Atrial fibrillation (AFib) is the most common sustained cardiac arrhythmia, affecting approximately 0.4% to 1% of the population in the United States. Although drug therapy is somewhat effective, the challenge of drug-refractory AFib persists. Drug-refractory symptomatic paroxysmal AFib has been treated with pulmonary vein isolation (PVI) either by radiofrequency (RF) ablation or cryoballoon ablation. However, data for cryoablation of drug-refractory persistent atrial fibrillation is limited. In this article, we report on 6 cases of persistent AFib that were recurrent after RF ablation but successfully treated with cryoballoon ablation.
A 34-year-old male with a past medical history significant for persistent AFib presented with symptoms of dizziness, lightheadedness, and palpitations for about 2 years. He underwent direct current cardioversion twice, but reverted to AFib after a few weeks. He was started on sotalol 80 mg BID, and later underwent PVI and a right atrial flutter ablation using radiofrequency energy. He continued sotalol and remained asymptomatic for the next 3 months. He then started developing symptoms again, and was found to have atrial fibrillation despite being on sotalol. The patient was having symptoms almost weekly, which were made worse during periods of stress. He had no other comorbid conditions, including obstructive sleep apnea. We decided to proceed with cryoballoon ablation after shared decision making. The patient underwent a successful procedure, using 2 freezes in each pulmonary vein, seeing early isolation in the active veins. He was released on sotalol and apixaban. After one week, he was asymptomatic and reported no complications from the procedure. At his clinic follow-up at 8 weeks, he reported no symptoms and had improved quality of life. He started exercising and working on losing weight. The dose of sotalol was reduced to 40 mg BID with the aim of discontinuing in the next few months. At 4 months, he had no recurrences.
A 60-year-old male with a past medical history of well-controlled hypertension was referred to our electrophysiology clinic for persistent AFib. The patient had symptoms of palpitations and fatigue for 2 years. He was initially started on rate control medicine, but continued to have symptoms. A plan was made for radiofrequency ablation after starting sotalol 120 mg BID. He underwent PVI with additional left atrial and right atrial flutter ablation using RF energy 6 months before referral to our clinic. Three weeks after the procedure, he reverted to AFib and underwent direct current cardioversion (DCCV) twice, 4 weeks apart. He continued to have symptoms and underwent repeat DCCV twice. The patient was switched from sotalol to amiodarone, 200 mg BID. He underwent successful cryoballoon ablation, using 2 freezes in each pulmonary vein, and seeing early isolation in the active veins. He was discharged on amiodarone 200 mg BID and rivaroxaban. The patient has had no recurrence at 10 weeks of follow-up, so the dose of amiodarone was reduced to 200 mg daily.
A 62-year-old male presented with a past medical history of atrial fibrillation and multiple unsuccessful attempts with DCCV for 15 years. He was diagnosed with sick sinus syndrome and underwent pacemaker placement 4 years ago. He also underwent PVI using radiofrequency energy. After 4 months, he underwent repeat PVI with radiofrequency energy. The patient was continued on sotalol throughout this period. After about a year after his second ablation procedure, he reported exertional fatigue; his pacemaker was interrogated, which showed atrial fibrillation. His sotalol was discontinued and his beta blocker dose was increased for better rate control. Since he continued to have fatigue, echocardiography was done, which showed a drop in ejection fraction (EF) from 45 percent one year ago to 26 percent. The patient reported shortness of breath on exertion and fatigue. Apart from AFib, he had a history of well-controlled hypertension. After shared decision making, the patient underwent cryoballoon ablation, using 2 freezes in each pulmonary vein, and seeing early isolation in the active veins. His symptoms improved in a week. Amiodarone 400 mg daily was started before ablation, and was reduced to 200 mg daily at 8-week follow-up. Repeat echocardiography showed improved EF to 45-50 percent.
This 68-year-old male had a past medical history significant for hypertension and atrial fibrillation for about 10 years. He underwent electrical cardioversion multiple times, but continued to have symptoms of palpitations and fatigue. He underwent PVI using radiofrequency energy. A few weeks before the procedure, the patient was started on sotalol 80 mg twice daily, which was continued after the procedure. He continued to have palpitations and atrial fibrillation. The patient was then switched to diltiazem, a rate control strategy. Echocardiogram 6 months after the procedure showed an estimated ejection fraction of 58 percent with normal left ventricular size and function, left atrial volume index of 43 ml per meters squared body surface area. Using shared decision making, cryoballoon ablation was planned for persistent atrial fibrillation, which he underwent successfully. We applied 2 freezes in each pulmonary vein, saw early isolation in the active veins. His symptoms resolved in a few days. Diltiazem was continued, and rate remained under very good control. He reported no symptoms at his 8-week follow-up. Pacemaker interrogation showed no atrial fibrillation after cryoballoon ablation (Figure 1).
