The impact of early cryoballoon ablation on clinical outcome in patients with atrial fibrillation: From the Korean cryoballoon ablation registry.

INTRODUCTION: Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long-term follow-up has not been clarified. The objective was to determine whether an early CBA (diagnosis-to-ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA. METHODS: The study included 2605 patients from Korean CBA registry data with follow-up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30-s after a 3-month blanking period. RESULTS: Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2 DS2 -VAS score. During mean follow-up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2-year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1-year and 2-year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412-0.984). CONCLUSION: Early CBA strategy, resulting in significantly lower ATs recurrence during 2-year follow-up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.

Real-world evidence demonstrates an appropriate atrial fibrillation population for hybrid convergent approach versus stand-alone cryoballoon ablation: A long-term safety and efficacy study.

INTRODUCTION: A hybrid convergent approach (endocardial and epicardial ablation) demonstrated superior effectiveness in a recent randomized study for long-standing persistent atrial fibrillation (LSPAF). Yet, there is a lack of real-world, long-term evidence as to which patients are best candidates for a hybrid convergent approach compared to standard endocardial cryoballoon pulmonary vein isolation (CB PVI). METHODS AND RESULTS: This single-center, retrospective analysis spanning from 2010 to 2015 compared two distinctly different atrial fibrillation (AF) cohorts; one treated with stand-alone cryoablation and one treated with a hybrid convergent approach. Baseline characteristics described candidates for each approach. The following criteria were utilized to determine CB PVI candidacy: (1) paroxysmal AF (PAF) (stage 3A) with failed class I/III antiarrhythmic drug (AAD) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD unwilling to undergo hybrid procedure. Selection criteria for the hybrid procedure included: (1) PAF refractory to both class I/III AAD and prior CB PVI (stage 3D) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD agreeable to hybrid procedure. Prior sternotomy was excluded. Serial electrocardiograms and continuous monitoring evaluated primary efficacy outcome of time-to-first recurrence of atrial arrhythmia after a 90-day blanking period. Secondary outcomes were procedure-related complications and AAD use (at discharge, 12, and 36 months). Kaplan-Meier methods evaluated arrhythmia recurrence. Of 276 patients, 197 (64.2 ± 10.6 years old; 66.5% male; 74.1% 3A-PAF; 18.3% 3B/3D-persistent AF; 1.0% 3C-LSPAF; 6.6% undetermined) underwent CB PVI and 79 (61.4 ± 8.1 years old; 83.5% male; 41.8% 3D-PAF; 45.5% 3B/3D-persistent AF; 12.7% 3C/3D-LSPAF) underwent hybrid procedure. Arrhythmia freedom through 36 months was 55.2% for CB PVI and 50.4% for hybrid (p = .32). Class I AAD utilization at discharge occurred in 38 (19.3%) patients in the CB PVI group and 5 (6.3%) patients in the hybrid group (p = .01). CB PVI class I AAD utilization at 12 months occurred in 14 (9.0) patients versus 0 patients for hybrid convergent (p = .004). Patients with one or more adverse event were as follows: two (1.0%) in the CB PVI group (both transient phrenic nerve palsy) and three (3.7%) in the hybrid group (two with significant bleeding and one with wound infection) (p = .14). CONCLUSION: This study demonstrated that patients with more complex forms of AF (3D-PAF or 3B/3C/3D-persistent/LSPAF) could be well managed with a convergent approach. In a real-world evaluation, outcomes match safety and efficacy thresholds achieved for patients with earlier, less complex AF etiologies treated by CB PVI alone.

One-year outcomes of pulmonary vein isolation with a novel cryoballoon: Primary results of the FROZEN AF trial.

INTRODUCTION: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open-label, prospective, single-arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. METHODS AND RESULTS: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow-up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re-initiated in 26.8% of patients after the 3-month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. CONCLUSIONS: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF.

Acute procedural efficacy and safety of a novel expandable diameter cryoballoon in atrial fibrillation ablation: Early results from a multicenter ablation registry.

