Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation - ADVENT

Jul 22, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Farapulse–Boston Scientific
Date Presented:
08/27/2023
Date Published:
06/24/2024
Date Updated:
07/22/2024
Original Posted Date:
08/27/2023
References

Contribution To Literature:

Highlighted text has been updated as of July 22, 2024.

The ADVENT trial showed that in patients with symptomatic paroxysmal AF who have failed prior AAD therapy, pulsed field catheter ablation is noninferior with respect to efficacy and safety to thermal ablation.

Description:

The goal of the trial was to compare the safety and efficacy of pulsed field catheter ablation for symptomatic paroxysmal atrial fibrillation (AF) with that of conventional thermal ablation techniques (radiofrequency or cryoballoon).

Study Design

  • Randomized
  • Multicenter
  • Single-blind
  • Noninferiority

Patients with symptomatic paroxysmal AF with prior antiarrhythmic drug (AAD) treatment failure were randomized to undergo pulsed field (n = 305) or thermal ablation (n = 302). Pulsed field energy was delivered to achieve pulmonary vein isolation (PVI). Thermal ablation could be with either radiofrequency or cryoballoon ablation. Use of class I or III AADs except amiodarone was permitted in the 3-month post-procedure blanking period. AF recurrence was monitored using trans-telephonic ECG weekly and with symptoms as well as 72-hour Holter monitoring at 6 and 12 months.

  • Total number screened: 741
  • Total number of enrollees: 607
  • Duration of follow-up: 12 months
  • Mean patient age: 62 years
  • Percentage female: 35%

Inclusion criteria:

  • Age ≥18 and ≤75 years
  • Symptomatic paroxysmal AF (≥2 episodes lasting <7 days each)
  • Treatment failure of ≥1 AAD (class I-IV) due to efficacy or intolerance

Exclusion criteria:

  • Persistent (>7-day duration) AF
  • ≥4 direct-current cardioversions (DCCVs) in past 12 months
  • Prior left-sided atrial ablation procedure or prior atrial surgery
  • Pulmonary vein structural abnormality
  • Hemodynamically significant valvular disease or prior valve replacement/repair
  • Presence of cardiac implantable electronic device
  • Left ventricular ejection fraction <40%

Other salient features/characteristics:

  • Mean CHA2DS2-VASc score: 1.7
  • Concomitant heart failure: 19%
  • Years since AF diagnosis: 3-4 years
  • Percentage of patients with interpretable pre- and post-procedure heart rate (HR) data: 62%

Principal Findings:

The primary efficacy outcome, freedom from composite of periprocedural PVI failure, atrial tachyarrhythmia ≥30 seconds, use of class I/III AAD or DCCV after the blanking period, amiodarone use at any time, or repeat ablation at 12 months, for pulsed field vs. thermal ablation, was: 73.3% vs. 71.3% (p for noninferiority >0.999, p for superiority = 0.708).

  • Successful PVI: 99.6% vs. 99.8%
  • Periprocedural PVI failure: 0.8% vs. 0.8%
  • Recurrent atrial arrhythmia: 17.2% vs. 16.4%
  • DCCV: 0.5% vs. 0.2%
  • Use of class I/III AAD: 8.1% vs. 9.2%
  • Amiodarone use: 0.5% vs. 2.5%
  • Repeat ablation: 0.5% vs. 0.5%

The primary safety outcome, composite of serious adverse events within 7 days post-procedure or atrioesophageal fistula or pulmonary vein stenosis at any time, for pulsed field vs. thermal ablation, was: 2.1% vs. 1.5% (p for noninferiority > 0.999).

Secondary safety outcomes for pulsed field vs. thermal ablation at 12 months:

  • Mean change in pulmonary vein cross-sectional area: -0.18 vs. -1.18 cm2
  • Death: 0.3% vs. 0%
  • Transient ischemic attack or stroke: 0.3% vs. 0.3%
  • Pericardial tamponade: 0.7% vs. 0%
  • Atrioesophageal fistula: 0% vs. 0%

Subanalysis of autonomic effects of pulsed field vs. thermal ablation:

  • Change from baseline HR at 6 months: +5.9 vs. +10.1 bpm, p = 0.02
  • Change from baseline HR at 12 months: +5.2 vs. +8.8 bpm, p = 0.03
  • HR variability and frequency of bradycardic events (HR <40 bpm for >30 seconds) were significantly higher at 6 and 12 months in pulsed field vs. thermal ablation (p < 0.001 for all)
  • Freedom from treatment failure at 12 months for pulsed field ablation, >10% vs. ≤10% HR increase: 76.0% vs. 73.4%, p = 0.73
  • Freedom from treatment failure at 12 months for thermal ablation, >10% vs. ≤10% HR increase: 74.6% vs. 67.9%, p = 0.42

Interpretation:

The ADVENT study is the first randomized trial of pulsed field ablation, demonstrating noninferior efficacy compared with conventional thermal ablation techniques. The predominantly nonthermal mechanism of pulsed field ablation has generated interest in its viability as a safer technique with less risk of esophageal or phrenic nerve injury. Although noninferiority safety was demonstrated, there were too few serious adverse periprocedural events in either treatment arm to test for superiority. The authors did observe significantly less narrowing of mean pulmonic vein area with pulsed field ablation, though no clinical episodes of pulmonic vein stenosis occurred in either treatment arm.

Following outcomes beyond 1 year may provide further insight into longer-term safety profiles of each technique, particularly after repeat ablation, as well as durability of ablation efficacy. Differences in specific populations such as those with heart failure or valvular heart disease will be important to assess. Additionally, these findings may not be generalizable to different pulsed field ablation systems or patients with persistent AF, opening further areas of potential investigation.

Decreased risk of collateral injury to epicardial atrial ganglionated plexi has been proposed as an unintended consequence of pulsed field ablation’s greater specificity for myocardial tissue compared to thermal ablation. These autonomic bundles have been implicated in the initiation and maintenance of AF, raising the question of decreased long-term efficacy with pulsed field versus thermal ablation. In a subanalysis of patients with 72-hour Holter monitoring at 6 and 12 months, reduced autonomic impairment following pulsed field ablation was evident with smaller increases in HR from baseline (reflecting intact vagal tone), more frequent bradycardia, and greater HR variability compared with radiofrequency or cryoballoon ablation. Change in resting HR was not associated with risk of treatment failure in any modality. Though nonrandomized, these data suggest electrical isolation by PVI was key to treatment success regardless of autonomic modulation by thermal ablation. However, the authors do note that decreasing vagal tone may suggest a special use case for thermal modalities in patients with tachycardia-bradycardia syndrome.

References:

Gerstenfeld EP, Mansour M, Whang W, et al. Autonomic Effects of Pulsed Field vs Thermal Ablation for Treating Atrial Fibrillation: Subanalysis of ADVENT. JACC Clin Electrophysiol 2024;Jun 24:[Epublished].

Reddy VY, Gerstenfeld EP, Natale A, et al., on behalf of the ADVENT Investigators. Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med 2023;389:1660-71.

Presented by Dr. Vivek Reddy Andreasen at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 27, 2023.

Clinical Topics: Arrhythmias and Clinical EP, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Ablation Techniques, Anti-Arrhythmia Agents, Atrial Fibrillation, ESC23


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