Pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy are at high risk of sudden cardiac death (SCD). We performed the present study to identify the arrhythmic mechanism of SCD, the relation to changes in LV function, and inducibility of malignant arrhythmias prior to SCD. Juvenile pigs (n=72) were instrumented with chronic stenoses on the proximal left anterior descending and circumflex arteries. Survival was only 29% three months after instrumentation and all of the deaths were sudden and without prodromal symptoms of heart failure. TTC staining demonstrated necrosis in only 9 animals averaging 2.3plusmn0.9% of the LV, with no difference between SCD and survivors. Implantable loop recorders (n=13) documented both ventricular fibrillation (n=6) and brady-asystole (n=2) as the arrhythmic mechanism of death. While regional and global function were depressed (anteroseptal wall-thickening 1.8±0.2 vs. 4.2±0.2 mm in shams, p<0.001; fractional shortening 21±2 vs. 31±1% in shams, p<0.01), there were no differences between SCD animals and survivors. LV mass increased in animals with ischemic cardiomyopathy and was greater in animals with SCD (4.0±0.2 vs. 3.1±0.1 g/kg in survivors, p<0.001). Serial programmed ventricular stimulation failed to induce any sustained arrhythmias. We conclude that pigs with viable dysfunctional myocardium and globally reduced LV function have a high rate of SCD with a spectrum of arrhythmias similar to patients with ischemic cardiomyopathy. The risk is independent of necrosis, but appears to increase with LV hypertrophy. Like patients with ischemic cardiomyopathy, programmed stimulation is insensitive to predict SCD when viable dysfunctional myocardium is the pathological substrate.