By Cara Pellegrini, MD

Assistant Professor of Medicine, University of California, San Francisco, Cardiology Division; Electrophysiology Section, San Francisco VA Medical Center

Dr. Pellegrini reports no financial relationships relevant to this field of study.

SYNOPSIS: VANISH, a multicenter, randomized, controlled trial, demonstrated a significant reduction in composite of death, ventricular tachycardia storm, or appropriate implantable cardioverter defibrillator shock in ischemic cardiomyopathy patients with ventricular arrhythmias on antiarrhythmic drug who underwent ablation as compared to those who were treated with escalation of antiarrhythmic drug therapy.

SOURCE: Sapp JL, Wells GA, Parkash R, et al. Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs. N Engl J Med 2016;375:111-121.

Although an implantable cardioverter defibrillator (ICD) can prevent sudden cardiac death in patients with an ischemic cardiomyopathy and ventricular arrhythmias, recurrent arrhythmias and ensuing ICD shocks are unpleasant and potentially harmful. Many patients also are placed on antiarrhythmic medications to suppress arrhythmias. Nonetheless, ventricular tachycardia (VT) recurs frequently. Whether VT ablation or escalation of antiarrhythmic drug therapy is the most appropriate management in this situation has not been clear, prompting the Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease (VANISH) trial.

Sapp et al performed a multicenter, randomized, controlled trial of patients with a history of myocardial infarction, ICD placement, and an episode of VT during treatment with amiodarone or another antiarrhythmic medication within the previous six months. Patients randomized to ablation continued on the same antiarrhythmic drug regimen. Those assigned to drug escalation received amiodarone if previously treated with another agent, high-dose amiodarone if they had been receiving a dose < 300 mg, or amiodarone plus mexiletine if their arrhythmia had recurred despite at least 300 mg of amiodarone daily. VT ablation approach and ICD settings were standardized. The primary outcome was a composite of death at any time after randomization, VT storm occurring after a 30-day blanking period, and an appropriate ICD shock occurring after a 30-day blanking period.

Researchers enrolled 259 patients, and mean follow-up was about 28 months. Significantly fewer patients in the ablation group experienced the primary outcome, 68.5% vs. 59.1%. There was no significant difference between groups in mortality (the study was not powered to detect a difference in mortality). The other two components of the composite outcome trended toward significance individually and drove the overall distinction. Notably, the planned subgroup analysis of the two-thirds of the study group who were on, and had failed, amiodarone prior to ablation showed a marked distinction between the patients (a 45% reduction in endpoints) vs. the group who were previously on another agent, mostly sotalol (no significant difference between treatment groups). Adverse events were present in both groups, with the ablation arm experiencing two cardiac perforations and three cases of major bleeding, and the drug escalation group experiencing three deaths thought to have been potentially related to antiarrhythmic drug use. The authors concluded that among patients with an ischemic cardiomyopathy and an ICD, catheter ablation was more effective than escalated antiarrhythmic drug therapy in reducing the rate of death at any time or VT storm or ICD shocks after a 30-day blanking period.


This study’s findings are noteworthy for several reasons. The management of these patients is critical, as they are truly a high-risk group. More than half the patients continued to experience VT, and more than one-quarter died during the just over two-year follow-up period. There was a relatively low number needed to treat of 11 patients to prevent one death/VT storm/ICD shock. The findings of this study are consistent with those of previous related trials, such as VTACH and SMASH-VT, and add to the growing body of evidence supporting an increased role for VT ablation in the management of patients with ischemic, scar-based VT.

In addition, this study’s interpretation has numerous limitations, first and foremost generalizability of the results. Although the study involved multinational cooperation (with researchers from Canada, Europe, the United States, and Australia), all but nine of the 259 patients were enrolled at Canadian centers. Access to an electrophysiologist highly skilled at VT ablation may be limited for many patients. This study was restricted to patients who already had experienced VT despite antiarrhythmic medication and does not address the potential role of VT ablation as a primary prevention, something that would reach an even larger population. Even in the ablation arm, more than half the group still reached the primary endpoint, leaving clinicians seeking more effective treatments for these patients.

It is interesting to ponder why those who failed to achieve VT control with amiodarone derived more relative benefit from ablation. Although not explicitly discussed in the paper, it appears that those who were already on amiodarone had an extremely low probability of event-free survival (i.e., mexiletine didn’t add much), rather than a magical greater effect of ablation in this group. This is perhaps the clearest take-home point of this study: If amiodarone has failed, it is time for a new strategy.