Pulmonary vein isolation (PVI) by catheter ablation is now a cornerstone treatment strategy for patients with symptomatic and drug refractory atrial fibrillation (AF) [
The primary end point of this study was the 12-month assessment of the freedom from atrial arrhythmia occurrence when comparing the effectiveness of RFC versus cryoballoon catheter ablation between the two groups of treated subjects. In both groups, the primary ablation strategy was PVI and additional linear lesions were only used to create a cavotricuspid line of block in patients with confirmed typical right atrial flutter. Both acute procedural success and freedom from atrial arrhythmias were evaluated in the 12-month effectiveness end point. In this study, freedom from atrial arrhythmia was denoted by the lack of detection of AF (≥30 seconds in duration), atrial flutter, or atrial tachycardia episodes. Arrhythmia assessments were conducted by ECG, 24-hour Holter monitoring, and ILR. When atrial arrhythmias were detected by ECG and Holter, these episodes were denoted as “clinical effectiveness” end points; and when atrial arrhythmias were found by ILR reports, these episodes of arrhythmia were denoted as “absolute effectiveness” end points. The secondary end point was the evaluation of (the postablation) 90-day blanking period to determine the duration period needed by each catheter type to achieve long-term stable normal sinus rhythm after the healing of injuries associated with the cardiac ablation lesion formation as determined by ILR examination.
This study examined subjects with paroxysmal AF which was defined as ≥2 AF episodes that terminated spontaneously within 7 days, and it included subjects with AF episodes ≤ 48 hours that were terminated by electrical or pharmacological cardioversion. Patient eligibility into the trial was determined by inclusion and exclusion criteria. For inclusion into the trial, the patients met all of the following criteria: (1) ≥1 documented ECG occurrence of nonvalvular symptomatic paroxysmal AF lasting > 30 seconds within 90 days of enrollment that was refractory or intolerant to ≥1 antiarrhythmic drug (including beta blockers); (2) age ≥ 18 and ≤79 years; (3) left atrial diameter < 50 mm (anteroposterior) by parasternal long axis view; and (4) left ventricular ejection fraction ≥ 50% during sinus rhythm (estimated by Simpson’s method). Patients were excluded from the trial if any of the following criteria was present: (1) a patient history of myocardial infarction or cardiac surgery within 90 days of enrollment; (2) a patient history of stroke or transient ischemic attack within 1 year of enrollment; (3) any uncontrolled thyroid dysfunction; or (4) a patient who was contraindicated or had an inability to maintain anticoagulation via oral pharmaceutical drug.
This trial was a prospective single center randomized study conducted with 89 consecutive subjects with nonvascular paroxysmal AF. The trial was funded by the Russian Federation which predefined the study timeframe and number of patients.
108 subjects were initially included in the study. Due to technical issues with the product supply chain, the first 19 subjects that met inclusion and exclusion criteria were treated with the RFC (Figure
Patient disposition chart.
Before the ablation procedure, all patients underwent a complete clinical history, including medical history review, physical examination, laboratory studies (including thyroid function testing), echocardiography, in-office ECG, and preablation Holter monitoring. All subjects were required to maintain an anticoagulation regime before the ablation procedure. If the subject was on warfarin, the international normalized ratio target was between 2 and 3 which was confirmed on the day before the ablation procedure. If the patient was taking a novel oral anticoagulant drug, the subject was required to maintain the pharmaceutical therapy for at least 4 consecutive weeks before the ablation procedure. All oral anticoagulant drugs were discontinued on the day before the procedure, and subjects were bridged with low-molecular weight heparin to maintain anticoagulation. On the day of the ablation procedure, a transesophageal echocardiography was performed to assess the left atrium for the presence of thrombi.
During the ablation procedure, subjects were sedated using general anesthesia which was initiated using propofol (2 mg/kg) and fentanyl (1-2 mg/kg). Venous access was obtained using a modified Seldinger technique, and two femoral venous routes were utilized. In the left femoral route, an 11 Fr sheath was utilized to deliver a 10 Fr phased-array ultrasound catheter (AcuNav, Acuson) which was used in the right atrium to visualize and direct the transseptal puncture. After transseptal puncture, the ultrasound catheter was removed, and the 11 Fr sheath was used to deliver a decapolar diagnostic catheter into the coronary sinus. In the right femoral route, an 8.5 Fr SL0 sheath was used to deliver the Brockenbrough needle (BRK, St. Jude Medical) for transseptal puncture. Immediately after transseptal puncture, a bolus of unfractionated heparin (100 U/kg) was administered, and an activated clotting time of ≥300 seconds was maintained throughout the ablation procedure with periodic heparin administration. Before catheter ablation, high-rate ventricular pacing was used to facilitate a left atriography.