INTRODUCTION: The major limitation of the current cryoballoon (CB) system is a fixed 28 mm balloon-size. We sought to analyze real-world early experience with novel-sized adjustable CB. METHODS: This multicenter observational study included 140 consecutive atrial fibrillation patients (71 years, 94 men, 86 paroxysmal) who underwent pulmonary vein (PV) isolation using expandable diameter CB capable of ablation at 28 or 31 mm. RESULTS: Out of 544 targeted PVs, 526 (96.7%) were successfully isolated by a size-adjustable CB with a 770 [690-870] second median application dose, while the remaining 18 required touch-up ablation. Among them, 326 (62.0%) PVs were isolated by a 31 mm balloon, and the rate was significantly higher for upper than lower PVs (73.0% vs. 45.7%, p < .0001) and highest for right superior (78.5%) and lowest for right inferior (39.9%) PVs. The biophysical parameters and time to isolation were comparable between the 28 and 31 mm balloons, however, the real-time PV potential monitoring capability was significantly higher for 31 mm than 28 mm balloons for the left superior PV. The esophageal temperature reached 15°C during left inferior PV ablation significantly more often with 31 mm than 28 mm balloons (43.1% vs. 18.2%, p = .008). Right phrenic nerve injury (PNI) occurred in 9 (6.4%) patients during applications (6 right superior, 2 right inferior PVs), and most occurred with a 31 mm balloon. CONCLUSIONS: Our real-world early data demonstrated high acute efficacy and safety of the novel-sized adjustable CB. The biophysical parameters were similar between the 28 and 31 mm balloons. No marked decrease in the incidence of PNI was observed even with 31 mm balloons.

Long-term clinical impact of early recurrence of atrial tachyarrhythmia after cryoballoon ablation in patients with atrial fibrillation.

INTRODUCTION: The impact of early recurrence of atrial tachyarrhythmia (ERAT) within the 90-day blanking period on long-term outcomes in atrial fibrillation (AF) patients undergoing cryoballoon ablation (CBA) is controversial. This study aimed to assess the relationship between ERAT and late recurrence of atrial tachyarrhythmia (LRAT) post-CBA. METHODS: Utilizing data from a multicenter registry in Korea (May 2018 to June 2022), we analyzed the presence and timing of ERAT (<30, 30-60, and 60-90 days) and its association with LRAT risk after CBA. LRAT was defined as any recurrence of AF, atrial flutter, or atrial tachycardia lasting more than 30 s beyond the 90 days. RESULTS: Out of 2636 patients, 745 (28.2%) experienced ERAT post-CBA. Over an average follow-up period of 21.2 ± 10.3 months, LRAT was observed in 874 (33.1%) patients. Patients with ERAT had significantly lower 1-year LRAT freedom compared to those without ERAT (42.6% vs. 85.5%, p < .001). Multivariate analysis identified ERAT as a potential predictor of LRAT, with a hazard ratio (HR) of 3.98 (95% confidence interval [CI], 3.47-4.57). Significant associations were noted across all examined time frames (HR, 3.84; 95% CI, 3.32-4.45 in <30 days, HR, 5.53; 95% CI, 4.13-7.42 in 30-60 days, and HR, 4.29; 95% CI, 3.12-5.89 in 60-90 days). This finding was consistently observed across all types of AF. CONCLUSION: ERAT during the 90-day blanking period strongly predicts LRAT in AF patients undergoing CBA, indicating a need to reconsider the clinical significance of this period.

Cryoablation of atrial fibrillation in "very severe" obese patients (BMI ≥ 40): Indications, feasibility, procedural safety and efficacy, and clinical outcome (the ICE-Obese Extreme).

