Serial secretoneurin measurement and risk of ventricular arrhythmias and death in patients with left ventricular systolic dysfunction

Background

Secretoneurin, a member of the granin protein family, is associated with the risk of mortality in patients with acute and chronic heart failure. Secretoneurin may play an important role in cardiomyocyte calcium handling, suggesting that it may influence cardiac arrhythmia risk. We hypothesized that baseline and serial measurements of circulating secretoneurin are associated with the risk of incident ventricular tachyarrhythmias (VA) and death, and that serial measurement would provide prognostic information beyond baseline values.

Methods

We measured circulating secretoneurin concentrations in blood samples obtained at 3-month intervals for one year in a prospectively enrolled cohort of ambulatory patients with left ventricular ejection fraction (LVEF) ≤ 35 % and a primary-prevention implanted cardioverter defibrillator (ICD). Associations between secretoneurin modeled as a time-dependent variable and the incidences of VA and death were assessed.

Results

154 patients (66 ± 14 years, LVEF 23 ± 8 %) were included in the analysis. During one-year follow-up, 26 (17 %) patients experienced VA, and 16 (10 %) died. Adjusting for age, sex, eGFR, and LVEF, baseline secretoneurin concentration was associated with the risk of death (hazard ratio (HR) per 10 pmol/L increase: 1.14 (95 % CI: 1.02–1.27), p = 0.020) but not VA (HR: 0.98 (0.81–1.19), p = 0.856). Using serial measurements at 3-month intervals, time-varying secretoneurin was associated with a similarly higher risk of death (HR: 1.14 (1.02–1.27), p = 0.017) but not of VA (HR: 0.97 (0.81–1.17), p = 0.776).

Conclusion

In stable ambulatory patients with reduced LV systolic function and a primary prevention indication for ICD, secretoneurin concentration was associated with the risk of death but not ventricular tachyarrhythmia.