Pulmonary Vein Isolation Using the Visually Guided Laser Balloon: Results of the U.S. Feasibility Study

Transcription

1 944 Pulmonary Vein Isolation Using the Visually Guided Laser Balloon: Results of the U.S. Feasibility Study SRINIVAS R. DUKKIPATI, M.D., IAN WOOLLETT, M.D., H. THOMAS McELDERRY, M.D., MARIE-CHRISTINE BÖHMER, M.D., SHEPHAL K. DOSHI, M.D., EDWARD P. GERSTENFELD, M.D., RODNEY HORTON, M.D., ANDRE D AVILA, M.D., DAVID E. HAINES, M.D.,# MIGUEL VALDERRABANO, M.D., J. MICHAEL MANGRUM, M.D., JEREMY N. RUSKIN, M.D., ANDREA NATALE, M.D., and VIVEK Y. REDDY, M.D. From the Helmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, New York, New York; Sentara Cardiovascular Research Institute, Norfolk, Virginia; University of Alabama at Birmingham, Birmingham, Alabama; Pacific Heart Institute, Santa Monica, California; University of California San Francisco School of Medicine, San Francisco, California; #William Beaumont Hospital, Royal Oak, Michigan; The Methodist Hospital, Houston, Texas; University of Virginia, Charlottesville, Virginia; Massachusetts General Hospital, Boston, Massachusetts; and Texas Cardiac Arrhythmia Institute, Austin, Texas, USA Visually Guided PV Isolation. Introduction: Visually guided laser balloon (VGLB) ablation is unique in that the operator delivers ablative energy under direct visual guidance. In this multicenter study, we sought to determine the feasibility, efficacy, and safety of performing pulmonary vein isolation (PVI) using this VGLB. Methods: Patients with symptomatic, drug-refractory paroxysmal atrial fibrillation (AF) underwent PVI using the VGLB with the majority of operators conducting their first-ever clinical VGLB cases. The primary effectiveness endpoint was defined as freedom from treatment failure that included: Occurrence of symptomatic AF episodes 1 minutes beyond the 90-day blanking, the inability to isolate 1 superior and 2 total PVs, occurrence of left atrial flutter or atrial tachycardia, or left atrial ablation/surgery during follow-up. Results: A total of 86 patients (mean age 56 ± 10 years, 67% male) were treated with the VGLB at 10 US centers. Mean fluoroscopy, ablation, and procedure times were 39.8 ± 24.3 minutes, ± 61.7 minutes, and ± 71.3 minutes, respectively. Acute PVI was achieved in 314/323 (97.2%) of targeted PVs. Of 84 patients completing follow-up, the primary effectiveness endpoint was achieved in 50 (60%) patients. Freedom from symptomatic or asymptomatic AF was 61%. The primary adverse event rate was 16.3% (8.1% pericarditis, phrenic nerve injury 5.8%, and cardiac tamponade 3.5%). There were no cerebrovascular events, atrioesophageal fistulas, or significant PV stenosis. Conclusions: This multicenter study of operators in the early stage of the learning curve demonstrates that PVI can be achieved with the VGLB with a reasonable safety profile and an efficacy similar to radiofrequency ablation. (J Cardiovasc Electrophysiol, Vol. 26, pp , September 2015) atrial fibrillation, catheter ablation, laser, pulmonary veins, visual guidance Drs. Woollett, McElderry, Doshi, Mangrum, Haines, and Reddy report participation on a research grant supported by CardioFocus. Drs. Dukkipati and McElderry report compensation for participation on a speaker s bureau and honoraria relevant to this topic; in addition, Dr. McElderry serves as consultant/advisory board member for Boston Scientific, ACT Med, Vytron US, St. Jude Medical, and Biosense Webster. Dr. Reddy serves as consultant/advisory board member for CardioFocus. Dr. Valderrabano reports research grants supported by Hansen Medical and Boston Scientific. Dr. Ruskin reports consultant fees from CardioInsight, Cardiome, Gilead Sciences, Medtronic, and Pfizer; honorarium from Sanofi Aventis; equity interest in InfoBionic and Portola. Other authors: No disclosures. Clinical Trials Registration: Clinicaltrials.gov Identifier: NCT Address for correspondence: Srinivas R. Dukkipati, M.D., Helmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY Fax: ; srinivas.dukkipati@mountsinai.org Manuscript received 8 February 2015; Revised manuscript received 25 April 2015; Accepted for publication 28 April doi: /jce Introduction Durable pulmonary vein (PV) isolation is the goal of catheterbased therapy for patients with paroxysmal atrial fibrillation (AF). 