BACKGROUND: Management of atrial fibrillation (AF) in very severe obese patients is challenging. Cryoballoon ablation (CBA) represents an effective rhythm control strategy. However, data in this patient group were limited. METHODS: Highly symptomatic AF patients with body mass index (BMI) ≥ 40 kg/m2 who had failed antiarrhythmic drug therapy and electrocardioversion and failure to achieve targeted body-weight-reduction underwent CBA. RESULTS: Data of 72 very severe obese AF patients (Group A) and 129 AF patients with normal BMI (Group B, BMI < 25 kg/m2) were consecutively collected. Group A had significantly younger age (60.6 ± 10.4 vs. 69.2 ± 11.2 years), higher BMI (44.3 ± 4.3 vs. 22.5 ± 1.6 kg/m2). Procedural pulmonary vein isolation (PVI) was successful in all patients (2 touch-up ablation in Group A). Compared to Group B, Group A had similar procedural (61.3 ± 22.6 vs. 57.5 ± 19 min), similar fluoroscopy time (10.1 ± 5.5 vs. 9.2 ± 4.8 min) but significantly higher radiation dose (2852 ± 2095 vs. 884 ± 732 µGym2). We observed similar rates of real-time-isolation (78.6% vs. 78.5%), single-shot-isolation (86.5% vs. 88.8%), but significantly longer time-to-sustained-isolation (53.5 ± 33 vs. 43.2 ± 25 s). There was significantly higher rate of puncture-site-complication (6.9% vs. 1.6%) in Group A. One-year clinical success in paroxysmal AF was (Group A: 69.4% vs. Group B: 80.2%; p < .001), in persistent AF was (Group A: 58.1% vs. Group B: 62.8%; p = .889). In Re-Do procedures Group A had a numerically lower PVI durability (75.0% vs. 83.6%, p = .089). CONCLUSION: For very severe obese AF patients, CBA appears feasible, leads to relatively good clinical outcome.

Raise-up technique for the creation of left atrial roof lesion: A useful technique with cryoballoon for persistent atrial fibrillation.

INTRODUCTION: Recent studies have reported the efficacy of the cryoballoon (CB)-guided left atrial roof block line (LARB) creation in patients with persistent atrial fibrillation (AF). However, it can be technically challenging to attach the balloon to the left atrial (LA) roof due to its anatomical variations. We designed a new procedure called the "Raise-up Technique," which may facilitate the firm adhesion of the CB to the LA roof during freezing. This study aimed to evaluate the efficacy of the Raise-up technique in LARB creation. METHODS AND RESULTS: In total, 100 consecutive patients with persistent AF who underwent CB-LARB creation were enrolled. Fifty-seven patients underwent LARB creation using the Raise-up technique (Raise-up group), and the remaining 43 did not use it (control group). The Raise-up technique was performed as follows: An Achieve catheter was inserted as deeply as possible into the upper branch of the right superior pulmonary vein to anchor the CB. The balloon was placed below the targeted site on the LA roof and frozen. When the temperature of the CB reached approximately -10°C and the CB was easier to attach to the LA tissue, the CB was raised and pressed against the LA roof immediately by sheath advancement. Then the balloon could be in firm contact with the target site on the roof. If necessary, additional sheath advancement after sufficient freezing (-20°C to -30°C) was allowed the CB to have more firm and broad contact with the target site. LARB creation without touch-up ablation was achieved in 54 of 57 patients (94.7%) in the Raise-up group and 33 of 43 patients (76.7%) in the control group (p < .05). The lesion size of the LARB in the Raise-up group was significantly larger than that in the control group (15.2 cm2 vs. 12.8 cm2, p < .05). Moreover, the width of the LARB lesion in the Raise-up group was wider than that in the control group (32.0 mm vs. 26.6 mm, p < .05). CONCLUSION: The Raise-up technique enabled the creation of seamless and thick LARB lesions with a single stroke. In addition, the CB-LARB lesions created using the Raise-up technique tended to be large, resulting in extensive debulking of the LA posterior wall arrhythmia substrates. In CB ablation for persistent AF, the Raise-up technique can be considered one of the key strategies for LARB creation.

Initial clinical experience of atrial fibrillation ablation guided by a cryoballoon-compatible, magnetic-based circular catheter.

