Balloon Cryoablation for the Treatment of Paroxysmal Atrial Fibrillation: Case Presentation

Endocardial catheter-based ablation for atrial fibrillation is in its second decade of clinical implementation. Early attempts at ablation for atrial fibrillation utilized radiofrequency (RF) energy delivered through a single electrode to eliminate focal sources of abnormal pulmonary vein electrical activity. In a majority of cases, however, it was recognized that it was not a single source of abnormal activity that needed to be ablated, but rather a wide-ranging network of electrical connections between the pulmonary veins and the atrial tissue that were the pathways for abnormal electrical signaling to initiate atrial fibrillation. 

The next logical step in the evolution of ablation for atrial fibrillation was to perform pulmonary vein isolation — a series of point-by-point RF ablations at the pulmonary vein ostia to create a contiguous band of destroyed atrio-venous tissues around the circumference of the pulmonary vein ostia that would no longer conduct electrical impulses. This approach was successful at eliminating atrial fibrillation in a significant number of patients. Unfortunately, this approach also led to significant pulmonary vein injury and the subsequent development of pulmonary vein stenosis in a distressingly large number of patients.

In recognition of the risk of pulmonary vein stenosis, the next evolution in the treatment of atrial fibrillation was to perform wide area circumferential ablation (WACA), in which the encircling point-by-point pulmonary vein lesions were not performed at the ostia but instead at 1-2 cm away from the ostia of the pulmonary veins. This approach significantly reduced the incidence of pulmonary vein stenosis, but also significantly increased the risk of leaving “gaps” in the encircling lesions where abnormal electrical impulses could still escape the pulmonary veins and induce atrial fibrillation. The gaps occurred as a result of atrial tissue that was temporarily damaged (and therefore temporarily electrically inactive) rather than completely destroyed. Acutely, veins appeared to be electrically isolated, but multiple studies have shown that acutely isolated veins frequently “reconnect” due to incomplete destruction of the atrial tissue. Furthermore, the areas of RF ablation that were contiguous but not continuous around the pulmonary veins created an atrial substrate that was prone to the development of atypical atrial flutters that circled around partially ablated tissues. 

A novel approach to the ablation of atrial fibrillation arrived in the form of balloon cryoablation. In this technique, a 23 or 28 mm balloon is introduced via a transseptal approach into the left atrium. A flexible-tipped wire is introduced through the lumen of the cryoballoon catheter and guided into the targeted pulmonary vein. The balloon is then inflated in the chamber of the left atrium and guided over the wire to the antrum of the targeted pulmonary vein. Liquid nitrogen is then pumped into the balloon and converted to nitrogen gas due to the temperature change at the balloon/tissue/blood interface. This conversion of liquid nitrogen to nitrogen gas is an endothermic reaction that requires the withdrawal of heat from the surrounding environment; the net result is that the balloon/tissue interface becomes extremely cold. The extremely cold temperature at the balloon/tissue interface is frequently cold enough to create irreversible injury to the tissue. 

In contrast to WACA (or other point-by-point methods of ablating atrial fibrillation), the balloon cryoablation technique creates a large circumferential ablative lesion around the pulmonary vein antrum rather than requiring a point-by-point ablative strategy. In this manner, a pulmonary vein may be effectively isolated en bloc within minutes rather than the typically longer times associated with point-by-point ablation.

Interestingly, atrial ablation by freezing rather than heating has been shown cytologically to create markedly less endothelial and cytoskeletal disruption than atrial ablation by radiofrequency “resistive heating.” In other words, cryoablation creates minimal cytoskeletal disruption and denuded endothelium, as is frequently seen with RF ablation. It is postulated that the lack of cytoskeletal and endothelial disruption reduces the risk of thrombus formation following ablation.

Case Presentation

The patient is a 64-year-old male who was initially diagnosed with paroxysmal atrial fibrillation about 5 years ago. He has been treated for hypertension with metoprolol tartrate 25 mg bid — with reportedly excellent control — for the last 12 years, and has no other significant past medical history. 

He first noticed very brief episodes of palpitations or flutters that started when he was 58 years old. Initially these episodes were discomforting but occurred very sporadically — “maybe once every few months” — and only lasted “just a few seconds up to 1 minute at the most,” so he did not seek treatment for them. Over the course of the next year, the episodes became more frequent and, occasionally, he would experience episodes that lasted up to 20 minutes. During these longer episodes, he noted that he would become easily short of breath with minimal activity — even during conversations — so he went to his PCP.

The PCP performed a comprehensive evaluation that, among other normal findings, noted normal blood pressure, a normal cardiac exam, normal basic blood work including thyroid function, and a normal 12-lead EKG. However, suspecting a recurrent arrhythmic problem, the PCP ordered a 30-day event monitor for the patient that ultimately documented several episodes of sustained atrial fibrillation.

