Cryoballoon Ablation Strategy in Persistent Atrial Fibrillation.

Background: Cryoballoon ablation is established for pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (AF). The objective was to evaluate CBA strategy in consecutive patients with persistent AF in the initial AF ablation procedure. Material and Methods: Prospectively, patients with symptomatic persistent AF scheduled for AF ablation all underwent cryoballoon PVI. Technical enhancements, laboratory management, safety, single-procedure outcome, predictors of recurrence, and durability of PVI were evaluated. Results: From 2007 to 2020, a total of 1,140 patients with persistent AF, median age 68 years, underwent cryoballoon ablation (CBA). Median left atrial (LA) diameter was 45 mm (interquantile range, IQR, 8), and Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age 65 to 74 years, Sex category (CHA2DS2-VASc) score was 3. Acute isolation was achieved in 99.6% of the pulmonary veins by CBA. Median LA time and median dose area product decreased significantly over time (p < 0.001). Major complications occurred in 17 (1.5%) patients including 2 (0.2%) stroke/transitory ischemic attack (TIA), 1 (0.1%) tamponade, relevant groin complications, 1 (0.1%) significant ASD, and 4 (0.4%) persistent phrenic nerve palsy (PNP). Transient PNP occurred in 66 (5.5%) patients. No atrio-esophageal fistula was documented. Five deaths (0.4%), unrelated to the procedure, occurred very late during follow-up. After initial CBA, arrhythmia recurrences occurred in 46.6% of the patients. Freedom from atrial arrhythmias at 1-, and 2-year was 81.8 and 61.7%, respectively. Independent predictors of recurrence were LA diameter, female sex, and use of the first cryoballoon generation. Repeat ablations due to recurrences were performed in 268 (23.5%) of the 1,140 patients. No pulmonary vein (PV) reconduction was found in 49.6% of the patients and 73.5% of PVs. This rate increased to 66.4% of the patients and 88% of PVs if an advanced cryoballoon was used in the first AF ablation procedure. Conclusion: Cryoballoon ablation for symptomatic persistent AF is a reasonable strategy in the initial AF ablation procedure.

Cardiac computed tomography angiography-derived analysis of left atrial appendage morphology and left atrial dimensions for the prediction of atrial fibrillation recurrence after pulmonary vein isolation.

BACKGROUND: Left atrial appendage (LAA) is a potential source of atrial fibrillation (AF) triggers. HYPOTHESIS: LAA morphology and dimensions are associated with AF recurrence after pulmonary vein isolation (PVI). METHODS: From cardiac computed tomography angiography (CCTA), left atrial (LA), pulmonary vein (PV), and LAA anatomy were assessed in cryoballoon ablation (CBA) patients. RESULTS: Among 1103 patients undergoing second-generation CBA, 725 (65.7%) received CCTA with 473 (42.9%) qualifying for detailed LAA analysis (66.3 ± 9.5 years). Symptomatic AF reoccurred in 166 (35.1%) patients during a median follow-up of 19 months. Independent predictors of recurrence were LA volume, female sex, and mitral regurgitation ≥°II. LAA volume and AF-type were dependent predictors of recurrence due to their strong correlations with LA volume. LA volumes ≥122.7 ml (sensitivity 0.53, specificity 0.69, area under the curve [AUC] 0.63) and LAA volumes ≥11.25 ml (sensitivity 0.39, specificity 0.79, AUC 0.59) were associated with recurrence. LA volume was significantly smaller in females. LAA volumes showed no sex-specific difference. LAA morphology, classified as windsock (51.4%), chicken-wing (20.7%), cactus (12.5%), and cauliflower-type (15.2%), did not predict successful PVI (log-rank; p = 0.596). CONCLUSIONS: LAA volume was strongly correlated to LA volume and was a dependent predictor of recurrence after CBA. Main independent predictors were LA volume, female sex, and mitral regurgitation ≥°II. Gender differences in LA volumes were observed. Individual LAA morphology was not associated with AF recurrence after cryo-PVI. Our results indicate that preprocedural CCTA might be a useful imaging modality to evaluate ablation strategies for patients with recurrences despite successful PVI.