INTRODUCTION: The circular catheter compatible with current cryoballoon system for atrial fibrillation (AF) ablation is exclusively sensed by impedance-based electro-anatomical mapping (EAM) system, limiting the accuracy of maps. We aim to investigate the feasibility and safety of a magnetic-based circular mapping catheter for AF ablation with cryoballoon. METHODS: Nineteen consecutive patients who underwent pulmonary vein isolation (PVI) with cryoballoon for paroxysmal or persistent AF were included. EAMs of left atrium (LA) created by the LASSOSTAR™NAV catheter (Lassostar map) before and after PVI were compared to that generated by a high-density mapping catheter (Pentaray map) from different aspects including structural similarity, PV angle, LA posterior wall (LAPW) and low voltage areas (LVAs), and the amplitude of far field electrograms (FFEs) recorded by catheters. RESULTS: All patients had successful PVI without major complications. With similar mapping time and density, the LA volume calculated from the Pentaray map and Lassostar map were comparable. There were no significant differences in PV angle of all PVs and PW area (16.8 ± 3.2 vs. 17.1 ± 2.8, p = .516) between Pentaray map and Lassostar map. High structural similarity score was observed between two maps (0.783 in RAO/LAO view and 0.791 in PA view). Lassostar map detected lesser but not statistically significant extension of LVA (13.9% vs. 18.3%, p = .07). Amplitude of FFE was larger at the right superior PV on Lassostar map (0.21 ± 0.16 vs. 0.14 ± 0.11 mV, p = .041) compared to that on the Pentaray map. CONCLUSION: In our initial experience, PVI with cryoballoon and magnetic-based circular LASSOSTAR™NAV catheter was safe and effective based on the accurate LA geometry it created.

Pulsed-field versus cryoballoon ablation for atrial fibrillation-Impact of energy source on sedation and analgesia requirement.

INTRODUCTION: Pulsed field ablation (PFA) represents a novel, nonthermal energy modality that can be applied for single-shot pulmonary vein isolation (PVI) in atrial fibrillation (AF). Comparative data with regard to deep sedation to established single-shot modalities such as cryoballoon (CB) ablation are scarce. The aim of this study was to compare a deep sedation protocol in patients receiving PVI with either PFA or CB. METHODS: Prospective, consecutive AF patients undergoing PVI with a pentaspline PFA catheter were compared to a retrospective CB-PVI cohort of the same timeframe. Study endpoints were the requirements of analgesics, cardiorespiratory stability, and sedation-associated complications. RESULTS: A total of 100 PVI patients were included (PFA n = 50, CB n = 50, mean age 66 ± 10.6, 61% male patients, 65% paroxysmal AF). Requirement of propofol, midazolam, and sufentanyl was significantly higher in the PFA group compared to CB [propofol 0.14 ± 0.04 mg/kg/min in PFA vs. 0.11 ± 0.04 mg/kg/min in CB (p = .001); midazolam 0.00086 ± 0.0004 mg/kg/min in PFA vs. 0.0006295 ± 0.0003 mg/kg/min in CB (p = .002) and sufentanyl 0.0013 ± 0.0007 µg/kg/min in PFA vs. 0.0008 ± 0.0004 µg/kg/min in CB (p < .0001)]. Sedation-associated complications did not differ between both groups (PFA n = 1/50 mild aspiration pneumonia, CB n = 0/50, p > .99). Nonsedation-associated complications (PFA: n = 2/50, 4%, CB: n = 1/50, 2%, p > .99) and procedure times (PFA 75 ± 31, CB 84 ± 32 min, p = .18) did not differ between groups. CONCLUSIONS: PFA is associated with higher sedation and especially analgesia requirements. However, the safety of deep sedation does not differ to CB ablation.

Pulmonary vein reconnection and repeat ablation characteristics following cryoballoon-compared to radiofrequency-based pulmonary vein isolation.

BACKGROUND: Despite advances in efficacy and safety of pulmonary vein isolation (PVI), atrial fibrillation (AF) recurrence after PVI remains common. PV-reconnection is the main finding during repeat PVI procedures performed to treat recurrent AF. OBJECTIVE: To analyze pulmonary vein (PV) reconnection patterns during repeat ablation procedures in a large cohort of consecutive patients undergoing radio frequency or cryoballoon-based PVI. METHODS: Retrospective analysis of PV-reconnection patterns and analysis of re-ablation strategies in consecutive index RF- and CB-based PVI and their respective re-ablation procedures during concomitant usage of both energy sources at a single high-volume center in Germany. RESULTS: A total of 610 first (06/2015-10/2022) and 133 s (01/2016-11/2022) repeat ablation procedures after 363 (60%) RF- and 247 (40%) CB-based index PVIs between 01/2015 and 12/2021 were analyzed. PV-reconnection was found in 509/610 (83%) patients at first and 74/133 (56%) patients at second repeat procedure. 465 of 968 (48%) initially via CB isolated PVs were reconnected at first re-ablation but 796 of 1422 initially RF-isolated PV (56%) were reconnected (OR: 0.73 [95% CI: 0.62-0.86]; p < .001). This was driven by fewer reconnections of the left PVs (LSPV: OR: 0.60 [95% CI: 0.42-0.86]; p = .005 and LSPV: 0.67 [0.47-0.95]; p = .026). PV-reconnection was more likely after longer, RF-based index PVI and in older females. Repeat procedures were shorter after CB-compared to after RF-PVI. CONCLUSIONS: Reconnection remains the most common reason for repeat AF ablation procedures after PVI. Our data suggest to preferentially use of the cryoballoon during index PVI, especially in older women.

