Metabolomic Profiling in Ischemic and Non-Ischemic Cardiomyopathy Patients With Ventricular Arrhythmias

Heart failure with reduced ejection fraction (HFrEF) is associated with significant metabolic remodeling, reflecting alterations in energy substrate utilization, mitochondrial function, and systemic metabolic pathways. Ventricular tachycardia (VT) remains a major cause of morbidity and mortality in this population. Despite advances in clinical management, the underlying metabolic mechanisms contributing to arrhythmogenesis in ischemic and non-ischemic cardiomyopathy are not fully elucidated.

Metabolomics has emerged as a powerful tool to characterize global metabolic changes and identify disease-specific biochemical signatures. However, comparative metabolomic data between ischemic and non-ischemic cardiomyopathy patients with documented ventricular tachycardia remain limited.

This prospective, single-center observational study aims to compare metabolomic pathways in patients with ischemic and non-ischemic cardiomyopathy with left ventricular ejection fraction below 40% and documented ventricular tachycardia detected by Holter monitoring or implantable cardiac devices. Patients will be recruited from Istanbul University-Cerrahpasa Cardiology Institute Hospital and categorized into two cohorts based on the etiology of cardiomyopathy.

Biological samples will be collected and analyzed using metabolomic approaches to identify differences in metabolic pathways and individual metabolite profiles between the two groups. The primary objective is to determine pathway-level alterations associated with ischemic versus non-ischemic cardiomyopathy in the presence of ventricular tachycardia. Secondary analyses will include evaluation of individual metabolites and their associations with clinical variables such as arrhythmia burden, left ventricular function, and relevant laboratory parameters.

This study is expected to provide novel insights into the metabolic basis of ventricular arrhythmias in heart failure and may contribute to improved risk stratification and the development of personalized therapeutic strategies.

Inclusion criteria

Age ≥18 years Diagnosis of ischemic or non-ischemic cardiomyopathy Left ventricular ejection fraction <40% Documented ventricular tachycardia detected by Holter monitoring, implantable cardioverter-defibrillator (ICD), pacemaker, or other implantable rhythm monitoring devices Availability of metabolomic sample collection Ability and willingness to provide informed consent

Exclusion criteria

History of cardiotoxic chemotherapy or radiotherapy Cirrhosis or advanced hepatic failure Active malignancy Acute decompensated heart failure at presentation Active infection or acute inflammatory disease End-stage renal disease requiring dialysis Absence of Holter monitoring or implantable rhythm monitoring data No documented ventricular tachycardia despite rhythm monitoring Inability to provide informed consent