Radiofrequency vs Cryoballoon Catheter Ablation for Pulmonary Vein Isolation in Patients With Atrial Fibrillation - Effect on Atrial Fibrillation Burden Assessed by Implantable Cardiac Monitor (RACE-AF Trial)

Atrial fibrillation (AF) is the most common heart rhythm disorder and carries considerable mortality, morbidity and socio-economic costs in western societies. Treatment options include anticoagulation to prevent thromboembolisms, antiarrhythmic or heart rate limiting drugs to control symptoms, and catheter or surgical ablation to potentially eliminate sources of atrial fibrillation. Curative treatment is difficult, but ablation has been shown to be superior to anti-arrhythmic drug treatment in the prevention of recurrent symptomatic atrial fibrillation in selected patients. The highest success rates are achieved in patients with self-limiting episodes (paroxysmal atrial fibrillation, PAF), where data from randomized controlled trials such as the recent MANTRA-PAF trial suggests ablation as a reasonable first line treatment option. Almost anticipatory to these recent studies, there has been an exponential growth in ablation procedures, which over the past decade has been offered increasingly to patients without prior antiarrhythmic drug treatment. The therapeutic concept for ablation is elimination of triggers of PAF by pulmonary vein isolation (PVI): Focal triggers of atrial fibrillation are primarily located around the ostia of the pulmonary veins draining into the left atrium, and the cornerstone of standard ablation strategies is to form an encircling lesion around the pulmonary vein to isolate the trigger areas, thereby preventing triggering of atrial fibrillation. However, success rates remain far below those achieved with ablation of other types of arrhythmias, and results of long-term follow up has shown annual rates of recurrence in the order of 5-10% even in patients with initially successful ablation, leading to long term cure rates at or well below 50%. This highlights the need for more effective ablation strategies to achieve better long-term cure rates for atrial fibrillation.

To meet this need, there has been a continuing development of ablation strategies and methods of ablation, including technologies for robotic steering of catheters and technologies to sense contact force between the ablation catheters and the heart to improve lesion formation. Cryoballoon ablation is emerging as a safe, efficacious and simple method to isolate pulmonary veins by a freeze-thaw lesion around the ostia, and seems to be the most promising alternative to radiofrequency (RF) ablation for atrial fibrillation. The latter is a complex procedure involving the use of electroanatomical computer mapping systems to generate three-dimensional models of the left atrium in each patient, and has a very long learning curve for operators. In contrast, cryoballoon ablation is achieved with a compliant balloon placed over a guiding catheter in the pulmonary vein ostia and designed for single shot isolation of each vein, without the use of a mapping system and with relatively short learning curves. However, there has been no direct comparison of the two methods in a randomized study, such as the one we are now proposing.

The underlying cause for recurrences of atrial fibrillation after ablation is presumed to be recovery of electrical connection to the pulmonary veins. This presumption is based on the finding of a high rate of reconnected pulmonary veins in patients with clinical recurrence undergoing a second ablation procedure, but whether it exceeds that found in patients without recurrence has not been systematically investigated in order to provide proof of concept. One problem in this regard, is the difficulty in assessing the true occurrence of atrial fibrillation since many episodes, particularly after ablation, are known to be asymptomatic and self limiting. This problem can now be overcome by continuous monitoring of the heart rhythm with a small subcutaneously implantable cardiac monitor which has been shown to reliably detect episodes of atrial fibrillation and determine the time spent in atrial fibrillation ("AF burden") This also raises the possibility that pre-ablation monitoring in the individual patient can identify specific patterns of atrial fibrillation that is either amenable or resistant to curative ablation, thereby improving patient selection for catheter ablation.

A considerable proportion of patients have to undergo more than one ablation procedure within the first year to achieve freedom from atrial fibrillation (30-50% depending on a number of clinical factors). Re-isolation of the pulmonary veins will eliminate atrial fibrillation in about 50-60% of these patients, but even so, as with initially successfully ablated patients there is a long-term recurrence rate. Whether this pattern of short and long-term recurrences, that carries considerable morbidity, socioeconomic costs and loss of quality of life, could be avoided by a routine strategy with a second ablation procedure with consolidating pulmonary vein isolation has not been investigated. Our study will provide hypothesis-generating data on this issue.

Thus, several key questions regarding ablation for atrial fibrillation lack definitive answers, including the following: