Pulsed Field or Cryoballoon Ablation for Paroxysmal Atrial Fibrillation — SINGLE SHOT CHAMPION

Authors, Journal, Affiliations, Type, DOI

• Authors: Tobias Reichlin, Thomas Kueffer, Patrick Badertscher, Peter Jüni, Sven Knecht, Gregor Thalmann, Nikola Kozhuharov, Philipp Krisai, Corinne Jufer, Jens Maurhofer, Dik Heg, Tiago V. Pereira, Felix Mahfoud, Helge Servatius, Hildegard Tanner, Michael Kühne, Laurent Roten, Christian Sticherling, for the SINGLE SHOT CHAMPION Investigators
• Journal: New England Journal of Medicine (N Engl J Med 2025;392:1497-507)
• Affiliations: Inselspital–University Hospital Bern; University Hospital Basel; University of Oxford; University of Bern
• Type: Investigator-initiated, randomized, controlled, noninferiority trial (two tertiary centers, Switzerland)
• DOI: https://doi.org/10.1056/NEJMoa2502280
• Funding: Inselspital (University Hospital Bern), University Hospital Basel; unrestricted grant from Boston Scientific (for implantable cardiac monitors only); Boston Scientific had no role in design, data, analysis, or manuscript

Overview

The SINGLE SHOT CHAMPION trial randomized 210 adults with symptomatic paroxysmal AF 1:1 to pulmonary-vein isolation by PFA (Farapulse pentaspline catheter, Boston Scientific) or cryoballoon ablation (Arctic Front, Medtronic) at two Swiss centers, with every patient receiving an implantable cardiac monitor (Reveal LinQ) for continuous rhythm monitoring. PFA met noninferiority (P<0.001) and achieved formal superiority (P=0.046) over cryoablation for first recurrence of atrial tachyarrhythmia between days 91–365 (37.1% vs 50.7%; difference −13.6 pp; 95% CI −26.9 to −0.3). PFA procedures were shorter (~55 vs ~73 min), recurrence was lower even during the blanking period, and safety was comparable. This is the first RCT to demonstrate a superiority signal for PFA over cryoablation in paroxysmal AF.

Keywords

Pulsed field ablation, cryoballoon ablation, paroxysmal atrial fibrillation, pulmonary vein isolation, implantable cardiac monitor, continuous rhythm monitoring, noninferiority trial, blanking period, atrial tachyarrhythmia recurrence

Key Takeaways

Background and Rationale

• Pulmonary-vein isolation is effective for paroxysmal AF; thermal ablation (RF and cryo) has been the mainstay with similar efficacy between them; recurrence remains common owing to PV reconnection and extra-PV triggers
• Prior PFA studies (including ADVENT) lacked continuous rhythm monitoring, limiting recurrence detection sensitivity
• PFA is a nonthermal modality using irreversible electroporation with high cardiac tissue selectivity; no atrioesophageal fistula reported to date in any PFA study

Design

• Randomized noninferiority trial, September 2022–November 2023; two tertiary centers (Bern + Basel)
• 210 patients: 105 PFA (Farapulse pentaspline), 105 cryoablation (Arctic Front)
• All patients received implantable cardiac monitor (Reveal LinQ) for continuous rhythm monitoring; data centrally adjudicated blind
• Blanking period 90 days; antiarrhythmic drugs permitted during blanking, required to be stopped thereafter
• Operators had ≥6 months PFA experience before trial enrollment
• Stratified randomization by center; 1:1 ratio

Patient Characteristics

• Mean age 64 years; 28% women
• Symptomatic paroxysmal AF documented on ECG/Holter ≥30s in past 24 months
• Eligibility for PVI per current guidelines; excluded: prior left atrial ablation, reversible cause AF, severe MR, LVEF <35%, NYHA III/IV
• Characteristics well-balanced between groups at baseline

Procedural Findings

• All patients underwent successful PVI as assigned
• Procedure time: 55 min (PFA) vs 73 min (cryo); difference −18.3 min (95% CI −25.1 to −11.6)
• Fluoroscopy time: 14.6 min (PFA) vs 15.1 min (cryo) — similar
• Cavotricuspid isthmus RF ablation performed in 13.3% (PFA) vs 11.4% (cryo); no ablation outside PVs
• High-sensitivity troponin day 1: 1920±954 ng/L (PFA) vs 1114±419 ng/L (cryo); difference +823 ng/L — PFA creates a larger ablation zone
• Left common pulmonary vein ostium: 6.7% (PFA) vs 20.0% (cryo) — random imbalance (potential PFA advantage); post-hoc subgroup analysis showed no treatment effect modification

