Abstract
The urge to facilitate the atrial fibrillation (AF) ablation procedure has led to the development of new ablation catheters specifically designed as ‘one-shot tools’ for pulmonary vein isolation (PVI). The purpose of this study was to compare the efficacy, safety, and procedure times for two such catheters using different energy sources.
One hundred and ten patients, referred for ablation of paroxysmal or persistent AF, were randomized to treatment with either the cryoballoon or the circular multipolar duty-cycled radiofrequency-based pulmonary vein ablation catheter (PVAC). Complete PVI was achieved in 98 vs. 93% patients in the cryoballoon and PVAC group, respectively, with complication rates of 8 vs. 2% (P = 0.2). Complete freedom from AF, without antiarrhythmic drugs, after one single ablation procedure was seen in 46% in the cryoballoon vs. 34% after 12 months (P = 0.2). Procedure times were comparable, but fluoroscopy time was shorter for the cryoballoon (32 ± 16 min) than for the PVAC procedures (47 ± 17 min) (P < 0.001). A significant improvement of quality of life (QoL) and arrhythmia-related symptoms was seen in both groups after ablation.
Both catheters proved comparably effective and safe in achieving acute PVI, apart from the shorter fluoroscopy times achieved with the cryoballoon. At follow-up, there was no statistically significant difference between the groups regarding freedom from AF and clinical success. The QoL increased to the same levels as for the general Swedish population in both groups.
This is the first randomized study comparing the cryoballoon and the radiofrequency-based circular ablation catheter [pulmonary vein ablation catheter (PVAC)] with regard to clinical outcome and safety.
Shorter fluoroscopy times can be achieved with a cryoballoon catheter as compared with a PVAC.
Introduction
Electrical isolation of the pulmonary veins (PVs), with the purpose of eliminating the trigger for AF episodes, still remains the cornerstone of atrial fibrillation (AF) ablation procedures.1
Although radiofrequency (RF) and cryoenergy are the most commonly used energy sources for pulmonary vein isolation (PVI), there is still no consensus on which one should be preferred. Since AF ablation is a challenging and time-consuming procedure with a long learning curve for the operator, new ablation catheters specifically designed as ‘one-shot tools’ for PVI have been developed to facilitate the procedure. With a more widespread use of such catheters, like the RF-based pulmonary vein ablation catheter (PVAC) and the cryoballoon, we considered it to be of great importance to compare, in a randomized study, the outcome, safety, and procedure times of AF ablations performed with these catheters. We also aimed to evaluate the quality of life (QoL) and arrhythmia-related symptoms prior to and up to12 months after treatment.
Methods
Patients
Patients with symptomatic, 12-lead electrocardiogram (ECG) verified AF, who had failed treatment with at least one antiarrhythmic drug (AAD) of Vaughan William Class I or III and who were scheduled for AF ablation, were asked to participate in the study. Exclusion criteria were long-standing persistent or permanent AF, previous AF ablation, congestive heart failure with New York Heart Association class IV, left ventricular ejection fraction (LVEF) <30%, and left atrial diameter >6 cm. After informed consent, the patients were randomized in a 1 : 1 ratio to ablation with the cryoballoon catheter (Arctic Front, Medtronic) or the circular multipolar duty-cycled RF PVAC (Ablation Frontiers, Medtronic). The AF types were defined in accordance with recent Expert Consensus Statement. Patients were treated with warfarin with therapeutic international normalized ratio (INR) levels for at least 3 weeks prior to ablation. Warfarin was withdrawn 2–3 days before the procedure and bridged by low-molecular-weight heparin and heparin when the INR levels dropped below 2. Heparin was stopped 4 h before the procedure, administered again as a bolus (100 U/kg) after the trans-septal puncture, thereafter the activated clotting time was kept between 250 and 350 s. All patients underwent a transthoracic and a transoesophageal echocardiography before the ablation procedure to assess LVEF, left atrial size, and to exclude left atrial thrombi. Pulmonary vein anatomy was visualized by a three-dimensional reconstruction from a computer tomography (CT) scan.
Ablation procedure
The procedure was performed with the patient awake, receiving diazepam as premedication and ketobemidone as analgetics during the procedure. After vascular access in the right femoral vein, a bipolar catheter was positioned in the right ventricular apex and a decapolar catheter in the coronary sinus (CS). The single trans-septal puncture was performed with a Brockenbrough needle (St Jude Medical) guided by bi-plane fluoroscopy and intracardiac pressures. The 8 French (F) trans-septal sheath (SL0, St Jude Medical) was then exchanged for a steerable 12 F or 10 F sheath (FlexCath, Medtronic), respectively, for the cryoballoon catheter and the PVAC. The endpoint of the procedure was a complete electrical isolation of all PVs, and the entrance block was confirmed with an additional 10- or 20-polar circular mapping catheter during sinus rhythm for the right PVs and during CS pacing for the left PVs. Pacing manoeuvres were used in selected cases when differentiation of far-field atrial signals from PV signals was needed. A maximum number of ablation applications was not defined. A waiting time or adenosine provocation after complete PV was not used. All procedures were performed by an experienced electrophysiologist, accustomed to both catheter types. The procedure time was defined as the time from the application of local anaesthetics to the withdrawal of all catheters and the ablation time as the time from the first to the last application.
The cryoablation procedure was performed with a 10.5 F cryoballoon catheter with the use of nitrous oxide (N2O). The 28 mm cryoballoon was chosen primarily unless the PV diameters were small and judged more suitable for the 23 mm balloon. Different positions were tried with the cryoballoon to ensure the highest occlusion rate possible before energy delivery. Two 5 min applications were routinely given per vein before the conduction block was evaluated. If PV potentials were still present, one or two extra cryoballoon applications were delivered to that vein before re-evaluation. If PVI could not be achieved after additional cryoballoon ablation attempts, a conventional 9 F, quadripolar cryoablation catheter (Freezor Max, Medtronic) was used until complete PVI was achieved. The phrenic nerve function was checked during the ablation of the right superior PV by visual inspection of the diaphragmatic movement under fluoroscopy every 20 s.
The radiofrequency ablation procedure was performed with the PVAC, a 9 F, decapolar, circular catheter with phased RF energy that can be delivered simultaneously through one up to five electrode pairs, independently selectable. Different ratios of bipolar and unipolar energy, 4:1 or 2:1, may be chosen by the operator. The energy delivery is controlled by a software algorithm that modulates power to reach the target temperature (60°C) with a maximum of 10 W per electrode. The PVAC was carefully positioned in the antrum of the veins under fluoroscopic guidance, and 60 s RF applications were delivered to electrodes with good tissue contact. Electrode pairs were deselected if the temperature did not reach >50°C. Energy delivery was prematurely switched off in case of catheter dislocation during the application or if the patient experienced intolerable pain. In case PVI was not achieved, a 7 F decapolar, 4 mm tip RF ablation catheter (Celcius, Biosense Webster) was used for touch-ups when judged to be necessary for PVI.
Follow-up
All patients were evaluated at 3, 6, and 12 months after the ablation with regard to symptoms, 12-lead ECG, side effects, and symptoms that could reflect procedure-related complications, such as dyspnoea and difficulties in swallowing. Antiarrhythmic drugs were withdrawn after 3 months if the patient was free from arrhythmia-related symptoms. A 3-month blanking period was used. If no symptomatic improvement was recognized with signs of arrhythmia reduction, either the drug regime was altered or a repeat ablation was advised. Patients were asked to seek healthcare in case of symptoms for ECG verification of the arrhythmia. A 7-day-Holter ECG recording was performed after 6 and 12 months unless the recurrence of AF had already been documented on a 12-lead ECG due to symptoms. A recurrence of AF was defined to be present if the duration exceeded 30 s. The indication for a repeat ablation was based on the patient's symptoms, QoL, and desire to be free from AAD therapy. A repeat CT scan was performed after 6 months or prior to a redo procedure to exclude PV stenosis. A reduction of the PV diameter by >50% was defined as a significant stenosis. The primary endpoint was complete freedom from AF without AAD at 12 months after one ablation procedure. Patients with clinical success were defined as those, who after one procedure, were free from symptomatic AF on previously failed AAD, displayed asymptomatic AF on Holter monitoring, or had a symptomatic improvement to the extent that a redo procedure was not desired, in addition to those who had reached primary endpoint.
