], 6.53; 95%CI, 2.38-17.89; P <  .001) and all-cause mortality (HR, 4.59; 95%CI, 2.35-8.94; P <  .001).

In ED patients without prior HF, gray zone NT-proBNP values were associated with higher long-term risks of HF hospitalization and all-cause mortality compared with rule-out values. Prospective studies are needed to determine whether structured evaluation of this population improves clinical outcomes.