Evaluation of microembolic signals on carotid ultrasound during pulmonary vein isolation with high-power short-duration and cryoballoon ablations: When and where do bubble and solid emboli arise?

INTRODUCTION: The underlying risks of asymptomatic embolization during high-power short-duration (HPSD) ablation for atrial fibrillation remain unclear. We aimed to evaluate microembolic signals (MESs) during HPSD ablation with power settings of 50 and 90 W in comparison with those during cryoballoon (CB) ablation using a novel carotid ultrasound-Doppler system that classifies solid and air bubble signals using real-time monitoring. METHODS AND RESULTS: Forty-seven patients underwent HPSD ablation using radiofrequency (RF), and 13 underwent CB ablation. MESs were evaluated using a novel pastable soft ultrasound probe equipped with a carotid ultrasound during pulmonary vein isolation. We compared the detailed MESs and their timing between RF and CB ablations. The number of MESs and solid signals were significantly higher in the RF group than in CB group (209 ± 229 vs. 79 ± 32, p = .047, and 83 ± 89 vs. 28 ± 17, p = .032, respectively). In RF ablation, the number of MESs, solid, and bubble signals per ablation point, or per second, was significantly higher at 90 W than at 50 W ablation. The MESs, solid, and bubble signals were detected more frequently in the bottom and anterior walls of the left pulmonary vein (LPV) ablation. In contrast, many MESs were observed before the first CB application and decreased chronologically as the procedure progressed. Signals were more prevalent during the CB interval rather than during the freezing time. Among the 28 patients, 4 exhibited a high-intensity area on postbrain magnetic resonance imaging (MRI). The MRI-positive group showed a trend of larger signal sizes than did the MRI-negative group. CONCLUSION: The number of MESs was higher in the HPSD RF group than in the CB group, with this risk being more pronounced in the 90 W ablation group. The primary detection site was the anterior wall of the LPV in RF and the first interval in CB ablation.

Current Balloon Devices for Ablation of Atrial Fibrillation.

Balloon-based catheter ablation is a valuable option for the treatment of atrial fibrillation (AF) because contiguous lesions can be created to achieve pulmonary vein isolation (PVI), and the method is less dependent than traditional ablation methods on the operator's skill and experience. Cryoballoon ablation is used universally worldwide, with its efficacy and safety being comparable to the efficacy and safety of standard radiofrequency ablation, and the procedure can be completed in a relatively short time. Hot balloon ablation was developed in Japan. The balloon maintains its compliance even during the energy delivery, and a large areal ablation lesion is created. Furthermore, the hot balloon system is the only system for which oesophageal cooling is a standard feature. Laser balloon ablation, which is performed under direct endoscopic vision, has proven to be effective and safe for achieving a PVI. The laser balloon system provides an improved field of view and automated circumferential ablation for a rapid and effective PVI. The authors have reviewed the currently available balloon systems as used for AF ablation, i.e., PVI, and have provided detailed insight and perspectives on the currently available cryoballoon and hot balloon technologies, plus laser balloon technology.

Prospective multicenter trial of the cryoballoon ablation system for superficial esophageal squamous cell carcinoma on the post-endoscopic resection scar. A CRYO-SCAR study (EPOC1902).

