Prediabetes predisposes to ischemia-related ventricular arrhythmias

Background –Sudden cardiac death, mainly due to malignant ventricular arrhythmias (VA) linked to coronary heart disease and acute myocardial infarction (AMI), is a leading cause of mortality. Obesity and associated prediabetes are the most relevant and lately most increasing risk factors for cardiovascular disease in Western societies. Independent of coronary heart disease, obesity and prediabetes promote a multimodal arrhythmic substrate increasing the susceptibility to VAs. Here, we aim to clarify the role of obesity and associated prediabetes in an ex vivo mouse model of AMI and their implication for arrhythmogenesis.

Methods – All experiments were performed ex vivo in retrogradely perfused hearts explanted from 32 – 36 week-old C57Bl/6J mice (n=11). Anterior AMI and ischemia-reperfusion injury were induced by occluding the left anterior descending artery with a ligature for 45 minutes. Seven mice received a normal chow diet, four mice were fed a high-fat diet over a 6-month period to generate a diet‑induced-obesity (DIO) phenotype, that is characterized by a prediabetic metabolic state. For VA susceptibility testing, we combined an endocardial catheter‑based technique for programmed ventricle stimulation with epicardial optical voltage mapping of the left anterior ventricular wall. VA susceptibility was quantified by an established scoring system.

Results –The number of induced VAs, VA susceptibility as well as the inducibility of ventricular tachycardias (VT) were increased in DIO mice compared to control (number of induced VAs: Lean: 5.6±0.6, DIO: 11.5±2.5, P=0.006; VA susceptibility: Lean: 12.3±1.9, DIO:  28.3±2.0, P=0.006; number of induced VTs: Lean: 0.7±0.3, DIO:  2.5±0.3, P=0.02, Figure 1). Epicardial optical mapping of the left anterior ventricular wall showed VAs originating from the peri-infarct zone.