From channel protein to body surface ECG: Investigating electrocardiographic effects of ion channel mutations using computational heart models

• Antragsteller: Dr. Sebastian Ley; Privatdozent Dr. Eberhard Scholz; Dr.-Ing. Gunnar Seemann
• Fachliche Zuordnung: Nuklearmedizin, Strahlentherapie, Strahlenbiologie
• Förderung: Förderung von 2009 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 78886816

Mutations that impact on cardiac electrophysiology have been of scientific interest throughout the last decade. By altering specific ion channel characteristics these mutations are associated with a high risk for the development of ventricular arrhythmias and sudden death. Although DNA analysis has enhanced our understanding of the underlying processes, inter-individual differences impede to quantitatively predict the effects of the mutated channels on the ECG. This project is focused on identifying and discriminating genotypes of mutations in a cardiac channelopathy called Long QT syndrome (LQTS) using a computational approach. Geometrical datasets of affected patients are constructed based on MRI. Together with detailed mathematical models of cardiac electrophysiology, the excitation conduction on the individual cardiac anatomy is simulated. A forward calculation allows the determination of electrical signals on the body surface and the extraction of standard ECG leads. For verification and optimization of the computational model, this calculated signals on the body surface is compared to 64 channel ECG recordings from patients. Effects of the sympathetic nervous system are included into the computer model of the LQTS as heart rate and adrenergic regulation influence ion channel characteristics and thereby cardiac activity. Especially the differences of the T wave morphology between the genotypes of LQTS will be used to derive ECG electrode positions that allow a new ECG-based discrimination of the mutation genotype.

• DFG-Verfahren: Sachbeihilfen