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.

Atrial fibrillation progression after cryoablation vs. radiofrequency ablation: the CIRCA-DOSE trial.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is a chronic progressive disorder. Persistent forms of AF are associated with increased rates of thromboembolism, heart failure, and death. Catheter ablation modifies the pathogenic mechanism of AF progression. No randomized studies have evaluated the impact of the ablation energy on progression to persistent atrial tachyarrhythmia. METHODS: Three hundred forty-six patients with drug-refractory paroxysmal AF were enrolled and randomly assigned to contact-force-guided RF ablation (CF-RF ablation, 115), 4 min cryoballoon ablation (CRYO-4, 115), or 2 min cryoballoon ablation (CRYO-2, 116). Implantable cardiac monitors placed at study entry were used for follow-up. The main outcome was the first episode of persistent atrial tachyarrhythmia. Secondary outcomes included atrial tachyarrhythmia recurrence and arrhythmia burden on the implantable monitor. RESULTS: At a median of 944.0 (interquartile range [IQR], 612.5-1104) days, 0 of 115 patients (0.0%) randomly assigned to CF-RF, 8 of 115 patients (7.0%) assigned to CRYO-4, and 5 of 116 patients (4.3%) assigned to CRYO-2 experienced an episode of persistent atrial tachyarrhythmia (P = .03). A documented recurrence of any atrial tachyarrhythmia ≥30 s occurred in 56.5%, 53.9%, and 62.9% of those randomized to CF-RF, CRYO-4, and CRYO-2, respectively; P = .65. Compared with that of the pre-ablation monitoring period, AF burden was reduced by a median of 99.5% (IQR 94.0%, 100.0%) with CF-RF, 99.9% (IQR 93.3%-100.0%) with CRYO-4, and 99.1%% (IQR 87.0%-100.0%) with CRYO-2 (P = .38). CONCLUSIONS: Catheter ablation of paroxysmal AF using radiofrequency energy was associated with fewer patients developing persistent AF on follow-up.

Progression of Atrial Fibrillation after Cryoablation or Drug Therapy.

BACKGROUND: Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation. METHODS: We report the 3-year follow-up of patients with paroxysmal, untreated atrial fibrillation who were enrolled in a trial in which they had been randomly assigned to undergo initial rhythm-control therapy with cryoballoon ablation or to receive antiarrhythmic drug therapy. All the patients had implantable loop recorders placed at the time of trial entry, and evaluation was conducted by means of downloaded daily recordings and in-person visits every 6 months. Data regarding the first episode of persistent atrial fibrillation (lasting ≥7 days or lasting 48 hours to 7 days but requiring cardioversion for termination), recurrent atrial tachyarrhythmia (defined as atrial fibrillation, flutter, or tachycardia lasting ≥30 seconds), the burden of atrial fibrillation (percentage of time in atrial fibrillation), quality-of-life metrics, health care utilization, and safety were collected. RESULTS: A total of 303 patients were enrolled, with 154 patients assigned to undergo initial rhythm-control therapy with cryoballoon ablation and 149 assigned to receive antiarrhythmic drug therapy. Over 36 months of follow-up, 3 patients (1.9%) in the ablation group had an episode of persistent atrial fibrillation, as compared with 11 patients (7.4%) in the antiarrhythmic drug group (hazard ratio, 0.25; 95% confidence interval [CI], 0.09 to 0.70). Recurrent atrial tachyarrhythmia occurred in 87 patients in the ablation group (56.5%) and in 115 in the antiarrhythmic drug group (77.2%) (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). The median percentage of time in atrial fibrillation was 0.00% (interquartile range, 0.00 to 0.12) in the ablation group and 0.24% (interquartile range, 0.01 to 0.94) in the antiarrhythmic drug group. At 3 years, 8 patients (5.2%) in the ablation group and 25 (16.8%) in the antiarrhythmic drug group had been hospitalized (relative risk, 0.31; 95% CI, 0.14 to 0.66). Serious adverse events occurred in 7 patients (4.5%) in the ablation group and in 15 (10.1%) in the antiarrhythmic drug group. CONCLUSIONS: Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).

Leadless Pacemaker Implantation in a Patient With Hypoplasia of the Left Brachiocephalic Vein.

Venous anomalies are typically asymptomatic and may be discovered unexpectedly at the time of implantation of a cardiac implantable electronic device. We report a case of leadless pacemaker implantation in a patient with hypoplasia of the left brachiocephalic vein who had previously undergone multiple interventions for relapsing right-sided breast cancer. The prevalence and etiology of this anatomic variant remain unknown. However, awareness of its existence may prevent complications during left-sided interventions. such as placement of a central venous line or a cardiac implantable electronic device. Alternative diagnostics and implantation strategies are discussed.

Les anomalies veineuses sont généralement asymptomatiques et peuvent être découvertes de façon inattendue au moment de l'implantation d'un dispositif cardiaque électronique. Nous présentons un cas d'implantation d'un stimulateur cardiaque sans sonde chez une patiente atteinte d'hypoplasie de la veine brachiocéphalique gauche qui avait déjà subi de nombreuses interventions en raison de la rechute d'un cancer du sein du côté droit. On ignore la prévalence et l'étiologie de cette variante anatomique. Toutefois, la sensibilisation à son existence peut permettre de prévenir les complications durant les interventions du côté gauche telles que la pose d'un cathéter veineux central ou l'implantation d'un dispositif cardiaque électronique. Les autres diagnostics et stratégies d'implantation font l'objet de discussions.

Randomized trial of conventional versus radiofrequency needle transseptal puncture for cryoballoon ablation: the CRYO-LATS trial.

BACKGROUND: Transseptal puncture to achieve left atrial access is necessary for many cardiac procedures, including atrial fibrillation ablation. More recently, there has been an increasing need for left atrial access using large caliber sheaths, which increases risk of perforation associated with the initial advancement into the left atrium. We compared the effectiveness of a radiofrequency needle-based transseptal system versus conventional needle for transseptal access. METHODS: This prospective controlled trial randomized 161 patients with symptomatic paroxysmal atrial fibrillation undergoing cryoballoon pulmonary vein isolation to transseptal access with a commercially available transseptal system (radiofrequency needle plus stiff pigtail wire; RF + Pigtail group) versus conventional transseptal access (standard group). The primary outcome was time required for left atrial access. Secondary outcomes included failure of the assigned transseptal system, radiation exposure, and complications. RESULTS: The median transseptal puncture time was significantly shorter using the radiofrequency needle plus stiff pigtail wire transseptal system compared with conventional transseptal (840 ± 323 vs. 956 ± 407 s, P = 0.0489). Compared to conventional transseptal puncture, fewer transseptal attempts were required (1.0 ± 0.5 RF applications vs. 1.3 ± 0.8 mechanical punctures, P = 0.0123) and the fluoroscopy time was significantly shorter (72.0 [IQR 48.0, 129.0] vs. 93.0 [IQR 60.0, 171.0] s, P = 0.0490) with the radiofrequency needle plus stiff pigtail wire transseptal system. Failure to achieve transseptal LA access with the assigned system was rarely observed (1.3% vs. 5.7%, P = 0.2192). There were no procedural complications observed with either system. CONCLUSIONS: The use of a radiofrequency needle plus stiff pigtail wire resulted in shorter time to left atrial access and reduced fluoroscopy time compared to left atrial access using conventional transseptal equipment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03199703.

Percutaneous left atrial appendage closure in patients with primary hemostasis disorders and atrial fibrillation.

