Ablation should be “preferred approach” in drug-resistant ventricular tachycardia

John Sapp

A multicentre, randomised controlled trial has shown that catheter ablation is superior to intensified antiarrhythmic drug therapy in reducing death, appropriate implantable cardioverter defibrillator (ICD) shock and ventricular tachycardia storm in patients with ischaemic cardiomyopathy, with an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy. Therefore, trial authors suggest that “catheter ablation should be preferred over escalation of antiarrhythmic drug therapy” in this patient population.  

Results of the VANISH (Ventricular tachycardia ablation of escalated antiarrhythmic drugs in ischaemic heart disease) trial were presented by John Sapp (Dalhousie University, Halifax, Canada) at a late-breaking clinical trial session of the 37th Heart Rhythm Society Scientific Sessions (HRS; 4–7 May, San Francisco, USA) and simultaneously published in the New England Journal of Medicine (NEJM).

“Ventricular tachycardia after myocardial infarction has substantial morbidity and mortality risk even with implantation of an ICD,” Sapp told delegates. “Prior studies have demonstrated that antiarrhythmic drug therapy can be effective in reducing recurrent cardiac ventricular arrhythmias in this setting—particularly sotalol and amiodarone.” Additionally, previous randomised studies (SMASH VT AND VTACH) have also demonstrated that catheter ablation for ventricular tachycardia can reduce recurrent ventricular arrhythmias, and yet, he noted, “first line therapy for ventricular tachycardia is often antiarrhythmic drug therapy.”

“Too many of us see these patients coming back with ventricular tachycardia despite drug therapy,” he continued, “so we set out to answer the question of what should we do in these circumstances.”  

In the study, 259 patients were randomised to receive either ablation (132 patients, median age 67±8.6 years, 93.2% male) or escalated antiarrhythmic drug therapy (127 patients, median age 70.3±7.3 years, 92.9% male) at 22 centres located in Canada, Europe, USA and Australia. In the antiarrhythmic drug therapy group, Sapp noted, patients on sotalol were escalated to amiodarone and those on amiodarone were escalated to high-dose amiodarone or if already on a high-dose, given mexiletine as well. Patients in the catheter ablation group underwent the procedure within two weeks and all inducible ventricular tachycardias were targeted for ablation. Sapp noted that these patients remained on baseline antiarrhythmic drug therapy to address arrhythmias that may have been suppressed.

The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm) or appropriate ICD shock.

Regarding the results of the study, Sapp said that over 27.9 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% in the escalated antiarrhythmic drug therapy group; therefore, the rate of primary outcome was “significantly lower” in the ablation group than in the escalated antiarrhythmic therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval [CI], 0.53 to 0.98; p=0.04). This difference was driven by trends toward reductions in rates of appropriate shocks and episodes of ventricular tachycardia storm. “We did not see a difference in mortality between the two groups,” Sapp noted.       

“Adverse events tended to be more frequent among patients treated with escalated antiarrhythmic drug therapy rather than catheter ablation,” Sapp highlighted. There were three deaths attributed to antiarrhythmic drug treatment (two from pulmonary toxicity and one from hepatic dysfunction) and there were significantly more episodes of liver dysfunction, tremor or ataxia or side effects due to therapy changes among the antiarrhythmic therapy group. However, there tended to be more frequent procedural complications among the patients in the ablation group including major bleeding, vascular injury, cardiac perforation and heart block.   

There are some caveats, Sapp noted, as the trial “was not powered to assess mortality and the effects on mortality should be interpreted with caution. Additionally, since the success of catheter ablation may depend on operator skill and experience, that could have influenced the outcome. We hope, however, that using a multicentre trial design will allow the results to be generalisable. And finally, during the course of the study, it became clear from several studies that prolonging ventricular tachycardia detection time was safe to program in secondary prophylaxis ICD patients. We did change the protocol to encourage that, but it occurred relatively late in the course of the study, so it is not entirely clear whether that it had a major impact on the outcome.”

There are some important considerations, Sapp said, “this is a very high risk population, they are very sick and 50% of the patients experienced a recurrence of ventricular arrhythmias and 25% died over three years of follow-up. Most of the deaths were due to heart failure or non-cardiac causes and that may explain why there was not a significant difference in mortality.”

Commenting on the results of the trial, Andrew Krahn (University of British Columbia, Vancouver, Canada) co-moderator of a press briefing at HRS said: “Patients are very accepting of just changing medicine to see how they do, but the real question is what to do when they have had another shock or get into an unstable situation. This trial really informs the question of whether it is OK to be aggressive. It is OK to get ahead of this and prevent the next one, and it comes with some costs.”

He added, “It is compelling that we have much work to do to try to improve the outcome of these patients regardless of which strategy we choose, because the event rates are still high.”


Thomas Deering (Piedmont Heart Hospital, Atlanta, USA) another co-moderator of the press briefing at HRS commented:
“Studies like this demonstrate that taking a more aggressive approach with a lower event rate is an appropriate possibility in patients, cognisant of the fact that the data are close. Because the natural tendency in these sick patients is to do nothing, and that has its consequences as well, as do the antiarrhythmic drugs.”

In the NEJM journal article, Sapp et al highlight that consensus statements and guidelines recommend the use of catheter ablation when antiarrhythmic drug therapy does not prevent recurrent ventricular tachycardia. However, these recommendations have been based largely on expert opinion and non-randomised case series. “This trial provides evidence that catheter ablation should be preferred over escalation of antiarrhythmic drug therapy for the reduction of recurrent ventricular tachycardia in this population,” they write.          

The study was funded by the Canadian Institutes of Health Research and received unrestricted research grants from St Jude Medical and Biosense Webster.