Abstract
Background
Cryoballoon pulmonary vein isolation (PVI) has emerged as an alternative to radiofrequency PVI for atrial fibrillation (AF). Data are lacking to define the rates and predictors of complications, particularly phrenic nerve injury (PNI).
Methods and Results
We evaluated a single‐center prospective registry of 450 consecutive patients undergoing cryoballoon PVI between 2011 and 2015. Patients were 59±10 years old, 26% were women, 58% had hypertension, their mean CHA 2 DS 2 VASc score was 1.7±1.3, 30% had persistent atrial fibrillation, and 92% received a second‐generation 28‐mm balloon. Predefined major complications were persistent PNI, pericardial effusion, deep vein thrombosis, arteriovenous fistula, atrioesophageal fistula, bleeding requiring transfusion, stroke, and death. PNI was categorized as persistent if it persisted after discharge from the laboratory. Logistic regression was performed to identify predictors of complications and specifically PNI. We identified a major complication in 10 (2.2%) patients. In 49 (10.8%) patients, at least transient PNI was observed; only 5 persisted beyond the procedure (1.1%). All cases of PNI resolved eventually, with the longest time to resolution being 48 days. We also describe 2 cases of PNI manifesting after the index hospitalization. Regression analysis identified 23‐mm balloon use (16.3% versus 5.2%, odds ratio 2.94, P=0.011) and increased age (62.8±7.7 versus 58.7±0.12 years, odds ratio 1.058, P=0.014) as independent significant predictors of PNI. There were no significant predictors of major complications.
Conclusions
In a large contemporary cohort, cryoballoon PVI is associated with low procedural risk, including lower rates of PNI than previously reported. Older age and 23‐mm balloon use were associated with PNI. Our low rate of PNI may reflect more sensitive detection methods, including compound motor action potential monitoring and forced double‐deflation.
Keywords: ablation, atrial fibrillation, catheter ablation, complications
Subject Categories: Catheter Ablation and Implantable Cardioverter-Defibrillator, Atrial Fibrillation, Arrhythmias, Electrophysiology
Introduction
Cryoballoon pulmonary vein isolation (PVI) has emerged as an alternative to radiofrequency PVI in the treatment of drug‐resistant atrial fibrillation (AF). Cryoballoon PVI, compared with radiofrequency PVI, offers potential advantages, including shorter procedure times,1, 2, 3 decreased hospital length of stay,1 and decreased fluoroscopy time.3 The data are limited that define the major complication rate of cryoballoon PVI. Additionally, previous literature identifies phrenic nerve injury (PNI) as the most frequent complication of cryoballoon PVI.4, 5, 6, 7, 8, 9 Methods including monitoring diaphragmatic electromyographic signals with compound motor action potential (CMAP)10, 11, 12, 13, 14 and immediate balloon deflation15 have been described to help detect PNI and decrease its incidence and long‐term persistence. Identifying predictors of major complications and PNI will assist in patient selection for this procedure.
Methods
Study Population
The study population included 450 consecutive patients undergoing cryoballoon PVI for AF at the University of Pittsburgh Medical Center between August 2011 and August 2015 as part of a prospective registry. Baseline clinical characteristics and detailed medical history, including specific AF history, were recorded for all patients. The University of Pittsburgh Institutional Review Board approved the study protocol.
All patients provided written informed consent for the ablation procedure. All patients underwent preprocedural cardiac computed tomography to assess pulmonary venous anatomy and transesophageal echocardiography to rule out intracardiac thrombus. Periprocedural anticoagulation was managed as per individual physician discretion.
Cryoballoon Ablation Procedure
The cryoballoon PVI procedure has been previously described in detail.16, 17, 18 In brief, all ablation procedures were performed with the patient under general anesthesia, avoiding paralytic agents after induction to allow monitoring of phrenic nerve function. All cases were performed by using the Arctic Front Cryoballoon (Medtronic) via a transseptal approach. For most cases, after confirming pulmonary vein occlusion via venography, two 180‐ to 240‐second lesions were applied in each pulmonary vein and additional lesions were applied if conduction persisted. Isolation was confirmed through elimination or dissociation of pulmonary vein potentials, differential pacing maneuvers, and high output pacing within the pulmonary veins to confirm exit block. For the right‐sided pulmonary veins, pacing was performed from the superior vena cava (SVC) to monitor phrenic nerve function, and ablation was immediately terminated with any decreased diaphragmatic excursion. CMAP monitoring10, 11, 12, 13, 14, 19 and immediate balloon deflation15 were used in a subset of patients once these techniques were described. A quadripolar pacing catheter was used in the SVC to detect phrenic nerve injury. Anticoagulation during the procedure was with intravenous heparin to maintain an activated clotting time of 300 to 400 seconds. For patients on warfarin, the procedure was performed with an international normalized ratio 1.5 to 2.5 and for novel oral anticoagulants, the agent was held 1 to 2 days before the procedure and usually restarted 6 hours after the procedure.
