Atrial fibrillation is significantly associated with morbidity and mortality and erodes the quality and quantity of life. It is standard of care to treat patients with AF and an increased risk of stroke with oral anticoagulation therapy, but the more daunting question many clinicians face is whether to pursue a “rate-only” or “rhythm” control strategy. Historical studies over the years have sought to answer this question but have found no significant difference in major clinical outcomes between the two strategies. There are opportunities based on new data to improve the natural history of the disease. The EAST AFnet trial for the first time revealed a significant morbidity and mortality advantage to rhythm control therapy when performed early in the disease process of AF and in the setting of comprehensive medical management that was maintained. The CABANA trial clearly demonstrated that catheter ablation was a more effective long-term treatment of AF in general and significantly lowers risk of AF progression compared to medical therapy. Like multiple prior trials of rhythm management strategies, when rhythm control was effective in these trials, independent of therapy assignment, there was a significantly lower risk of adverse outcomes and death. These contemporary data provide optimism that the pervasive mortality risk in patients with AF observed over the past 50 years may be improved by the timing, use, and efficacy of use of therapeutic interventions.

Response to “Delay in AF ablation costs lives”Andrew J. Sessions BS1, Heidi T. May, PhD, MSPH2, Brian G. Crandall, MD2, John D. Day, MD3, Michael J. Cutler DO, PhD2, Christopher A. Groh MD4, Leenapong Navaravong MD4, Ravi Ranjan MD, PhD4, Benjamin A. Steinberg MD, MHS4, T. Jared Bunch, MD4Corresponding Author: Dr. T. Jared BunchUniversity of Utah School of Medicine, Salt Lake City, Utah, USADepartment of Cardiology, Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, Utah, USASt. Marks Hospital, Salt Lake City, UtahDepartment of Internal Medicine, Division of Cardiology, University Hospital, Salt Lake City, Utah, USAAddress for correspondence: T. Jared Bunch, M.D.University of Utah School of Medicine Division of Cardiology, Department of Internal Medicine 50 N Medical Drive Salt Lake City, Utah 84132 Phone: 801-585-7676Short Title: Impact of delays in catheter ablationFunding : None

Background: Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Anticoagulation use and efficacy impact long-term risk of dementia in AF patients in observational trials. Methods: The Cognitive Decline and Dementia in Patients with Non-Valvular Atrial Fibrillation (CAF) Trial was a randomized, prospective, open-label vanguard clinical study with blinded endpoint assessment involving patients with moderate- to high-risk (CHADS2 or CHA2DS2-Vasc scores of ≥2) non-valvular AF assigned to dabigatran etexilate or warfarin. The primary endpoint was incident dementia or moderate cognitive decline at 24 months. Results: A total of 101 patients were enrolled, of which 50 received dabigatran and 51 warfarin anticoagulation. The mean age was 73.7±6.0 years and 54(53.5%) were male. Prior stroke and stroke risk factors were similar between groups. Average INR over the study was 2.41±0.68 in the warfarin group. No patient experienced a stroke or developed dementia. Mini-Mental Status Evaluation, Hachinski Ischemic scale, cognitive subscale of the Alzheimer’s Disease Assessment Scale, Disability Assessment for Dementia, Quality of Life Improvement as assessed by Minnesota Living with Heart Failure Scale and the Anti-Clot Treatment Scale Quality of Life Survey scores did not vary at baseline or change over 2 years. Biomarker analysis indicated a similar efficacy of anticoagulation strategies Conclusion: Use of dabigatran and well-managed warfarin therapy were associated with similar risks of stroke, cognitive decline, and dementia at 2 years, suggestive that either strategy is acceptable to mitigate these risks. The results of this Vanguard study did not support the pursuit of a larger formally powered study.

Background: There exists variability in the administration of inpatient sotalol therapy for symptomatic atrial fibrillation(AF). The impact of this variability on patient in-hospital and 30-day post-hospitalization costs and outcomes is not known. Also, the cost impact of intravenous sotalol, which can accelerate drug loading to therapeutic levels, is unknown. Methods: 133 AF patients admitted for sotalol initiation at an Intermountain Healthcare Hospital from January 2017-December 2018 were included. Patient and dosing characteristics were described descriptively, and the impact of dosing schedule was correlated with daily hospital costs/clinical outcomes during the index hospitalization and for 30 days. The CMS reimbursement for 3-day sotalol initiation is $9,263.51. Projections of cost savings were made considering a 1-day load using intravenous sotalol that costs $2,500.00 to administer. Results: The average age was 70.3±12.3 years, 60.2% were male with comorbidities of: hypertension(83%), diabetes(36%), and coronary artery disease(53%). Mean ejection fraction was 59.9±7.8% and median QTc was 453.7±37.6 ms before sotalol. No ventricular arrhythmias developed, but bradycardia(<60 bpm) was observed in 37.6% of patients. The average length of stay was 3.9±4.6(median: 2.2) days. Post-discharge outcomes and rehospitalization rates stratified by length of stay were similar. The cost per day was estimated at $2,931.55 (1:$2,931.55, 2:$5,863.10, 3:$8,794.65, 4:$11,726.20). Conclusions: Inpatient sotalol dosing is markedly variable and results in the potential of both cost gain and loss to a hospital. In consideration of estimated costs, there is the potential for $871.55 cost savings compared to a 2-day oral load and $3,803.10 compared to a 3-day oral load.