Impact of age on the outcome of cryoballoon ablation as the primary approach in the interventional treatment of atrial fibrillation: Insights from a large all-comer study.

INTRODUCTION: The objective was to analyze the impact of patient age on clinical characteristics, procedural results, safety, and outcome of cryoballoon ablation (CBA) as the primary approach in the interventional treatment of symptomatic atrial fibrillation (AF). METHODS AND RESULTS: The single-center prospective observational study investigated consecutive patients who underwent initial left atrial ablation for symptomatic paroxysmal (PAF) or persistent AF (persAF). Age groups (A-F) of less than 40, 40-49, 50-59, 60-69, 70-79 and more than or equal to 80 years were evaluated. Follow-up (FU) included ECG, Holter monitoring and assessment of AF-symptoms. From 2012 to 2016, a total of 786 patients (64 ± 11 years, range 21-85) underwent CBA. With advancing age, more cardiovascular comorbidities and larger LA diameter were observed, more females were included (each p < .001). PAF (57%) and persAF (43%, p = .320) were equally distributed over all age groups. Age was neither related to procedural parameters, nor to the complication rate (3.9%, p = .233). Median FU was 38 months. Two non-procedure related noncardiac deaths occurred late during FU. Freedom from arrhythmia was independent of age at 18 months (p = .210) but decreased for patients more than or equal to 70 years at 24 months (p = .02). At 36 months, freedom from arrhythmia was 66%-74% (groups A-D), 54% (E) and 49% (F), respectively (p = .002). LA diameter and persAF were independent predictors, whereas age was a dependent predictor of recurrence. CONCLUSION: CBA as the primary approach in the initial ablation procedure is safe and highly effective in the young, middle aged, and elderly population. LA diameter and persAF, but not ageing, were independent predictors for arrhythmia recurrence.

Catheter Ablation in Complex Atrial Arrhythmias: Pilot Study Evaluating a 3D Wide-Band Dielectric Imaging System.

BACKGROUND: Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) is a standard in atrial fibrillation (AF) ablation but might not be enough in complex atrial arrhythmias (AA). An open three-dimensional wide-band dielectric imaging system (3D-WBDIS) has been introduced to guide CBA. MATERIAL AND METHODS: Pilot study evaluating feasibility and safety of 3D-WBDIS in combination with CBA and optional radiofrequency ablation (RFA) in patients with complex AA defined as (1) history of persistent AF, (2) additional atrial tachycardia/flutter, or (3) previous left atrial ablation. RESULTS: Prospectively, seventeen patients, 68.9 ± 12.2 years of age, with complex AA were enrolled. In 70 pulmonary veins (PV), balloon positioning maneuvers (n = 129) were guided additionally by the occlusion tool (1.84/PV). Compared to angiography, its sensitivity and specificity was 94.5, and 85%, respectively. CBA-PVI was achieved in 100% of PVs including variants. In 68 maps, the median number of mapping points was 251.0 (interquartile range (IQR) 298.0) with a median map volume of 52.8 (IQR 83.9) mL. Following CBA, six additional arrhythmias (two right and two left atrial flutter, one left atrial appendage tachycardia, and one atrioventricular nodal reentry tachycardia) were identified and successfully ablated by means of RFA in five patients (29.4%). Left atrial and fluoroscopy times were 88 (IQR 40) and 20 (IQR 10) minutes, respectively. Dose area product was 1,100 (IQR 1252) cGyxcm2. Freedom from AA after 6 months follow-up time and 90 days blanking period was documented in 10/17 (59%) patients, and 8/17 (47%) without a blanking period. No major complication was observed. CONCLUSION: The combined use of CBA with optional RFA guided by a novel 3D-WBDIS is feasible and safe in patients suffering from complex AA. The occlusion tool shows high sensitivity and specificity for assessment of the balloon occlusion. Additional arrhythmias were successfully mapped and ablated. Short-term outcome is promising, and subsequent prospective, larger outcome studies are necessary to confirm our observations.

Benefit of ultra-high-density mapping-guided radiofrequency reablation in pulmonary vein isolation non-responders after initial cryoballoon procedure.

