Predictors of first pass isolation of the pulmonary veins in real world ablations: An analysis of 2671 patients from the REAL-AF registry.

INTRODUCTION: During atrial fibrillation ablation (AFA), achievement of first pass isolation (FPI) reflects effective lesion formation and predicts long-term freedom from arrhythmia recurrence. We aim to determine the clinical and procedural predictors of pulmonary vein FPI. METHODS: We reviewed AFA procedures in a multicenter prospective registry of AFA (REAL-AF). A multivariate ordinal logistic regression, weighted by inverse proceduralist volume, was used to determine predictors of FPI. RESULTS: A total of 2671 patients were included with 1806 achieving FPI in both vein sides, 702 achieving FPI in one, and 163 having no FPI. Individually, age, left atrial (LA) scar, higher power usage (50 W), greater posterior contact force, ablation index >350 posteriorly, Vizigo™ sheath utilization, nonstandard ventilation, and high operator volume (>6 monthly cases) were all related to improved odds of FPI. Conversely sleep apnea, elevated body mass index (BMI), diabetes mellitus, LA enlargement, antiarrhythmic drug use, and center's higher fluoroscopy use were related to reduced odds of FPI. Multivariate analysis showed that BMI > 30 (OR 0.78 [0.64-0.96]) and LA volume (OR per mL increase = 1.00 [0.99-1.00]) predicted lower odds of achieving FPI, whereas significant left atrial scarring (>20%) was related to higher rates of FPI. Procedurally, the use of high power (50 W) (OR 1.32 [1.05-1.65]), increasing force posteriorly (OR 2.03 [1.19-3.46]), and nonstandard ventilation (OR 1.26 [1.00-1.59]) predicted higher FPI rates. At a site level, high procedural volume (OR 1.89 [1.48-2.41]) and low fluoroscopy centers (OR 0.72 [0.61-0.84]) had higher rates of FPI. CONCLUSION: FPI rates are affected by operator experience, patient comorbidities, and procedural strategies. These factors may be postulated to impact acute lesion formation.

Evaluating temperature gradients across the posterior left atrium with radiofrequency ablation.

INTRODUCTION: Esophageal injury is a well-known complication associated with catheter ablation. Though novel methods to mitigate esophageal injury have been developed, few studies have evaluated temperature gradients with catheter ablation across the posterior wall of the left atrium, interstitium, and esophagus. METHODS: To investigate temperature gradients across the tissue, we developed a porcine heart-esophageal model to perform ex vivo catheter ablation on the posterior wall of the left atrium (LA), with juxtaposed interstitial tissue and esophagus. Circulating saline (5 L/min) was used to mimic blood flow along the LA and alteration of ionic content to modulate impedance. Thermistors along the region of interest were used to analyze temperature gradients. Varying time and power, radiofrequency (RF) ablation lesions were applied with an externally irrigated ablation catheter. Ablation strategies were divided into standard approaches (SAs, 10-15 g, 25-35 W, 30 s) or high-power short duration (HPSD, 10-15 g, 40-50 W, 10 s). Temperature gradients, time to the maximum measured temperature, and the relationship between measured temperature as a function of distance from the site of ablation was analyzed. RESULTS: In total, five experiments were conducted each utilizing new porcine posterior LA wall-esophageal specimens for RF ablation (n = 60 lesions each for SA and HPSD). For both SA and HPSD, maximum temperature rise from baseline was markedly higher at the anterior wall (AW) of the esophagus compared to the esophageal lumen (SA: 4.29°C vs. 0.41°C, p < .0001 and HPSD: 3.13°C vs. 0.28°C, p < .0001). Across ablation strategies, the average temperature rise at the AW of the esophagus was significantly higher with SA relative to HPSD ablation (4.29°C vs. 3.13°C, p = .01). From the start of ablation, the average time to reach a maximum temperature as measured at the AW of the esophagus with SA was 36.49 ± 12.12 s, compared to 16.57 ± 4.54 s with HPSD ablation, p < .0001. Fit to a linear scale, a 0.37°C drop in temperature was seen for every 1 cm increase in distance from the site of ablation and thermistor location at the AW of the esophagus. CONCLUSION: Both SA and HPSD ablation strategies resulted in markedly higher temperatures measured at the AW of the esophagus compared to the esophageal lumen, raising concern about the value of clinical intraluminal temperature monitoring. The temperature rise at the AW was lower with HPSD. A significant time delay was seen to reach the maximum measured temperature and a modest increase in distance between the site of ablation and thermistor location impacted the accuracy of monitored temperatures.

