Improving Arrhythmia Risk Assessment by Local Myocardial Electromechanical Profiling in Patients with Congenital Long-QT Syndrome

• Applicant: Peter Deißler
• Subject Area: Cardiology, Angiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 529532291

The long-QT syndrome (LQTS) is an inherited arrhythmia syndrome, based on mutations in ion channels or ion-channel-associated proteins, and is associated with an increased risk of ventricular tachyarrhythmias and sudden cardiac death. Up to 250,000 people are affected in Europe alone. Despite intensive research, risk stratification of affected patients remains challenging and therapy-related side effects are common. Novel approaches to individualized (preventive) arrhythmia management could therefore improve patients’ prognosis and quality of life by providing tailored treatment strategies and improving patient categorization. Classically, the LQTS has been considered an “electrical-only” disease, disregarding the fact that the heart is a mechano-sensitive organ that can convert mechanical deformation into electrical activity. As a result, the role of mechanical alterations in LQTS and other arrhythmia syndromes was largely ignored and has only become apparent in recent years. Recent studies show that the integration of electrical and mechanical parameters is a powerful tool for risk stratification in LQTS and other arrhythmia-prone diseases. Therefore, this research project aims to provide a better pathophysiological understanding of the disease by targeting the dual character of the LQTS as an electromechanical disease by studying both, myocardial electrics and mechanics. However, linking electrical and mechanical heterogeneities, as a basis for deeper mechanistic understanding, improved arrhythmia-risk assessment, and potential therapeutic approaches remains technically challenging. To overcome and address these issues, I will perform real-time invasive and non-invasive analyses of electromechanical function in animal models of LQTS and genotyped LQTS patients over the course of this research project. Throughout the studies, I will use a combination of state-of-the-art imaging techniques such as ECG imaging, tissue-phase mapping MRI, echocardiography, and non-contact electroanatomic mapping catheters in LQTS patients and a large animal model of LQTS. My work will provide novel insights into arrhythmia induction and evaluate individualized risk stratification tools based on electromechanical mapping. These findings can then be applied clinically to patients with LQTS and possibly other diseases with ventricular arrhythmias and electromechanical dispersion, such as hypertrophic cardiomyopathy or heart failure. Ultimately, an enhanced understanding of the electromechanical interplay in arrhythmogenesis may lead to new treatment strategies that target the dual (electromechanical) nature of arrhythmia formation.

• DFG Programme: WBP Fellowship
• International Connection: Netherlands
• Host: Professor Dr. Paul G. A. Volders