Long-term prognostic value of multiple circulating biomarkers for ventricular arrhythmias in patients with left ventricular hypertrabeculation

Abstract Background Left ventricular hypertrabeculation (LVHT) is a rare morphologic phenotype of the heart with heterogeneous manifestations and variable prognosis [1,2]. Ventricular arrhythmia (VA) has been recognized as an independent risk factor that significantly impacts the mortality of LVHT patients [1,3]. However, knowledge regarding the prognosis and risk stratification of VAs in LVHT is currently limited. Purpose To explore the long-term predictive value of multiple circulating biomarkers reflecting cardiac function, endothelial function, inflammation, and oxidative stress for the development of VAs in LVHT patients. Methods This longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2012 and December 2020 at a national-level medical center. All participants possessed thorough profiles of multiple biomarkers [N-terminal pro-brain natriuretic peptide, big endothelin-1 (big ET-1), high-sensitivity C-reactive protein, uric acid and free fatty acid] and had no previously documented ventricular arrhythmic events. The cohort were followed annually until October 2022. VA was defined as a composite of non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, and appropriate therapy of implantable cardioverter defibrillator. Potential predictors for VAs in the LVHT cohort were evaluated by multivariable Cox regression. Restricted cubic spline (RCS) analysis was employed to explore the nonlinear association between plasma big ET-1 and clinical outcomes. Differences in the cumulative incidence of VAs according to big ET-1 levels and/or the extent of hypertrabeculation were analyzed by Kaplan-Meier curves. Results A total of 265 morphologically diagnosed LVHT patients (44.2 ± 17.0 years, 65.7% male) were included in this study. Over a median follow-up of 4.34 years, 82 (30.9%) patients experienced ventricular arrhythmic events. Multivariable Cox regression analysis identified that baseline levels of big ET-1 (hazard ratio 1.513, 95% confidence interval 1.136-2.013) and isolated hypertrabeculation in left ventricular lateral wall (LVLW) (hazard ratio 1.810, 95% confidence interval 1.023-3.202) were independently associated with the occurrence of VAs. RCS analysis illustrated that the susceptibility to VAs was remarkably raised with the increase of big ET-1 levels. LVHT patients with higher plasma big ET-1 suffered from more severe cardiac dysfunction and remodeling. Individuals who displayed elevated concentrations of big ET-1 and isolated LVLW hypertrabeculation were at a significantly greater risk of developing VAs. Conclusions Introducing routine assessments for plasma big ET-1 and the extent of hypertrabeculation at baseline can offer valuable support in the risk stratification and clinical management of ventricular arrhythmic events in patients with LVHT.Prognositc value of big ET-1 for VAsbig ET-1/LVLW hypertrabeculation & VAs