1 Although acute PV isolation is almost always studyachieved, chronic efficacy is limited by PV reconnections that can be in part be attributed to the technical difficulty in achieving circumferential, continuous and transmural lesions with point-by-point ablation. 2,3 To this end, balloon catheters have been designed to help facilitate this process. 4-6 One such balloon catheter is the visually guided laser balloon (VGLB), which is a compliant, variable diameter balloon that utilizes a maneuverable 30 light arc to deliver laser energy at operator determined sites under real-time endoscopic visualization. 7 Preclinical experience with the VGLB has demonstrated that a high rate of circumferential and transmural lesions can be achieved, and in a multicenter clinical PV remapping study this translated to 86% of PVs remaining durably isolated at 3 months. 7,8 Limited clinical experience with the VGLB has demonstrated reasonable safety and an efficacy similar to radiofrequency ablation This balloon is approved for clinical use in Europe and is currently under clinical investigation in the US. In this manuscript, we report the results

2 Dukkipati et al. Visually Guided PV Isolation 945 Figure 1. The Kaplan-Meier curve for the primary effectiveness endpoint is shown for the follow-up period of 1 year. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology s website: of the nonrandomized, multicenter, US feasibility study with this VGLB. Materials and Methods The study was a prospective, nonrandomized, single arm, multicenter study designed to assess the feasibility and safety of VGLB ablation for the treatment of patients with symptomatic paroxysmal AF. The study enrolled 100 patients and was conducted at 10 clinical sites in the United States, 9 of which treated patients. The Ethics Committee or Institutional Review Board of each participating institution approved the study and all patients provided written informed consent. Patient Selection and Study Design Patients with drug-refractory and symptomatic paroxysmal AF who were deemed candidates for catheter ablation were eligible for the study. Key inclusion criteria were: age years, symptomatic paroxysmal AF with at least 2 episodes in the 6 months prior to enrollment ( 1 minutes and <24 hours duration) and at least 1 episode documented in the prior 1 year, failure of at least 1 antiarrhythmic drug (AAD; Class I, II, or III). Key exclusion criteria were: any pulmonary vein >32 mm in average diameter, AF secondary to a reversible cause, AF episodes that lasted longer than 30 days and were terminated via cardioversion, left atrial thrombus, a left ventricular ejection fraction <30%, left atrial diameter >50 mm, former left-sided cardiac ablation, history of any valvular cardiac surgical procedure, coronary artery bypass grafting within the prior 6 months or any cardiac surgery within the prior 3 months, myocardial infarction within 60 days prior to enrollment, a stroke/transient ischemic attack within prior 12 months. At baseline, patients underwent physical examination and had a 12-lead electrocardiogram (ECG) and 24-hour Holter monitoring. Transthoracic echocardiograms were performed to assess LA size and left ventricular ejection fraction. A CT or MRI scan was performed to determine pulmonary vein size and anatomy. Within one week prior to the procedure, a transesophageal echocardiogram was also performed to rule out left atrial thrombus. AADs could be continued until the day of procedure. Typically, warfarin was started 1 month prior to ablation to achieve international normalized ratio levels between 2 and 3 and was continued through the procedure. At the discretion of the investigator, oral anticoagulation therapy could be stopped 3 5 days (optional under overlapping low molecular weight heparin therapy) prior to procedure. Predischarge physical examination, 12-lead ECG and echocardiogram were performed. Oral anticoagulation therapy was resumed targeting an INR of 2 3. After the 90-day blanking period, all AADs were required to be stopped. However, amiodarone was stopped immediately after ablation. β-blockers were recommended for all patients on discharge. Office follow-up was performed at 1, 3, 6, and 12 months after the procedure and included 12-lead ECG and 24-hour Holter monitoring as well as weekly and symptomatic event recorder transmissions. A repeat CT or MRI scan was performed at 3 and 12 months postprocedure to assess for PV stenosis. Visually Guided Laser Balloon Ablation The VGLB system (known as HeartLight, from CardioFocus Inc., Marlborough, MA, USA) was previously described in detail. 