Throughout the RFC catheter ablation procedure, a circular mapping catheter (LASSO, Biosense Webster) was positioned at the level of each pulmonary vein (PV) before each ablation. A 3.5 mm irrigated tip RFC ablation catheter (ThermoCool, Biosense Webster) was used, and RFC energy was delivered with a maximum temperature setting of 44°C and a power of 35 watts (with a flow rate of 17 ml/min of saline at the irrigated tip). RFC ablation catheter and multielectrode circular diagnostic catheter placement was facilitated with the usage of a 3D electroanatomical mapping system (CARTO XP, Biosense Webster).
During the cryoballoon ablation procedure, the cryoballoon was delivered to the left atrium over a guidewire using a dedicated cryoballoon catheter sheath (FlexCath, Medtronic). The 28 mm first-generation cryoballoon (Arctic Front, Medtronic) was used exclusively, and before each cryoablation, balloon-to-PV occlusion was tested with the injection of a radiopaque contrast agent. Confirmation of occlusion was demonstrated by the retrograde retention of contrast agent as viewed by fluoroscopy. At each PV, a 300-second cryoablation was performed, and 2-3 applications of cryoablation were used at each vein. During right-sided PV ablations, a decapolar diagnostic catheter was placed in the superior vena cava and cranial to the right superior PV in order to pace the right phrenic nerve (25 mA at a cycle length of 2 seconds) resulting in diaphragmatic contractions. Cryoablation was immediately terminated at any sign of diminished diaphragmatic contraction, and the cryoballoon was repositioned before the continuation of ablation. For all RFC and cryoballoon ablation procedures, acute PVI was tested by entrance and exit block testing, and cavotricuspid lesions were confirmed by line of block testing.
After each ablation procedure, an ILR (Reveal XT, Medtronic) was implanted in the subdermal space of the left superior chest of each subject, and AF detection parameters were set to evaluate R-R interval variability. Before discharge from the hospital, all subjects were evaluated by neurological examination, ECG, echocardiography, and visual assessment (of the femoral venous puncture site(s) for observation of bleeding). All complications were noted in the subject’s medical records, and procedure related complications were further denoted as a study significant complication. At the time of hospital discharge, subjects were restarted on their previous oral anticoagulation drug and additionally given beta blockers. In cases of early recurrence of atrial arrhythmia during the 90-day blanking period, antiarrhythmic drugs (classes I and III) were used to manage the short-term arrhythmia symptoms with the exception of amiodarone which was not used in this study.
Study follow-up included in-office subject visits at 1, 2, 3, 6, and 12 months after the index ablation. During each visit, an ECG was recorded, and additionally, data were retrieved from the 24-hour Holter monitors and the ILRs. If subjects had a suspected arrhythmia event at any time during the 12-month follow-up period, additional in-office visits were completed to assess the potential arrhythmia using ECG, Holter monitoring, and ILR derived data.
Statistical data analyses were conducted using IBM SPSS Statistics 23. Mean values were given with a corresponding standard deviation, and discrete count data were accompanied by percentages. Continuous variables were analyzed using the
The mean age of the study population was
Patient demographic characteristics at baseline.
Patient characteristic | RFC | Cryoballoon | |
---|---|---|---|
Age (mean ± SD) | 55.6 ± 12.0 | 57.6 ± 8.2 | 0.364 |
Age > 60 years, | 16 (36.4%) | 18 (40.0%) | 0.828 |
Male, | 19 (43.2%) | 22 (48.9%) | 0.672 |
BMI kg/m2 (mean ± SD) | 29.8 ± 4.2 | 29.9 ± 4.0 | 0.981 |
LA diameter, cm (mean ± SD) | 4.0 ± 0.4 | 4.1 ± 0.3 | 0.129 |
| |||
CHA2DS2-VASc score, | |||
Mean | 1.3 ± 1.0 | 1.3 ± 0.8 | 0.971 |
0 | 11 (25.0%) | 7 (15.6%) | 0.379 |
1 | 14 (31.8%) | 20 (44.4%) | |
2 | 13 (29.5%) | 15 (33.3%) | |
3 | 6 (13.6%) | 3 (6.7%) | |
History of TIA, | 4 (9.1%) | 5 (11.1%) | 1.000 |
IHD, | 2 (4.5%) | 4 (8.9%) | 0.677 |
Hypertension, | 34 (77.3%) | 35 (77.8%) | 1.000 |
Diabetic mellitus, | 6 (13.6%) | 2 (4.4%) | 0.157 |
| |||
Drugs, | |||
Antiarrhythmic drugs | 44 (100.0%) | 45 (100.0%) | 1.000 |
Anticoagulation | 44 (100.0%) | 45 (100.0%) | 1.000 |
Long-term ablation effectiveness.