BACKGROUND AND AIMS: Endoscopic resection (ER) is a minimally invasive treatment for superficial esophageal squamous cell carcinoma (SESCC). Post-ER scars complicate en bloc resection, even with advanced techniques, such as endoscopic submucosal dissection. The cryoballoon ablation system (CBAS) effectively manages Barrett's esophagus but has limited evidence in SESCC treatment, particularly on post-ER scars. This study aimed to evaluate the efficacy and safety of the CBAS for treating SESCC on post-ER scars. METHODS: This prospective study was conducted at two tertiary referral centers in Japan in patients endoscopically diagnosed with T1a SESCC on the post-ER scar. Focal CBAS was used for cryoablation, with specific criteria for lesion selection and treatment method. The primary endpoint was local complete response (L-CR) rate of the primary lesion 48 weeks after the first cryoablation as evaluated by an independent central evaluation committee. RESULTS: From October 2020 to October 2021, 15 patients with 17 lesions underwent cryoablation, with two requiring repeat cryoablation. The L-CR rate for primary and all lesions evaluated by the central evaluation committee was 100%. The endoscopist's evaluation was consistent with these results. The median procedure time was 9 min. Eight patients experienced no pain, and the highest pain score reported on a numeric 1-10 rating scale was 3. The technical success rate was 94.7% (18/19). Throughout the median follow-up period of 14.3 months, recurrences, deaths, or severe treatment-related adverse events were not reported. CONCLUSIONS: CBAS is a potentially safe and effective approach for SESCC on post-ER scars and represents an encouraging alternative to traditional endoscopic treatments.

Impact of wall thickness on the tissue cooling effect of cryoballoon ablation.

AIMS: Understanding of the tissue cooling properties of cryoballoon ablation during pulmonary vein (PV) isolation is lacking. The purpose of this study was to delineate the depth of the tissue cooling effect during cryoballoon freezing at the pulmonary venous ostium. METHODS AND RESULTS: A left atrial-PV model was constructed using a three-dimensional printer with data from a patient to which porcine thigh muscle of various thicknesses could be affixed. The model was placed in a 37°C water tank with a PV water flow at a rate that mimicked biological blood flow. Cryofreezing at the PV ostium was performed five times each for sliced porcine thigh muscle of 2, 4, and 6 mm thickness, and sliced muscle cooling on the side opposite the balloon was monitored. The cooling effect was assessed using the average temperature of 12 evenly distributed thermocouples covering the roof region of the left superior PV. Tissue cooling effects were in the order of the 2, 4, and 6 mm thicknesses, with an average temperature of -41.4 ± 4.2°C for 2 mm, -33.0 ± 4.0°C for 4 mm, and 8.0 ± 8.7°C for 6 mm at 180 s (P for trend <0.0001). In addition, tissue temperature drops were steeper in thin muscle (maximum temperature drop per 5 s: 5.2 ± 0.9°C, 3.9 ± 0.7°C, and 1.3 ± 0.7°C, P for trend <0.0001). CONCLUSION: The cooling effect of cryoballoon freezing is weaker in the deeper layers. Cryoballoon ablation should be performed with consideration to myocardial thickness.

Incidence of phrenic nerve injury during pulmonary vein isolation using different cryoballoons: data from a large prospective ablation registry.

AIMS: Phrenic nerve injury (PNI) is the most common complication during cryoballoon ablation. Currently, two cryoballoon systems are available, yet the difference is unclear. We sought to compare the acute procedural efficacy and safety of the two cryoballoons. METHODS: This prospective observational study consisted of 2,555 consecutive atrial fibrillation (AF) patients undergoing pulmonary vein isolation (PVI) using either conventional (Arctic Front Advance) (AFA-CB) or novel cryoballoons (POLARx) (POLARx-CB) at 19 centers between January 2022 and October 2023. RESULTS: Among 2,555 patients (68.8 ± 10.9 years, 1,740 men, paroxysmal AF[PAF] 1,670 patients), PVIs were performed by the AFA-CB and POLARx-CB in 1,358 and 1,197 patients, respectively. Touch-up ablation was required in 299(11.7%) patients. The touch-up rate was significantly lower for POLARx-CB than AFA-CB (9.5% vs. 13.6%, p = 0.002), especially for right inferior PVs (RIPVs). The touch-up rate was significantly lower for PAF than non-PAF (8.8% vs. 17.2%, P < 0.001) and was similar between the two cryoballoons in non-PAF patients. Right PNI occurred in 64(2.5%) patients and 22(0.9%) were symptomatic. It occurred during the right superior PV (RSPV) ablation in 39(1.5%) patients. The incidence was significantly higher for POLARx-CB than AFA-CB (3.8% vs. 1.3%, P < 0.001) as was the incidence of symptomatic PNI (1.7% vs. 0.1%, P < 0.001). The difference was significant during RSPV (2.5% vs. 0.7%, P < 0.001) but not RIPV ablation. The PNI recovered more quickly for the AFA-CB than POLARx-CB. CONCLUSIONS: Our study demonstrated a significantly higher incidence of right PNI and lower touch-up rate for the POLARx-CB than AFA-CB in the real-world clinical practice.

