Impact of first-line cryoablation for atrial fibrillation on healthcare utilization, arrhythmia disease burden and efficacy outcomes: real-world evidence from the Cryo Global Registry.

BACKGROUND: Cryoballoon ablation (CBA) is an effective first-line treatment for symptomatic atrial fibrillation (AF), as recently demonstrated by three randomized trials. This sub-analysis of the Cryo Global Registry aims to examine current clinical practices of first-line CBA. METHODS: AF patients treated with first-line CBA were compared to CBA in antiarrhythmic drug (AAD)-refractory patients at 12 months. Efficacy was examined using time-to-first atrial arrhythmia recurrence following a 90-day blanking period. Healthcare utilization was evaluated by repeat ablations and hospitalizations. Disease burden was examined by assessing quality of life (QOL) and patients' reporting of symptoms. RESULTS: Of 1394 patients, 433 (31.1%) were treated with first-line CBA, which was more frequent in high-volume centers. Serious procedure-related adverse event rates were similar. Efficacy at 12 months was higher in the first-line group (87.8 vs. 81.6%, HRunadj 0.64 (95% CI 0.47-0.88); p < 0.01) regardless of the centers' CBA experience; when controlling for baseline characteristics, the difference was not significant (HRadj 0.87 (95% CI 0.56-1.37); p = 0.55). No difference was observed in repeat ablations and hospitalizations between cohorts. First-line patients experienced a larger mean reduction in symptoms and were prescribed AADs at a lower rate at 12-month follow-up (9.7 vs. 29.9%). QOL improved in both cohorts from baseline to 12 months with no significant difference between groups (p = 0.29). CONCLUSIONS: In this global real-world experience, first-line CBA in patients with symptomatic AF is effective, with a larger symptom reduction compared with CBA after AAD failure and without a difference in healthcare utilization at mid-term follow-up. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.

Cryoballoon ablation for paroxysmal atrial fibrillation in Japan: 2-year safety and efficacy results from the Cryo AF Global Registry.

PURPOSE: Catheter ablation is a recommended rhythm control therapy after failed or intolerant antiarrhythmic drug (AAD) treatment for patients with atrial fibrillation (AF). This study evaluates clinical performance and safety of pulmonary vein isolation (PVI) using the cryoballoon (Arctic Front Advance) in Japan. METHODS: Cryo AF Global Registry is a prospective, multi-center registry. Patients with paroxysmal AF (PAF) were treated at 10 Japanese hospitals. Efficacy was evaluated by freedom from a ≥ 30-s recurrence of AF/atrial flutter (AFL)/atrial tachycardia (AT), AF-related symptoms, and quality of life using the EQ-5D-3L questionnaire. The safety endpoint was serious device- and procedure-related adverse events. RESULTS: The study included 352 patients with PAF (65 ± 10 years of age, 36% female, 36% without prior failure of AAD). Mean duration since first diagnosis of AF was 3.0 ± 5.5 years. Serious device- and procedure-related adverse event rate was 2.6% (95% CI: 1.2-4.8%). Freedom from AF/AFL/AT was 88.5% (95% CI: 84.7-91.4%) at 12 months and 86.7% (95% CI: 81.1-90.8%) at 24 months. The number of patients with ≥ 1 AF symptom was significantly decreased from 88% at enrollment to 22% (p < 0.01) at 12-month follow-up. General quality of life using EQ-5D did not improve significantly after 12 months in the summary score. However, in the visual analog scale score, there was improvement (5.8 ± 18.4; p < 0.01). CONCLUSIONS: This study demonstrates that cryoablation used for PVI is a safe and effective treatment in real-world use for patients with PAF in Japan.

Cryoballoon Ablation for the Treatment of Atrial Fibrillation in Patients With Concomitant Heart Failure and Either Reduced or Preserved Left Ventricular Ejection Fraction: Results From the Cryo AF Global Registry.