BACKGROUND OR PURPOSE: We report our single-center experience with percutaneous left atrial appendage closure (LAAC) in patients with non-valvular atrial fibrillation (NVAF) and primary hemostasis disorders (HD). METHODS: Consecutive patients with primary HD who underwent a percutaneous LAAC were included. Baseline characteristics, procedural data, and clinical outcomes were prospectively collected and compared with the overall LAAC cohort without HD. RESULTS: Since 2013, among 229 LAAC, 17 patients (7%) had a primary HD: thrombocytopenia (n = 5), myelodysplastic syndrome (n = 6), von Willebrand syndrome (n = 4), type A hemophilia (n = 1), and dysfibrinogenemia (n = 1). The HD population's age ranged from 61 to 87 years, and the median CHA2DS2VASc was 5. Periprocedural plasmatic management was required in 47% of patients. The immediate LAAC implantation success rate was 100%. Patients received a direct oral anticoagulant (DOA) (n = 9), dual antiplatelet (n = 6), aspirin (n = 1), or no therapy (n = 1) during the first six postoperative weeks, followed with single antiplatelet (n = 16) or no therapy (n = 1) during lifelong. After 20 months, the technical success rate and procedural success rate were 100% and 94%. Zero device-/procedure-related complication and only one life-threatening bleeding occurred. Compared to patients without HD (n = 212), a baseline history of bleeding was less frequent (53% vs 91%, p < 0.001), and more patients received a perioperative blood transfusion (47% vs 4%, p < 0.001) in the HD group. The efficacy and safety outcomes did not differ between HD and non-HD cohorts. CONCLUSIONS: Percutaneous LAAC in primary HD carriers appeared as safe and as effective as in overall LAAC population for stroke and bleeding prevention at midterm follow-up. Percutaneous left atrial appendage closure in patients with atrial fibrillation and primary hemostasis disorders. The percutaneous LAAC in primary hemostasis disorders and AF carriers requires a multidisciplinary approach. Cardiologist, anesthesiologist, and hematologist discussion is a cornerstone to assess anticoagulant contraindication, LAAC feasibility, periprocedural management, and follow-up (high). This multidisciplinary care is illustrated by the case of a 61-year-old male with hemophilia type A and recurrent hemarthrosis. Pre-LAAC assessment confirmed procedural indication and cactus LAA anatomy (left). After plasmatic management with factor VIII infusion, a WATCHMAN™ no. 21 was successfully implanted (middle). During follow-up, without antithrombotic regime, no ischemic or hemorrhagic complication occurred (right). LAA, left atrial appendage; LAAC, left atrial appendage closure; TEE, transesophageal echocardiography. Percutaneous LAAC in primary HD carriers appeared as safe and as effective as in overall LAAC population for stroke and bleeding prevention at midterm follow-up.

Association of Atrial Fibrillation Burden With Health-Related Quality of Life After Atrial Fibrillation Ablation: Substudy of the Cryoballoon vs Contact-Force Atrial Fibrillation Ablation (CIRCA-DOSE) Randomized Clinical Trial.

Importance: Patients with atrial fibrillation (AF) have impaired health-related quality of life primarily owing to symptoms related to AF episodes; however, quality of life can be influenced by AF therapies, AF complications, the frequency of follow-up visits and hospitalizations, illness perceptions, and patient factors, such as anxiety or depression. Objective: To determine the association between change in AF burden and quality of life in the year following ablation. Design, Setting, and Participants: The current study is a secondary analysis of a prospective, parallel-group, multicenter, single-masked randomized clinical trial (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation: Double Short vs Standard Exposure Duration [CIRCA-DOSE] study), which took place at 8 Canadian centers. Between September 2014 and July 2017, 346 patients older than 18 years with symptomatic, primarily low-burden AF refractory to antiarrhythmic therapy referred for first catheter ablation were enrolled. All patients received an implantable cardiac monitor at least 30 days before ablation and were followed up with up to December 2018. Data were analyzed from April 2020 to June 2021. Interventions: Patients were randomized 1:1:1 to contact force-guided radiofrequency ablation, 4-minute cryoballoon ablation, or 2-minute cryoballoon ablation. The exposure in the present analysis is the absolute difference in AF burden prior to ablation and 12 months following ablation, as evaluated by the Atrial Fibrillation Effect on Quality of Life (AFEQT) Score. Main Outcomes and Measures: Absolute difference in quality of life from baseline to 12 months postablation. Results: Of 346 included patients, 231 (66.7%) were male, and the median (interquartile range) age was 60 (52-66) years. A total of 328 patients (94.8%) had paroxysmal AF. The median (interquartile range) preablation AF burden was 2.0% (0.1-11.9), and the AF burden decreased to 0% at 12 months postablation. At 12 months, a 1-point improvement in AFEQT score was observed for every absolute reduction in daily AF burden of 15.8 minutes (95% CI, 7.2-24.4; P < .001), or every 0.63% (95% CI, 0.30-0.95; P < .001) reduction in relative AF burden from baseline. Conclusions and Relevance: In patients with primarily low-burden paroxysmal AF, the reduction in AF burden following ablation may be associated with a clinically meaningful improvement in quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT01913522.

Prevalence and outcome of early recurrence of atrial tachyarrhythmias in the Cryoballoon vs Irrigated Radiofrequency Catheter Ablation (CIRCA-DOSE) study.

