Description:

Igor R. Efimov, PhD
The Alisann and Terry Collins Professor and Chairman,
Department of Biomedical Engineering
George Washington University

Animal models of cardiac diseases have been studied for decades to investigate the mechanisms of arrhythmia initiation and maintenance with the aim to develop life-saving prevention and therapy. However, few clinical advances resulted from these investigations so far.  Many mechanistic discoveries made by cardiac electrophysiologists using animal models failed to translate to humans. For example, despite significant efforts of the generations of scientists, we do not have effective pharmacological agents preventing or aborting sudden cardiac death caused by ventricular fibrillation. To address this problem our laboratory conducted for more than a decade experimental investigations of arrhythmia mechanisms in explanted human hearts procured from patients undergoing transplant or donors whose hearts were not used for transplantation. “Omics” studies employing genome, proteome, transcriptome and other molecular biology approaches revealed that pathological mechanisms usually multifactorial and often cannot be reduced to a single gene or protein defect. Furthermore, pro-arrhythmic SNPs identified by GWAS studies are predominantly located in the regulatory but not in the protein-coding regions of DNA. Moreover, SNPs in the regulatory elements could have impact on transcription of multiple genes. Optical and electrical mapping studies revealed the mechanisms of normal and pathological electrophysiology specific to human, which often differ from those previously discovered in animal models. However, arrhythmias in the human heart follow fundamental principles of arrhythmia initiation and maintenance conceptually described by non-linear dynamics theory during the last century.