Cryoablation to Delay Progression of Persistent Atrial Fibrillation (EARLY-AF Study)

Atrial fibrillation (AF) is a progressive disease that often starts with predominately sinus rhythm interrupted by paroxysms of AF. As the left atrium becomes more diseased, it progresses into persistent AF and achieving rhythm and rate control becomes more difficult. Whereas traditional teaching has put rate and rhythm control on the same weight, more recent evidence such as from the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) has demonstrated better patient outcomes with early rhythm control to maintain sinus rhythm and delay progression of AF into its persistent phase.1 In the EAST-AFNET 4, only 20% of patients receiving early rhythm control had catheter ablation as the rhythm-control strategy.1 With improvement in ablation technology, safety, and efficacy throughout the years, evidence on whether catheter ablation is better than antiarrhythmic drugs (AADs) remains incomplete.

The EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) study was a randomized controlled trial in which 303 patients with paroxysmal untreated AF were randomized in a 1:1 fashion to initial rhythm-control therapy with cryoballoon ablation or to AAD therapy.2 All patients received implantable cardiac monitors, and recurrent atrial arrhythmias were strictly monitored.2 At the initial 1-year conclusion of the study, patients undergoing ablation had a significantly lower risk of recurrence than did those taking AADs (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.35-0.66; p < 0.001).2 The results of the 3-year follow-up study of the original randomized cohort demonstrated a lower incidence of progression into persistent AF or recurrent atrial tachyarrhythmia (1.9% in the ablation group vs. 7.4% in the AAD group; HR, 0.25; 95% CI, 0.09-0.7).2 The results of the EARLY-AF 1-year and 3-year studies together with those of the similar STOP AF First (Cryoballoon Catheter Ablation in Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) trial provided reproducible and reliable evidence that catheter ablation should be considered as a first-line strategy in patients with AF to achieve rhythm control and to delay progression of disease.3


  1. Kirchhof P, Camm AJ, Goette A, et al.; EAST-AFNET 4 Trial Investigators. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med 2020;383:1305-16.
  2. Andrade JG, Deyell MW, Macle L, et al.; EARLY-AF Investigators. Progression of atrial fibrillation after cryoablation or drug therapy. N Engl J Med 2023;388:105-16.
  3. Wazni OM, Dandamudi G, Sood N, et al.; STOP AF First Trial Investigators. Cryoballoon ablation as initial therapy for atrial fibrillation. N Engl J Med 2021;384:316-24.

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

Keywords: AHA Annual Scientific Sessions, AHA22, Atrial Fibrillation, Catheter Ablation, Cryosurgery, Anti-Arrhythmia Agents

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