Sudden Cardiac Death (SCD) accounts for about half of all cardiac deaths, with 25% being first manifestation of cardiac diseases
Ventricular arrhythmias are a major cause of SCD with their mechanism varying with structural or electrical conditions
Repolarization and conduction heterogeneity are of primary importance for the genesis of lethal arrhythmias
While therapies exist to prevent arrhythmic death , the identification of patients at risk remains the major challenge
Objectives
To characterize repolarization and conduction heterogeneity in the human heart, first in experimental settings, and later in patients using novel high-resolution methods
To provide new risk stratification parameters for SCD
To develop novel personalized therapies for patients at risk of dying suddenly, based on a patient-specific detailed understanding of the mechanisms of ventricular fibrillation.
A special emphasis will also be placed on training clinical and postdoctoral fellows
Methodology
The role of abnormal electrophysiological heterogeneity in the initiation and maintenance of Ventricular Fibrillation (VF) in the human heart Using explanted human hearts from end-stage heart failure patients and from donors, whose hearts were not used for transplantation, the distribution of activation and repolarization properties will be studied in healthy and failing human hearts and subjects with various genetic abnormalities.
Non-invasive electrocardiographic substrate mapping of electrophysiological heterogeneity and VF Human hearts will be studied in a unique model of the human thorax previously developed in collaboration between RHYTHM members in order to establish a detailed high-resolution electrocardiographic (ESM) method to map myocardial repolarization and its dispersion noninvasively.
Patient-specific computer models for risk stratification and therapy optimization A unified whole-heart simulation strategy will be adopted that will combine state-of-the-art modelling and simulation approaches to develop human, biventricular, computational models that are superior to existing models.
Novel non-invasive markers and tools for SCD prevention Novel markers of SCD based on ESM and novel wearable technologies for screening and SCD prevention will be developed. The initial studies will be performed in the experimental human torso model, followed by clinical validation in patients.
Electrocardiographic substrate mapping guided ablation of VF in patients The ultimate goal is to develop novel approaches for the treatment of VF, and prevention of such life-threatening arrhythmias based on the identification of the arrhythmogenic substrate. Clinical research will be performed to investigate and localize regions of abnormal tissue properties using novel high-resolution mapping tools and MRI imaging techniques and then determine their relationship with arrhythmogenic activity mapped during subsequently induced VF. Ablation therapy will be proposed in the case of well-defined and localized arrhythmogenic sites.
