Prognostic Value of Multiple Circulating Biomarkers for Ventricular Arrhythmias in Left Ventricular Hypertrabeculation　― Longitudinal Cohort Study ―

Abstract

Background: Ventricular arrhythmia (VA) is an independent risk factor for adverse outcomes in patients with left ventricular hypertrabeculation (LVHT). This study explored the predictive value of biomarkers for VAs in LVHT.

Methods and Results: This cohort study retrospectively enrolled 265 LVHT patients (mean [±SD] age 44.2±17.0 years, 65.7% male) with data available for N-terminal pro B-type natriuretic peptide, big endothelin-1, high-sensitivity C-reactive protein, uric acid, and free fatty acid. The primary outcome was a composite of non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, and appropriate implantable cardioverter defibrillator therapy. Over a median follow-up of 4.34 years, 82 (30.9%) patients experienced VAs. Multivariable Cox regression analysis revealed that baseline concentrations of big endothelin-1 were independently associated with the occurrence of VAs (hazard ratio 1.513; 95% confidence interval 1.136–2.013; P=0.005). Restricted cubic spline analysis showed that susceptibility to VAs increased markedly with increases in big endothelin-1 concentrations. Subgroup analysis revealed that LVHT patients with big endothelin-1 concentrations >0.63 pmol/L should be closely monitored for VAs, particularly when higher concentrations are accompanied by cardiomyopathies, left ventricular (LV) end-diastolic diameters ≥60 mm, or LV ejection fraction <50%. Individuals with elevated big endothelin-1 concentrations and isolated hypertrabeculation in the LV lateral wall had a significantly greater risk of VAs (log-rank P=0.002).

Conclusions: Big endothelin-1 concentrations and the location of hypertrabeculation can help with risk stratification for VAs in LVHT.