BACKGROUND: Early recurrence of atrial tachyarrhythmia (ERAT) is common after pulmonary vein isolation (PVI) and has been associated with an increased risk of late atrial fibrillation (AF) recurrence. OBJECTIVE: The purpose of this study was to determine the incidence and outcomes of patients experiencing ERAT after PVI using advanced-generation ablation technologies. METHODS: This is a prespecified substudy of the CIRCA-DOSE (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation: Double-Short vs Standard Exposure Duration) trial, a prospective, randomized, multicenter study comparing PVI with contact force-guided radiofrequency ablation to secondary-generation cryoballoon ablation for paroxysmal AF. All study patients received an implantable cardiac monitor to allow continuous rhythm monitoring. ERAT was defined as any recurrent atrial tachyarrhythmia within the first 90 days after AF ablation. RESULTS: ERAT occurred in 61% of the 346 patients at a median of 12 days (range 1-90 days) after ablation. ERAF was a significant predictor of late recurrence (60.1% with ER vs 25.9% without ER; P <.001) and symptomatic atrial tachyarrhythmia (31.6% with ERAF vs 6.7% without ERAF; P <.001). Receiver operating curve analyses revealed a strong correlation between ERAT timing and burden and late recurrence. Multivariate analysis identified ER timing (hazard ratio [HR] 2.90; 95% confidence interval [CI] 1.41-5.95; P = .004) and burden (HR 1.05 per 1% ER burden; 95% CI 1.04-1.07; P <.001) as strong independent predictors of late recurrence. Incidence rate, timing, burden, and prognostic significance of ER did not differ between the study groups. CONCLUSION: ERAT remains common after PVI despite use of advanced-generation ablation technologies. Early AF recurrence beyond 3 weeks after ablation is associated with increased risk of late recurrence.

Safety and effects of volume loading during transesophageal echocardiography in the pre-procedural work-up for left atrial appendage closure.

BACKGROUND: In patients undergoing left atrial appendage (LAA) closure, an accurate sizing of the LAA is key to optimize device sizing, procedural success and reduce complications. Previous studies have shown that intraprocedural volume loading increases LAA dimensions and improves device sizing. However, the safety and effects on LAA and device sizing of administering a fluid bolus during pre-procedural transesophageal echocardiography (TEE) are unknown. The aim of this study was to determine the safety and impact on LAA dimensions and device sizing of an intravenous (IV) fluid bolus administered during TEE in the setting of the pre-procedural work-up for LAA closure. METHODS: The study included a total of 72 patients who underwent TEE to assess suitability for LAAC and received a 500 ml IV bolus of normal saline. The LAA landing zone (LZ) and depth were measured by TEE before and after volume loading, and these measurements were used to predict the device size implanted during a subsequent percutaneous LAAC procedure. RESULTS: There were no complications associated with volume loading. The baseline mean LZ was 19.6 ± 3.6 mm at 90o, and 20.2 ± 4.1 mm at 135o. Following fluid bolus, the maximum diameter increased 1.5 ± 1.0 mm at 90o (p<0.001), and 1.3 ± 1.0 mm at 135o (p<0.001). The baseline mean depth of the LAA was 26.5 ± 5.5 mm at 90o, and 23.9 ± 5.8 mm at 135o. After fluid bolus, the mean depth increased by 1.5 ± 1.8 mm (p<0.001) and 1.6 ± 2.0 (p<0.001), at 90o and 135o, respectively. Sizing based on post-bolus measurements of the LZ significantly improved the agreement with the final device size selection during the procedure in 71.0% of cases (vs. 42.0% with pre-bolus measurements). CONCLUSIONS: Volume loading during ambulatory TEE as part of the pre-procedural work-up of LAAC is safe and significantly increases LAA dimensions. This strategy may become the new standard, particularly in centers performing LAAC with no TEE guidance, as it improves LAA sizing and more accurately predicts the final device size.

Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation.