End point | RFC | Cryoballoon | OR | 95% CI | |
---|---|---|---|---|---|
Absolute effectiveness, | 29 (65.9) | 23 (51.1) | 1.85 | 0.79–4.35 | 0.157 |
Clinical effectiveness, | 36 (81.8) | 25 (55.6) | 3.6 | 1.37–9.46 | 0.008 |
Reablation, | 6 (13.6) | 13 (28.9) | 0.39 | 0.13–1.14 | 0.12 |
There was 100% subject compliance at all scheduled follow-up visits (RFC = 220 visits and cryoballoon = 225 visits). Absolute effectiveness (as measured with ILR reporting) was 65.9% in the RFC group and 51.1% in the cryoballoon group at the end of the 12 month follow-up period. By comparison, clinical effectiveness as reported by ECG and 24-hour Holter monitoring was 81.8% in the RFC group and 55.6% in the cryoballoon treated group at the 12-month follow-up (Figure
Effectiveness of ablation during the follow-up. Implantable loop recorders detected more episodes of arrhythmia recurrence compared to standard monitoring methods (ECG and Holter) after radiofrequency ablation. This difference was not significant after cryoballoon ablation.
Arrhythmia recurrence rate during the 12-month follow-up.
In our current study, the RFC and cryoballoon catheters were compared in patients with paroxysmal AF for both efficacy and safety; however, our study is one of the first clinical reviews of both ablation catheters while patients were under ILR surveillance during the follow-up period. The study results demonstrated that both catheters have equivalent efficacy when examining patients by ILR interrogation and reporting the absolute effectiveness at 12 months after the index ablation (freedom from atrial arrhythmia) (Figure
Kaplan-Meier estimates showing the cumulative freedom from all recurrent atrial arrhythmias after the radiofrequency ablation and cryoballoon pulmonary vein isolation. The average period of the recurrent arrhythmia development in the RFC group was 337,
Recently, several RFC versus cryoballoon studies have been reported, and meta-analyses of these trials have demonstrated that RFC and cryoballoon share similar efficacy and safety profiles [
Specifically, our study demonstrated the prevalence of the absolute effectiveness end points following a cryoballoon ablation (suggesting a prevalence of symptomatic AF recurrence following a cryoballoon ablation). In our study, there were two cryoballoon treated patients with asymptomatic recurrences: one patient had a short burst of AF at night time and the other patient had an AF episode with a heart rate that was near normal range. By comparison, RFC ablation had a lower incidence of the efficacy end point failure by clinical effectiveness examination, but the absolute effectiveness was matched with the cryoballoon reporting in our study. These findings demonstrated that standard monitoring methods (ECG and Holter) may overestimate the effectiveness of RFC ablation. Furthermore, a true comparison of RFC versus cryoballoon technology should be done in a large randomized population while using ILRs. Neither FIRE AND ICE nor the current meta-analyses use ILRs [
This study was one of the first comparison trials conducted in the Russian Federation comparing RFC and cryoballoon ablation, and hence, the current sample size is small, clinical to other recent randomized studies. Also, the study was conducted on older technology, and it is known that both RFC and cryoballoon now have advanced catheter offerings.
In our study, RFC and cryoballoon ablation had similar absolute effectiveness at 12 months after the initial index ablation. Traditional follow-up methods (ECG and Holter) were effective when assessing the efficacy of the cryoballoon ablation because of the infrequent nature of asymptomatic episodes of atrial arrhythmias; however, in the RFC group, a continuous monitoring method (ILR) was necessary to accurately assess long-term efficacy. The effectiveness of cryoballoon ablation may be assessed within a few days after index ablation, as it remained stable during the one-year follow-up period suggesting that the cryoballoon procedure may not require a blanking period following the index ablation.
Atrial fibrillation
Implantable loop recorder
Pulmonary vein
Pulmonary vein isolation
Radiofrequency current.
The authors declare that they have no conflicts of interest.