Commentary: Cryoballoon vs. radiofrequency ablation for atrial fibrillation—a study of outcome and safety based on the ESC-EHRA atrial fibrillation ablation long-term registry and the Swedish catheter ablation registry

This editorial refers to ‘Cryoballoon vs. radiofrequency ablation for atrial fibrillation: a study of outcome and safety based on the ESC-EHRA atrial fibrillation ablation long-term registry and the Swedish catheter ablation registry’ by D. Mörtsell et al., on pages 581–589. Atrial fibrillation (AF) is the most common sustained arrhythmia and directly affects morbidity and mortality.1 Maintenance of stable sinus rhythm is intended in symptomatic patients, and catheter ablation aiming at isolation of the pulmonary veins provides the most effective treatment option with encouraging clinical outcome data.1,2 Multiple energy sources and various devices have been introduced and extensively evaluated. While radiofrequency (RF)-based pulmonary vein isolation (PVI) in combination with a 3D mapping system was considered the ‘gold standard’ for a long time, the cryoballoon (CB) has emerged as the most common alternative ablation tool for PVI and is now established as the second ‘gold standard’.3,4 The present study sought to compare the second-generation cryoballoon (CB2) and irrigated RF energy for catheter ablation of AF regarding clinical efficacy and safety by analysing data from two large prospective registries [the AF Ablation Long-Term registry within the EURObservational Research Programme (AFA EORP) and the Swedish catheter ablation registry], and therefore, represents results of a real-world mixed population of both paroxysmal and persistent AF patients.5 The recently published FIRE AND ICE trial, which prospectively randomized paroxysmal atrial fibrillation (PAF) patients to either RF or CB-based PVI, demonstrated non-inferiority of CB ablation vs. RF ablation in terms of efficacy and safety.3 Cryoballoon-based AF ablation is currently the only established ‘singe-shot’ ablation modality and is not only readily applicable and easy to learn, but is also—because of its ‘over-the-wire’ strategy—a particularly safe tool, resulting in a low incidence of perforation and pericardial effusion or tamponade.3,5,6 Furthermore, the incidence of phrenic nerve (PN) palsy—as the most common balloon-associated complication—can be kept considerably low by implementing safety algorithms such as PN pacing and monitoring of the compound motor action potential.3,6 The heterogeneity of the patient population in the present study by Mörtsell et al.5 lends strength to the safety aspect since it mirrors a real-world ablation practice. The simplification of and straight forward approach to PVI using the CB reproducibly results in significantly shorter procedure times when compared with RF. In contrast, due to the purely fluoroscopic guidance of CB ablation, longer fluoroscopy times compared with RF ablation were demonstrated.3,5 Benefits of CB ablation over RF-based PVI were assessed in the analysis of the secondary endpoints of the FIRE AND ICE study. Thus, the hospitalization rate for cardiovascular and non-cardiovascular causes and the rate of reablation and electrical cardioversion after CB ablation were significantly lower.3 The study by Mörtsell et al.5 was able to reproduce these benefits and showed a lower reablation rate for the CB group, which possibly emphasizes another important superiority of CB-based PVI. Persistent AF relates to a more difficult underlying substrate and tends to be more challenging to ablate than PAF. While the mechanisms of, and therefore, the ablation strategy for PAF is well defined, the underlying pathophysiology of persistent AF is less well understood and still controversial. PVI for persistent, and especially long-standing persistent, AF is associated with limited success rates.1,7 To improve recurrence after catheter ablation, ablation strategies beyond PVI may be applied to modulate and target additional arrhythmogenic substrates. The most commonly used strategies are the ablation of complex fractionated atrial electrograms and/or the creation of linear lesions.1 The additional benefit of these extensive ablation strategies is increasingly controversial following the results of recent comparative studies.8,9 Therefore, PVI currently remains the only established ablation endpoint for AF and, according to the current European AF guidelines,1 ablation beyond PVI is not recommended for patients with persistent AF undergoing a first attempt at ablation. Although RF ablation is considered the gold standard for ablation of persistent AF, studies using CB in these patients—presumably due to the high durability of PVI and also the potential for additional substrate modification due to the beneficial mismatch of the PVs and the oversized 28 mm CB, thus also covering substantial parts of the posterior left atrial wall—showed satisfying clinical outcomes.5,10 The recently published CRYO4PERSISTENT study did not only focus on recurrence of AF after previous CB-based PVI but also on symptoms and could demonstrate a significant improvement in the patients’ quality of life following CB ablation in persistent AF.10 These findings are confirmed by the analysis of Mörtsell et al.,5 which reports a lower EHRA score—a measure of AF-related symptoms—for the CB group and a lower rate of continued antiarrhythmic drugs after CB-based AF ablation, all of which may have not only a positive impact on the patients’ quality of life, but also a positive health economic impact on long-term favouring the CB technology. To date, there is no data from randomized studies comparing CB ablation vs. RF ablation in patients with persistent AF. The FIRE AND ICE II randomized outcome trial has been designed to compare the efficacy and safety of PVI using CB vs. RF ablation with a contact-force sensing catheter in patients with persistent AF. The study is currently in preparation and the study protocol will be released shortly. Conflict of interest: L.R. and A.M. report no conflict of interest. K.-H.