BACKGROUND: Guidelines recommend a trial of one or more antiarrhythmic drugs before catheter ablation is considered in patients with atrial fibrillation. However, first-line ablation may be more effective in maintaining sinus rhythm. METHODS: We randomly assigned 303 patients with symptomatic, paroxysmal, untreated atrial fibrillation to undergo catheter ablation with a cryothermy balloon or to receive antiarrhythmic drug therapy for initial rhythm control. All the patients received an implantable cardiac monitoring device to detect atrial tachyarrhythmia. The follow-up period was 12 months. The primary end point was the first documented recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) between 91 and 365 days after catheter ablation or the initiation of an antiarrhythmic drug. The secondary end points included freedom from symptomatic arrhythmia, the atrial fibrillation burden, and quality of life. RESULTS: At 1 year, a recurrence of atrial tachyarrhythmia had occurred in 66 of 154 patients (42.9%) assigned to undergo ablation and in 101 of 149 patients (67.8%) assigned to receive antiarrhythmic drugs (hazard ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66; P<0.001). Symptomatic atrial tachyarrhythmia had recurred in 11.0% of the patients who underwent ablation and in 26.2% of those who received antiarrhythmic drugs (hazard ratio, 0.39; 95% CI, 0.22 to 0.68). The median percentage of time in atrial fibrillation was 0% (interquartile range, 0 to 0.08) with ablation and 0.13% (interquartile range, 0 to 1.60) with antiarrhythmic drugs. Serious adverse events occurred in 5 patients (3.2%) who underwent ablation and in 6 patients (4.0%) who received antiarrhythmic drugs. CONCLUSIONS: Among patients receiving initial treatment for symptomatic, paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy, as assessed by continuous cardiac rhythm monitoring. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).

Quality of Life and Health Care Utilization in the CIRCA-DOSE Study.

OBJECTIVES: This study evaluated the impact of contact force-guided radiofrequency ablation versus cryoballoon ablation on quality of life and health care utilization. BACKGROUND: Traditional outcome parameters, such as arrhythmia-free survival, are insufficient to evaluate the clinical impact of atrial fibrillation (AF), as it fails to the capture patient- and health system-level differences in treatment approaches. METHODS: The CIRCA-DOSE (Cryoballoon Vs. Contact-Force Atrial Fibrillation Ablation) study randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency or cryoballoon ablation. Health-related quality-of-life (HRQOL) was assessed at baseline, and at 6 and 12 months post-ablation using a disease-specific and generic HRQOL instruments. Health care utilization (hospitalization, emergency department visits, and cardioversion) and antiarrhythmic drug use for the 12 months preceding ablation was compared with the 12 months following ablation. RESULTS: Disease-specific and generic HRQOL was moderately to severely impaired at baseline and improved significantly at 6 and 12 months of follow-up (median improvement in AFEQT [Atrial Fibrillation Effect on QualiTy of Life] score 32.4 [interquartile range: 17.7 to 48.9]). When compared with the 12 months pre-ablation, the proportion and absolute number of cardioversions decreased significantly (41.1% vs. 10.1% of patients, 137 vs. 35 events; p < 0.0001). Similar significant reductions in emergency department visits (66.7% vs. 25.1% of patients, 224 vs. 87 events; p < 0.0001), and hospitalizations (25.5% vs. 14.5% of patients, 86 vs. 50 events; p < 0.001) were observed. There were no significant differences between randomized groups. CONCLUSIONS: In this multicenter randomized trial, catheter ablation with advanced-generation technologies resulted in a significant improvement in HRQOL and a significant reduction in health care utilization in the year following AF ablation. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation [CIRCA-DOSE]; NCT01913522).

Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: Results from the multicenter STOP Persistent AF trial.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation to treat patients with symptomatic drug-refractory atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to assess the safety and efficacy of PVI using the cryoballoon catheter to treat patients with persistent AF. METHODS: STOP Persistent AF (ClinicalTrials.gov Identifier: NCT03012841) was a prospective, multicenter, single-arm, Food and Drug Administration-regulated trial designed to evaluate the safety and efficacy of PVI-only cryoballoon ablation for drug-refractory persistent AF (continuous episodes <6 months). The primary efficacy endpoint was 12-month freedom from ≥30 seconds of AF, atrial flutter (AFL), or atrial tachycardia (AT) after a 90-day blanking period. The prespecified performance goals were set at >40% and <13% for the primary efficacy and safety endpoints, respectively. Secondary endpoints assessed quality of life using the AFEQT (Atrial Fibrillation Effect on Quality of Life) and SF (Short Form)-12 questionnaires. RESULTS: Of 186 total enrollments, 165 subjects (70% male; age 65 ± 9 years; left atrial diameter 4.2 ± 0.6 cm; body mass index 31 ± 6) were treated at 25 sites in the United States, Canada, and Japan. Total procedural, left atrial dwell, and fluoroscopy times were 121 ± 46 minutes, 102 ± 41 minutes, and 19 ± 16 minutes, respectively. At 12 months, the primary efficacy endpoint was 54.8% (95% confidence [CI] 46.7%-62.1%) freedom from AF, AFL, or AT. There was 1 primary safety event, translating to a rate of 0.6% (95% CI 0.1%-4.4%). AFEQT and SF-12 assessments demonstrated significant improvements from baseline to 12 months postablation (P <.001). CONCLUSION: The STOP Persistent AF trial demonstrated cryoballoon ablation to be safe and effective in treating patients with drug-refractory persistent AF characterized by continuous AF episodes <6 months.