Background Heart failure (HF) and atrial fibrillation (AF) often coexist; yet, outcomes of ablation in patients with AF and concomitant HF are limited. This analysis assessed outcomes of cryoablation in patients with AF and HF. Methods and Results The Cryo AF Global Registry is a prospective, multicenter registry of patients with AF who were treated with cryoballoon ablation according to routine practice at 56 sites in 26 countries. Patients with baseline New York Heart Association class I to III (HF cohort) were compared with patients without HF. Freedom from atrial arrhythmia recurrence ≥30 seconds, safety, and health care utilization over 12-month follow-up were analyzed. A total of 1303 patients (318 HF) were included. Patients with HF commonly had preserved left ventricular ejection fraction (81.6%), were more often women (45.6% versus 33.6%) with persistent AF (25.8% versus 14.3%), and had a larger left atrial diameter (4.4±0.9 versus 4.0±0.7 cm). Serious procedure-related complications occurred in 4.1% of patients with HF and 2.6% of patients without HF (P=0.188). Freedom from atrial arrhythmia recurrence was not different between cohorts with either paroxysmal AF (84.2% [95% CI, 78.6-88.4] versus 86.8% [95% CI, 84.2-89.0]) or persistent AF (69.6% [95% CI, 58.1-78.5] versus 71.8% [95% CI, 63.2-78.7]) (P=0.319). After ablation, a reduction in AF-related symptoms and antiarrhythmic drug use was observed in both cohorts (HF and no-HF), and freedom from repeat ablation was not different between cohorts. Persistent AF and HF predicted a post-ablation cardiovascular rehospitalization (P=0.032 and P=0.001, respectively). Conclusions Cryoablation to treat patients with AF is similarly effective at 12 months in patients with and without HF. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02752737.

Safety of cryoballoon ablation for the treatment of atrial fibrillation: First European results from the cryo AF Global Registry.

BACKGROUND: Cryoballoon ablation for the treatment of patients with atrial fibrillation (AF) has been utilized in Europe for >15 years. OBJECTIVES: Report patient and procedural characteristics that influence the safety of cryoablation for the treatment of AF. METHODS: Patients enrolled in the prospective, multicenter Cryo AF Global Registry were treated at 38 European centers. Freedom from a ≥30s episode of AF/atrial flutter (AFL)/atrial tachycardia (AT) at 12-months and serious complications were analyzed. Univariate and multivariable models identified baseline patient and procedural characteristics that predicted a procedure-related complication. RESULTS: Of the 1418 subjects who completed an index procedure, the cohort was 62 ± 11 years of age, 37.7% female, and 72.2% paroxysmal AF (PAF). The mean procedure, left atrial dwell, and fluoroscopy times were 81 ± 34, 54 ± 25, and 14 ± 13 min, respectively. Among the 766 patients with 12-month follow-up, freedom from a ≥30 s AF/AFL/AT recurrence was 83.3% (95% CI: 79.8%-86.3%) and 71.6% (95% CI: 64.6%-77.4%) in patients with PAF and persistent AF. The serious procedure- and device-related adverse event rates were 4.7% and 2.0%. No baseline patient characteristic independently predicted a procedure-related adverse event; however, prolonged procedure duration (OR = 1.01 [95% CI: 1.00-1.01]), use of general anesthesia (OR = 1.71 [95% CI: 1.01-2.92]), and delivery of a cavotricuspid isthmus line (OR = 3.04 [95% CI: 1.01-9.20]) were each independently associated with the occurrence of a serious procedural safety event (all p < .05). CONCLUSIONS: Cryoballoon ablation is safe and effective in real-world use across a broad cohort of patients with AF.

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.

Repeat Ablation for Atrial Fibrillation Recurrence Post Cryoballoon or Radiofrequency Ablation in the FIRE AND ICE Trial

Background: The FIRE AND ICE trial assessed efficacy and safety of pulmonary vein (PV) isolation using cryoballoon versus radiofrequency current (RFC) ablation in patients with drug refractory, symptomatic, paroxysmal atrial fibrillation (AF). The purpose of the current study was to assess index lesion durability as well as reablation strategy and outcomes in trial patients undergoing a reablation procedure. Methods: Patients with reablation procedures during FIRE AND ICEwere retrospectively consented and enrolled at 13 trial centers. The first reablation for each patient was included in the analysis. Documented arrhythmias before reablation, number and location of reconnected PVs, lesions created during reablations, procedural characteristics, and acute as well as long-term outcomes were assessed. Results: Eighty-nine (36 cryoballoon and 53 RFC) patients were included in this study. Paroxysmal atrial fibrillation was the predominant recurrent arrhythmia (69%) before reablation. Reablations occurred at a median of 173 and 182 days (P=0.54) in the cryoballoon and RFC cohorts, respectively. The number of reconnected PVs was significantly higher in the RFC than the cryoballoon group (2.1±1.4 versus 1.4±1.1; P=0.010), which was driven by significantly more reconnected left superior PVs and markedly more reconnected right superior PVs. The number of (predominantly RFC) lesions applied during reablation was significantly greater in patients originally treated with RFC (3.3±1.3 versus 2.5±1.5; P=0.015) with no difference in overall acute success (P=0.70). After reablation, no differences in procedure-related rehospitalization or antiarrhythmic drug utilization were observed between cohorts. Conclusions: At reablation, patients originally treated with the cryoballoon had significantly fewer reconnected PVs, which may reflect RFC catheter instability in certain left atrial regions, and thus required fewer lesions for reablation success. Repeat ablations were predominantly performed with RFC and resulted in similar acute success, duration of hospitalization, and antiarrhythmic drug prescription between the study cohorts.

