Relevance of sympathetic innervation and myocardial substrate for ventricular arrhythmogenesis in patients with non-ischemic cardiomyopathy

• Applicant: Dr. Christiane Jungen
• Subject Area: Cardiology, Angiology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 447558597

Ventricular tachycardias (VTs), the most common cause of sudden cardiac death, are a major cause of morbidity and mortality in patients with non-ischemic cardiomyopathy (NICM). Catheter ablation aims to prevent VT recurrences in NICM patients, but this interventional therapy still constitutes a challenge with higher recurrences compared with rates of patients after myocardial infarction. NICM patients present with a heterogenic phenotype of dilated or hypokinetic non-dilated cardiomyopathy. Whereas fibrosis is the hallmark for NICM, it comprises various patterns, distributions and architectures on tissue level. The underlying cause of arrhythmogenesis is, besides others, related to heterogeneity in myocardial tissue and cardiac sympathetic innervation. In NICM, sympathetic innervation is not well characterised, but initial studies in post-myocardial infarction patients suggest that areas of mismatch between electro-anatomical voltage and sympathetic innervation are relevant targets during catheter ablation. Up to now, current ablation strategies do not use innervation information or detect mismatch areas. The goal of this project proposal is to determine the relevance of sympathetic innervation for the myocardial substrate in order to deepen the understanding of arrhythmogenicity in patients with NICM. To achieve this, analysis and correlation of imaging data depicting the sympathetic nervous system (I123-MIBG SPECT imaging), cardiac fibrosis (cardiac magnetic resonance imaging) and the cardiac substrate (electroanatomical voltage imaging) will be performed after having developed dedicated analysis tools. Additionally, cardiac biopsies will be used to determine the amount, architecture and distribution of fibrosis in correlation with the different parts of the autonomic nervous system in these patients. This deep phenotyping together with the knowledge of successful ablation target sites will improve the understanding of the relevance of sympathetic innervation for the arrhythmogenic substrate. The generated deeper understanding of the mechanisms underlying VTs in NICM patients will be the basis for the development of substrate-based and individualized therapies.

• DFG Programme: WBP Fellowship
• International Connection: Netherlands
• Host: Professorin Dr. Katja Zeppenfeld