INTERVENE: Indian Trial of Endocardial Ventricular Substrate Ablation to Prevent Recurrent VT Events

Sudden cardiac death (SCD) accounts for approximately 50% of all cardiac death, representing an estimated annual incidence ranging from 250,000 to 350,000 cases in the United States. The pathophysiologic mechanism for sudden death in the majority of these patients is thought to be ventricular tachycardia (VT) related to coronary artery disease (CAD), which can then degenerate to ventricular fibrillation (VF). Patients who survive an initial episode of VT/VF are prone to an extremely high incidence of recurrent life-threatening events (~25% at one year). Even in patients without a history of VT/VF, the presence of CAD and left ventricular (LV) dysfunction confers a two-year mortality rate of 22%. If VT is inducible at electrophysiological testing, the two-year mortality is ~30%.

The pathogenesis of VT in the setting of CAD is reentry in the area of the scarred myocardium. After an MI, the tissue can be broadly divided into three zones: the dense scar, the surrounding live myocardial tissue, and the intervening border zone. After a myocardial infarction (MI), the "border zone" between dense scar and live tissue contains electrically-active live myocardial fibrils interspersed in areas of infarcted, fibrotic tissue-setting the stage for local reentrant circuits that result in VT.

The use of antiarrhythmic medications (AADs) to suppress the occurrence/recurrence of VT/VF in these high-risk patients has been mostly disappointing. In large clinical trials, most AADs have not only proved to be inefficacious, but to actually increase mortality. The one potential exception appears to be Amiodarone: one study suggests some mortality benefit (GESICA), while others suggest that Amiodarone provides significant antiarrhythmic benefits without a change in mortality (EMIAT, CAMIAT, SCD-HeFT). However, even the use of Amiodarone is plagued with multiple organ toxicities, ranging from pulmonary fibrosis to hepatitis, and thyroid dysfunction.

An important alternative to such questionably efficacious antiarrhythmics is the implantable cardio-defibrillator (ICD), which can accurately and effectively detect and terminate VT/VF, resulting in a significant mortality benefit in both the primary and secondary prevention of sudden cardiac death. Yet, despite these beneficial results, ICD implantation cannot be considered a cure for VT. In addition, it is common for patients to experience painful high-voltage shocks secondary to recurrent ventricular arrhythmias, or to lose consciousness prior to the delivery of therapy. Moreover, the considerable cost of ICDs severely limits their availability in the developing world-where public and/or private health insurance systems are rudimentary at best, and where the incidence of coronary artery disease is four times higher than that of the developed world-highlighting the urgency of establishing an alternative therapy for post-MI patients with ventricular arrhythmias that is both accessibly and effective.

One such option may be catheter ablation of ventricular arrhythmias. It has been well described that for hemodynamically-stable VT circuits, careful ventricular mapping to identify sites critical to the maintenance of a given circuit, followed by discrete applications of catheter-based radiofrequency (RF) energy, can effectively eliminate VT.