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For ventricular tachycardia (VT), catheter ablation is often seen as an option of last resort, however, some are questioning whether there has been too much emphasis on antiarrhythmic medication.

In the VANISH2 trial, investigators worked to answer this question focusing specifically on patients with VT and ischemic cardiomyopathy after myocardial infarction (MI). The researchers studied 416 patients for a roughly 4-year period, comparing those whose first-line treatment consisted of catheter ablation with those whose first-line treatment consisted medication with either sotalol or amiodarone.

Patients in both groups experienced adverse events, but the primary endpoint — a composite of any-cause of death, VT storm, appropriate implantable cardioverter–defibrillator (ICD) shock, or sustained VT — occurred in more patients who received medication than in those who received ablation (50.7% vs 60.6%; hazard ratio, 0.75; 90% CI, 0.58-0.97; P = .03).

Adverse events within 30 days post-procedure included death in 1% of patients and nonfatal adverse events in 11.3% of patients, while adverse events in the antiarrhythmic drug treatment group included death from pulmonary toxic effects in 0.5% of patients and nonfatal adverse events in 21.6% of patients.

“An initial strategy of catheter ablation resulted in a lower risk of the composite outcome, although both approaches were associated with adverse events and were found to have imperfect efficacy,” said lead author John Sapp Jr, MD, professor, Division of Cardiology, Dalhousie University, Halifax, Nova Scotia, Canada. 

What’s New in VANISH2

VANISH2 built on a prior study, the VANISH1 trial, which compared catheter ablation with dose increase of antiarrhythmic medication or additional antiarrhythmic medication in survivors of MI who were already taking medication, but continuing to have recurrent VT.

During a mean (SD) of 27.7 (± 17.1) months of follow-up, the primary outcome — a composite of death, VT storm, or appropriate ICD shock — occurred in 59.1% of patients in the ablation group vs 68.5% in the escalated therapy group. There was no significant difference in death between the groups. However, two cardiac perforations and three cases of major bleeding occurred in the ablation group. In the escalated-therapy group, there were two deaths from pulmonary toxic effects and one from hepatic dysfunction.

In VANISH1, ablation “had an effect comparable to medical therapy, but the subjects were patients who had failed medical therapy and were faced with the alternative of escalating the dose of amiodarone or switching from amiodarone to sotalol vs undergoing ablation,” Sapp said.

Current practice guidelines recommend ablation only if antiarrhythmic medication has failed. But since the publication of these guidelines, several studies have investigated whether ablation can serve as first-line therapy for patients with cardiomyopathy and VT.

Will These Studies Be Guideline Changing?

The PARTITA trial included patients with ischemic and nonischemic cardiomyopathy and primary or secondary indication for ICD. The first phase of the trial consisted of observation until the first appropriate shock (phase A). After this, patients were randomized to either immediate ablation or continuation of standard therapy (phase B), with a primary composite endpoint of death from any cause or hospitalization for worsening heart failure. VT ablation after the first appropriate shock was found to be associated with a reduced risk for the composite endpoint, as well as lower mortality and fewer ICD shocks than standard therapy.

The PAUSE-SCD trial looked at first-line catheter ablation of monomorphic VT in cardiomyopathy concurrent with ICD implantation. Patients were randomized to either ablation plus ICD or conventional medical therapy plus ICD. The primary outcome was a composite endpoint of VT recurrence, cardiovascular hospitalization, or death. Of the participants, roughly one third had ischemic cardiomyopathy, one third had nonischemic cardiomyopathy, and one third had arrhythmogenic cardiomyopathy.

At 31 months, the primary outcome occurred in 49.3% of those in the ablation group vs 65.5% of those in the control group with the difference between the groups driven primarily by reduction in VT recurrence in the ablation group. Moreover, there was a statistically significant reduction in ICD shocks and anti-tachycardia pacing in those who underwent ablation vs in control individuals. However, there were no differences in cardiovascular hospitalization or mortality between groups. 

Both trials “showed that catheter ablation soon after ICD implant or after an ICD shock reduced VT recurrences, but the effect on mortality is less certain,” wrote Arvindh Kanagasundram and coauthors in an editorial accompanying the results published in 2022.

The SURVIVE-VT trial — also published in 2022 — randomized patients with ischemic cardiomyopathy and appropriate ICD shock to ablation or antiarrhythmic therapy. The primary outcome was a composite of cardiovascular death, appropriate ICD shock, unplanned hospitalization for worsening heart failure, or severe treatment-related complications.

Ablation was found to significantly reduce the composite endpoint, with the difference driven by a significant reduction in severe treatment-related complications. However, there was no difference in cardiac mortality.

Clinical Decision-Making

“Since the publication of these studies, we lowered our threshold of offering VT ablation not only as a salvage procedure if medication failed but also as a first-line procedure,” said Konstantinos Aronis, MD, PhD, director of the Adult Congenital Heart Disease Complex Ablation Program and associate director of the Ventricular Tachycardia Ablation Program, Johns Hopkins School of Medicine, Baltimore. “These studies examined the question of medication vs ablation as first-line therapy for patients with certain cardiomyopathies, and all showed the general superiority of ablation of antiarrhythmic medications.”

VANISH2 differs from previous studies because of its larger size, said Aronis, an assistant professor of medicine, Division of Cardiology, Johns Hopkins. He described VANISH2 as “very well done,” adding that the “message of all these is clear: Ablation is superior to antiarrhythmic medication, in terms of the combined endpoint including hospitalization for heart failure or receiving appropriate ICD shocks, although it doesn’t necessarily confer benefit over medication when it comes to mortality.”