Quality of life
Quality of life was assessed using the Swedish Short Form-36 Health Survey (SF-36), and symptoms by the symptom severity questionnaire (SSQ), before and at 6 and 12 months after the ablation. The eight QoL variables measured by the SF-36 were converted according to the manual to a scale ranging from 0 to 100, with a higher score representing better QoL. Symptoms were assessed by five variables in the SSQ (palpitations, fatigue, dizziness, lack of energy, dyspnoea) and were each scored with regard to severity on a 5-grade scale with a higher value representing more pronounced symptoms. All patients, even those who had undergone a redo procedure, were included in the analysis. The study complies with the Declaration of Helsinki and the Regional Ethics Review Board approved the research protocol. All patients gave written informed consent to participate in the study.
Statistics
The sample size was calculated to detect a difference of 25% in the outcomes between the two treatment groups with a power of 80% and a type I error of 5%. Calculation was based on early reports of >80% success for PVAC after 6 months follow-up2 compared with 53% for the cryoballoon from our previous study.3 Continuous variables are expressed as mean values ± 1 standard deviation and were, when appropriate, compared with the use of Student's t-test. Categorical variables are presented as percentage or ratios and were compared with the use of Pearson χ2 analysis or Fisheŕs exact test. Quality of life variables and sum of SSQ parameters are expressed as mean values with confidence intervals. Repeated measures analysis of variance was used for within and between group comparisons. A P < 0.05 was considered significant.
Results
Patients
Starting in March 2009, a total of 110 patients were included in the study. One patient was by miscommunication randomized to RF ablation leaving 54 patients in the cryo group and 56 patients in the RF group. Baseline characteristics are shown in Table 1. Due to technical problems with the cryoballoon (despite one catheter exchange) or the cryoconsole, a switch to another ablation strategy was required in four patients during the procedure. They were excluded from further analysis. A left common PV ostium was seen in four cryoballoon patients and in seven PVAC patients. Additional PVs were isolated in two cryoballoon patients and in one PVAC patient.
Patient characteristics at baseline
| Cryoballoon (n = 54) | PVAC (n = 56) | |
|---|---|---|
| Gender (male/female), n | 43/11 | 40/16 |
| Age (years) | 59 ± 9 | 62 ± 7 |
| BMI (kg/m2) | 28 ± 4 | 27 ± 3 |
| Atrial size (mm) | 40 ± 6 | 42 ± 5 |
| Hypertension, n | 22 | 35 |
| Structural heart disease, n | 5 | 7 |
| Ischaemic heart disease | 4 | 6 |
| Congestive heart disease | 1 | 0 |
| Vitium organis cordis | 0 | 1 |
| CHADS2 score | 0.6 ± 0.9 | 0.9 ± 0.9 |
| AF types, n: | ||
| Paroxysmal | 39 | 37 |
| Persistent | 15 | 19 |
| History of AF, years (range) | 8 ± 7(1–32) | 8 ± 8(1–40) |
| AADs tried, n | 2.0 ± 1.3 | 2.0 ± 1.5 |
| Ongoing amiodarone | 15 | 9 |
| Cryoballoon (n = 54) | PVAC (n = 56) | |
|---|---|---|
| Gender (male/female), n | 43/11 | 40/16 |
| Age (years) | 59 ± 9 | 62 ± 7 |
| BMI (kg/m2) | 28 ± 4 | 27 ± 3 |
| Atrial size (mm) | 40 ± 6 | 42 ± 5 |
| Hypertension, n | 22 | 35 |
| Structural heart disease, n | 5 | 7 |
| Ischaemic heart disease | 4 | 6 |
| Congestive heart disease | 1 | 0 |
| Vitium organis cordis | 0 | 1 |
| CHADS2 score | 0.6 ± 0.9 | 0.9 ± 0.9 |
| AF types, n: | ||
| Paroxysmal | 39 | 37 |
| Persistent | 15 | 19 |
| History of AF, years (range) | 8 ± 7(1–32) | 8 ± 8(1–40) |
| AADs tried, n | 2.0 ± 1.3 | 2.0 ± 1.5 |
| Ongoing amiodarone | 15 | 9 |
AF, atrial fibrillation; BMI, body mass index; CHADS2, risk score for thromboembolism; n, numbers; PVAC, pulmonary vein ablation catheter; RF, radiofrequency.