Safety of Transesophageal Echocardiography to Guide Structural Cardiac Interventions.

BACKGROUND: Despite the widespread use of transesophageal echocardiography (TEE) to guide structural cardiac interventions, studies evaluating safety in this context are lacking. OBJECTIVES: This study sought to determine the incidence, types of complications, and factors associated with esophageal or gastric lesions following TEE manipulation during structural cardiac interventions. METHODS: This was a prospective study including 50 patients undergoing structural cardiac interventions in which TEE played a central role in guiding the procedure (mitral and tricuspid valve repair, left atrial appendage closure, and paravalvular leak closure). An esophagogastroduodenoscopy (EGD) was performed before and immediately after the procedure to look for new injuries that might have arisen during the course of the intervention. Patients were divided in 2 cohorts according to the type of injury: complex lesions (intramural hematoma, mucosal laceration) and minor lesions (petechiae, ecchymosis). The factors associated with an increased risk of complications were assessed. RESULTS: Post-procedural EGD showed a new injury in 86% (n = 43 of 50) of patients, with complex lesions accounting for 40% (n = 20 of 50) of cases. Patients with complex lesions presented more frequently with an abnormal baseline EGD (70% vs. 37%; p = 0.04) and had a higher incidence of post-procedural dysphagia or odynophagia (40% vs. 10%; p = 0.02). Independent factors associated with an increased risk of complex lesions were a longer procedural time under TEE manipulation (for each 10-min increment in imaging time, odds ratio: 1.27; 95% confidence interval: 1.01 to 1.59) and poor or suboptimal image quality (odds ratio: 4.93; 95% confidence interval: 1.10 to 22.02). CONCLUSIONS: Most patients undergoing structural cardiac interventions showed some form of injury associated with TEE, with longer procedural time and poor or suboptimal image quality determining an increased risk. Imaging experts performing this technique should be aware of the nature of potential complications, to take the necessary precautions to prevent their occurrence and facilitate early diagnosis and treatment.

Prevalence and clinical impact of spontaneous and adenosine-induced pulmonary vein reconduction in the Contact-Force vs. Cryoballoon Atrial Fibrillation Ablation (CIRCA-DOSE) study.

BACKGROUND: Use of intraprocedural observation and pharmacologic challenges have been proposed as means to differentiate permanent pulmonary vein (PV)-left atrial conduction block from inadequate ablation lesions. OBJECTIVE: The purpose of this study was to determine the prevalence and clinical impact of spontaneous and adenosine-provoked reconnection using contemporary atrial fibrillation (AF) ablation technologies. METHODS: The CIRCA-DOSE (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration) study enrolled 346 patients with paroxysmal AF and randomized them to contact force-guided radiofrequency ablation (CF-RF) or cryoballoon ablation. Patients underwent provocative testing with adenosine after a 20-minute observation period. All patients received an implantable cardiac monitor for arrhythmia monitoring. RESULTS: Spontaneous reconnection was observed in 5.4% of PVs (71/1318) during the 20-minute postprocedure observation period, and dormant conduction was elicited in 5.7% of PVs (75/1318). Both spontaneous reconnection and dormant conduction were more common after CF-RF compared to cryoballoon ablation (P = .03 and P <.0001, respectively). Acute PV reconnection (spontaneous or adenosine-provoked) was associated with a significantly higher incidence of recurrent atrial tachyarrhythmia in the cryoballoon group (hazard ratio [HR] 2.39; 95% confidence interval [CI] 1.44-3.96; P = .0007) but not in the CF-RF group (HR 1.47; 95% CI 0.84-2.58; P = .16). In the absence of acute reconnection, the freedom from recurrent arrhythmia did not differ between groups (HR 0.95; 95% CI 0.6057-1.495; P = .83). CONCLUSION: Patients without spontaneous or adenosine-provoked reconnection had better outcomes compared to those with acute PV reconnection, suggesting that efforts should be directed toward ensuring an ideal ablation lesion at the first attempt in order to achieve durable PV isolation.