AIMS: Symptomatic atrial arrhythmias despite complete pulmonary vein isolation (PVI) are common. The purpose was to evaluate ultra-high-density multi-electrode electroanatomical mapping-guided radiofrequency ablation (RFA) in PVI non-responders. METHODS AND RESULTS: Ultra-high-density multi-electrode electroanatomical mapping-guided RFA in consecutive symptomatic atrial fibrillation (AF) patients after initial cryoballoon PVI was performed. Patients were included if all pulmonary veins (PVs) were still isolated. Radiofrequency targets were atrial tachycardia (AT), extra-PV trigger, and/or substrate. Procedural results and outcome were evaluated. Of 95 patients, 67 (70.5%) with complete PVI were included (70 years, CHA2DS2Vasc 2.9, left atrium 45 mm, persistent AF 45%, AT 45%). The median time to reablation was 26 months. One hundred and seven maps (1.6/patient) and 11.890 ± 9.018 electrograms were acquired in 33 ± 12 min. Twenty-eight percent of the left atrial (LA) wall showed pathological voltage signals, predominantly at the anterior (37%) and septal wall (26%). Atrial tachycardia (49 left, 4 right) were ablated in 35 patients (52%), extra-PV trigger in two patients (3%). One atrioventricular nodal re-entry tachycardia and seven right atrial isthmus ablation (10%) were performed. In 32 patients (48%), no AT was present and substrate-based ablation was performed. Mean LA area ablated was 7 ± 6 cm2 (7%). No major complication occurred. The mean follow-up time was 772 ± 317 days. Freedom from atrial arrhythmia recurrence off antiarrhythmic drugs was 49% at 12 months. CONCLUSION: Pulmonary vein isolation non-responders are older, mainly suffering from complex atrial arrhythmias. Left atrial substrate is predominantly located at the anterior and septal wall. Ultra-high-density multi-electrode electroanatomical mapping-guided RFA is safe and effective. At 1 year, 5 out of 10 patients were in stable sinus rhythm off antiarrhythmic drugs.

The fourth cryoballoon generation with a shorter tip to facilitate real-time pulmonary vein potential recording: Feasibility and safety results.

INTRODUCTION: Time-to-isolation (TTI) guided ablation protocols have been developed to ensure durable pulmonary vein isolation (PVI) in cryoballoon ablation (CBA). The aim was to determine the feasibility and safety of the fourth generation cryoballoon (CBG4) with a shortened tip. METHODS AND RESULTS: Consecutive patients scheduled for initial atrial fibrillation (AF) ablation were prospectively included. PVI with the 28 mm CBG4 and the latest 20 mm spiral-mapping catheter (SMC) was performed. A total of 302 pulmonary veins (PVs) in 76 patients (64.8 ± 10.4 years, paroxysmal AF 49%) were treated with 617 applications. Left atrium (LA) time, fluoroscopy time, and dose-area product were 65.5 ± 19.2 minutes, 14.6 ± 5.6 minutes, and 1094 (738; 2097) cGy·cm2 , respectively. PVI in cryoballoon technique was achieved in 302 of 302 (100%) PVs. TTI was determined in 256 (84.8%) of PVs. The mean TTI was 45.3 ± 26.4 seconds. Single-shot isolation was achieved in 247 (82%) PVs. In 6 of 302 (2.0%) PV the SMC was changed to a stiff wire to isolate the PV because of instability, and in 17 of 302 (5.6%) of PVs, the 23 mm CB was used to isolate. No radiofrequency touch-up applications were applied. The mean nadir balloon temperature was -44.8°C ± 6.6°C. Balloon dislodgement during positioning occurred in 3 of 617 (0.5%) applications without complications. One PN palsy occurred which resolved until discharge. One patient suffered from the inflammatory syndrome. CONCLUSION: The CBG4 with a shorter distal tip seems to be safe and effective, and allows determining the TTI in 84.8% of PVs. In case of balloon instability, the exchange of the SMC to a stiff wire or, in small PV, the 23 mm cryoballoon facilitate PVI.

Lessons from individualized cryoballoon sizing. Is there a role for the small balloon?

