Cryoablation: Sooner or Later?

  • Peter Ochieng
    Division of Cardiac Anesthesiology, Department of Critical Care, Anesthesia, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Adam A. Dalia
    Corresponding author: Adam A. Dalia, MD, MBA, FASE, Instructor in Anesthesiology, Harvard Medical School, Division of Cardiac Anesthesia, Department of Anesthesia, Critical Care and Pain Medicine, The Massachusetts General Hospital, 55 Fruit St. Boston, MA 02114, Cell: (520) 265-7168; Tel: 617-643-4065
    Division of Cardiac Anesthesiology, Department of Critical Care, Anesthesia, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Jonathan E. Tang
    Division of Cardiothoracic and Vascular Anesthesia, Department of Anesthesiology, Ohio State University Wexner Medical Center, Columbus, OH
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Published:January 19, 2023DOI:
      Atrial fibrillation (AF) is the one of the most common arrhythmias seen clinically, with an estimated prevalence of greater than 33 million cases worldwide.1 In a vulnerable atrial substrate, a rapid triggering event is able to initiate reentrant waves that lead to the formation of atrial fibrillation.2 As time is spent in atrial fibrillation, atrial remodeling can lead to paroxysmal episodes that increase in frequency and duration causing progression to more persistent AF subtypes, which are not only associated with a decrease in quality of life, but also may be more resistant to treatment; this leads to the saying “AF begets AF”.3,4,5 Studies show that early rhythm control therapy is associated with a lower risk of adverse cardiovascular outcomes.6 Given the procedural risks of catheter ablation and studies showing that catheter ablation, compared with medical therapy, does not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest, current guidelines recommend the use of antiarrhythmic medications as initial therapy for maintenance of sinus rhythm in symptomatic patients.7,8,9
      In November 2022, the New England Journal of Medicine published the results of Andrade et al 3-year follow up to the Early Aggressive Invasive Intervention for Atrial Fibrillation (EARLY AF) trial.10 The EARLY AF trial is a multicenter, randomized trial with blinded end-point adjudication, comparing the use of cryoballoon ablation against the use of antiarrhythmic drugs in the prevention of atrial fibrillation/tachycardia recurrence using continuous cardiac monitoring over the trial period. The trial was based out of 18 centers in Canada, between January 2017 and December 2018 and enrolled 303 patients, with 154 randomly assigned to received catheter ablation, and the remaining 149 patients received antiarrhythmic therapy. On initial report at one year, the primary end point was time to the first documented recurrence of any atrial tachyarrhythmia (atrial flutter/fibrillation/atrial tachycardia) after initiation of antiarrhythmic medication, or 91-365 days after catheter ablation (0-90 days is considered a blanking period, in which expert consensus from 2017 states that any atrial tachyarrhythmias during this period are not to be considered for first clinical failure of the primary end point). At the end of the initial report there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy.11
      In this current analysis at 3-years post-treatment, the primary end point was time to first occurrence of persistent atrial fibrillation (which was defined as an episode of continuous atrial tachyarrhythmia lasting 7 days or longer, or lasting 46 hours to 7 days but requiring cardioversion for termination). Over the three-year period 63 patients who were initially assigned to the antiarrhythmic medication arm underwent catheter ablation after documented arrhythmia recurrence, and 27 patients assigned to the cryoballoon ablation. At the end of three years, initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation (Hazard Ratio 0.25; 95% Confidence Interval 0.09-0.70) and recurrent atrial tachyarrhythmia than initial use of antiarrhythmic drugs. (Hazard Ratio 0.51; 95% Confidence Interval 0.38-0.67). Cryoballoon ablation was also associated with lower AF burden (time spent in AF) when compared to use of antiarrhythmic medications.
      Andrade et al recognizes this trial was performed with cryoballoon ablation, and that the outcomes may not be generalizable to other ablation techniques. However, if the reduction in time to AF and AF burden is essential for slowing down the progression of AF and cardiac remodelling, the use of radiofrequency ablation may be of benefit as well. Previous studies have shown that to there is no/minimal difference in time to first recurrence or over AF burden.12,13,14,15 In regard to catheter ablation therapy versus antiarrhythmic medication therapy, previous studies compared ablation therapy in patient which drug therapy which already failed, giving an edge to ablation therapy.
      Early intervention in patients with AF offers additional potential benefits besides ones listed above. One benefit is the reduction in needing additional interventions to lower burden of arrythmia. It has been shown that patients with long standing AF require repeat ablations to decrease the burden of arrythmias. 18 Additionally, repeat ablation is a predictor of complications of AF ablation. 19
      There are several potential areas for future studies. A longer-term follow-up of patients in the EARLY AF trial could further show how early ablation can keep patients out of AF as composed to ablation being performed using current guidelines. The EARLY AF study patients had few coexisting conditions and were at low risk for progression of AF. 10 A potential study could be early catheter ablation against current ablation guidelines in patients with multiple comorbidities. Another potential future study can be to compare the need for additional ablation in patient who have catheter ablation as initial therapy vs. the current guidelines.
      As perioperative physicians, we should be aware that patients with AF are at increased risk of adverse effects when they present within the perioperative setting. Preoperative AF has been shown to be associated with an increase in postoperative adverse effects in patients undergoing non-cardiac surgery (NCS). 20 Prasada et all found that pre-existing AF is independently associated with heart failure hospitalization, postoperative motility and stroke within 30 days of NCS.20 These outcomes not only increase the burden on patients quality of life but also increases health care expenditures especially as the prevalence of AF is projected to increase by 3-fold by 2050.21 As early catheter ablation prevents AF disease progression and maintenance of sinus rhythm, it could help decrease the perioperative risks that the patients have.
      Although the current guidelines recommend medical therapy as the initial strategy for rhythm control this shows the potential benefits of early catheter ablation as an alternative. It is time to consider catheter ablation as a first line therapy for AF. There have been two other multicenter randomized studies; Cryo-FIRST and STOP AF FIRST, that compared cryoablation to antiarrhythmic drugs as first line therapy and they both showed similar results to the EARLY AF trial.16,17 The results of the trails continue to build the case for catheter ablation as a first line treatment for AF.


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