N-terminal pro-B-type natriuretic peptide for prediction of ventricular arrhythmias: Data from the SMASH study

Abstract

Background: Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations predict heart failure (HF) and mortality, but whether NT-proBNP predicts ventricular arrhythmias (VA) is not clear.

Hypothesis: We hypothesize that high NT-proBNP concentrations associate with the risk of incident VA, defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia.

Methods: In a prospective, observational study of patients treated with implantable cardioverter defibrillator (ICD), we analyzed NT-proBNP concentrations at baseline and after mean 1.4 years in association to incident VA.

Results: We included 490 patients (age 66 ± 12 years, 83% men) out of whom 51% had a primary prevention ICD indication. The median NT-proBNP concentration was 567 (25-75 percentile 203-1480) ng/L and patients with higher concentrations were older with more HF and ICD for primary prevention. During mean 3.1 ± 0.7 years, 137 patients (28%) had ≥1 VA. Baseline NT-proBNP concentrations were associated with the risk of incident VA (hazard ratio [HR]: 1.39, 95% confidence interval [95% CI]: 1.22-1.58, p < .001), HF hospitalizations (HR: 3.11, 95% CI: 2.53-3.82, p < .001), and all-cause mortality (HR: 2.49, 95% CI: 2.04-3.03, p < .001), which persisted after adjusting for age, sex, body mass index, coronary artery disease, HF, renal function, and left ventricular ejection fraction. The association with VA was stronger in secondary versus primary prevention ICD indication: HR: 1.59 (95% CI: 1.34-1.88 C-statistics 0.71) versus HR: 1.24, 95% CI: 1.02-1.51, C-statistics 0.55), p-for-interaction = 0.06. Changes in NT-proBNP during the first 1.4 years did not associate with subsequent VA.

Conclusions: NT-proBNP concentrations are associated with the risk of incident VA after adjustment for established risk factors, with the strongest association in patients with a secondary prevention ICD indication.

Keywords: ICD; N-terminal pro-B-type natriuretic peptide; NT-proBNP; implantable cardioverter defibrillator; sudden cardiac death; ventricular arrhythmias.