7 Briefly, the VGLB catheter is a variablediameter, compliant balloon that is delivered through a 12-Fr deflectable sheath. Within the central shaft of the balloon catheter is a 2-Fr endoscope that allows real-time visualization of target tissue. The central shaft also contains lumens for circulating the balloon-filling media (D 2 O) to allow cooling of the balloon, and a maneuverable optical fiber that generates a 30 arc/spot of both visible and near-infrared ablative light energy. This arc of light can be advanced, retracted, and rotated to any location along the surface of the balloon to allow aiming and then ablation using diode laser energy (980 nm). The catheter tip is equipped with a flexible tip to cause minimal trauma. The shaft of the catheter contains a radiopaque marker that can be visualized on fluoroscopy and is 180 opposite the position of the partially obscured portion of the endoscopic view. This allows correlation of the location and orientation of the radiopaque marker to the endoscopic image allowing delineation of superior, inferior, anterior, and posterior directions. All procedures were performed under general anesthesia. Transseptal puncture was performed using a standard 8-Fr sheath and a Brockenbrough needle with fluoroscopy guidance. Intracardiac echocardiography (ICE) use was required. The 8-Fr sheath was then exchanged for a 12-Fr ID deflectable sheath over a inch or inch guidewire. A second transseptal puncture was performed with an 8-Fr sheath and was positioned in the left atrium for use with a circular mapping catheter. Intravenous heparin was administered as boluses and as a continuous infusion to maintain an activated clotting time >300 seconds. Using the deflectable sheath, the VGLB catheter was inflated at the ostium of the target PV. Using visual guidance, ablation lesions were delivered in a circumferential, contiguous, and overlapping manner around the PV. When ablation behind the partially obscured area behind the central shaft was required, the balloon was partially deflated, rotated, and re-inflated to allow visualization and ablation in this area. Rarely was energy delivered behind the partially obscured area. After placement of the initial encircling lesion set, the circular mapping catheter was used to assess for electrical

3 946 Journal of Cardiovascular Electrophysiology Vol. 26, No. 9, September 2015 Figure 2. The graph shows the proportion of patients that had failure of the primary effectiveness endpoint based on cause. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology s website: isolation of the PV. If the PV was not isolated, the VGLB catheter was again used to deliver lesions to the area of anatomical breakthrough. All PVs were targeted in a similar manner. During ablation of the right-sided PVs, phrenic nerve pacing was performed from the superior vena cava to monitor for phrenic nerve injury demonstrated as a reduction in capture via reduced movement of the diaphragm. Ablation was terminated with loss of capture of the phrenic nerve. In all patients, an esophageal temperature probe was placed in the esophagus to monitor for excessive heating. Ablation was stopped if the esophageal temperature exceeded 38.5 C. After 30 minutes postablation of the last PV, all PVs were reassessed for electrical isolation. A circular mapping catheter was used to identify entrance block. Optionally, exit block could be confirmed. Usage of isoproterenol was recommended but was not required by the protocol. The typical dose of laser energy used was 8.5 Watts 20 seconds and less commonly, 7 14 Watts per lesion. The 5.5 Watt/30 seconds dose was used when ablation was required in regions of moving blood (not stagnant) along the periphery of the endoscopic view to minimize the risk of thrombus formation. Stagnant blood is often visualized in the center of the balloon and represents blood from the target PV that is completely occluded by the balloon and ablation is avoided in this region due to risk of thrombus formation. Lesion overlap during ablation was approximately 50% for the 5.5 Watt/30 seconds dose and approximately 30% for other doses. Study Endpoints The primary effectiveness endpoint was defined as freedom from treatment failure that included: (i) the occurrence of symptomatic AF episodes lasting 1 minute beyond the 90-day blanking period and during the 12 months of followup, (ii) left-sided heart ablation or cardiac surgery during follow-up, (iii) failure to achieve isolation in 1 superior PV and 2 PVs overall, and (iv) and occurrence of left atrial flutter or atrial tachycardia during follow-up. Secondary endpoints included: (i) freedom from symptomatic or asymptomatic AF recurrence lasting 1 minute, (ii) technical (acute) success in achieving PV isolation in targeted veins, and (iii) success on previously ineffective AAD. Figure 3. The 3 secondary effectiveness endpoints are shown. Technical success was defined as the percentage of targeted PVs that were successfully isolated acutely. Freedom from any AF represents the percentage of patients that were free of symptomatic or asymptomatic atrial arrhythmias off drugs at the conclusion of the 12 months of follow-up. There were no patients that had clinical success on previously failed AADs. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology s website: For this study a primary safety endpoint was defined as the occurrence of any primary adverse event that included a transient ischemic attack within 1 month of ablation, cerebrovascular accident including stroke and air embolism, major bleeding requiring transfusion within 1 week of treatment, pericardial effusion, cardiac perforation or tamponade, coronary artery spasm within 1 month of treatment, PV stenosis, damage to cardiac valves, pericarditis, myocardial infarction within 1 week of procedure, diaphragmatic paralysis within 6 months of treatment, atrioesophageal fistula within 6 months of treatment, and death during the 12-month evaluation period and cause possibly related or unknown. Statistics Continuous variables with normal distribution were tested for normality using the Shapiro-Wilk test and are represented as mean ± standard deviation. Continuous data with skewed distribution are represented as median and interquartile ranges (IQR). Comparisons between groups were made using Student s 2-sample t-test (pooled). Categorical variables are represented as relative frequencies and were compared using Fisher exact test. Kaplan-Meier curves were used to estimate the AF free survival. Statistical analysis was performed using SAS version 9.2 (SAS Institute Inc., Cary, NC, USA). Patient Demographics Results A total of 100 patients were initially enrolled (consented) for the study, with 14 patients being withdrawn prior to ablation. Ten of the 14 withdrew consent and 4 were withdrawn for other reasons including equipment unavailability in 1, inability to place esophageal temperature probe in 1, presence of concealed left lateral bypass tract in 1, and patient postponement of procedure in 1. There were no patients that were excluded due to PV size. The baseline demographics of the remaining 86 patients (9 US clinical sites) are

4 Dukkipati et al. Visually Guided PV Isolation 947 TABLE 1 Patient Demographics TABLE 3 Primary Adverse Events N = 86 Age, mean ± SD, years (limits) 56.7 ± 10.3 (26 75) Gender, M/F, n (%) 58 (67.4%)/28 (32.6%) Duration of AF, median years 3.0 (IQR 6.1) Coronary artery disease, n (%) 11 (12.8%) Hypertension, n (%) 45 (52.3%) Congestive heart failure, n (%) 8 (9.3%) Diabetes mellitus, n (%) 14 (16.3%) Stroke or transient ischemic attack, n (%) 1 (1.2%) Ejection fraction, mean ± SD, % (limits) 59 ± 7 (30 73) LA diameter, mean ± SD, cm (limits) 4.0 ± 0.5 ( ) History of atrial flutter, n (%) 25 (29.1%) Antiarrhythmic medications, n (%) Class I 44 (51.1%) Class II 39 (45.3%) Class III 46 (53.5%) N = 86 Cardiac tamponade 3 (3.5%) Pericardial effusion without tamponade 1 (1.2%) Phrenic nerve injury Total 5 (5.8%) Persistent at 12 months 1 (1.2%) Stroke/TIA 0 (0%) Atrio-esophageal fistulas 0 (0%) PV stenosis 0 (0%) Death 1 (1.2%) Major bleeding requiring transfusion 0 (0%) Coronary artery spasm 0 (0%) Cardiac valve damage 0 (0%) Pericarditis 7 (8.1%) Myocardial infarction 0 (0%) Total number of events 17 Primary adverse event rate 14 (16.3%) A patient is only counted once in the overall primary adverse event rate. TABLE 2 Procedure Data N = 86 PVs isolated, n (%) 314/323 (97.2%) PVs isolated on first attempt, n (%) 263/314 (83.8%) Catheter per pt., mean ± SD 1.03 ± 0.18 Attempts to isolate PV, mean ± SD 1.2 ± 0.6 Fluoroscopy time, mean ± SD, min 39.8 ± 24.3 Ablation time, mean ± SD, min ± 61.7 Procedure time, mean ± SD, min ± 71.3 Ablations per PV, mean ± SD 40.8 ± 15.3 Percentage of total ablation time based on power 5.5 W 49.73% 7 W 2.32% 8.5 W 30.60% 10 W 17.86% 12 W 0.78% 14 W 0.02% detailed in Table 1. Limited data from 79 of these patients were previously reported as part of a much larger multicenter initial experience with the VGLB. 9 The mean age of the patients was 56.7 ± 10.3 years (67.4% male). The median duration of AF was 3.0 years (IQR 6.1) with 51,1%, 45.3%, and 53.5% failing treatment with class I, II, and III antiarrhythmic drugs, respectively. The mean LA diameter was 4.0 ± 0.5 cm and the mean left ventricular ejection fraction was 59 ± 7%. Procedural Characteristics As shown in Table 2, overall acute PV isolation was achieved in 314/323 (97.2%) PVs, with 263 (83.8%) PVs being isolated following the first visually guided encirclement of the PV. An average of 40.8 ± 15.3 ablation lesions were delivered per PV. A mean of 1.2 ± 0.6 attempts were needed to isolate the PV. The mean fluoroscopy, ablation, and procedure times were 39.8 ± 24.3, ± 61.7, and ± 71.3 min, respectively. Of the total ablation time, 49.73% was at a power setting of 5.5 W and only 0.80% was at 12 W. Operator Characteristics There were 16 different primary operators that conducted the 86 procedures in this study. Only one operator had con- ducted a VGLB ablation prior to the initiation of this study, at a site outside of the United States. By the conclusion of this study, only 2 of 16 of the operators (12.5%) had conducted more than 10 VGLB ablations. Thus, the outcomes of this study have incorporated the operator learning curve for use of the VGLB. Clinical Outcomes and Safety Of the 86 patients who underwent ablation, 2 were unavailable for efficacy: because of early loss to follow-up in 1 patient, and due to an unrelated death of 1 patient (see below). Thus, the efficacy results do not include these 2 patients and is based on the remaining 84 patients. The primary effectiveness endpoint was met in 50/84 patients (60%) as illustrated in Figures 1 and 2. The main reason for failure was a documented symptomatic episode of AF lasting 1 minute after the blanking period, which occurred in 27 patients (32.1%). Thus, the freedom from symptomatic AF in was 67.9%. Others reasons for treatment failure included incomplete vein isolation in 5 patients (5.8%), additional left-sided heart ablation using a radiofrequency ablation catheter in 1 (1.2%), and left-sided ablation during follow-up in 1 (1.2%). With respect to the secondary effectiveness endpoints, freedom from any symptomatic or asymptomatic AF 1 minutes was achieved in 51/84 (60.7%) patients. Technical (acute) success was reported in 314/323 PVs (97.2%). Success on previously ineffective AAD did not occur (Fig. 3). Of the 76 patients who had all PVs successfully isolated with the VGLB and were able to complete follow-up, the freedom from symptomatic AF 1 minutes off drugs was 64.5%. There were a total of 17 primary adverse events in 14 patients yielding a primary adverse event rate of 16.3% (Table 3). There were 7 (8.1%) patients that had postprocedural pericarditis, 3 (3.5%) developed cardiac tamponade that was successfully drained in 2 cases, whereas 1 patient had to undergo surgical repair. Phrenic nerve injury occurred in 5 (5.8%) patients, with 1 (1.2%) having persistent phrenic nerve palsy at 12 months. Cerebrovascular events or atrio-esophageal fistulas did not occur. There was no significant PV stenosis (>50% diameter decrease) related to VGLB ablation.