BACKGROUND: Cryoablation for paroxysmal atrial fibrillation (PAF) is well established. The single-big-balloon strategy has been preferred for pulmonary vein isolation (PVI) using the second generation cryoballoon (CBG2). Individual PV-morphologies raise the question if an individualized anatomic approach using the 23-mm or 28-mm CB is reasonable. METHODS: Consecutive patients were prospectively enrolled in the non-randomized single-center study. Patients were treated with the 28-mm CB, if any PV was >21mm, the 23-mm CB, if all PV were ≤21mm, or both sizes, if PVI was difficult. The primary endpoint was arrhythmia-free survival. The secondary endpoint considered procedural results and complications. RESULTS: Overall, 197 patients with symptomatic PAF (64±11 years, 36% female) were included. Acute PVI was achieved in 99.9% of PV. Based on preprocedural imaging, the 28-mm CB was applied as the primary catheter in 47% (92/197 patients), the 23-mm CB in 53% (105/197, p=0.23). The 23-mm CB group included more females, patients with short left atrial (LA)-diameters (each p<0.01), and smaller patients (p=0.04). Both CB-sizes were used in 24% (47/197). Additional 23-mm CB usage was necessary in 23% (21/92) of patients, mainly because of insufficient PV-occlusion with the 28-mm CB. Additional 28-mm CB usage was necessary in 25% (26/105, p=0.82), mainly because PV diameters were larger than initially measured. Both CB-sizes were equally safe and effective with a low complication rate and an overall success rate of 86% at 12 and 71% at 18 months (6% on antiarrhythmic drugs). No predictors for AF-recurrence were identified. CONCLUSION: CB ablation can sometimes be challenging. The 28-mm CB is the preferred catheter in all patients. If balloon positioning is difficult, the 23-mm CB is an option to achieve PVI in small veins. Further studies need to investigate if the 23-mm CB could be beneficial as the primary CB in females with small body height and short LA diameter.

Cryoballoon ablation for persistent atrial fibrillation - Large single-center experience.

BACKGROUND: Different catheter ablation (CA) strategies have been established in the treatment of persistent atrial fibrillation (persAF). Pulmonary vein isolation (PVI) only might be an option for the initial ablation procedure. There is a paucity of outcome data on second-generation cryoballoon (CBG2) PVI in persAF. METHODS: Patients with symptomatic drug-refractory persAF who underwent initial CA of AF were prospectively enrolled and PVI was performed with CBG2. The primary composite endpoint was freedom from AF, atrial tachycardia, or related symptoms after a 3-month blanking period. The secondary endpoint referred to periprocedural complications. RESULTS: One hundred seventy-three consecutive patients (64±10 years, 29% female) with symptomatic drug-refractory persAF were identified. Acute PVI was achieved in 100% of pulmonary veins with the CB technique. The left atrial procedure time was 112±30min. Major complications occurred in 1.7% (3 of 173 patients) including two phrenic nerve palsies (1%), which resolved until discharge, and one pericardial effusion (0.6%). Follow-up ≥12 months was completed for 157 of 173 patients (91%). Median follow-up was 14 months. At 12 months, the primary composite endpoint was achieved in 129 of 157 patients (82%). However, 22 of 129 patients at risk (17%) were still on antiarrhythmic drugs. A relapse during the blanking period was identified as the only independent predictor for AF recurrence. CONCLUSION: PVI using the second-generation cryoballoon is a reasonable treatment option for patients with symptomatic drug-refractory persAF with a favorable rate of freedom from AF and a low complication rate.

Outcome of paroxysmal atrial fibrillation ablation with the cryoballoon using two different application times: the 4- versus 3-min protocol.