Follow‐Up
Patient follow‐up was as per standard protocol with outpatient visits at 6 weeks, 3 months, 6 months, 1 year, and yearly thereafter postprocedure. At the time of the procedure, complications were noted and systematically recorded in the registry by the operator. In addition, retrospective chart review of all procedure notes, hospitalizations, office visits, and emergency department visits was performed to assess for additional complications postprocedure. Predefined major complications were persistent PNI, symptomatic pericardial effusion, deep vein thrombosis, arteriovenous fistula, atrioesophageal fistula, major bleeding, stroke, or death. Major bleeding was defined as a bleed requiring transfusion. “Persistent PNI” was defined as PNI that persisted or occurred beyond discharge from the electrophysiology laboratory, while episodes of PNI that resolved before discharge from the laboratory without recurrence were termed “transient PNI.” “Long‐term PNI” was defined as PNI lasting >6 months. Identification of complications was based on objective evidence of any of the predefined complications or after workup of new symptoms postprocedure.
Statistical Analysis
Statistical analysis was performed by using STATA (version 14.0, Statacorp LP). Continuous variables are presented as mean±SD. Categorical variables are presented as percentages and absolute frequencies. Logistic regression analyses were performed to identify predictors of PNI or major complications. Variables found to be associated with the outcomes in univariable analyses at P<0.2 were selected for multivariable analyses. The variables were analyzed separately for major complications and PNI. The criterion for statistical significance was set at P<0.05.
Results
Study Population
All 450 consecutive patients who underwent cryoballoon PVI between August 2011 and August 2015 were included in the final analysis. There were 9 physicians who performed the procedures described, with a mean of 56.4±70.2 and median of 27 cryoballoon procedures per operator and a range of 2 to 170. The study population was a mean of 59±9.9 years old, and 26% were women, with a mean CHA2DS2VASc score of 1.7±1.3 and left atrial dimension of 4.3±2.4 cm. Hypertension was present in 57.6% of the patients, persistent AF was present in 30% of the patients, and 75% had AF duration >1 year. The second‐generation 28‐mm cryoballoon was used in 92% of procedures. Additional baseline characteristics for the total study population, patients stratified by major complications, and patients with phrenic nerve injury are shown in Table 1.
Table 1.
Total Study Population (N=450) | Major Complications (n=10) | |
---|---|---|
Age, y | 59.1±9.9 | 61.2±10.9 |
Women | 25.8% (n=116) | 40% (n=4) |
Duration of symptoms >1 y | 74.6% | 62.5% |
Persistent AF | 30.2% (n=136) | 40% (n=4) |
Previous AF ablation | 11.1% (n=50) | 0% (n=0) |
Hypertension | 57.6% (n=259) | 60.0% (n=6) |
Diabetes mellitus | 13.3% (n=60) | 10% (n=1) |
Heart failure | 12.0% (n=54) | 20.0% (n=2) |
Coronary artery disease | 16.0% (n=72) | 20.0% (n=2) |
Left ventricular ejection fraction (%) | 55±7 | 50±10 |
Left atrial size, mm | 4.3±2.4 | 4.0±0.9 |
Body mass index, kg/m2 | 31.3±6.0 | 30.5±4.7 |
Height, m | 1.8±0.1 | 1.7±0.1 |
Weight, lb | 215±50 | 198±36 |
CHA2DS2VASC score | 1.7±1.3 | 1.9±1.4 |
23‐mm balloon use | 6.4% (n=29) | 20.0% (n=2) |
Procedural time, min | 136±49 | 130±37 |
Fluoroscopy time, min | 33.0±17 | 28.4±6.1 |
AF indicates atrial fibrillation.
Major Complications
Major complications occurred in 10 (2.2%) patients (Table 2). Major complications included 5 cases of persistent PNI, 3 episodes of symptomatic pericardial effusion, 1 deep vein thrombosis, and 1 arteriovenous fistula. There were no major bleeds, periprocedural strokes, atrioesophageal fistulas, or periprocedural deaths. The details of each individual major complication are outlined in Table 3.
Table 2.
Complication | No. (%) (N=450) | |
---|---|---|
Major complications | ||
Total | 10 | 2.2% |
Persistent phrenic nerve injury | 5 | 1.1% |
Symptomatic pericardial effusion | 3 | 0.67% |
Deep vein thrombosis | 1 | 0.22% |
Arteriovenous fistula | 1 | 0.22% |
Bleed/hematoma requiring transfusion | 0 | 0% |
Stroke | 0 | 0% |
Death | 0 | 0% |
PNI | 49 | 10.8% |
Temporary phrenic nerve injury | 44 | 9.7% |
Persistent phrenic nerve injury | 5 | 1.1% |
Long‐term phrenic nerve injury (>6 mo) | 0 | 0% |
PNI indicates phrenic nerve injury.
Table 3.
Complication | Summary |
---|---|
Persistent PNI | During isolation of RSPV diminished diaphragmatic excursion noted and cryoablation immediately terminated. At that time, improved within 10 min. CXR 1 day postoperatively with right hemidiaphragm elevation. Resolved by CXR 20 days postoperatively |
Persistent PNI | During isolation of RSPV, diminished diaphragmatic excursion was noted and cryoablation was immediately terminated. Return of phrenic nerve function noted in 10 to 15 min, but diminished. CXR postoperatively revealed right hemidiaphragm elevation. Resolved within 48 d on CXR |
Persistent PNI | No PNI detected during procedure. Patient called 6 days postoperatively with SOB, and CXR revealed right hemidiaphragm elevation. These symptoms resolved within 1 mo. CXR 30 days postoperatively revealed resolution of PNI |
Persistent PNI | During isolation of RSPV, there was loss of phrenic nerve capture. Cryboablation was immediately terminated, and there was active deflation. There was ≈75% excursion recovery at 20 min. Symptomatically resolved by discharge on postoperatively day 2, and there was no evidence of hemidiaphragm elevation on CXR on postoperative day 1 |
Persistent PNI | No PNI detected during the procedure. At 15 days postprocedure, the patient presented to the ED with SOB, and CXR revealed right hemidiaphragm elevation. Symptoms improved and CXR 34 days postoperatively with resolution of diaphragm elevation |
Right femoral arteriovenous fistula and pseudoaneurysm | Postprocedure, patient experienced prolonged bleeding from right groin puncture site. Arterial duplex studies revealed right femoral pseudoaneurysm and arteriovenous fistula that was repaired with vascular surgery 5 days postoperatively |
Right saphenous vein deep vein thrombosis | At 6 days postoperative, developed swelling inferior to right groin insertion site; prompted to go to the ED, where he was noted to have a right saphenous deep vein thrombosis. Was found to be subtherapeutic on warfarin at the time and was bridged to therapeutic; at follow‐up 2 months postprocedure, symptoms were noted to be resolved |
Pericardial effusion | Patient developed pleuritic chest pain postoperatively; echocardiography revealed pericardial effusion that resolved over 4 days on repeat echocardiograms |
Pericardial effusion | Pericardial effusion noted postoperatively with symptoms; resolved on repeat echocardiogram 7 days postoperatively |
Pericardial effusion | Developed pleuritic chest pain during the admission and found to have pericardial effusion. Required monitoring in PACU overnight. On phone call 1 week postoperative, patient reported resolution of pain |
CXR indicates chest radiograph; ED, emergency department; PACU, postanesthesia care unit; PNI, phrenic nerve injury; RSPV, right superior pulmonary vein; SOB, shortness of breath.
There were 3 symptomatic echocardiogram‐confirmed pericardial effusions that presented during the postprocedural period; all resolved within 1 week without intervention. There was 1 case of a right femoral pseudoaneurysm and arteriovenous fistula requiring surgical intervention. There was 1 right saphenous vein deep vein thrombosis that was discovered 6 days postprocedure.
Univariate logistic regression analysis did not reveal any significant potential predictors of major complications.
Phrenic Nerve Injury
In our study population, PNI (transient and persistent) was the most common complication, occurring in 49 (10.8%) procedures, of which PNI was persistent in 5 (1.1%) cases. Two of the persistent PNI cases were not detected in the laboratory during SVC pacing but rather discovered on chest radiography with right hemidiaphragm elevation during follow‐up after the patients reported symptoms. Persistent PNI resolved in all cases at 2, 20, 30, 34, and 48 days postprocedure (Table 3). The distribution of veins for the cases of PNI was 73% right superior, 23% right inferior, and 4% right middle pulmonary veins.
Univariate analysis identified age (62.8±7.7 years versus 58.7±0.12 years, P=0.006) and use of the 23‐mm balloon (16.3% versus 5.3%, P=0.005) as associated with PNI (Table 4). There was no significant difference between estimated vein orifice area for veins with PNI compared with right‐sided veins without PNI (Table 4). Variables selected for multivariate analysis by using a cutoff of P<0.2 included redo procedures, age, hypertension, use of 23‐mm balloon, CHA2DS2VASc score, early procedures, and total fluoroscopy time. Multivariate analysis identified 23‐mm balloon use (odds ratio 2.94, P=0.011) and age (odds ratio 1.058, P=0.014) as significant independent predictors for PNI.
Table 4.
No PNI | PNI | Univariable | Multivariable | |||
---|---|---|---|---|---|---|
Characteristic | n=401 | n=49 | OR (95% CI) | P Value | OR (95% CI) | P Value |
Redo | 48 (12.0) | 2 (4.1) | 0.313 (0.074–1.330) | 0.116 | 0.300 (0.069–1.310) | 0.192 |
Age, y | 58.7±10.1 | 62.8±7.7 | 1.050 (1.014–1.087) | 0.006 | 1.058 (1.013–1.106) | 0.014 |
CHF | 45 (11.2) | 7 (14.3) | 1.219 (0.552–2.694) | 0.628 | ||
HTN | 226 (56.4) | 33 (67.3) | 1.597 (0.852–2.995) | 0.155 | 1.546 (0.705–3.394) | 0.609 |
Female sex | 104 (26.0) | 12 (24.5) | 0.926 (0.465–1.844) | 0.820 | ||
Height, mm | 1.77±0.1 | 1.75±0.1 | 0.157 (0.009–2.893) | 0.213 | ||
23‐mm balloon use | 21 (5.2) | 8 (16.3) | 3.531 (1.471–8.476) | 0.005 | 2.938 (1.118–7.723) | 0.011 |
CHA2DS2VASc score | 1.65±1.3 | 1.92±1.3 | 1.157 (0.934–1.433) | 0.183 | 0.855 (0.618–1.184) | 0.832 |
Persistent AF | 122 (30.4) | 14 (28.6) | 0.915 (0.475–1.762) | 0.760 | ||
Body mass index, kg/m2 | 31.1±5.9 | 31.2±6.6 | 0.996 (0.948–1.047) | 0.882 | ||
Early (first third of procedures) | 129 (32.2) | 21 (42.8) | 1.581 (0.865–2.891) | 0.137 | 1.482 (0.756–2.906) | 0.624 |
Total procedure time, min | 136±51 | 321±36 | 0.998 (0.991–1.005) | 0.613 | ||
Total fluoroscopy time, min | 32.4±16 | 37.4±19 | 1.016 (0.999–1.033) | 0.065 | 1.014 (0.993–1.035) | 0.203 |
Values are presented as mean±SD or n (%). AF indicates atrial fibrillation; CHF, congestive heart failure; HTN, hypertension; PNI, phrenic nerve injury.
Procedural characteristics, including cryoballoon temperature data, number of lesions, and freeze times, were available for 68.0% of patients. These procedural characteristics were compared for the right‐sided veins with PNI and the right‐sided veins without PNI (Table 5). Patients with PNI had a significantly shorter total freeze time (301±148 versus 404±117 seconds, P<0.001) and number of lesions per vein (1.9±0.7 versus 2.3±0.6, P=0.006). There were no significant differences in mean 30‐second temperature or nadir temperature.
Table 5.
Veins With PNI | Right‐Sided Veins Without PNI | P Value | |
---|---|---|---|
Maximal negative temperature, °C | −50.6±5.4 | −52.0±6.0 | 0.124 |
Average 30‐s temperature, °C | −33.6±4.0 | −33.7±4.4 | 0.935 |
Total freeze duration, s | 301±148 | 404±117 | 0.001 |
No. of lesions | 1.9±0.7 | 2.3±0.6 | 0.006 |
PNI indicates phrenic nerve injury.
Discussion
The main findings of our study were that in our cohort of 450 consecutive cases, the major complication rate of cryoballoon PVI was 2.2%. We identified no predictors of major complications. Overall, the most frequent complication was PNI, which was usually transient and eventually resolved in all cases. We identified increased age and use of a 23‐mm balloon as predictors of PNI.
Our major complication rate is consistent with previously published rates of major complications: 2% to 5.1%.5, 20, 21, 22 The lack of significant predictors for major complications is consistent with most previous studies5 and likely is limited by a lack of statistical power, given the low rate of complications (Table 6).1, 5, 6, 9, 15, 20, 23, 24, 25 A previous study has identified predictors that included female sex and procedures performed in July or August.21 Further research in larger cohorts may identify additional predictors of major complications. Alternatively, cryoballoon PVI may have such a low rate of major complications that no predictors will be identified for most specific complications.
Table 6.
Total Population | Major Complications | Total PNI | Persistent PNI | Predictors of Complications | Predictors of PNI | Year | Reference |
---|---|---|---|---|---|---|---|
450 | 2.2% | 10.8% | 1.1% | None | Age, 23‐mm balloon use | 2016 | Present study |
345 | 5.9% | N/A | 3.2% | None | None | 2016 | Knight et al23 |
500 | 2.0% | 7.2% | 2.2% | None | None | 2015 | Mugnai et al5 |
316 | N/A | 10.0% | 4.5% | N/A | None | 2015 | Saitoh et al6 |
115 | N/A | 3.5% | 2.6% | N/A | None | 2014 | Metzner et al9 |
158 | 5.1% | 6.9% | 3.8% | Persistent AF, lower body height | 23‐mm balloon | 2014 | Boho et al20 |
65 | N/A | 6.0% | 0.0% | N/A | Short distance between RSPV and SVC, lower 30‐s temperature | 2013 | Kuhne et al24 |
163 | 6.1% | 11.2% | None | 23‐mm balloon | 2013 | Packer et al25 | |
130 | N/A | 16.9% | 0.0% | N/A | 23‐mm balloon | 2013 | Ghosh et al15 |
346 | 2.9% | 7.5% | 6.9% | None | 23‐mm balloon | 2008 | Neumann et al16 |
57 | 7.0% | 7.0% | 3.5% | None | 23‐mm balloon | 2007 | Van Belle et al26 |
AF indicates atrial fibrillation; N/A, not available; PNI, phrenic nerve injury; RSPV, right superior pulmonary vein; SVC, superior vena cava.
The most common complication was PNI; the overwhelming majority of cases resolved before discharge from the electrophysiological laboratory, and the persistent cases resolved within 2 months. Other study populations have described long‐term resolution of all or nearly all PNI cases.5, 6, 7, 16 Despite the apparent temporary nature of phrenic nerve injury occurring during cryoballoon PVI, it is important to continue to use methods to reduce the incidence of PNI and identify predictors to aid in patient selection and guide estimation of risks and benefits of the procedure in individual patients. We found that the use of the 23‐mm balloon and increased age were associated with PNI. We have compared our study with other literature that reviewed complication rates, PNI rates, and predictors and found we had identified a similar or an improved PNI and major complication rate (Table 6).
We did identify 2 cases of persistent PNI that were not detected during the procedure but were discovered after discharge from the electrophysiological laboratory. Both cases were identified when the patients presented as outpatients with symptoms and confirmed with right hemidiaphragm elevation on chest radiography. These cases highlight the possibility of delayed PNI, which is currently not widely described. Both cases used SVC pacing but not CMAP monitoring. Possibilities include missed injury during the procedure (with SVC pacing below balloon position, which is unlikely given operator experience, and in 1 case, stored cine confirms appropriate position) versus a subtle injury not detected during the procedure with progression over the next several days. Delayed manifestation of PNI has not, to our knowledge, been described before.
Previous studies have established a decrease in CMAP of 30% to 35% as highly sensitive for detecting PNI, with a decrease in 30% correlating with a c‐statistic of 0.965.11, 14 It is unclear if CMAP would have detected subtle injury in these cases. Regardless, our findings emphasize the importance of follow‐up and monitoring for complications after the index cryoballoon procedure.
In our cohort, there was increased 23‐mm balloon use for patients with PNI which has been reported in previous studies.15, 16, 26 An increased risk of PNI is likely when the balloon is positioned distal toward the vein, which occurs more frequently with the 23‐mm balloon compared with the 28‐mm balloon given its smaller size.16, 20, 26, 27 Another hypothesis may be that the 28‐mm balloon represents later cases in which the operator has gained experience; however, even when we controlled for early versus late cases, the effect of the 23‐mm balloon was seen.
We saw that the patients who had PNI were older than patients without PNI, which is also a novel finding. This may be a result of deeper tissue penetration in advanced age because of changes in extracellular matrix or possible age‐related shifts in relative position of the phrenic nerve relative to the right pulmonary veins.28, 29 While PVI has been shown to be effective and safe when evaluating major complications in elderly populations,30 this slight increase in incidence of PNI is important to note when offering cryoballoon PVI to elderly patients.
We did not see an increase in vein size for cases with PNI. Given that there were no differences in maximum negative temperature or average 30‐second temperature for patients with PNI, it is unlikely that more aggressive freezing contributed to PNI. In fact, the patients with PNI had lower total freezing duration and number of lesions, which is likely a result of no further ablation performed after PNI was detected. These data suggest that nerve anatomy is the determinant of likelihood of PNI.
Since the adoption of cryoballoon PVI for AF, methods to reduce the incidence of PNI have emerged. Monitoring using surface electrodes during phrenic nerve pacing to detect a 30% to 35% reduction in diaphragmatic CMAP has decreased the incidence of PNI by allowing for early detection.14, 19 Additionally, double deflation or rapid balloon deflation, which leads to more rapid tissue rewarming, reduces the risk of persistent PNI.15
Limitations
Our study has several potential limitations. It is a retrospective observational study of a prospective registry involving only a single center and, thus, its generalizability may be limited. It is important to note that this is one of the larger studies to date looking at complications in cryoballoon PVI. Given the small percentage of major complications, some potential predictors may not have been identified. All patients had at least 1 month of follow‐up, and given that the overwhelming majority of PNI occurs acutely because of its pathophysiology, it is likely that most of the PNIs were detected by using our surveillance methods. However, it is possible that any delayed PNI may have gone undetected. Additionally, it is possible that operator experience affected the complication and PNI rates; however, when comparing the first one‐third of cryoballoon procedures with the second two‐thirds of procedures performed at our institution, we did not see a significant difference in PNI rates. Finally, we did not include the procedural characteristics in the multivariate analysis because the differences in these characteristics were likely a result of acute PNI (ie, shorter freeze time and number of lesions); however, in doing this, we may have missed some predictors of PNI.
Conclusions
In a prospective observational cohort of 450 consecutive cases, the major complication rate of cryoballoon PVI was 2.2% with no identified predictors of major complications. The most frequent complication was PNI, which resolved in all cases. We identified use of 23‐mm balloon and increased age as predictors for PNI. We also observed delayed PNI in 2 patients not detected during the procedure. Cryoballoon PVI can be safely performed with a low incidence of major complications.
Disclosures
Dr Saba reports a research grant from Boston Scientific (significant), Medtronic (modest), and St. Jude Medical (modest). Dr Jain reports research support from Medtronic (modest). The remaining authors have no conflicts of interest to disclose.
(J Am Heart Assoc. 2016;5:e003724 doi: 10.1161/JAHA.116.003724)
This article was handled independently by N.A. Mark Estes, MD, as a guest editor. The editors had no role in the evaluation of the manuscript or in the decision about its acceptance.
References
- 1. Siddoway D, Friehling M, Voigt A, Saba S, Jain S. Improved resource utilization with similar efficacy during early adoption of cryoballoon pulmonary vein isolation as compared with radiofrequency ablation for paroxysmal atrial fibrillation. J Atr Fibrillation. 2015;7(5):15–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Kuhne M, Suter Y, Altmann D, Ammann P, Schaer B, Osswald S, Sticherling C. Cryoballoon versus radiofrequency catheter ablation of paroxysmal atrial fibrillation: biomarkers of myocardial injury, recurrence rates, and pulmonary vein reconnection patterns. Heart Rhythm. 2010;7:1770–1776. [DOI] [PubMed] [Google Scholar]