A 60-year-old male with a past medical history significant for hypertension and diastolic heart failure was referred for persistent AFib, which had been persistent for 8-10 years. He underwent 3 direct current cardioversions. One year ago, he also underwent PVI with right-sided atrial flutter ablation using radiofrequency energy. Before the procedure, he was started on sotalol, which was later continued at 80 mg twice daily. The patient underwent repeat radiofrequency ablation after 2 months for the recurrent AFib. Echocardiogram showed normal ejection fraction, mild concentric left ventricular hypertrophy, moderate to severe mitral regurgitation, and severe left atrial enlargement with a left atrial size of 5.17 cm and left atrial volume index of 70 ml per meters squared body surface area. The patient had a few hospital admissions for the acute decompensated diastolic heart failure and atrial fibrillation with rapid ventricular response. Although his rate became controlled with diltiazem, he continued to have palpitations. After shared decision making, he underwent successful cryoablation, using 2 freezes in each pulmonary vein, seeing early isolation in the active veins. The patient remained asymptomatic after the procedure, and was continued on sotalol 80 mg BID. He was doing well at his 8-week follow-up, with no further symptomatic AFib.
This 70-year-old male had a past medical history of hypothyroidism, hyperlipidemia, hypertension, and persistent AFib for 15 years. He had undergone 3-4 direct current electrical cardioversions, but continued to be in atrial fibrillation. He underwent PVI ablation using radiofrequency energy 8 years ago for his symptomatic atrial fibrillation. His symptoms were mainly fatigue on physical activity, which affected his quality of life. He developed recurrent atrial fibrillation and underwent repeat PVI after an unsuccessful DCCV. He felt better for a few months, but developed recurrent atrial fibrillation. During this time, he was continued on dofetilide as an antiarrhythmic. Diltiazem was added for better rate control. The patient was followed periodically, and his fatigue improved along with his palpitations. Six months ago, he was admitted for AFib with rapid ventricular response, and was treated with an increased dose of rate control medicine. Transthoracic echocardiogram (TTE) was performed, which showed normal ejection fraction, mild left concentric left ventricular hypertrophy, mild left atrial enlargement with left atrial volume index of 36 ml per meter squared body surface area, and mild mitral regurgitation. Using shared decision making, the patient underwent cryoballoon ablation, using 2 freezes in each pulmonary vein, and early isolation was seen in the active veins. He has had no recurrence at 8-week follow-up.
Mechanisms of Maintenance of Atrial Fibrillation
Persistent atrial fibrillation is present when AFib lasts longer than 7 days or requires termination, either with drugs or direct current cardioversion. Longstanding persistent AFib lasts for ≥1 year. The exact mechanism for AFib is poorly understood, but there are proposed mechanisms. Both structural and electrophysiological mechanisms play a role. Structural changes include increased proliferation and differentiation of fibroblasts into myofibroblasts and formation of fibrosis. Because of the shorter refractory period as well as abrupt changes in myocyte fiber orientation, the pulmonary veins have more potential to initiate and perpetuate AFib.
Methods, Efficacy, and Safety of Catheter Ablation for AFib
Catheter ablation has proven to be an effective treatment for atrial fibrillation, with increased experience and new development in techniques. In 2010, Cappato et al published an updated report on the methods, efficacy, and safety of catheter ablation for atrial fibrillation;5 a questionnaire was developed by an independent steering committee and distributed among electrophysiology laboratories at 521 centers in 24 countries. Complete interviews were collected from 182 centers between 2003 and 2006, of which 85 centers reported to have performed 20,825 procedures on 16,309 patients. All centers included paroxysmal AFib, 85.9% included persistent AFib, and 47.1% included longstanding persistent AFib. Data relative to the modality of the energy delivery was made available for 17,729 patients, of whom 12,068 (68.1%) received RF ablation, 207 (1.2%) underwent cryoablation, and 5 (.002%) received ultrasound ablation. Results showed that catheter ablation was effective in approximately 80% of the patients after 1.3 procedures per patient, with approximately 70% of patients not requiring antiarrhythmic drugs (AADs) in intermediate follow-up (18 months). The success rate was higher in paroxysmal AFib compared to persistent and long-lasting AFib. Major complications including death, pneumothorax, tamponade, hemothorax, stroke, transient ischemic attacks, and others happened in 4.5% of patients.