Impact of Female Sex on Clinical Outcomes in the FIRE AND ICE Trial of Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Data on predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation (AF) are limited. We sought to assess the association of baseline covariates with clinical outcomes in the 750 patients with drug-refractory paroxysmal AF enrolled in FIRE AND ICE. METHODS: In a 2-part analysis, univariate and multivariable Cox regression models were first used to identify baseline patient characteristics predictive of catheter ablation efficacy determined by the clinical end points of (1) atrial arrhythmia recurrence (primary efficacy failure), (2) cardiovascular rehospitalization, and (3) repeat ablation. Propensity score stratification methods were then used to account for differences in baseline characteristics between sexes. RESULTS: Female sex (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.08-1.73; P=0.010) and prior direct current cardioversion (HR, 1.40; 95% CI, 1.07-1.82; P=0.013) were independently associated with atrial arrhythmia recurrence. Female sex (HR, 1.36; 95% CI, 1.02-1.80; P=0.035) and hypertension (HR, 1.48; 95% CI, 1.09-2.00; P=0.013) independently predicted cardiovascular rehospitalization. A longer history of AF (HR, 1.03; 95% CI, 1.00-1.06; P=0.039) increased the rate of repeat ablation. Women continued to have higher rates of primary efficacy failure and cardiovascular rehospitalization after propensity score adjustment, with adjusted HRs of 1.51 (95% CI, 1.16-2.18; P<0.05) and 1.40 (95% CI, 1.15-2.17; P<0.05), respectively. CONCLUSIONS: After catheter ablation of paroxysmal AF, female sex was associated with an almost 40% increase in the risks of primary efficacy failure and cardiovascular rehospitalization. Primary efficacy failure was also adversely impacted by a history of direct current cardioversion, whereas hypertension had a negative impact on cardiovascular rehospitalization. History of AF was the only predictor of repeat ablation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01490814.

Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial.

AIMS: The primary safety and efficacy endpoints of the randomized FIRE AND ICE trial have recently demonstrated non-inferiority of cryoballoon vs. radiofrequency current (RFC) catheter ablation in patients with drug-refractory symptomatic paroxysmal atrial fibrillation (AF). The aim of the current study was to assess outcome parameters that are important for the daily clinical management of patients using key secondary analyses. Specifically, reinterventions, rehospitalizations, and quality-of-life were examined in this randomized trial of cryoballoon vs. RFC catheter ablation. METHODS AND RESULTS: Patients (374 subjects in the cryoballoon group and 376 subjects in the RFC group) were evaluated in the modified intention-to-treat cohort. After the index ablation, log-rank testing over 1000 days of follow-up demonstrated that there were statistically significant differences in favour of cryoballoon ablation with respect to repeat ablations (11.8% cryoballoon vs. 17.6% RFC; P = 0.03), direct-current cardioversions (3.2% cryoballoon vs. 6.4% RFC; P = 0.04), all-cause rehospitalizations (32.6% cryoballoon vs. 41.5% RFC; P = 0.01), and cardiovascular rehospitalizations (23.8% cryoballoon vs. 35.9% RFC; P < 0.01). There were no statistical differences between groups in the quality-of-life surveys (both mental and physical) as measured by the Short Form-12 health survey and the EuroQol five-dimension questionnaire. There was an improvement in both mental and physical quality-of-life in all patients that began at 6 months after the index ablation and was maintained throughout the 30 months of follow-up. CONCLUSION: Patients treated with cryoballoon as opposed to RFC ablation had significantly fewer repeat ablations, direct-current cardioversions, all-cause rehospitalizations, and cardiovascular rehospitalizations during follow-up. Both patient groups improved in quality-of-life scores after AF ablation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01490814.