Venous vascular closure system vs. figure-of-eight suture following atrial fibrillation ablation: the STYLE-AF Study.

AIMS: Simplified ablation technologies for pulmonary vein isolation (PVI) are increasingly performed worldwide. One of the most common complications following PVI are vascular access-related complications. Lately, venous closure systems (VCSs) were introduced into clinical practice, aiming to reduce the time of bed rest, to increase the patients' comfort, and to reduce vascular access-related complications. The aim of the present study is to compare the safety and efficacy of using a VCS to achieve haemostasis following single-shot PVI to the actual standard of care [figure-of-eight suture and manual compression (MC)]. METHODS AND RESULTS: This is a prospective, multicentre, randomized, controlled, open-label trial performed at three German centres. Patients were randomized 1:1 to undergo haemostasis either by means of VCS (VCS group) or of a figure-of-eight suture and MC (F8 group). The primary efficacy endpoint was the time to ambulation, while the primary safety endpoint was the incidence of major periprocedural adverse events until hospital discharge. A total of 125 patients were randomized. The baseline characteristics were similar between the groups. The VCS group showed a shorter time to ambulation [109.0 (82.0, 160.0) vs. 269.0 (243.8, 340.5) min; P < 0.001], shorter time to haemostasis [1 (1, 2) vs. 5 (2, 10) min; P < 0.001], and shorter time to discharge eligibility [270 (270, 270) vs. 340 (300, 458) min; P < 0.001]. No major vascular access-related complication was reported in either group. A trend towards a lower incidence of minor vascular access-related complications on the day of procedure was observed in the VCS group [7 (11.1%) vs. 15 (24.2%); P = 0.063] as compared to the control group. CONCLUSION: Following AF ablation, the use of a VCS results in a significantly shorter time to ambulation, time to haemostasis, and time to discharge eligibility. No major vascular access-related complications were identified. The use of MC and a figure-of-eight suture showed a trend towards a higher incidence of minor vascular access-related complications.

Safety and efficacy of the second-generation cryoballoon for left atrial appendage electrical isolation in canines.

AIMS: Left atrial appendage electrical isolation (LAAEI) has demonstrated a significant enhancement in the success rate of atrial fibrillation (AF) ablation. Nevertheless, concerns persist about the safety of LAAEI, particularly regarding alterations in left atrial appendage (LAA) flow velocity and the potential risks of thrombus. This study aimed to assess the efficacy and safety of LAAEI, investigating changes in LAA flow velocity in canines. METHODS AND RESULTS: The study comprised a total of 10 canines. The LAAEI procedure used by a 23 mm cryoballoon of the second generation was conducted at least 180 s. Intracardiac ultrasonography (ICE) was employed to quantify the velocity flow of the LAA both prior to and following LAAEI. Following a 3-month period, subsequent evaluations were performed to assess the LAA velocity flow and the potential reconnection. Histopathological examination was conducted. Left atrial appendage electrical isolation was effectively accomplished in all canines, resulting in a 100% acute success rate (10/10). The flow velocity in the LAA showed a notable reduction during LAAEI as compared with the values before the ablation procedure (53.12 ± 5.89 vs. 42.01 ± 9.22 cm/s, P = 0.007). After the follow-up, reconnection was observed in four canines, leading to a success rate of LAAEI of 60% (6/10). The flow velocity in the LAA was consistently lower (53.12 ± 5.89 vs. 44.33 ± 10.49 cm/s, P = 0.006), and no blood clot development was observed. The histopathological study indicated that there was consistent and complete injury to the LAA, affecting all layers of its wall. The injured tissue was subsequently replaced by fibrous tissue. CONCLUSION: The feasibility of using cryoballoon ablation for LAAEI was confirmed in canines, leading to a significant reduction of LAA flow velocity after ablation. Some restoration of LAA flow velocity after ablation may be linked to the passive movement of the LAA and potential reconnecting. However, this conclusion is limited to animal study; more clinical data are needed to further illustrate the safety and accessibility of LAAEI in humans.