5 948 Journal of Cardiovascular Electrophysiology Vol. 26, No. 9, September 2015 One patient with cardiac tamponade who underwent percutaneous pericardiocentesis was discharged home in stable condition after 4 days of hospitalization. On the second day after discharge he experienced sudden cardiac death. The presumed cause of death was felt to be due to undiagnosed severe triple vessel coronary artery disease (despite a negative nuclear stress test 4 months prior) that was documented only upon autopsy. The death was found to be related to the procedure, but unlikely related to the VGLB catheter (adjudication of the independent Clinical Oversight Committee). Discussion In this multicenter US feasibility trial, we demonstrated that PV isolation using the VGLB could be performed with reasonable safety and an efficacy that is similar to standard radiofrequency ablation in the operator s primary learning curve. Acute electrical isolation was achieved in 97.2% of targeted PVs, with 83.8% of them being isolated after the initial visually guided encirclement. The mean number of attempts to achieve isolation was 1.2 attempts per PV. The variable diameter and compliant nature of the balloon allowed it to adapt to different PV anatomies, allowing the vast majority of patients to achieve isolation of all PVs with a single catheter. Procedure times were comparable to radiofrequency ablation procedures. The main primary adverse events were postprocedural pericarditis in 8.1%, phrenic nerve injury in 5.8%, and cardiac tamponade in 3.5%. The primary effectiveness endpoint was achieved in 60% and the drug-free rate of freedom from symptomatic or asymptomatic AF was 61%, which is similar to the clinical experience with radiofrequency ablation. Preclinical porcine experiments utilizing the VGLB have demonstrated that high rates of circumferential and transmural lesions can be achieved. 7 At 4 weeks following PV isolation using the VGLB, all targeted PVs had circumferential lesions on gross examination, and 96.7% of histological sections had transmural lesions. This translated to a very high rate of durable PV isolation in a multicenter PV remapping study. 8 After approximately 90 days following VGLB ablation, 86% of PVs were still isolated, with 62% of patients demonstrating durable PV isolation of all PVs. However, freedom from AF following 2 procedures in that series was only 71.2% at 1 year. In this study, the single procedure drug-free rate of freedom from symptomatic or asymptomatic AF was 61%, which is in line with other published studies. 9,10,12,13 It would be reasonable to expect that high rates of durable PV isolation would translate to higher clinical success. Although nonpulmonary vein triggers may be partially responsible for this observed disparity, another potential explanation is that the level of electrical isolation achieved with the VGLB is more ostial than desired, thereby leaving potentially arrhythmogenic areas in the antrum intact It is also possible that the chronic efficacy results will also improve as the operators move further in the learning curve. 10 There are several factors that may improve upon the observed efficacy in this study. Ablation lesions delivered by the VGLB are not always readily apparent on endoscopic visualization, and therefore tracking of lesion location is very important to ensure lesion contiguity. During this US Feasibility study, lesion tracking was performed manually by tracing the location of lesions on a clear film that was superimposed on the screen containing the endoscopic view. Balloon rotation or position change relative to the PV ostium required repositioning of the film on the endoscopic view leading to potential inaccuracy and lesion gaps. In the current generation VGLB system, lesion tracking is automated and is performed by recording video images of the prior lesions. This allows lesion tracking to be more accurate and could potentially yield a higher rate of lesion contiguity. However, whether this translates to higher rates of durable PV isolation is unknown at this time. In this study, operators had limited prior experience with the VGLB and prior studies have demonstrated that durable PV isolation rates improve with increased operator experience. In the multicenter PV remapping study, after 90 days following ablation, those operators with 10 case experience with the VGLB had a durable PV isolation rate of 89% versus 73.1% (P = 0.011) for those with <10 case experience. 