Figures are mean values ± 1 standard deviation unless otherwise stated.
Patient characteristics at baseline
| Cryoballoon (n = 54) | PVAC (n = 56) | |
|---|---|---|
| Gender (male/female), n | 43/11 | 40/16 |
| Age (years) | 59 ± 9 | 62 ± 7 |
| BMI (kg/m2) | 28 ± 4 | 27 ± 3 |
| Atrial size (mm) | 40 ± 6 | 42 ± 5 |
| Hypertension, n | 22 | 35 |
| Structural heart disease, n | 5 | 7 |
| Ischaemic heart disease | 4 | 6 |
| Congestive heart disease | 1 | 0 |
| Vitium organis cordis | 0 | 1 |
| CHADS2 score | 0.6 ± 0.9 | 0.9 ± 0.9 |
| AF types, n: | ||
| Paroxysmal | 39 | 37 |
| Persistent | 15 | 19 |
| History of AF, years (range) | 8 ± 7(1–32) | 8 ± 8(1–40) |
| AADs tried, n | 2.0 ± 1.3 | 2.0 ± 1.5 |
| Ongoing amiodarone | 15 | 9 |
| Cryoballoon (n = 54) | PVAC (n = 56) | |
|---|---|---|
| Gender (male/female), n | 43/11 | 40/16 |
| Age (years) | 59 ± 9 | 62 ± 7 |
| BMI (kg/m2) | 28 ± 4 | 27 ± 3 |
| Atrial size (mm) | 40 ± 6 | 42 ± 5 |
| Hypertension, n | 22 | 35 |
| Structural heart disease, n | 5 | 7 |
| Ischaemic heart disease | 4 | 6 |
| Congestive heart disease | 1 | 0 |
| Vitium organis cordis | 0 | 1 |
| CHADS2 score | 0.6 ± 0.9 | 0.9 ± 0.9 |
| AF types, n: | ||
| Paroxysmal | 39 | 37 |
| Persistent | 15 | 19 |
| History of AF, years (range) | 8 ± 7(1–32) | 8 ± 8(1–40) |
| AADs tried, n | 2.0 ± 1.3 | 2.0 ± 1.5 |
| Ongoing amiodarone | 15 | 9 |
AF, atrial fibrillation; BMI, body mass index; CHADS2, risk score for thromboembolism; n, numbers; PVAC, pulmonary vein ablation catheter; RF, radiofrequency.
Figures are mean values ± 1 standard deviation unless otherwise stated.
Procedure
Complete PVI was achieved in 98% (49 of 50) of cryoballoon-treated patients and in 93% (52 of 56) of PVAC-treated patients (P = 0.37). The 28 mm cryoballoon was used during 46 procedures and the 23 mm balloon during 4 procedures. The number of cryoballoon applications was 9 ± 2 per patient with a temperature of −43.5 ± 4.7°C and the number of PVAC applications was 41 ± 13 per patient. An additional ablation catheter, using the same allocated energy source, was more frequently required in the cryoballoon group, 24 of 50 procedures (48%), than in the PVAC group, 11 of 56 procedures (20%), (P = 0.002) (Table 2). The procedure time did not differ between the two groups. The ablation time, from first to last application, was shorter with the cryoballoon than the PVAC, while the energy delivery duration showed the opposite pattern (Table 3). The exposure to fluoroscopy (dose and time) for PVAC procedures significantly exceeded those for cryoballoon procedures (Table 3). A cavotricuspid isthmus ablation was performed in two PVAC patients with a documented isthmus-dependent atrial flutter. One cryoballoon patient displayed a typical atrioventricular-nodal re-entry tachycardia, induced by catheter manipulation, which was ablated during the same procedure. Procedure time, ablation time, and energy delivery duration were adjusted for these extra ablations.
