Clinical Genetic Testing for Atrial Fibrillation: Are We There Yet?

Important progress has been made toward unravelling the complex genetics underlying atrial fibrillation (AF). Initial studies were aimed to identify monogenic causes; however, it has become increasingly clear that the most common predisposing genetic substrate for AF is polygenic. Despite intensive investigations, there is robust evidence for rare variants for only a limited number of genes and cases. Although the current yield for genetic testing in early onset AF might be modest, there is an increasing appreciation that genetic culprits for potentially life-threatening ventricular cardiomyopathies and channelopathies might initially present with AF. The potential clinical significance of this recognition is highlighted by evidence that suggests that identification of a pathogenic or likely pathogenic rare variant in a patient with early onset AF is associated with an increased risk of death. These findings suggest that it might be warranted to screen patients with early onset AF for these potentially more sinister cardiac conditions. Beyond facilitating the early identification of genetic culprits associated with potentially malignant phenotypes, insight into underlying AF genetic substrates might improve the selection of patients for existing therapies and guide the development of novel ones. Herein, we review the evidence that links genetic factors to AF, then discuss an approach to using genetic testing for early onset AF patients in the present context, and finally consider the potential value of genetic testing in the foreseeable future. Although further work might be necessary before recommending uniform integration of genetic testing in cases of early onset AF, ongoing research increasingly highlights its potential contributions to clinical care.

Ablation or drug therapy for initial atrial fibrillation.

Atrial fibrillation (AF) is a chronic heart rhythm disorder, characterized by exacerbations interspersed with clinical remissions. Antiarrhythmic drugs (AADs) are traditionally considered to be the preferred initial therapy for the maintenance of sinus rhythm however, these medications have modest efficacy and significant adverse effects. Recent clinical trials have evaluated the role of catheter ablation as the initial therapeutic intervention, demonstrating that cryoballoon ablation significantly reduces atrial tachyarrhythmia recurrence and arrhythmia burden, produces clinically meaningful improvements in symptoms and quality of life, and significantly decreases healthcare resource utilization. In contrast to AADs, catheter ablation appears to be a disease modifying therapy, significantly reducing the progression to more advanced forms of AF. These findings are relevant to patients, providers, and healthcare systems, helping inform the decision regarding the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

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.

The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: The EARLY-AF (NCT02825979), STOP AF First (NCT03118518), and Cryo-FIRST (NCT01803438) randomised controlled trials (RCTs) demonstrated that cryoballoon pulmonary vein isolation reduces atrial fibrillation (AF) recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). The present study developed a cost-effectiveness model (CEM) of first-line cryoablation compared with first-line AADs for PAF, from the Canadian health care payer's perspective. METHODS: Data from the 3 RCTs were analysed to estimate key CEM parameters. The model structure used a decision tree for the first 12 months and a Markov model with a 3-month cycle length for the remaining lifetime time horizon. Costs were set at 2023 Canadian dollars, health benefits were expressed as quality-adjusted life years (QALYs), and both were discounted 3% annually. Probabilistic sensitivity analysis (PSA) considered parameter uncertainty. RESULTS: The statistical analysis estimated that first-line cryoablation generates a 47% reduction (P < 0.001) in the rate of AF recurrence, a 73% reduction in the rate of subsequent ablation (P < 0.001), and a 4.3% (P = 0.025) increase in health-related quality of life, compared with first-line AADs. The PSA indicates that an individual treated with first-line cryoablation accrues less costs (-$3,862) and more QALYs (0.19) compared with first-line AADs. Cryoablation is cost-saving in 98.4% of PSA iterations and has a 99.9% probability of being cost-effective at a cost-effectiveness threshold of $50,000 per QALY gained. Cost-effectiveness results were robust to changes in key model parameters. CONCLUSIONS: First-line cryoballoon ablation is cost-effective when compared with AADs for patients with symptomatic PAF.

Adherence to direct or vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a long-term observational study.