- 3. Kojodjojo P, O'Neill MD, Lim PB, Malcolm‐Lawes L, Whinnett ZI, Salukhe TV, Linton NW, Lefroy D, Mason A, Wright I, Peters NS, Kanagaratnam P, Davies DW. Pulmonary venous isolation by antral ablation with a large cryoballoon for treatment of paroxysmal and persistent atrial fibrillation: medium‐term outcomes and non‐randomised comparison with pulmonary venous isolation by radiofrequency ablation. Heart. 2010;96:1379–1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Koektuerk B, Yorgun H, Hengeoez O, Turan CH, Dahmen A, Yang A, Bansmann PM, Gorr E, Hoppe C, Turan RG, Horlitz M. Cryoballoon ablation for pulmonary vein isolation in patients with persistent atrial fibrillation: one‐year outcome using second generation cryoballoon. Circ Arrhythm Electrophysiol. 2015;8:1073–1079. [DOI] [PubMed] [Google Scholar]
- 5. Mugnai G, de Asmundis C, Ciconte G, Irfan G, Saitoh Y, Velagic V, Stroker E, Wauters K, Hunuk B, Brugada P, Chierchia G‐B. Incidence and characteristics of complications in the setting of second‐generation cryoballoon ablation. A large single‐center study of 500 consecutive patients. Heart Rhythm. 2015;12:1476–1482. [DOI] [PubMed] [Google Scholar]
- 6. Saitoh Y, Irfan G, Ciconte G, Mugnai G, Sieira J, Di Giovanni G, Baltogiannis G, Conte G, Hunuk B, Stroker E, Velagic V, Overeinder I, de Asmundis C, Chierchia G‐B, Brugada P. Persistence of phrenic nerve palsy following 28‐mm cryoballoon ablation: a four‐year single center experience. Pacing Clin Electrophysiol. 2015;38:807–814. [DOI] [PubMed] [Google Scholar]
- 7. Kühne M, Knecht S, Altmann D, Kawel N, Ammann P, Schaer B, Osswald S, Sticherling C. Phrenic nerve palsy during ablation of atrial fibrillation using a 28‐mm cryoballoon catheter: predictors and prevention. J Interv Card Electrophysiol. 2012;36:47–54. [DOI] [PubMed] [Google Scholar]
- 8. Aytemir K, Gurses KM, Yalcin MU, Kocyigit D, Dural M, Evranos B, Yorgun H, Ates AH, Sahiner ML, Kaya EB, Oto MA. Safety and efficacy outcomes in patients undergoing pulmonary vein isolation with second‐generation cryoballoon. Europace. 2015;17:379–387. [DOI] [PubMed] [Google Scholar]
- 9. Metzner A, Rausch P, Lemes C, Reissman B, Bardyszewski A, Tilz R, Rillig A, Mathew S, Deiss S, Kamioka M, Toennis T, Lin T, Ouyang F, Kuck K‐H, Wissner E. The incidence of phrenic nerve injury during pulmonary vein isolation using the second‐generation 28 mm cryoballoon. J Cardiovasc Electrophysiol. 2014;25:466–470. [DOI] [PubMed] [Google Scholar]
- 10. Franceschi F, Koutbi L, Mancini J, Attarian S, Prevot S, Deharo JC. Novel electromyographic monitoring technique for prevention of right phrenic nerve palsy during cryoballoon ablation. Circ Arrhythm Electrophysiol. 2013;6:1109–1114. [DOI] [PubMed] [Google Scholar]
- 11. Franceschi F, Dubuc M, Guerra PG, Delisle S, Romeo P, Landry E, Koutbi L, Rivard L, Macle L, Thibault B, Talajic M, Roy D, Khairy P. Diaphragmatic electromyography during cryoballoon ablation: a novel concept in the prevention of phrenic nerve palsy. Heart Rhythm. 2011;8:885–891. [DOI] [PubMed] [Google Scholar]
- 12. Franceschi F, Koutbi L, Gitenay E, Hourdain J, Maille B, Trévisan L, Deharo J‐C. Electromyographic monitoring for prevention of phrenic nerve palsy in second‐generation cryoballoon procedures. Circ Arrhythm Electrophysiol. 2015;8:303–307. [DOI] [PubMed] [Google Scholar]
- 13. Andrade JG, Dubuc M, Ferreira J, Guerra PG, Landry E, Coulombe N, Rivard L, Macle L, Thibault B, Talajic M, Roy D, Khairy P. Histopathology of cryoballoon ablation‐induced phrenic nerve injury. J Cardiovasc Electrophysiol. 2013;25:187–194. [DOI] [PubMed] [Google Scholar]
- 14. Lakhani M, Saiful F, Parikh V, Goyal N, Bekheit S, Kowalski M. Recordings of diaphragmatic electromyograms during cryoballoon ablation for atrial fibrillation accurately predict phrenic nerve injury. Heart Rhythm. 2014;11:369–374. [DOI] [PubMed] [Google Scholar]
- 15. Ghosh J, Sepahpour A, Chan KH, Singarayar S, McGuire MA. Immediate balloon deflation for prevention of persistent phrenic nerve palsy during pulmonary vein isolation by balloon cryoablation. Heart Rhythm. 2013;10:646–652. [DOI] [PubMed] [Google Scholar]