8 Increased operator experience has also been shown to result in decreased procedure, fluoroscopy, and ablation times with improved acute procedural outcomes including ability to achieve PV isolation with first encircling lesions set and a lower rate of complications. 9,10 In the initial experience with the VGLB, included in this study, laser energy may have been under-dosed, which may have resulted in sub-optimal efficacy. In this study, 50% of the ablation time was at the lowest energy dose of 5.5 W, which is less likely to be sufficient to achieve transmurality at certain locations of thick atrial tissue. For example, the ridge between the left PVs and left atrial appendage is an area that has been shown to account for the majority of PV reconnections involving the left veins following VGLB ablation. 8 In the multicenter VGLB ablation remapping study, the left atrial appendage ridge accounted for 10 of 11 (91%) PV reconnections involving the left-sided PVs. 8 On the other hand, higher dosing of laser energy has resulted in better clinical efficacy. Bordignon et al. compared a high (>8.5 Watts) vs. low energy ( Watts) dosing strategies and demonstrated that outcomes are markedly improved with higher energy delivery. 17 During a median follow-up of 311 days, the freedom from AF was 83% in the high energy dosing arm versus 60% in the low energy arm (P = 0.04). In addition, using a high energy dosing strategy resulted in 89% of PVs being isolated after the first encircling lesion set compared to 69% with the low energy dosing arm (P = 0.009). For comparison, in this study, 84% of PVs were isolated following initial encirclement, with 50% of the ablation time being at 5.5 W. The main primary adverse event related to VGLB ablation was pericarditis, which was seen in 8.1% of patients. This complication is a frequent, underdiagnosed, and a rarely reported complication of atrial fibrillation ablation and is to be expected with transmural ablation lesions resulting in pericardial irritation. 1 Similar to other balloon catheter technologies, 18 phrenic nerve injury does occur with the VGLB, and the rate of this complication in this study was 5.8%. However, persistent phrenic nerve palsy at 12 months occurred in only 1 patient. Cardiac tamponade occurred in 3.5% of patients treated with the VGLB, which is more than that reported with cryoballoon ablation. 19,20 This may be in part be due to the relative operator inexperience in this study and the fact that the VGLB, although having a flexible end at the catheter tip, is not delivered over a guidewire as is the cryoballoon. To compensate for this issue, since the completion of this study, this tip of the VGLB catheter has been modified to make it atraumatic. The safety of this modified

6 Dukkipati et al. Visually Guided PV Isolation 949 VGLB catheter has been quite favorable in single-center experiences; 10 prospective multicenter studies are necessary to determine how this performs in a multicenter experience. Limitations This was a nonrandomized study and the true safety and efficacy of VGLB ablation in relation to other technologies can only be made with comparative, randomized studies. A duration of at least 60 seconds of AF was required to be deemed a failure rather than the standard 30 seconds definition that is commonly used. Thus the freedom from AF in this study may be higher than would be seen with the standard definition. In addition, the AF monitoring strategy that was employed used only weekly or symptom driven recordings that may have failed to pick up additional cases of asymptomatic AF and that may have resulted in an overestimation of the actual efficacy of VGLB ablation. The majority of operators in this study had very little, if any, experience with the VGLB. Comparisons to other strategies are also best performed once operators for the VGLB have advanced through the learning curve, which is likely to be approximately cases. PV diameter and stenosis assessment was done at the individual centers and not by a core laboratory. Conclusions In this multicenter, nonrandomized, single arm study, PV isolation using the VGLB was shown to be feasible with reasonable procedural safety and an efficacy similar to radiofrequency ablation. Similar to other balloon technologies, phrenic nerve injury does occur. Along with other favorable initial single-center experiences with the VGLB, this multicenter registry sets the stage for randomized, multicenter, comparative studies to radiofrequency ablation. References 1. 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