Study Question

How does the efficacy and safety of catheter ablation as first-line therapy compare with antiarrhythmic drug (AAD) therapy for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) and implantable cardioverter-defibrillators (ICDs)?

Methods

VANISH2 (Ventricular Tachycardia Antiarrhythmics or Ablation in Structural Heart Disease 2) is an international, multicenter, randomized, open-label trial.¹ Patients with ICM and a history of myocardial infarction who experienced significant VT events (e.g., VT storm, appropriate ICD shock, or sustained monomorphic VT requiring intervention with drug or antitachycardia pacing) within the previous 6 months were randomized 1:1 to catheter ablation (n = 203) or AAD therapy (n = 213) with sotalol or amiodarone. The primary endpoint was a composite of all-cause death, VT storm, appropriate ICD shock, or treated sustained VT below the ICD detection rate after 14 days post-randomization.

Results

• At a median follow-up of 4.3 years, the primary endpoint occurred in 50.7% of patients in the ablation group and 60.6% in the AAD group (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.58-0.97; p = 0.03).
• Ablation was associated with fewer appropriate ICD shocks (29.6% vs. 38.0%; HR, 0.75; 95% CI, 0.53-1.04) and fewer episodes of treated sustained VTs below the ICD detection rate (4.4% vs. 16.4%; HR, 0.26; 95% CI, 0.13-0.55).
• All-cause death was similar between groups (22.2% for ablation group vs. 25.4% for AAD group; HR, 0.84; 95% CI, 0.56-1.24).
• Adverse events within 30 days of catheter ablation included death (1%), nonfatal adverse events (11.3%), and major bleeding (1%). In the AAD group, 21.6% experienced drug-related adverse events, including pulmonary toxicity (0.5%) and pulmonary infiltrates or fibrosis (3.3%).

Conclusions

Catheter ablation as a first-line treatment for VT in patients with ICM reduces the risk of recurrent VT episodes requiring ICD shock or medical intervention compared with AAD therapy. Although mortality was similar between groups, catheter ablation was associated with fewer nonfatal adverse events and improved quality of life by reducing VT burden.

Perspective

VANISH2 is a well-designed and -executed study with bias-free endpoints and clinically relevant findings.¹ It provides strong evidence for catheter ablation as a preferred first-line treatment (rather than AADs) for VT in patients with ICM. The reduction in the composite primary endpoint (HR, 0.75; p = 0.03) was driven by fewer episodes of treated sustained VT below the ICD detection rate. Most benefits were seen in healthier patients eligible for sotalol (HR, 0.64; 95% CI, 0.46-0.93), suggesting this subgroup may tolerate ablation better. Thus, the study highlights the benefits of ablation in reducing VT recurrence and ICD shocks, which are critical for improving patient quality of life. However, the study also underscores the procedural risks associated with ablation (1% procedural mortality and 1.5% stroke rate) and drug-related adverse events (21.6%), including pulmonary toxicity.

These findings may influence clinical practice by encouraging earlier consideration of catheter ablation in eligible patients, particularly those at higher risk for AAD-related adverse effects. The trial results may apply mainly to expert centers, as VT ablation is complex. Overall, this is a step forward in VT management providing useful data for informed patient discussions; however, more research is needed to refine treatment. Of note, most of the trial participants were male (>92%) and White race (>60%).

References

1. Sapp JL, Tang ASL, Parkash R, et al. Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia. N Engl J Med. 2025;392(8):737-747. doi:10.1056/NEJMoa2409501