Background: Recent randomized controlled trials (RCT) suggest that ablation is superior to antiarrhythmic drugs (AAD) as an initial therapy for paroxysmal atrial fibrillation (pAF) to prevent arrhythmia recurrences. We performed an updated meta-analysis of RCTs, to include recent data from cryoballoon-based ablation, and to compare arrhythmia-free survival and adverse events between ablation and AAMs. Methods: We searched MEDLINE and EMBASE from inception to December 2020. We included RCT comparing patients with pAF undergoing ablation or receiving AADs as an initial therapy. We combined data using the random-effects model to calculate hazards ratio (HR) for arrhythmia-free survival and odds ratio (OR) for adverse events. Results: Five studies from 2005-2020 involving 985 patients were included (495 patients and 490 patients underwent ablation and medication as initial therapy, respectively). Patients who underwent ablation had higher freedom from atrial tachyarrhythmias (AT) during the 12-24 months follow-up period (pooled HR=0.48, 95% CI:0.40-0.59, p<0.001) (Figure 2). In a subgroup analysis of ablation method used, both cryoablation group (pooled HR=0.49, 95% CI:0.38-0.64, p<0.001) (Figure 2A) and radiofrequency ablation group (pooled HR=0.47, 95%CI:0.35-0.64, p<0.001) (Figure 2B) showed reduction in AT recurrence compared to AAD group. There were no differences in adverse events including cerebrovascular accident, pericardial effusion or tamponade, pulmonary vein stenosis, acute coronary syndrome, deep vein thrombosis and pulmonary embolism, and bradycardia requiring a pacemaker. Conclusion: Catheter ablation (both cryoablation and radiofrequency ablation) is superior to AAD as an initial therapy for pAF in efficacy for reducing AT recurrences without a compromise in adverse events.

Reflections from the Book of the Dead: Weighing the Impact of Epicardial Fat on Atrial Fibrillation Vulnerability T. Jared Bunch MDDepartment of Medicine, School of Medicine, University of Utah, Salt Lake City, UtahAddress for correspondence: T. Jared Bunch, M.D.University of Utah School of Medicine Department of Internal Medicine Division of Cardiovascular Medicine 30 North 1900 East, Room 4A100 Salt Lake City, UT 84132 Phone: 801-213-2387 E-mail: [email protected]

Background: Multiple strategies have advocation for power titration and catheter movement during atrial fibrillation (AF) ablation. Comparative favoring evidence regarding the efficacy, logistics, and safety of a higher power, shorter duration (HPSD) ablation strategy compared to a lower power, longer duration (LPLD) ablation strategy is insubstantial. We performed a meta-analysis to compare arrhythmia-free survival, procedure times, and complication rates between the two strategies. Methods: We searched MEDLINE, EMBASE and Cochrane Library from inception to April 2020. We included studies comparing patients underwent HPSD and LPLD strategies for AF ablation and reporting either of the following outcomes: freedom from atrial tachyarrhythmia (AT) including AF and atrial flutter, procedure time, or periprocedural complications. We combined data using the random-effects model to calculate odds ratio (OR) and weight mean difference (WMD) with 95% confidence interval (CI). Results: Nine studies from 2006-2020 involving 2,282 patients were included (1,369 patients underwent HPSD strategy and 853 patients underwent LPLD strategy). HPSD strategy was not associated with an increased freedom from AT at 12-month follow-up (OR= 1.41, 95%CI:0.90-2.21). There was a significant reduction in the HPSD group for total procedure (WMD=49.60, 95%CI:29.76-69.44) and ablation (WMD=17.92, 95%CI:13.63-22.22) times, but not for fluoroscopy time (WMD=1.15, 95%CI:-0.67-2.97). HPSD was not associated with a reduction in esophageal ulcer/atrioesophageal fistula (OR=0.35, 95%CI:0.12-1.06) or pericardial effusion/cardiac tamponade rates (OR=0.96, 95%CI:0.24-3.79). Conclusions: When compared to a LPLD strategy, HPSD strategy does not improve recurrent AT nor reduce periprocedural complication risks. However, a HPSD strategy can significantly reduce total procedure and ablation times.