PURPOSE: The second-generation cryoballoon (CBG2) is highly effective for pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (PAF). One-year outcome data are consistent among different research groups. First results suggest that a shortened application time might be equally effective. The objective of the study was to compare procedural and outcome data for a 240 and 180-s protocol. METHODS: Prospectively, consecutive patients with symptomatic PAF underwent initial PVI with CBG2. In succession, two groups were created: the application time was 240 s in group 1 and 180 s in group 2. In both groups, a bonus application was applied. Periprocedural data, complications, and freedom from atrial fibrillation (AF)/AT/symptoms were compared between the groups. RESULTS: From May 2012 to June 2013, 114 patients (57 per group, 38% female) were included. The mean left atrial dwelling time decreased by 19 min (-16%) in group 2 compared to group 1 (p = 0.005). Intraprocedural pulmonary vein (PV) reconduction occurred infrequently (0.4% in both groups, p = 1.0). One persistent PNP occurred and resolved during the follow-up. Complications were without significant differences. One patient was lost to follow-up. The cumulative rates of freedom from recurrence at 12 months are 76.8% in group 1 and 83.6% in group 2. After a mean follow-up of 491 ± 208 days, the rates of freedom from AF/AT/symptoms at last visit were 38/57 (67%) and 44/56 (78.6%) in groups 1 and 2 (p = 0.14), respectively. Female sex was identified as a predictor for recurrence. CONCLUSIONS: Compared to a protocol with cryoballoon applications of 240 s, a shortened application time to 180 s results in a faster procedure with comparable high rates of freedom from AF at 16 months. Female sex seems to be predictive for recurrences; this finding has to be reconfirmed in a larger population.

Comparison of the first and second cryoballoon: high-volume single-center safety and efficacy analysis.

BACKGROUND: Cryoballoon (CB) ablation results in >70% freedom from atrial fibrillation at 1 year. Single-center data of the first (CBG1) and second (CBG2) cryoballoon, recently introduced, were analyzed to compare safety and efficacy. METHODS AND RESULTS: From March 2011 to December 2012, CB ablation with spiral mapping was performed consecutively in 484 patients with symptomatic atrial fibrillation. CBG1 was used in 364 of 484 (75%) and CBG2 in 120 of 484 (25%) patients. Periprocedural data were analyzed. Acute pulmonary vein (PV) isolation with CB only was achieved in 99.86% and 100% of veins with CBG1 and CBG2, respectively (P=0.43). Number of applications until PV isolation decreased significantly with CBG2 (1.45±0.81 versus 1.28±0.64; P=0.001). Procedural, left atrial, and fluoroscopy time were reduced by -5%, -11%, and -15% (P<0.05), respectively. Two balloons were used less frequently. Time to isolation decreased significantly with 23-mm (48 versus 33 seconds; P<0.0001) and 28-mm CBG2 (76 versus 52 seconds; P<0.0001). Early PV reconduction rarely occurred with CBG2 (2.6% versus 0.42%; P=0.0023). In-hospital atrial fibrillation recurrence rates were similar. Balloon temperatures were significantly warmer with 23-mm CBG2 and a trend for colder balloon temperature with 28-mm CBG2 were observed compared with their predecessors. Comparable low rates of phrenic nerve palsy were recorded (1.1% versus 1.7%; P=0.64). Esophageal temperatures were similar. Major complication rates were low (3.3% versus 3.33%; P=1.0). CONCLUSIONS: CBG2 attains high rates of acute PV isolation within a significant faster and less complex procedure. Time to isolation is shorter, and PV isolation is achieved with fewer applications using CBG2. These enhancements were not at the cost of complications. Long-term success rates remain to be demonstrated.

Cryoballoon in AF ablation: impact of PV ovality on AF recurrence.