Distribution of veins treated with an additional ablation catheter for touch-ups
| LSPV | LIPV | RSPV | RIPV | LCO | Total | |
|---|---|---|---|---|---|---|
| Cryo ablation | 8/46 | 8/46 | 1/50 | 11/50 | 2/4 | 30/198a |
| RF ablation | 1/49 | 5/49 | 2/56 | 9/55 | 0/7 | 17/217a |
| LSPV | LIPV | RSPV | RIPV | LCO | Total | |
|---|---|---|---|---|---|---|
| Cryo ablation | 8/46 | 8/46 | 1/50 | 11/50 | 2/4 | 30/198a |
| RF ablation | 1/49 | 5/49 | 2/56 | 9/55 | 0/7 | 17/217a |
Figures denote the number of veins treated with an additional ablation catheter apart from the cryoballoon or the PVAC/total number of ablated veins.
aFigure includes extra PVs treated with cryoballoon (2) and PVAC (1).
LCO, left common ostium; LI, left inferior; LS, left superior; PV, pulmonary vein; RF, radiofrequency; RI, right inferior, RS, right superior.
Distribution of veins treated with an additional ablation catheter for touch-ups
| LSPV | LIPV | RSPV | RIPV | LCO | Total | |
|---|---|---|---|---|---|---|
| Cryo ablation | 8/46 | 8/46 | 1/50 | 11/50 | 2/4 | 30/198a |
| RF ablation | 1/49 | 5/49 | 2/56 | 9/55 | 0/7 | 17/217a |
| LSPV | LIPV | RSPV | RIPV | LCO | Total | |
|---|---|---|---|---|---|---|
| Cryo ablation | 8/46 | 8/46 | 1/50 | 11/50 | 2/4 | 30/198a |
| RF ablation | 1/49 | 5/49 | 2/56 | 9/55 | 0/7 | 17/217a |
Figures denote the number of veins treated with an additional ablation catheter apart from the cryoballoon or the PVAC/total number of ablated veins.
aFigure includes extra PVs treated with cryoballoon (2) and PVAC (1).
LCO, left common ostium; LI, left inferior; LS, left superior; PV, pulmonary vein; RF, radiofrequency; RI, right inferior, RS, right superior.
Procedure-related data
| Cryoballoon (n = 50) | PVAC (n = 56) | P value | |
|---|---|---|---|
| Procedure time (min) | 165 ± 40 | 167 ± 40 | 0.78 |
| Ablation time (min) | 108 ± 39 | 122 ± 33 | 0.04 |
| Energy delivery duration (min) | 54 ± 17 | 41 ± 12 | <0.001 |
| Fluoroscopy time (min) | 32 ± 16 | 47 ± 17 | <0.001 |
| Fluoroscopy dose (µGy/m2) | 3174 ± 1780 | 4245 ± 2170 | 0.007 |
| Cryoballoon (n = 50) | PVAC (n = 56) | P value | |
|---|---|---|---|
| Procedure time (min) | 165 ± 40 | 167 ± 40 | 0.78 |
| Ablation time (min) | 108 ± 39 | 122 ± 33 | 0.04 |
| Energy delivery duration (min) | 54 ± 17 | 41 ± 12 | <0.001 |
| Fluoroscopy time (min) | 32 ± 16 | 47 ± 17 | <0.001 |
| Fluoroscopy dose (µGy/m2) | 3174 ± 1780 | 4245 ± 2170 | 0.007 |
µGy/m2, micro Grey per square metre body surface; n, numbers; PVAC, pulmonary vein ablation catheter.
Figures are mean values ± 1 standard deviation.
