A prespecified substudy of the VANISH2 trial suggests first-line catheter ablation is superior to sotalol for reducing arrhythmia events in eligible patients with ischaemic cardiomyopathy and ventricular tachycardia (VT).¹ In patients ineligible for sotalol, ablation showed comparable efficacy to amiodarone but with a markedly better long-term safety profile.
Methodology
The VANISH2 (Ventricular Tachycardia Antiarrhythmics or Ablation in Ischaemic Heart Disease 2) trial (NCT02830360) was a multicentre, randomised controlled trial comparing first-line antiarrhythmic drug (AAD) therapy to catheter ablation. This substudy analysed outcomes based on the trial's stratification criteria.¹˒²
A total of 416 patients with a prior myocardial infarction (MI) and clinically significant VT were followed for a median of 4.3 years. Patients were stratified by drug eligibility. The sotalol-eligible stratum (n=199) included patients with better renal and cardiac function (e.g., estimated glomerular filtration rate ≥30 mL/min, left ventricular ejection fraction ≥20%, NYHA class I-II). All other patients were placed in the amiodarone-eligible stratum (n=217).
The primary endpoint was a composite of death, appropriate implantable cardioverter-defibrillator (ICD) shock, VT storm, or treated sustained VT below the ICD detection limit.
Results
In the sotalol-eligible stratum, the primary endpoint occurred in 46% of patients assigned to catheter ablation versus 59% assigned to sotalol (HR 0.64; 95% CI 0.43–0.94; p=0.02). This was driven by lower rates of appropriate ICD shocks (28% vs 45%) and treated sustained VT below the ICD detection rate (2.1% vs 17.3%) in the ablation group.
In the amiodarone-eligible stratum, the primary endpoint occurred in 55% of the ablation group and 61% of the amiodarone group, a non-significant difference (HR 0.86; 95% CI 0.61–1.22). However, ablation was associated with a lower rate of treated sustained VT below the ICD detection rate (6.5% vs 15.6%; HR 0.41; 95% CI 0.17–0.99; p=0.048).
Safety outcomes differed significantly in the amiodarone stratum. Compared to ablation, patients receiving amiodarone had a threefold increase in noncardiac death (16.5% vs 5.6%), a twofold increase in respiratory failure (11.0% vs 4.6%), a 50% increase in heart failure hospitalisation (31.2% vs 19.4%), and a threefold increase in pneumonia (11.9% vs 3.7%).
In Practice
These findings support considering first-line catheter ablation for sotalol-eligible patients to achieve better arrhythmia suppression. For patients with more severe disease who are only eligible for amiodarone, the efficacy of ablation and drug therapy was comparable. However, the significant long-term safety risks associated with amiodarone, particularly the increased noncardiac mortality and pulmonary toxicity, suggest that ablation may be a preferable strategy. Clinical decisions should balance the up-front procedural risks of ablation against the long-term risks of AAD therapy, incorporating individual patient comorbidities and preferences.
References
1. Nery PB, Wells GA, Tang ASL, et al. Catheter Ablation vs Sotalol or Amiodarone for Ventricular Tachycardia: A Substudy of the VANISH2 Trial. JACC. 2026;87(2):157-168. https://doi.org/10.1016/j.jacc.2025.09.1595
2. 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. https://doi.org/10.1056/NEJMoa2409501
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