Transesophageal echocardiography complications associated with interventional cardiology procedures.

BACKGROUND: Although there have been several reports documenting complications related with transesophageal echocardiography (TEE) manipulation following cardiac surgery, there is a paucity of data regarding the safety of TEE used to guide catheter-based interventions. The aim of this study was to determine the prevalence, types and risk factors of complications associated with procedures requiring active TEE guidance. METHODS: This study included 1249 consecutive patients undergoing either transcatheter aortic valve implantation (TAVI), Mitraclip, left atrial appendage occlusion (LAAO) or paravalvular leak closure (PVLC). Patients were divided into 2 cohorts based on the degree of probe manipulation required to guide the procedure and the risk of developing a TEE-related complication: low-risk (TAVI, n = 1037) and high-risk (Mitraclip, LAAO and PVLC, n = 212). Patients were further analyzed according to the occurrence of major and minor TEE-related complications. RESULTS: The overall incidence of TEE-related complications was 0.9% in the TAVI group and 6.1% in the rest of the cohort (P < .001). Patients in the high-risk cohort had also a higher incidence of major-complications (2.8% vs 0.6%, P = .008), and factors associated with an increased risk were being underweight, having a prior history of gastrointestinal bleeding and the use of chronic steroids/immunosuppressive medications. Procedural time under TEE-manipulation was longer in patients exhibiting complications and was an independent predictor of major complications (OR = 1.13, 95% CI 1.01-1.25, for each 10 minutes increments in imaging time). Patients with major complications undergoing Mitraclip had the longest median time under TEE-manipulation (297 minutes) and a risk of developing a major-complication that was 10.64 times higher than the rest of the cohort (95% CI 3.30-34.29, P < .001). CONCLUSION: The prevalence of TEE-related complications associated with interventional procedures is higher than previously reported. Undergoing a prolonged procedure, particularly in the setting of Mitraclip, was the main factor linked to TEE-related complications.

Sustained quality-of-life improvement post-cryoballoon ablation in patients with paroxysmal atrial fibrillation: Results from the STOP-AF Post-Approval Study.

BACKGROUND: Pulmonary vein isolation by catheter ablation is a class IA indication for the treatment of symptomatic, drug-refractory, paroxysmal atrial fibrillation (PAF). Quality of life (QoL) has been identified as a clinically meaningful endpoint but has not been comprehensively evaluated to date. OBJECTIVE: The purpose of this study was to evaluate the effects of cryoballoon ablation on long-term QoL. METHODS: As part of the STOP-AF Post-Approval Study, QoL was assessed using the Short Form-12 Health Survey (SF-12) along with evaluation of arrhythmia-related symptoms through 36 months. A multivariate linear mixed effects regression was used to determine the association between atrial fibrillation symptoms and QoL scores, and univariate linear regressions were used to assess predictors of 36-month change in QoL scores. RESULTS: Three hundred thirty-five subjects fully completed SF-12 forms at baseline, with 319, 308, 291, and 278 subjects completing surveys at the subsequent follow-up visits. Both physical and mental composite scores increased significantly from baseline (P <.001), and all arrhythmia symptoms significantly decreased from baseline (P <.001), with 62.0% of subjects reporting no symptoms at 6 months compared to 5.7% at baseline (P <.001). Presence of dyspnea and fatigue at baseline were univariate predictors of physical QoL improvement (P = .045 and 0.0497, respectively), whereas each year of age and each year of PAF duration were predictors of a decrease in mental QoL (P = .014 and .04, respectively). CONCLUSION: Cryoballoon ablation for treatment of PAF results in a significant, and sustained, QoL improvement. The observed improvement in physical and mental health likely may be mediated by a reduction in symptom and arrhythmia burden.

Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring: A Randomized Clinical Trial.