Procedure-related data
| Cryoballoon (n = 50) | PVAC (n = 56) | P value | |
|---|---|---|---|
| Procedure time (min) | 165 ± 40 | 167 ± 40 | 0.78 |
| Ablation time (min) | 108 ± 39 | 122 ± 33 | 0.04 |
| Energy delivery duration (min) | 54 ± 17 | 41 ± 12 | <0.001 |
| Fluoroscopy time (min) | 32 ± 16 | 47 ± 17 | <0.001 |
| Fluoroscopy dose (µGy/m2) | 3174 ± 1780 | 4245 ± 2170 | 0.007 |
| Cryoballoon (n = 50) | PVAC (n = 56) | P value | |
|---|---|---|---|
| Procedure time (min) | 165 ± 40 | 167 ± 40 | 0.78 |
| Ablation time (min) | 108 ± 39 | 122 ± 33 | 0.04 |
| Energy delivery duration (min) | 54 ± 17 | 41 ± 12 | <0.001 |
| Fluoroscopy time (min) | 32 ± 16 | 47 ± 17 | <0.001 |
| Fluoroscopy dose (µGy/m2) | 3174 ± 1780 | 4245 ± 2170 | 0.007 |
µGy/m2, micro Grey per square metre body surface; n, numbers; PVAC, pulmonary vein ablation catheter.
Figures are mean values ± 1 standard deviation.
Complications
Five periprocedural complications occurred, of which four were related to a cryoballoon and one to a PVAC procedure, P = 0.19. In the cryoballoon group, a major groin haematoma requiring intervention or prolonged hospitalization occurred in two patients. A suspected phrenic nerve paralysis was seen related to two procedures, one procedure with each balloon size. Both were resolved, one within minutes and the other within 24 h. One PVAC patient had a major groin haematoma. A repeat CT scan, performed after 6 months in all, but five patients (two in the cryoballoon and three in PVAC group), did not show any PV stenoses. A <50% narrowing of the PV was seen in one cryoballoon patient and in five PVAC patients, P = 0.21.
Follow-up
Freedom from AF, without symptoms and with no AF episodes documented on 7-day-Holter monitoring or 12-lead ECG, without AAD treatment after one procedure 6 months after ablation, was achieved in 52% (26/50) cryoballoon patients and 38% (21/56) PVAC patients, P = 0.13. Complete freedom from arrhythmia-related symptoms was reported by 56 vs. 50% (P = 0.54), respectively, of the cryoballoon and PVAC patients, of which one cryoballoon and seven PVAC patients were still on AAD and one patient from the cryo group had an asymptomatic AF episode on 7-day-Holter monitoring. The predefined clinical success was reached by 62% (31/50) in the cryoballoon-treated group compared with 61% (34/56) in the PVAC-treated group, P = 0.89 (Figure 1). One patient, defined as failure in the cryoballoon group, suffered from AF at 6 months, but had developed amiodarone-related thyreotoxicosis and was therefore difficult to evaluate.
Different measures of outcomes at 6 and 12 months after ablation (one procedure) including primary efficacy (with primary endpoint at 12 month), no arrhythmia symptoms, and clinical success.
At 12 months follow-up, the primary endpoint was 46% (23/50) for the cryogroup and 34% (19/56) for the PVAC group, P = 0.21. At that time 54 and 38%, P = 0.09, respectively, of the cryoballoon and PVAC patients were free from symptoms after one procedure, among whom, asymptomatic AF was observed on Holter in one cryo patient; AAD was used in three cryoablated and in two PVAC-ablated patients. Clinical success was reached by 60% (30/50) in the cryogroup compared with 54% (30/56) in the PVAC group, P = 0.51 (Figure 1). Two of the five patients (one in each group) with incomplete PVI were free from arrhythmias after 6 and 12 months. Episodes of ECG-verified suspected left atrial tachycardia was seen in one patient (PVAC group) and was easily suppressed by β-blocking agents at 12 months. No apparent difference was seen in the outcome between patients with paroxysmal AF (PAF) and with persistent AF, although this study was not designed to make such comparison. At 12 months, a mean of 1.2 procedures per patient had been performed in each group, while 7 cryo- and 10 PVAC patients were scheduled for a redo procedure.
Quality of life
Questionnaires were responded by at least 95% of patients at each time point.
