Cryoablation: Sooner or Later?

Abstract

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. 1Chugh SS, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014 Feb 25;129(8):837-47.2Iwasaki YK, Nishida K, Kato T, Nattel S. Atrial fibrillation pathophysiology: implications for management. Circulation. 2011 Nov 15;124(20):2264-74.3Wijffels MC, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995 Oct 1;92(7):1954-68.4Dudink EAMP, et al. The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey. Europace. 2018 Jun 1;20(6):929-9345de Vos CB, et al. Progression from paroxysmal to persistent atrial fibrillation clinical correlates and prognosis. J Am Coll Cardiol. 2010 Feb 23;55(8):725-31.6Kirchhof P, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 1;383(14):1305-1316.7Packer DL, et al. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Apr 2;321(13):1261-1274.8Hindricks G, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 Feb 1;42(5):373-498.9January CT, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019 Jul 9;74(1):104-132.10Andrade JG, et al. Progression of Atrial Fibrillation after Cryoablation or Drug Therapy. N Engl J Med. 2022 Nov 7. Article in Press.11Andrade JG, et al. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):305-315.12Kuck KH, et al. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016 Jun 9;374(23):2235-45.13Hoffmann E, et al. Outcomes of cryoballoon or radiofrequency ablation in symptomatic paroxysmal or persistent atrial fibrillation. Europace. 2019 Sep 1;21(9):1313-1324.14Chen YH, et al. Cryoablation vs. radiofrequency ablation for treatment of paroxysmal atrial fibrillation: a systematic review and meta-analysis. Europace. 2017 May 1;19(5):784-794.15Andrade JG, et al. Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring: A Randomized Clinical Trial. Circulation. 2019 Nov 26;140(22):1779-1788.16Kuniss, Malte et al. “Cryoballoon ablation vs. antiarrhythmic drugs: first-line therapy for patients with paroxysmal atrial fibrillation.” Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology vol. 23,7 (2021): 1033-1041.17Wazni, Oussama M et al. “Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.” The New England journal of medicine vol. 384,4 (2021): 316-32418McCarthy, P.M, et al. Surgery and Catheter Ablation for Atrial Fibrillation: History, Current Practice, and Future Directions. J. Clin. Med. 2022, 11, 210.19Nándor Szegedi, et al. Repeat procedure is a new independent predictor of complications of atrial fibrillation ablation, EP Europace, Volume 21, Issue 5, May 2019, Pages 732–73720Prasada, Sameer et al. “Preoperative Atrial Fibrillation and Cardiovascular Outcomes After Noncardiac Surgery.” Journal of the American College of Cardiology vol. 79,25 (2022): 2471-2485.21Morin D.P.,et al. "The state of the art: atrial fibrillation epidemiology, prevention, and treatment". Mayo Clin Proc 2016;91:1778-1810.