Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia (VANISH2)

Authors, Journal, Affiliations, Type, DOI

• Authors: John L. Sapp, Anthony S.L. Tang, Ratika Parkash, William G. Stevenson, Jeff S. Healey, and the VANISH2 Study Team
• Journal: New England Journal of Medicine
• Affiliations: 22 centres in Canada, United States, and France; lead centre: QEII Health Sciences Centre, Dalhousie University, Halifax, Canada
• Type: Investigator-initiated, multicenter, open-label, randomized controlled trial with blinded adjudication of end-point events
• DOI: https://doi.org/10.1056/NEJMoa2409501
• Publication date: November 16, 2024 online; N Engl J Med 2025;392:737-47

Overview

VANISH2 is the first large RCT to compare catheter ablation with systematic antiarrhythmic drug therapy (sotalol or amiodarone) as first-line treatment in patients with ischemic cardiomyopathy and clinically significant ventricular tachycardia who had no prior antiarrhythmic drug exposure. Among 416 patients followed for a median of 4.3 years, catheter ablation led to a significantly lower rate of a composite primary endpoint (death, VT storm, appropriate ICD shock, or treated sustained VT) compared with drug therapy (50.7% vs 60.6%; HR 0.75; P=0.03). Drug-related adverse events were substantially more common in the drug therapy arm (21.6% nonfatal vs 3.4%). Mortality alone did not differ significantly. The trial challenges the conventional "drugs first, ablation after failure" paradigm.

Keywords

Ventricular tachycardia, catheter ablation, antiarrhythmic drugs, ischemic cardiomyopathy, sotalol, amiodarone, ICD, electrical storm, randomized controlled trial

Key Takeaways

Background and Context

• ICDs improve survival in ischemic cardiomyopathy but do not prevent VT; approximately one-third of ICD patients will have episodes and receive shocks within 3 years of implantation
• Recurrent VT is associated with impaired quality of life, more HF hospitalizations, and worse survival; VT storm carries particularly high mortality
• Prior VANISH trial (Sapp et al., NEJM 2016) showed that ablation + continuation of baseline antiarrhythmic medications was superior to escalation of antiarrhythmic drugs (HR ~0.72)
• Current guidelines recommend drugs first, ablation after drug failure; VANISH2 was designed to test whether ablation should be first-line

Study Design

• International multicenter, open-label RCT with blinded adjudication; 22 centres in Canada, USA, France
• Enrollment: November 2016 – June 2022; follow-up completed June 2024
• Inclusion: Previous MI; clinically significant VT within 6 months while NOT on antiarrhythmic drugs (sustained monomorphic VT terminated by pharmacologic/electrical cardioversion; ≥3 ATP-treated VT episodes including ≥1 symptomatic; ≥5 monomorphic VT episodes; ≥1 appropriate ICD shock; or ≥3 VT episodes within 24 hours)
• All patients had an ICD
• Exclusion: Prior antiarrhythmic drug treatment for VT was not an exclusion; rather, no history of nonresponse to drugs was required
• 1:1 randomization stratified by sotalol vs amiodarone eligibility and enrolling centre
• Catheter ablation performed within 14 days after randomization; 200 of 203 ablation-group patients underwent the procedure
• Sotalol dose: 120 mg orally twice daily; Amiodarone: 400 mg BD ×2 weeks → 400 mg daily ×4 weeks → 200 mg maintenance
• ICD programming standardized per evidence-based guidelines
• Follow-up: 3 and 6 months post-randomization then every 6 months; median 4.3 years (IQR 2.5–5.7)
• 8 COVID-19-era patients excluded; followed in a registry

Primary Endpoint

• Composite: death from any cause during follow-up OR (>14 days after randomization) VT storm (≥3 VT events within 24 hours), appropriate ICD shock, or treated sustained VT below ICD detection limit
• The 14-day exclusion window was imposed to allow adequate drug dosing or ablation performance before outcome assessment

Results — Primary Endpoint

• Primary endpoint event: Catheter ablation 103/203 (50.7%) vs drug therapy 129/213 (60.6%); HR 0.75 (95% CI 0.58–0.97; P=0.03)
• Ablation significantly superior; approximately 1 in 10 patients fewer experienced a primary endpoint event