Primary Endpoint

• First recurrence of atrial tachyarrhythmia (≥30s) days 91–365:
  • PFA: 39/105 patients (KM cumulative incidence 37.1%)
  • Cryo: 53/105 patients (KM cumulative incidence 50.7%)
  • Difference: −13.6 pp (95% CI −26.9 to −0.3)
  • P<0.001 for noninferiority; P=0.046 for superiority
• Per-protocol analysis: 37.1% vs 51.7%; difference −14.6 pp (95% CI −28.0 to −1.2; P<0.001 NI)
• Adjusted sensitivity analysis: HR 0.66 (95% CI 0.43–1.01)

Secondary Arrhythmia Endpoints

• Recurrence days 1–90 (blanking period): PFA lower by −20.0 pp (95% CI −33.2 to −6.8) — lower early recurrence with PFA, suggesting less procedural inflammation
• Recurrence days 1–365: Difference −18.2 pp (95% CI −31.5 to −4.9)
• Atrial arrhythmia burden days 91–365: 1.4% (PFA) vs 1.9% (cryo); difference −0.5 pp (95% CI −1.4 to 0.4) — not statistically significant
• Arrhythmia burden days 1–90: −2.4 pp (95% CI −4.5 to −0.3) — significantly lower with PFA
• Quality of life (EQ-5D-5L): Similar at 3 and 12 months in both groups

Secondary Clinical Endpoints

• Hospitalisation/ED for AF recurrence: 2 (PFA) vs 8 (cryo); rate ratio 0.25 (95% CI 0.05–1.15)
• Repeat ablation: 16 (PFA) vs 10 (cryo); rate ratio 1.60 (95% CI 0.76–3.37) — numerically more repeats in PFA arm
• Death: 1 (PFA, cancer at 11 months) vs stroke/TIA: PFA had 1 periprocedural stroke; cryo had 1 TIA at 7 months and 1 stroke at 10 months

Safety

• Safety composite (cardiac tamponade → drainage, persistent phrenic nerve palsy >24h, serious vascular complications, stroke/TIA, atrioesophageal fistula, death within 30 days):
  • PFA: 1 event (1.0%) — 1 periprocedural stroke
  • Cryo: 2 events (1.9%) — 2 cardiac tamponades requiring drainage
• No atrioesophageal fistula, no PV stenosis, no persistent phrenic nerve palsy in either group

Comparison with ADVENT Trial

• ADVENT (NEJM 2023; n=607; 30 US centers): PFA NI to thermal (RF/cryo combined) but no superiority signal
• Three factors explain the discrepancy:
  1. ADVENT operators had no prior PFA experience; SINGLE SHOT CHAMPION required ≥6 months
  2. ADVENT used intermittent Holter monitoring (lower sensitivity); SINGLE SHOT CHAMPION used continuous ICM monitoring
  3. ADVENT compared PFA vs mixed RF+cryo; this trial compared PFA vs cryo only

Mechanistic Insights

• Higher troponin with PFA suggests a broader ablation zone — "pulmonary-vein ablation" rather than just isolation — potentially more durable lesions
• Lower early recurrence (blanking period) supports reduced procedural inflammation with PFA — consistent with rare post-PFA pericarditis data
• Blanking period concept may require reassessment for PFA given the apparent absence of inflammatory-driven early recurrence

Limitations of the Document

• Small trial (n=210); superiority P-value borderline (P=0.046)
• Only pentaspline PFA catheter (Farapulse) — not generalizable to other PFA platforms
• Implantable cardiac monitors inserted post-ablation — no baseline AF burden assessment
• Random imbalance in left common ostium (6.7% PFA vs 20% cryo) — potential confound, though subgroup analysis reassuring
• Follow-up limited to 1 year (3-year follow-up planned)
• Generic EQ-5D-5L quality-of-life scale — less sensitive than AF-specific scales
• Two high-volume Swiss centers with experienced operators — limited generalizability to lower-volume settings

Key Concepts Mentioned

• concepts/Pulsed-Field-Ablation — primary intervention; first RCT to show superiority of PFA over cryoablation
• concepts/Catheter-Ablation-AF — clinical context: PVI for paroxysmal AF; blanking period concept challenged

Key Entities Mentioned

• entities/Atrial-Fibrillation — paroxysmal AF; treatment with PVI

Wiki Pages Updated

• wiki/sources/pfa-cryo-singleshotchampion-nejm-2025.md — created
• wiki/concepts/Pulsed-Field-Ablation.md — updated with SINGLE SHOT CHAMPION data; superiority signal; blanking period; repeat ablation; troponin; comparisons with ADVENT
• wiki/concepts/Catheter-Ablation-AF.md — updated PFA section with SINGLE SHOT CHAMPION; blanking period challenge
• wiki/sourceindex.md — entry added
• wiki/wikiindex.md — entries updated