BACKGROUND: Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence after atrial fibrillation (AF) ablation. METHODS: We randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency ablation (CF-RF; n=115), 4-minute cryoballoon ablation (Cryo-4; n=115), or 2-minute cryoballoon ablation (Cryo-2; n=116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 after ablation or a repeat ablation procedure at any time. Secondary end points included freedom from symptomatic arrhythmia and AF burden. All patients received an implantable loop recorder. RESULTS: One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring was 53.9%, 52.2%, and 51.7% with CF-RF, Cryo-4, and Cryo-2, respectively (P=0.87). One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring was 79.1%, 78.2%, and 73.3% with CF-RF, Cryo-4, and Cryo-2, respectively (P=0.26). Compared with the monitoring period before ablation, AF burden was reduced by a median of 99.3% (interquartile range, 67.8%-100.0%) with CF-RF, 99.9% (interquartile range, 65.3%-100.0%) with Cryo-4, and 98.4% (interquartile range, 56.2%-100.0%) with Cryo-2 (P=0.36). Serious adverse events occurred in 3 patients (2.6%) in the CF-RF group, 6 patients (5.3%) in the Cryo-4 group, and 7 patients (6.0%) in the Cryo-2 group, with no significant difference between groups (P=0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure (P<0.001 vs cryoballoon groups). CONCLUSIONS: In this multicenter, randomized, single-blinded trial, CF-RF and 2 different regimens of cryoballoon ablation resulted in no difference in 1-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913522.

A randomized clinical trial of early invasive intervention for atrial fibrillation (EARLY-AF) - methods and rationale.

BACKGROUND: The ideal management of patients with newly diagnosed symptomatic atrial fibrillation (AF) remains unknown. Current practice guidelines recommend a trial of antiarrhythmic drugs (AAD) prior to considering an invasive ablation procedure. However, earlier ablation offers an opportunity to halt the progressive patho-anatomical changes associated with AF, as well as impart other important clinical benefits. OBJECTIVE: The aim of this study is to determine the optimal initial management strategy for patients with newly diagnosed, symptomatic atrial fibrillation. METHODS/DESIGN: The EARLY-AF study (ClinicalTrials.govNCT02825979) is a prospective, open label, multicenter, randomized trial with a blinded assessment of outcomes. A total of 298 patients will be randomized in a 1:1 fashion to first-line AAD therapy, or first-line cryoballoon-based pulmonary vein isolation. Patients with symptomatic treatment naïve AF will be included. Arrhythmia outcomes will be assessed by implantable cardiac monitor (ICM). The primary outcome is time to first recurrence of AF, atrial flutter, or atrial tachycardia (AF/AFL/AT) between days 91 and 365 following AAD initiation or AF ablation. Secondary outcomes include arrhythmia burden, quality of life, and healthcare utilization. DISCUSSION: The EARLY-AF study is a randomized trial designed to evaluate the optimal first management approach for patients with AF. We hypothesize that catheter ablation will be superior to drug therapy in prevention of AF recurrence.

Hemodynamic impact of percutaneous left atrial appendage closure in patients with paroxysmal atrial fibrillation.

PURPOSE: Percutaneous left atrial appendage (LAA) closure has become a valid alternative to anticoagulation therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). However, scarce data exist on the impact of LAA closure on left atrial and ventricular function. We sought to assess the acute hemodynamic changes associated with percutaneous LAA closure in patients with paroxysmal AF. METHODS: The study population consisted of 31 patients (mean age 73 ± 10 years; 49% women) with paroxysmal AF who underwent successful percutaneous LAA closure. All patients were in sinus rhythm and underwent 2D transthoracic echocardiography at baseline and the day after the procedure. A subset of 14 patients underwent preprocedural cardiac computed tomography (CT) with 3D LA and LAA reconstruction. RESULTS: Left ventricular systolic function parameters and LA volumetric indexes remained unchanged after the procedure. No significant changes in left ventricular stroke volume (72.4 ± 16.0 vs. 73.3 ± 15.7 mL, p = 0.55) or LA stroke volume (total 15.6 ± 4.2 vs. 14.6 ± 4.2 mL, p = 0.21; passive 9.0 ± 2.8 vs. 8.3 ± 2.6 mL, p = 0.31; active 10.3 ± 5.6 vs. 10.0 ± 6.4 mL, p = 0.72) occurred following LAA closure. Mean ratio of LAA to LA volume by 3D CT was 10.2 ± 2.3%. No correlation was found between LAA/LA ratio and changes in LA stroke volume (r = 0.35, p = 0.22) or left ventricular stroke volume (r = 0.28, p = 0.33). CONCLUSIONS: The LAA accounts for about 10% of the total LA volume, but percutaneous LAA closure did not translate into any significant changes in LA and left ventricular function.