Results — Secondary Endpoints

• Death from any cause: Ablation 45 (22.2%) vs drugs 54 (25.4%); HR 0.84 (95% CI 0.56–1.24) — not significant
• Appropriate ICD shock (>14 days): Ablation 60 (29.6%) vs drugs 81 (38.0%); HR 0.75 (95% CI 0.53–1.04) — not significant
• VT storm (>14 days): Ablation 44 (21.7%) vs drugs 50 (23.5%); HR 0.95 (95% CI 0.63–1.42) — not significant
• Treated sustained VT below ICD detection limit (>14 days): Ablation 9 (4.4%) vs drugs 35 (16.4%); HR 0.26 (95% CI 0.13–0.55) — highly significant; largest effect size
• ICD shock + ATP burden: 1,383 episodes (1.91/person-year) ablation vs 2,195 episodes (6.14/person-year) drugs; mean difference −4.22 events/person-year (95% CI −9.01 to 0.56)

Safety

• Ablation group (30-day procedure-related):
  • Death: 2 patients (1.0%)
  • Nonfatal adverse events: 23 patients (11.3%)
  • Nonfatal stroke: 2 patients (1.0%)
  • Cardiac perforation: 1 patient (0.5%)
  • Vascular injury (including 2 with major bleeding): 5 patients
• Drug therapy group:
  • Death from pulmonary toxicity attributed to AAD: 1 patient (0.5%)
  • Pulmonary infiltrates or fibrosis attributed to AAD: 7 patients (3.3%)
  • Nonfatal adverse events attributed to AAD (leading to drug discontinuation or dose reduction): 46 patients (21.6%)
  • Gastrointestinal, neurologic, thyroid-related, or liver-related adverse effects: 25 patients
• Crossover: 3 drug-therapy patients underwent catheter ablation; 17 ablation-group patients received antiarrhythmic drugs (6 for AF, 2 for PVCs, remainder for VT)
• During trial overall: 24% of all patients died; 26% had VT storm; 37% received appropriate ICD shock; 11% had treated VT below ICD detection limit — underscoring severity of disease burden despite treatment

Limitations of the document

• Not powered for individual components: Trial was designed to detect 35% relative risk reduction in composite primary endpoint; underpowered for mortality and individual secondary endpoints
• Operator/centre variability: Catheter ablation efficacy may depend on team experience; however, consistency across 22 centers supports generalizability
• Open-label design: No blinding of treatment assignment (though end-point adjudication was blinded)
• Technology may change: Future advances in ablation technology or new antiarrhythmic drugs may alter interpretation
• ICD programming: Standardized protocol; future studies may identify alternative settings that reduce sub-threshold VT
• Long-term amiodarone effects: Median 4.3 years may underestimate cumulative amiodarone toxicity — adverse effects increase with time and longer follow-up needed
• Generalizability to non-ischemic cardiomyopathy: Trial restricted to post-MI patients; not applicable to DCM, ACM, or other substrates

Key Concepts Mentioned

• concepts/VT-Ablation-Ischemic-Cardiomyopathy — primary topic; first-line ablation vs AAD strategy
• concepts/Electrical-Storm — key component of primary endpoint; ablation arm numerically lower but not significantly different
• concepts/Amiodarone-Pulmonary-Toxicity — 1 death, 7 pulmonary infiltrates/fibrosis in drug arm over 4.3 years

Key Entities Mentioned

• entities/Sotalol — first-line AAD for patients without severe ventricular dysfunction, renal impairment, or electrical storm
• entities/Amiodarone — preferred for severe ventricular dysfunction or electrical storm; 400 mg BD ×2w → 400 mg daily ×4w → 200 mg maintenance

Wiki Pages Updated

• wiki/sources/vt-ablation-vanish2-nejm-2025.md — created
• wiki/concepts/VT-Ablation-Ischemic-Cardiomyopathy.md — created
• wiki/concepts/Electrical-Storm.md — updated
• wiki/concepts/Amiodarone-Pulmonary-Toxicity.md — updated
• wiki/wikiindex.md — updated
• wiki/sourceindex.md — updated