The patient was then referred to an EP who thoroughly evaluated the patient and the pertinent records. An echocardiogram was obtained which revealed normal LV size and systolic function. There was mild diastolic dysfunction but no left ventricular hypertrophy. The left atrium was mildly enlarged at 4.0 cm. The patient was then prescribed flecainide acetate 50 mg bid (in addition to the metoprolol he was already taking) with significant improvement in symptoms. He was started on aspirin 81 mg daily based on a CHADS₂ (and CHADS VASc) score of 1. Over the course of the succeeding year, however, episodes of atrial fibrillation recurred. Similar to his initial presentation, the episodes were very sporadic and transient at first. With time, the episodes became more frequent and longer lasting, and were creating a significant, negative impact on the patient’s quality of life.

The EP discussed options including increasing the dosage of flecainide, changing to an alternate antiarrhythmic, or considering catheter ablation for atrial fibrillation. The patient opted for ablation.

The patient underwent pulmonary vein isolation using irrigated radiofrequency energy in a WACA strategy. The procedure was acutely successful and, despite pleuritic chest discomfort for the first few days, the patient noted an almost immediate improvement in how he felt. After 3 months, the flecainide was discontinued. 

Over the course of the next year, the patient had episodes in which he felt like he was more tired than normal or occasionally short of breath, but he did not feel that he was having atrial fibrillation as he had no feeling or sensation of being out of rhythm. A 24-hour Holter was prescribed which showed only normal sinus rhythm with infrequent PACs. After a few more months of intermittent symptoms, the patient had an episode of severe shortness of breath while skiing in the Rocky Mountains, and was taken to a local hospital where he was found to be in atrial fibrillation with a rapid ventricular response. Interestingly, this patient who, prior to his initial ablation, had been acutely aware of his atrial fibrillation was now no longer “aware” of atrial fibrillation, even though he was highly symptomatic as a result of the condition. Fortunately, the prolonged episode of atrial fibrillation spontaneously terminated and he returned home without further incident. 

At this point, the patient was referred to our center for further evaluation and management. Following review and confirmation of the above-noted information, we recommended resuming flecainide at 50 mg bid (with continuation of the metoprolol and aspirin he was still taking). We also discussed the potentially beneficial role of an implantable loop recorder (ILR) monitoring of his atrial fibrillation, as he was still highly symptomatic but no longer aware of his episodes of atrial fibrillation. 

He resumed flecainide but decided to hold off on the ILR implantation. Over the next several months, he had multiple instances where he felt “not right” or “short of breath” or “just so tired,” but he did not think he was having episodes of atrial fibrillation. An event monitor documented episodes of atrial fibrillation that sometimes — but not invariably — correlated with symptoms of dyspnea, fatigue, and malaise. At this point, the patient recognized that his ability to accurately discern atrial fibrillation was impaired, and he agreed to undergo ILR implantation. 

Following implantation of an ILR, it was clear that he was having a significant burden of atrial fibrillation despite the flecainide and prior ablation. The dose of flecainide was increased to 100 mg bid, but there was no significant change in his atrial fibrillation burden (as documented on the ILR) or in his intermittent symptoms. We again discussed options including further increasing the dose of flecainide, switching to an alternate antiarrhythmic, or considering repeat ablation using a relatively new technology at the time: balloon cryoablation. The patient opted for repeat ablation.

He underwent the balloon cryoablation approximately 1 year ago. During the mapping portion of the ablation, there was clear evidence of “reconnection” of three of the four pulmonary veins — the RIPV remained electrically isolated from the prior ablation. The RSPV was also observed to be a source of frequent PACs as well as an initiator of atrial fibrillation. The ablation was completed in 2 hours and 3 minutes, with a left atrial dwell time of 64 minutes. The fluoroscopy time was 11 minutes, and the total contrast was 14 ml of Oxilan 300.

Following ablation, the patient again felt significant improvement, although this time without the post-ablation pleuritic pain. The flecainide was continued for 6 weeks post ablation, at which time it was discontinued. At his 6-week, 3-month, 6-month, and 1-year follow-ups, he has continued to have no evidence of symptoms of recurrent atrial fibrillation, and his arrhythmia-free status has been confirmed by the ILR monitor. He continues to take aspirin 81 mg daily.

Summary

Balloon cryoablation for paroxysmal atrial fibrillation has been proven to be a safe and effective therapy. Our institution has noted a significant decrease in procedure time, fluoroscopy time, and left atrial dwell time when compared to traditional radiofrequency pulmonary vein isolation procedures. 

Disclosures: Dr. Wickliffe and Dr. Dan report payment by Medtronic for development of educational presentations including service on speakers’ bureaus. Dr. Dan reports he is a consultant with Medtronic and Biosense Webster; he also reports travel/accomodations expenses covered or reimbursed by Medtronic and Biosense Webster.