All QoL variables in the SF-36 questionnaire increased after ablation except for bodily pain, which remained at the same level over time. After 6 months, the increase was significant for all parameters except for the general health variable, which did not reach statistical significance in the cryoballoon group (P = 0.08) until after 12 months as compared with baseline. No further significant changes were seen between 6 and 12 months. The groups were comparable with respect to absolute score values at different time points and in the change of QoL from baseline to after ablation (Figure 2). According to the SSQ, the symptom scores decreased significantly between baseline and 6 months after which they remained unchanged (Figure 3) without any differences between the groups.
Comparison of QoL SF-36 scores between baseline and 6 and 12 months after AF ablation within cryoballoon and PVAC groups, respectively. Mean values are presented for each variable with 95% confidence interval, depicted by vertical bars, given for baseline and 6 months follow-up. Dotted line represents an age-matched general Swedish population. P values are given for the comparison between baseline and 6 months within each group (cryoballoon/PVAC). PF, physical functioning (P≤ 0.0001/<0.001); RP, role limitation due to physical problems (P≤ 0.0001/<0.0001); BP, bodily pain (P = 0.11/0.48); GH, general health (P = 0.08/0.009); VT, vitality (P≤ 0.0001/<0.0001); SF, social functioning (P≤ 0.001/<0.0001); RE, role limitation due to emotional problems (P= 0.002/<0.001); MH, mental health (P≤ 0.001/<0.0001).
Comparison of symptom severity score at three different time points. Bars denote mean value with confidence interval for the sum of five symptom variables (palpitations, fatigue, dizziness, lack of energy, and dyspnoea), each scored with 1–5 with a higher value representing a more pronounced symptom.
Discussion
This is the first randomized study comparing the efficacy and safety of the cryoballoon and the PVAC when used for AF ablation. In our study, both catheters achieve a high rate of PVI and a low complication rate, as seen in other studies.3–10
Our primary efficacy rates of 52 and 38% at 6 months and 46 and 34% at 12 months with the cryoballoon and the PVAC, respectively, must be regarded as moderate. The early reports of >80% arrhythmia-free survival with PVAC at 6 months2 set the basis for our hypothesis that AF ablation with the PVAC would be superior to the cryoballoon, which in our previous study showed a lower, 53%, efficacy rate.3 The present study, however, could not support such superiority, and on the contrary, there was a trend towards a favour for the cryoballoon. Success rates reported by others, which are mainly prospective, non-randomized case series of AF ablations with 6 and 12 months follow-ups, vary greatly between 49 and 89% for cryoballoon5,11 and 52–85% for PVAC ablations12,13. Varying AF populations, follow-up strategies, and definitions used for success make, however, comparisons between studies difficult. We used the recommended definition of success according to the published consensus statement,1 as our primary endpoint. Van Belle et al,5 who used the same primary endpoint, reported a 49% success rate with the cryoballoon in PAF patients followed for 12 months, which is comparable with our study even though we even included patients with persistent AF. Higher rates of freedom from arrhythmias after AF ablation with the cryoballoon were reported in patients with PAF (74%) than in those with persistent AF (42%).4 One report on AF ablation with the PVAC in patients with PAF showed a 55% success rate after 12 months, decreasing to 49% after 24 months,7 as compared with a 61% arrhythmia-free survival in a mixed AF population after 12 months,10 using the same primary endpoint. The highest efficacy rates seem to be the early reports with smaller patient series and shorter follow-ups.2,13,14
A relatively long clinical history of AF, mean 8 years (range 1–40 years), as compared with others,4,6,8,14–16 may partly explain the apparently lower efficacy rates seen in our study. A recent small cryoballoon study showed that, when used as a first line treatment in patients with lone PAF, the success rate was as high as 89% after 14 months,11 which may support the concept that AF duration may be important for the outcome. Other studies of the PVAC with similar AF durations as in our study have, however, reported similar or even better outcomes.7,10 and in one of these studies,7 the AF burden rather than duration was more predictive for the outcome.
One has to bear in mind that the primary goal of an AF ablation procedure is to reduce symptoms and increase QoL, so even though the primary success rate, as defined in our study, is low, the clinical success rate of ∼60% is acceptable after one procedure. Our study confirms a significantly increased QoL and symptom reduction, which is consistent with previous reports.17,18 In fact, after the AF ablation, QoL was comparable with that of a normal Swedish population.
