Gene Therapy for Post-infarction Ventricular Tachycardia

Abstract

Cardiac arrhythmias are a leading cause of morbidity and mortality in the developed world. In particular, cardiac arrest or sudden cardiac death is the leading cause of death in these countries. Death generally results from a ventricular tachyarrhythmia, and pathology data have shown that cardiac arrest victims very frequently have evidence of coronary atherosclerosis with either acute ischemia or healed myocardial infarction. In this work, we describe an animal model that reproducibly has inducible ventricular tachyarrhythmias after healing of a myocardial infarction scar and a gene delivery method that allows gene transfer to the scar and surrounding myocardial tissues. Use of the method allows gene delivery to the arrhythmia model for testing of hypotheses related to ventricular tachyarrhythmia mechanisms and for efficacy testing of proposed gene therapies. To date, all work in this area has been preclinical, but it is our hope that continued development in this area will 1 day allow translation of this method into clinical practice.

Keywords: Arrhythmia; Cardiac ischemia; Gene delivery; Gene therapy; Myocardial infarction; Ventricular fibrillation; Ventricular tachycardia.