Our objectives were to measure long-term adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and to identify patient factors associated with adherence. Using linked, population-based administrative data from British Columbia, Canada, an incident cohort of adults prescribed OACs for AF was identified. We calculated the proportion of days covered (PDC) as a time-dependent covariate for each 90-day window from OAC initiation until the end of follow-up. Associations between patient attributes and adherence were assessed using generalized mixed effect linear regression models. 30,264 patients were included. Mean PDC was 0.69 (SD 0.28) over a median follow-up of 6.7 years. 54% of patients were non-adherent (PDC < 0.8). After controlling for confounders, factors positively associated with adherence were number of drug class switches, history of stroke or transient ischemic attack, history of vascular disease, time since initiation, and age. Age > 75 years at initiation, polypharmacy (among VKA users only), and receiving DOAC (vs. VKA) were negatively associated with adherence. PDC decreased over time for VKA users and increased for DOAC users. Over half of AF patients studied were, on average, nonadherent to OAC therapy and missed 32% of their doses. Several patient factors were associated with higher or lower adherence, and adherence to VKA declined during therapy while DOAC adherence increased slightly over time. To min im ize the risk stroke, adherence-supporting interventions are needed for all patients with AF, particularly those aged > 75 years, those with prior stroke or vascular disease, VKA users with polypharmacy, and DOAC recipients.

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.).

Same-day discharge for atrial fibrillation ablation: outcomes and impact of ablation modality.

AIMS: Same-day discharge is increasingly common after catheter ablation for atrial fibrillation (AF). However, the impact of same-day discharge on healthcare utilization after ablation and whether this differs by ablation modality remains uncertain. We examined the safety, efficacy, and subsequent healthcare utilization of a same-day discharge protocol for AF ablation, including radiofrequency (RF) and cryoballoon ablation, in a contemporary cohort. METHODS AND RESULTS: All consecutive patients for whom full healthcare utilization data were available at two centres and who underwent AF ablation from 2018 to 2019 were included. Same-day discharge was the default strategy for all patients. The efficacy and safety outcomes were proportions of same-day discharge and readmission/emergency room (ER) visits, and post-discharge complications, respectively. Of the 421 patients who underwent AF ablation (mean 63.3 ± 10.2 years, 33% female), 90.5% (381/421) achieved same-day discharge with no difference between RF and cryoballoon ablation (89.8 vs. 95.1%, adjusted P = 0.327). Readmission ≤30 days occurred in 4.8%, with ER visits ≤30 days seen in 26.1% with no difference between ablation modalities (P = 0.634). Patients admitted overnight were more likely to present to the ER (40.0 vs. 24.7% with same-day discharge, P = 0.036). The overall post-discharge complication rate was low at 4/421 (1.0%), with no difference between ablation modality (P = 0.324) and admission/same-day discharge (P = 0.485). CONCLUSION: Same-day discharge can be achieved in a majority of patients undergoing RF or cryoballoon ablation for AF. Healthcare utilization, particularly ER visits, remains high after AF ablation, regardless of ablation modality or same-day discharge.

Cryoablation as a first-line therapy for atrial fibrillation: current status and future prospects.

INTRODUCTION: Atrial fibrillation (AF) is a common chronic and progressive heart rhythm disorder. For those in whom sinus rhythm is desired, contemporary clinical practice guidelines recommend antiarrhythmic drugs (AADs) as the initial therapy. However, these medications have modest efficacy and are associated with significant adverse effects. AREAS COVERED: The current article reviews the evidence surrounding first-line catheter ablation, particularly the emerging evidence surrounding the use of cryoballoon ablation as a first-line therapy. The focus of the review is on the outcomes of arrhythmia freedom, quality of life, health-care utilization, and safety. In addition, the article will review novel cryoablation systems. EXPERT OPINION: Recent evidence suggests that cryoballoon ablation significantly improves arrhythmia outcomes (e.g. freedom from any atrial tachyarrhythmia or symptomatic atrial tachyarrhythmia, reduction in arrhythmia burden), patient-reported outcomes (e.g. symptoms and quality of life), and health-care resource utilization (e.g. hospitalization), without increasing the risk of adverse events. These findings are relevant to patients, providers, and health-care systems, as they help inform the decision-making regarding the initial choice of rhythm-control therapy in patients with treatment-naive AF.