About Cryoballoon Ablation
Cryoballoon ablation is a minimally invasive procedure that efficiently creates circumferential lesions around the pulmonary veins, a common source of atrial fibrillation. It ablates with the use of coolant (rather than heat) delivered through a catheter. This freezing technology allows the catheter to adhere to the tissue during ablation, allowing for greater catheter stability. In December 2010, the FDA approved the Arctic Front Cardiac CryoAblation Catheter System (Medtronic) for the treatment of drug-refractory paroxysmal atrial fibrillation. The FDA approval was based on the pivotal STOP AF (Sustained Treatment of Paroxysmal Atrial Fibrillation) trial, which demonstrated safety and efficacy of the technique in treating and eradicating PAF. The study showed 69.9% of patients treated with the cryoballoon were free from AFib at 1 year compared to 7.3% patients treated with drugs only. In addition, the study demonstrated limited procedure-related adverse effects (3.1%), and showed that patients enrolled in the study displayed a significant reduction in symptoms, a decrease in the use of drug therapy, and a substantial improvement in both physical and mental quality of life measures.
Achieving point-by-point ablation through radiofrequency ablation is technically challenging and highly dependent on the expert’s dexterity. A balloon-based ablation system such as the cryoballoon theoretically eliminates the need for point-by-point ablation by creating a single circumferential lesion around the PV by one or two applications of cryoenergy. Complications such as atrio-esophageal fistula and PV stenosis are less likely with cryoablation as compared to radiofrequency ablation. The rate of atrial arrhythmia and atrial flutter after PVI are also less likely with cryoablation. However, no head-to-head studies have been done with cryoablation vs RF ablation.
Our technique for cryoablation included both fluoroscopy with dye injection and intracardiac echocardiography imaging for positioning the cryoballoon at the antrum of the pulmonary veins. Monitoring included an esophageal temperature probe and pacing the right phrenic nerve while ablating at the right-sided pulmonary veins. In each case, two freezes were performed at each pulmonary vein: 180 seconds for the first freeze, and 120 seconds for the second freeze. Isolation of the active veins by signals on the Achieve catheter (Medtronic) was typically seen in the first 30 seconds. Mapping demonstrated loss of voltage at the pulmonary vein antra after cryoballoon ablation.
We report on 6 consecutive cases of persistent atrial fibrillation treated initially with RF ablation and then with cryoballoon ablation for recurrences. The Arctic Front Advance™ Cryoablation System (Medtronic) is approved in the U.S. for the treatment of drug-refractory, recurrent, symptomatic paroxysmal AFib and in Europe for the treatment of atrial fibrillation. However, early results from the CRYO4PERSISTENT AF study using the Arctic Front Advance Cryoballoon System for the treatment of persistent atrial fibrillation seem promising. We present a novel approach to treat recurrent persistent atrial fibrillation using cryoballoon ablation when AFib recurs after RF ablation. Although we still need more data to prove whether this technique has long-lasting effects for persistent AFib, based on the above case reports and literature review, it should be considered a reasonable option for the treatment of persistent AFib.
Disclosures: The authors have no conflicts of interest to report regarding the content herein.
- Hintringer F. Cryoablation of atrial fibrillation. Br Med Bull. 2016;120(1):101-109.
- Haïssaguerre M, Hocini M, Sanders P, et al. Catheter ablation of long-lasting persistent atrial fibrillation: clinical outcome and mechanisms of subsequent arrhythmias. J Cardiovasc Electrophysiol. 2005;16(11):1138-1147.
- Jalife J. Mechanisms of persistent atrial fibrillation. Curr Opin Cardiol. 2014;29(1):20-27.
- Veenhuyzen GD, Simpson CS, Abdollah H. Atrial fibrillation. CMAJ. 2004;171(7):755-760.
- Cappato R, Calkins H, Chen SA, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3(1):32-38.