INTRODUCTION: Complete occlusion of the pulmonary veins (PV) is crucial for successful PV isolation. While two different sizes of cryoballoons (23 and 28 mm) are available, complete occlusion is not always achieved in any given PV. We investigated the role of PV ostial anatomy during cryoballoon PV occlusion grading and atrial fibrillation (AF) recurrence rate. METHODS: PV ostial diameter was analyzed in 168 consecutive patients (111 men, 61 ± 10 years, 124 paroxysmal (px) and 44 persistent AF) using cardiac computed tomography (CT) prior to procedure. The ovality index at the PV ostial level was calculated in any given PV. During follow-up, 7-day holter monitors were performed at 1, 3, 6, 9, 12, 18 and 24 months post-ablation. RESULTS: The success rate at 12 ± 6 months follow-up was 69% including a 3-month blanking period (px AF: 66%; persistent AF 77%). The ovality index of the left-sided PVs was significantly larger ("more oval") than that of the right-sided PVs (p<0.001). An optimized PV occlusion in all individual PVs (complete occlusion, grading 4/4) was achieved during ablation in 49% of patients with AF recurrence and in 73% of patients without AF recurrence (p=0.004). Patients with AF recurrence had "more oval" left-sided PVs compared to patients free from AF recurrence (LSPV 0.40 ± 0.2 vs. 0.33 ± 0.2; p=0.04 and LIPV 0.41 ± 0.3 vs. 0.32 ± 0.2; p=0.03), whereas no significant association was found for right sided PVs. CONCLUSION: The ostial PV anatomy seems to have an important impact on clinical outcome and should be considered when planning and performing cryoballoon AF ablation procedures.

A novel double cryoballoon strategy in persistent atrial fibrillation: a pilot study.

AIMS: Cryoballoon technology is a promising technique in paroxysmal atrial fibrillation (AF) ablation. However, success rates in patients with persistent AF have not been convincing. There is a trend toward performing more extensive procedures that are referred to as 'pulmonary vein isolation plus.' To combine pulmonary vein isolation (PVI) and antral substrate modification, we used both the 23-mm and 28-mm cryoballoon in a single approach in patients with persistent AF. METHODS AND RESULTS: 33 consecutive patients (26 men, age 60 ± 10 years, LA size 44 ± 5 mm) with persistent AF were prospectively included. All patients underwent the "double balloon strategy:" at least two applications at each pulmonary vein (PV) using the smaller 23-mm balloon to isolate the PV at the ostial level plus at least one additional freeze by the 28-mm balloon at the wide PV antral level. 7-day Holter monitors were performed during follow-up at 1, 3, 6, 9, 12, 18 and 24 months post-ablation. 131 of 133 PVs were targeted and isolated (98.4 %). A mean of 14 ± 2 cryoballoon applications per patient or 3.5 ± 1.5 applications per vein were performed. After a single procedure and mean follow-up of 15 ± 3 months, 69.7 % of patients remained in sinus rhythm (3-month blanking period). There were no major complications. CONCLUSIONS: In persistent AF, the "double balloon strategy;" combining the small and large cryoballoon allowed ostial PV isolation followed by antral cryoablation is feasible, safe and associated with a favorable outcome.

Pulmonary vein electrophysiology during cryoballoon ablation as a predictor for procedural success.

BACKGROUND: Cryoballoon technique is an innovative alternative to radiofrequency ablation for atrial fibrillation (AF). However, with current cryoballoon application techniques, the operator has no access to electrical information for 300 s during the freezing cycle. OBJECTIVE: The objective of this study is to investigate the novel approach of real-time monitoring of pulmonary vein (PV) potentials throughout freezing using a circular mapping catheter introduced into the central lumen of the cryoballoon catheter. METHODS: Patients had paroxysmal or persistent AF. Standard balloon catheters (23 or 28 mm diameter, 10.5 F shaft) were used. A coaxial mapping catheter (shaft diameter 0.9 mm; 15 mm loop with six electrodes) was advanced through the lumen of the cryoballoon catheter, replacing the guide wire. The primary procedural end point was successful PV isolation and real-time PV potential recording. Secondary end points were procedural data, complications, and the time to successful PV isolation. RESULTS: In 141 consecutively enrolled patients, balloon positioning and ablation were successful in 439/568 veins (77%). Real-time recording of PV conduction during the freeze cycle was possible in 235/568 PVs (41%). Main reasons for failure to obtain real-time PV recordings were a distal position of the circular mapping catheter or insufficient catheter-vessel wall contact during ablation. A cutoff value of 83 s to PV isolation was predictive of stable procedural PV isolation without reconduction. One minor hemoptysis was observed possibly related to the mapping catheter. CONCLUSIONS: This study, the largest to date, showed that real-time monitoring of PV conduction during cryoballoon freezing can be safely performed with a circular mapping catheter. A cutoff time of 83 s to PV isolation was predictive of sustained procedural PV isolation success without reconduction.