One of the issues Aronis focuses on when discussing ablation vs medication with patients experiencing VT is their motivation for seeking treatment. “Some people may look for an intervention that helps them live longer vs helping them feel better, but others may not be as concerned about living longer and may be more concerned about avoiding getting shocked or being hospitalized.”

Luigi Di Biase MD, PhD, system director of Electrophysiology, Montefiore Health System and professor of medicine in cardiology, Albert Einstein College of Medicine, Bronx, New York, said he agrees. There are “two sides of the coin,” he said. “On the one hand, although ablation is probably superior, there are complications. But on the other hand, medications like amiodarone can also lead to mortality. Giving medication isn’t as safe as one might think and is also associated with side effects and complications.” In VANISH2, the “illness severity in the patients might account for the complications, rather than the treatment itself,” he suggested adding that the authors “should be commended and congratulated for performing an RCT [randomized controlled trial] in those with such a high burden of complications.”

Many additional variables can affect the success and outcome of ablations, Di Biase pointed out. These include the facility in which the ablation is being performed and the experience of the operators. So the decision to perform ablation vs prescribing medication “should be determined on a patient-by-patient, location-by-location basis.”

Di Biase added that observational studies have shown that being free of VT recurrence following ablation is “ associated with enhanced survival, a lower rate of worsening heart failure and the need for a heart transplant.” Earlier access to VT ablation has been “associated with a lower recurrence rate” and shouldn’t necessarily be regarded as a “ treatment of last resort.” 

Will It Help Patients With Nonischemic VT?

VANISH2 included patients with ischemic cardiomyopathy. “This isn’t exactly a ‘narrow’ category, but it is a subcategory of patients with VT,” said Timothy Markman, MD, assistant professor of medicine and cardiovascular disease, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

He pointed out that nonischemic cardiomyopathy is “more challenging to manage with ablation, compared to ischemic cardiomyopathy, because these patients are more heterogeneous, while ischemic cardiomyopathy patients are more similar than different, and therefore easier to treat.” For this reason, we can’t necessarily extrapolate these findings to patients with nonischemic VT.

Aronis said he agrees. “Patients with ischemic cardiomyopathy usually have a discrete scar. This presentation differs from many of the nonischemic cardiomyopathies, which may have multiple scars, or scars that don’t come from a previous MI. The technical challenges and complexities of ablation are much higher than they are for ischemic cardiomyopathies.”

Aronis speculated that nonischemic cardiomyopathies with a discrete scar might be comparable to the presentation of the patients in the VANISH2 study. “But we can’t say for sure.”

Ablation vs Medication for Premature Ventricular Contractions

The specialists said they agree that considerations surrounding premature ventricular contractions (PVCs) differ from those of VT and that the findings of VANISH2 can’t necessarily be applied to PVCs.

“Certainly, an increasing body of data suggests some benefits in being more aggressive with offering ablation for PVCs,” Markman said. “But ablating PVCs differs from ablating VT, and so much depends on where the PVCs are coming from.”

Aronis said he agrees. “PVCs fall into different categories, depending on where they come from. Similar to the difference between ischemic cardiomyopathies and nonischemic cardiomyopathies, when the PVCs come from a standard, easy-to-access location such as the traditional outflow tract, they’re easier to ablate. But those that come from hard-to-get-to locations are associated with higher risks.”

In exploring the reasons for ablation, Aronis mentioned symptomatic relief as one reason, “which is subjective and differs from patient to patient, since each patient might have a different tolerance for the symptoms.”

The other reason is that a high PVC burden (> 10%) can be associated with the development of cardiomyopathy, and an ablation may be helpful in saving the heart muscle. “We also have to anticipate the potential complexity of the procedure, compared to the potential side effects of the medications,” Aronis said.

Sapp added that PVCs are generally “more mappable,” so if they’re reachable, ablation has a higher success rate. “But we have to be able to see them in the lab and track them, and they have to be in a spot where we can reach them with a catheter.”

Failure can occur “when the PVCs are originating from deep within the heart muscle or close to a delicate or important structure that can be damaged,” Sapp continued. On the other hand, many patients with PVCs are often younger and healthier, “so we want to be cautious about drug therapy. Amiodarone, for example, has an impressive list of potential side effects, many of which are dose-dependent.”

Future Directions

“The findings of VANISH2 are clear and consistent with findings of other studies that show ablation for VT to be superior to any antiarrhythmic drug we have available,” concluded Markman, author of an accompanying editorial. “I think most of us already understood this clinically, but it’s good to have a randomized study to confirm it. So this is an important study with huge value added.” The findings will “help get us to a point where ablation should be offered to most if not all patients with VT and ischemic cardiomyopathy as first-line therapy.”

Markman pointed to a “disappointing” finding in VANISH2: Many patients had recurrent VT. “This tells us we still have a long way to go. Yes, ablation is better than currently available antiarrhythmic drugs, but it continues to evolve, and we need to focus on achieving better outcomes.”

This study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Cardiovascular Network of Canada, and the Dalhousie University Faculty of Medicine and Department of Medicine and by unrestricted investigator-initiated research grants from Johnson & Johnson and Abbott. Aronis declared no relevant financial relationships. Sapp reported receiving grants or contracts from Abbott Canada, Johnson & Johnson, and Medtronic and is a consultant for Varian Medical Systems, Inc. He holds a patent for a needle ablation catheter and a patent for localization of ventricular arrhythmias. Di Biase had served as a consultant for Biosense Webster, Inc., Stereotaxis, I-Rhythm, Abbott, Boston Scientific, Medtronic, Biotronik, AtriCure, Haemodinamics, Siemens, and Zoll Medical. Markman received educational honoraria from Abbot Laboratories, Biosense Webster, Inc., Boston Scientific, and Medtronic. He is a consultant to Propharma.