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

Abstract

Objectives: Ventricular arrhythmia (VA) is an independent risk factor for adverse clinical outcomes in patients with left ventricular hypertrabeculation (LVHT). This study aimed to explore the predictive value of multiple circulating biomarkers for VAs in this particular population.

Methods: This retrospective longitudinal cohort study consecutively enrolled 265 LVHT patients (44.2 ± 17.0 years, 65.7% male) with thorough biomarker profiles of N-terminal pro-brain natriuretic peptide, big endothelin-1, high-sensitivity C-reactive protein, uric acid and free fatty acid. The primary outcomes were a composite endpoint consisting of non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, and appropriate therapy of implantable cardioverter defibrillator.

Results: Over a median follow-up of 4.34 years, a total of 82 (30.9%) patients encountered ventricular arrhythmic events. Multivariable Cox regression analysis identified that baseline levels of big endothelin-1 [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.14-2.01] and isolated hypertrabeculation in left ventricular lateral wall (LVLW) (HR 1.81, 95% CI 1.02-3.20) were independently associated with the occurrence of VAs. Restricted cubic spline analysis illustrated that the susceptibility to VAs was remarkably raised with the increase of plasma big endothelin-1. Subgroup analysis revealed that LVHT patients with big endothelin-1 levels above 0.63pmol/L should be closely monitored for VAs, particularly when accompanied by cardiomyopathies (HR 2.91, 95%CI 1.39-6.12), left ventricular end-diastolic diameters ≥60mm (HR 2.78, 95%CI 1.19-6.49), or left ventricular ejection fractions <50% (HR 2.55, 95%CI 1.20-5.43). Kaplan-Meier curves suggested that individuals exhibiting elevated big endothelin-1 levels at baseline and isolated hypertrabeculation in LVLW faced a significantly greater risk of experiencing VAs, compared to those with normal big endothelin-1 levels and non-isolated LVLW hypertrabeculation (Log-Rank P=0.002).

Conclusions: Introducing routine assessments for plasma big endothelin-1 and the location of hypertrabeculation can provide further assistance in the risk stratification of ventricular arrhythmic events in patients with LVHT.

Note:
Funding declaration: This research was supported by the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences (Grant No. NCRC2020012) and the National Natural Science Foundation of China (Grant No. 82000323).

Conflict of Interests: The authors have no conflict of interests to declare in this study.

Ethical Approval: Ethics Approval Statement: The study was conducted in full compliance with the Declaration of Helsinki, Good Clinical Practice guidelines, and relevant local laws and regulations. It was registered in China Medical Research Registration and Information Recording System (Registration number: MR-11-23-023712) and obtained approval from the Ethics Committee of Fuwai Hospital (Ethics approval number: 2022-1837). Written informed consents were collected from all patients before the study began.

Keywords: Left ventricular hypertrabeculation, biomarker, Big endothelin-1, Ventricular arrhythmia