Both ablation catheters used in this study were constructed for the purpose of simultaneous energy delivery around the PV, a one-shot ablation tool. The different catheter designs, however, makes this concept more true for the cryoballoon with its contiguous cryolesion surfaces than for the PVAC with its multipolar circular non-contiguous electrode design, resulting more in simultaneously applied point-to-point lesions with its inherent limitations. Theoretically, these inherent differences may partly explain the potentially better outcome with the cryoballoon vs. the PVAC. The PVAC uses a combination of unipolar RF energy, expected to create deeper lesions, and bipolar RF, expected to result in contiguous adjacent lesions. In our study, the RF energy was rarely delivered through all five pairs of the PVAC electrodes simultaneously, because energy was not switched on to electrodes indicating poor tissue contact and also since patients, despite analgetics, tended to experience intolerable pain when energy was delivered through all electrode pairs simultaneously. One may therefore speculate if a deeper sedation, enabling the use of more electrode pairs simultaneously, would have reduced the risk of conduction gaps and thereby potentially would have improved the outcome figures for the PVAC. This limitation may also explain the relatively high number of RF applications needed to achieve PVI and consequently the higher exposure to fluoroscopy. Two randomized studies, comparing the PVAC with an irrigated tip ablation catheter, showed comparable outcomes between the groups.8,9 In these studies, where at least in one of them8, patients were under deeper sedation than in our study, all electrode pairs were expected to be used simultaneously until only local gaps were remaining. Up to date, there is only one small randomized study comparing the effect of the cryoballoon with that of the irrigated tip ablation catheter using the point-by-point technique,16 which reports comparable outcomes between the techniques, in concordance with three case control studies.6,19,20
Our study protocol did not include a waiting time or adenosine provocation to reveal dormant PV conduction after complete PVI, which if used may have affected our results. Limited data exist on the usefulness of such manoeuvres for revealing reconnection21–23 and for the clinical outcome23,24 after PVI with the cryoballoon and the PVAC. In the absence of randomized trials, it is difficult, however, to draw any definite conclusions about their individual or combined role for each of these new catheters.
Both catheter types tested in the present study have previously been associated with shorter procedure times compared with the point-by-point technique.6,8,9,16 In our study, the cryoballoon and the PVAC groups had similar procedure times. The shorter ablation time in the cryoballoon group did, however, not translate into shorter procedure times, which may be related to the more time-consuming preparation of the cryoballoon catheter as it is first introduced. The higher fluoroscopy exposure observed for the PVAC is a clear disadvantage and may be explained by the many repositionings, and the need for fluoroscopy during the ablation to ensure catheter stability. Our procedure and fluoroscopy times for the cryoballoon procedures were comparable with others,4,14 but among the higher reported for the PVAC procedures.8,10 An additional ablation catheter was more frequently used during the cryoballoon, than during the PVAC procedures and seems to vary greatly in previous reports.2,6,15,25 This difference may be related to the option to deliver energy focally through selected electrodes with PVAC. The technical failure with the cryo equipment is another disadvantage that may need to be addressed.
The overall low complication rates are in line with other reports.4,5,7
Limitations
In our study, we did not use a waiting time or adenosine provocation to reveal dormant PV conduction after complete PVI, which as previously discussed, may have affected the outcome. The use of a limited number of electrodes on the PVAC for reasons discussed may have reduced the full potential of this ablation catheter and may therefore be a limitation to this study. As our power calculation was based on the first reports of the PVAC, a larger study population might have resulted in a statistically significant difference regarding primary outcome between the groups.
Conclusion
The cryoballoon and the PVAC proved comparably effective and safe in achieving acute PVI, although PVAC procedures were associated with longer fluoroscopy times. The 12-month efficacy rates of 46 and 34% for the cryoballoon and the PVAC group, respectively, were moderate and failed to reach statistically significant difference. Nevertheless, the significant improvement of arrhythmia-related symptoms and increase of QoL to the same level as for the general Swedish population in both groups after ablation supports further use of these ablation catheters.
Conflict of interest: none declared.
Funding
This work was supported by the Swedish Heart and Lung Foundation.