New evidence: Cryoballoon ablation vs. antiarrhythmic drugs for first-line therapy of atrial fibrillation.

Atrial fibrillation (AF) is a commonly encountered chronic and progressive heart rhythm disorder, characterized by exacerbations and remissions. Contemporary clinical practice guidelines recommend a trial of antiarrhythmic drugs (AADs) as the initial therapy for sinus rhythm maintenance; however, these medications have modest efficacy and are associated with significant adverse effects. Recently, several trials have demonstrated that an initial treatment strategy of cryoballoon catheter ablation significantly improves arrhythmia outcomes (e.g. freedom atrial tachyarrhythmia and reduction in arrhythmia burden), produces clinically meaningful improvements in patient-reported outcomes (e.g. symptoms and quality of life), and significantly reduces subsequent healthcare resource utilization (e.g. hospitalization), without increasing the risk of serious or any adverse events. These findings are relevant to patients, providers, and healthcare systems, helping inform the decision regarding the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

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.

Influence of Monitoring Strategy on Assessment of Ablation Success and Postablation Atrial Fibrillation Burden Assessment: Implications for Practice and Clinical Trial Design.

BACKGROUND: Various noninvasive intermittent rhythm monitoring strategies have been used to assess arrhythmia recurrences in trials evaluating pharmacological and invasive therapeutic interventions for atrial fibrillation (AF). We determined whether a frequency and duration of noninvasive rhythm monitoring could be identified that accurately detects arrhythmia recurrences and approximates the AF burden derived from continuous monitoring using an implantable cardiac monitor (ICM). METHODS: The rhythm history of 346 patients enrolled in the CIRCA-DOSE trial (Cryoballoon Versus Contact-Force Irrigated Radiofrequency Catheter Ablation) was reconstructed. Using computer simulations, we evaluated event-free survival, sensitivity, negative predictive value, and AF burden of a range of noninvasive monitoring strategies, including those used in contemporary AF ablation trials. RESULTS: A total of 126 290 monitoring days were included in the analysis. At 12 months, 164 patients experienced atrial arrhythmia recurrence as documented by the ICM (1-year event-free survival, 52.6%). Most noninvasive monitoring strategies used in AF ablation trials had poor sensitivity for detecting arrhythmia recurrence. Sensitivity increased with the intensity of monitoring, with serial (3) short-duration monitors (24-/48-hour ECG monitors) missing a substantial proportion of recurrences (sensitivity, 15.8% [95% CI, 8.9%-20.7%] and 24.5% [95% CI, 16.2%-30.6%], respectively). Serial (3) longer-term monitors (14-day ECG monitors) more closely approximated the gold standard ICM (sensitivity, 64.6% [95% CI, 53.6%-74.3%]). AF burden derived from short-duration monitors significantly overestimated the true AF burden in patients with recurrences. Increasing monitoring duration resulted in improved correlation and concordance between noninvasive estimates of the invasive AF burden (R2 = 0.85 and interclass correlation coefficient = 0.91 for serial [3] 14-day ECG monitors versus ICM). CONCLUSIONS: The observed rate of postablation atrial tachyarrhythmia recurrence is highly dependent on the arrhythmia monitoring strategy employed. Between-trial discrepancies in outcomes may reflect different monitoring protocols. On the basis of measures of agreement, serial long-term (7-14 day) intermittent monitors accumulating at least 28 days of annual monitoring provide estimates of AF burden comparable with ICM. However, ICMs outperform intermittent monitoring for arrhythmia detection, and should be considered the gold standard for clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01913522.

Cryoballoon Ablation as Initial Treatment for Atrial Fibrillation: JACC State-of-the-Art Review.