- 16. Neumann T, Vogt J, Schumacher B, Dorszewski A, Kuniss M, Neuser H, Kurzidim K, Berkowitsch A, Koller M, Heintze J, Scholz U, Wetzel U, Schneider MAE, Horstkotte D, Hamm CW, Pitschner HF. Circumferential pulmonary vein isolation with the cryoballoon technique. J Am Coll Cardiol. 2008;52:273–278. [DOI] [PubMed] [Google Scholar]
- 17. Sarabanda AV, Bunch TJ, Johnson SB, Mahapatra S, Milton MA, Leite LR, Bruce GK, Packer DL. Efficacy and safety of circumferential pulmonary vein isolation using a novel cryothermal balloon ablation system. J Am Coll Cardiol. 2005;46:1902–1912. [DOI] [PubMed] [Google Scholar]
- 18. Klein G, Oswald H, Gardiwal A, Lüsebrink U, Lissel C, Yu H, Drexler H. Efficacy of pulmonary vein isolation by cryoballoon ablation in patients with paroxysmal atrial fibrillation. Heart Rhythm. 2008;5:802–806. [DOI] [PubMed] [Google Scholar]
- 19. Mondésert B, Andrade JG, Khairy P, Guerra PG, Dyrda K, Macle L, Rivard L, Thibault B, Talajic M, Roy D, Dubuc M, Shohoudi A. Clinical experience with a novel electromyographic approach to preventing phrenic nerve injury during cryoballoon ablation in atrial fibrillation. Circ Arrhythm Electrophysiol. 2014;7:605–611. [DOI] [PubMed] [Google Scholar]
- 20. Bohó A, Mišíková S, Spurný P, Komanová E, Sudzinová A, Hudák M, Kerekanič M, Stančák B. Complications of circumferential pulmonary vein isolation using the cryoballoon technique: incidence and predictors. Int J Cardiol. 2014;171:217–223. [DOI] [PubMed] [Google Scholar]
- 21. Baman TS, Jongnarangsin K, Chugh A, Suwanagool A, Guiot A, Madenci A, Walsh S, ILlg KJ, Gupta SK, Latchamsetty R, Bagwe S, Myles JD, Crawford T, Good E, Bogun F, Pelosi F Jr, Morady F, Oral H. Prevalence and predictors of complications of radiofrequency catheter ablation for atrial fibrillation. J Cardiovasc Electrophysiol. 2011;22:626–631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Natale A, Packer D, Skanes A, Ambrogi F, Biganzoli E. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3:32–38. [DOI] [PubMed] [Google Scholar]
- 23. Knight B, Novak P, Sangrigoli R, Champagne J, Dubuc M, Adler S, Svinarich T, Essebag V, Jain SK, John R, Mansour M. Second generation cryoballoon ablation in paroxysmal atrial fibrillation patients: 12 month safety and efficacy from the STOP‐AF post‐approval study. Heart Rhythm. 2016;13:PO01–PO38. [DOI] [PubMed] [Google Scholar]
- 24. Kühne M, Knecht S, Altmann D, Kawel N, Ammann P, Schaer B, Osswald S, Sticherling C. Phrenic nerve palsy during ablation of atrial fibrillation using a 28‐mm cryoballoon catheter: predictors and prevention. J Interv Card Electrophysiol. 2013;36:47–54. [DOI] [PubMed] [Google Scholar]
- 25. Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, Dubuc M, Reddy V, Nelson L, Holcomb RG, Lehmann JW, Ruskin JN, Investigators SAC. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation. J Am Coll Cardiol. 2013;61:1713–1723. [DOI] [PubMed] [Google Scholar]
- 26. Van Belle Y, Janse P, Rivero‐Ayerza MJ, Thornton AS, Jessurun ER, Theuns D, Jordaens L. Pulmonary vein isolation using an occluding cryoballoon for circumferential ablation: feasibility, complications, and short‐term outcome. Eur Heart J. 2007;28:2231–2237. [DOI] [PubMed] [Google Scholar]
- 27. Kuck K‐H, Furnkkranz A. Cryoballoon ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2010;21:1427–1431. [DOI] [PubMed] [Google Scholar]
- 28. Lindsey ML, Goshorn DK, Squires CE, Escobar GP, Hendrick JW, Mingoia JT, Sweterlitsch SE, Spinale FG. Age‐dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. Cardiovasc Res. 2005;66:410–419. [DOI] [PubMed] [Google Scholar]
- 29. Kwak H‐B. Aging, exercise, and extracellular matrix in the heart. J Exerc Rehabil. 2013;9:338–347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Lioni L, Letsas KP, Efremidis M, Vlachos K, Giannopoulos G, Kareliotis V, Deftereos S, Sideris A. Catheter ablation of atrial fibrillation in the elderly. J Geriatr Cardiol. 2014;11:291–295. [DOI] [PMC free article] [PubMed] [Google Scholar]