Can phrenic nerve injury be anticipated by larger cryoballoons?

Recently, a novel size-adjustable cryoballoon has been introduced in clinical practice, which can be inflated to two different diameters (28 and 31 mm). The 31 mm cryoballoon is specifically designed to achieve better contact with remodeled pulmonary veins (PVs) that have wider ostia while avoiding deep cannulation, thereby potentially reducing the risk of phrenic nerve injury (PNI) associated with deep balloon cannulation. However, we encountered two cases of PNI during cryoballoon ablation using the novel system among our initial 25 consecutive case series. Herein, we present two cases that exhibited PNI during freezing of the right superior PV with a size-adjustable balloon. While larger balloons are expected to create a larger area of isolation, the safety of this novel balloon system needs to be evaluated in a large-scale clinical study.

Long-term efficacy and safety of cryoballoon ablation of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis evaluated long-term efficacy and safety of cryoballoon ablation (CB) of atrial fibrillation (AF). METHODS: PubMed, Cochrane Library, and Web of Science were searched until July 31, 2023, for published works investigating efficacy and safety of CB of AF in which mean/median follow-up time was not less than 36 months. Safety was assessed by adverse events. Efficacy was assessed by AF recurrence, defined as any atrial arrhythmias lasting more than 30 s. RESULTS: A total of 19 clinical studies were included. After an average of 58.1 months of follow-up, the overall AF recurrence rate was about 37%. The predictors of recurrence were duration of AF (HR 1.00; 95% CI [1.00 ∼ 1.01]), early recurrence of atrial fibrillation (HR 3.96; 95%CI [1.12 ∼ 14.02]), left atrial diameter (HR 1.04; 95%CI [1.02 ∼ 1.06]), and persistent AF (HR1.47; 95% CI [1.19 ∼ 1.82]). In terms of safety, the incidence of transient phrenic paralysis (PNP) was the highest, about 3%; followed by vascular complications (about 2%); pseudoaneurysm, permanent PNP, and all-cause death was (about 1%); and pericardial effusion and stroke / TIA was very low. CONCLUSION: CB is associated with low rates of severe complications and reasonable success rates.

Clinical impact of cryoballoon posterior wall isolation using the cross-over technique in persistent atrial fibrillation.

BACKGROUND AND AIMS: Successful left atrial posterior wall isolation (LAPWI) using only the cryoballoon (CB) is technically challenging for the treatment of atrial fibrillation (AF). This study aimed to evaluate the efficacy of the cross-over technique, wherein an overlapped ablation is performed by placing the CB from both directions in contact with the LAPW. METHODS: This was a single-center, retrospective, observational study of 194 consecutive patients with persistent atrial fibrillation (PerAF) who underwent a first-time procedure of pulmonary vein isolation (PVI) + PWI (108 patients) or PVI-only (86 patients) using the CB. The cross-over technique was applied in all LAPWI. RESULTS: For ablation of the LA roof and bottom, respectively, a mean of 8.6 ± 1.0 (right to left [R→L] 4.3 ± 1.1 and left to right [L→R] 4.3 ± 1.1) and 9.1 ± 1.2 (R→L 4.6 ± 1.6 and L→R 4.5 ± 1.2) CB applications were delivered. LAPW was successfully isolated solely using the CB in 99.1% of patients. Although the PVI + PWI group had significantly longer procedure time, no severe adverse events were observed in either group. During a median follow-up of 19 months, freedom from recurrence of all atrial tachyarrhythmias was achieved in 93.5% of the PVI + PWI group and 72.9% of the PVI-only group (p = .011). CONCLUSIONS: LAPWI performed solely with the CB using the cross-over technique is feasibly, safe, and was independently associated with a significantly higher freedom from recurrence of atrial tachyarrhythmias compared with PVI alone in patients with PerAF.