Atrial fibrillation (AF), the most common sustained arrhythmia observed in clinical practice, is a chronic and progressive disorder characterized by exacerbations and remissions. Guidelines recommend antiarrhythmic drugs as the initial therapy for the maintenance of sinus rhythm; however, antiarrhythmic drugs have modest efficacy to maintain sinus rhythm and can be associated with significant adverse effects. An initial treatment strategy of cryoballoon catheter ablation in patients with treatment-naïve AF has been shown to significantly improve arrhythmia outcomes (freedom from any, or symptomatic atrial tachyarrhythmia), produce clinically meaningful improvements in patient-reported outcomes (symptoms and quality of life), and significantly reduce subsequent health care resource use (hospitalization), and it does not increase the risk of serious or any adverse events compared with initial antiarrhythmic drug therapy. These findings are relevant to inform patients, providers, and health care systems regarding the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

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.

Anticoagulation management of postoperative atrial fibrillation after cardiac surgery: A systematic review.

BACKGROUND: Postoperative atrial fibrillation (POAF) often complicates cardiac surgery and is associated with increased mortality and risk of thromboembolism. However, the optimal oral anticoagulation (OAC) strategy is uncertain. We performed a systematic review to examine the OAC practice patterns and efficacy in these circumstances. METHODS: MEDLINE and EMBASE were searched from 2000 to 2019 using the search terms cardiac surgical procedures, cardiac surgery, postoperative complications, atrial fibrillation, atrial flutter, and terms for anticoagulants. Collected data included anticoagulation patterns (time of initiation, type, and duration) and outcomes (stroke, bleeding, and mortality). RESULTS: From 763 records, 4 prospective and 13 retrospective studies were included totaling 44,908 patients with 8929 (19.9%) who developed POAF. Anticoagulation rates ranged from 4% to 43% (mean 21% overall). Sixteen studies used warfarin, 3 nonvitamin K OAC (NOAC), and 2 both. Four studies reported the use of bridging unfractionated or low-molecular-weight heparin. Concomitant antiplatelet therapy was reported in half the studies, ranging from 80% to 99%. OAC use was associated with lower risk of thromboembolic events in two retrospective studies (including a national Danish cohort with 2108 patients with POAF). Patients discharged on warfarin experienced reduced mortality in a large, single center, retrospective analysis, but no association was observed in the Danish cohort. CONCLUSION: There is wide practice variation in the uptake, timing of initiation, duration, and choice of OAC for POAF following cardiac surgery. The evidence is largely retrospective and insufficient to assess the efficacy of different OAC strategies. Further studies are warranted to guide clinical practice.

Autonomic Alterations After Pulmonary Vein Isolation in the CIRCA-DOSE (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation) Study.

Background The natural history of autonomic alterations following catheter ablation of drug-refractory paroxysmal atrial fibrillation is poorly defined, largely because of the historical reliance on non-invasive intermittent rhythm monitoring for outcome ascertainment. Methods and Results The study included 346 patients with drug-refractory paroxysmal atrial fibrillation undergoing pulmonary vein isolation using contemporary advanced-generation ablation technologies. All patients underwent insertion of a Reveal LINQ (Medtronic) implantable cardiac monitor before ablation. The implantable cardiac monitor continuously recorded physical activity, heart rate variability (measured as the SD of the average normal-to-normal), daytime heart rate, and nighttime heart rate. Longitudinal autonomic data in the 2-month period leading up to the date of ablation were compared with the period from 91 to 365 days following ablation. Following ablation there was a significant decrease in SD of the average normal-to-normal (mean difference versus baseline of 19.3 ms; range, 12.9-25.7; P<0.0001), and significant increases in daytime and nighttime heart rates (mean difference versus baseline of 9.6 bpm; range, 7.4-11.8; P<0.0001, and 7.4 bpm; range, 5.4-9.3; P<0.0001, respectively). Patients free of arrhythmia recurrence had significantly faster daytime (11±11 versus 8±12 bpm, P=0.001) and nighttime heart rates (8±9 versus 6±8 bpm, P=0.049), but no difference in SD of the average normal-to-normal (P=0.09) compared with those with atrial fibrillation recurrence. Ablation technology and cryoablation duration did not influence these autonomic nervous system effects. Conclusions Pulmonary vein isolation results in significant sustained changes in the heart rate parameters related to autonomic function. These changes are correlated with procedural outcome and are independent of the ablation technology used. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01913522.