PRIME score for prediction of permanent pacemaker implantation after transcatheter aortic valve replacement.

OBJECTIVES: We sought to produce a simple scoring system that can be applied at clinical visits before transcatheter aortic valve replacement (TAVR) to stratify the risk of permanent pacemaker (PPM) after the procedure. BACKGROUND: Atrioventricular block is a known complication of TAVR. Current models for predicting the risk of PPM after TAVR are not designed to be applied clinically to assist with preprocedural planning. METHODS: Patients undergoing TAVR at the University of Colorado were split into a training cohort for the development of a predictive model, and a testing cohort for model validation. Stepwise and binary logistic regressions were performed on the training cohort to produce a predictive model. Beta coefficients from the binary logistic regression were used to create a simple scoring system for predicting the need for PPM implantation. Scores were then applied to the validation cohort to assess predictive accuracy. RESULTS: Patients undergoing TAVR from 2013 to 2019 were analyzed: with 483 included in the training cohort and 123 included in the validation cohort. The need for a pacemaker was associated with five preprocedure variables in the training cohort: PR interval > 200 ms, Right bundle branch block, valve-In-valve procedure, prior Myocardial infarction, and self-Expandable valve. The PRIME score was developed using these clinical features, and was highly accurate for predicting PPM in both the training and model validation cohorts (area under the curve 0.804 and 0.830 in the model training and validation cohorts, respectively). CONCLUSIONS: The PRIME score is a simple and accurate preprocedural tool for predicting the need for PPM implantation after TAVR.

2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.

Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Development and validation of an automated algorithm for end point adjudication for a large U.S. national registry.

BACKGROUND: Clinical events committee (CEC) evaluation is the standard approach for end point adjudication in clinical trials. Due to resource constraints, large registries typically rely on site-reported end points without further confirmation, which may preclude use for regulatory oversight. METHODS: We developed a novel automated adjudication algorithm (AAA) for end point adjudication in the National Cardiovascular Data Registry Left Atrial Appendage Occlusion (LAAO) Registry using an iterative process using CEC adjudication as the "gold standard." A ≥80% agreement rate between automated algorithm adjudication and CEC adjudication was prespecified as clinically acceptable. Agreement rates were calculated. RESULTS: A total of 92 in-hospital and 127 post-discharge end points were evaluated between January 1, 2016 and June 30, 2019 using AAA and CEC. Agreement for neurologic events was >90%. Percent agreement for in-hospital and post-discharge events was as follows: ischemic stroke 95.7% and 94.5%, hemorrhagic stroke 97.8% and 96.1%, undetermined stroke 97.8% and 99.2%, transient ischemic attack 98.9% and 98.4% and intracranial hemorrhage 100.0% and 94.5%. Agreement was >80% for major bleeding (83.7% and 90.6%) and major vascular complication (89.1% and 97.6%). With this approach, <1% of site reported end points require CEC adjudication. Agreement remained very good during the period after algorithm derivation. CONCLUSIONS: An AAA-guided approach for end point adjudication was successfully developed and validated for the LAAO Registry. With this approach, the need for formal CEC adjudication was substantially reduced, with accuracy maintained above an 80% agreement threshold. After application specific validation, these methods could be applied to large registries and clinical trials to reduce the cost of event adjudication while preserving scientific validity.

Use of oral anticoagulants in patients with valvular atrial fibrillation: findings from the NCDR PINNACLE Registry.

Recent data suggest direct oral anticoagulants are as safe and efficacious as warfarin among select patients with valvular heart disease and atrial fibrillation (AF). However, real-world treatment patterns of AF stroke prophylaxis in the setting of valvular AF are currently unknown. Accordingly, using the prospective, ambulatory National Cardiovascular Data Registry Practice Innovation and Clinical Excellence (PINNACLE) Registry, we sought to characterize overall use, temporal trends in use, and the extent of practice-level variation in the use of any direct oral anticoagulant and warfarin among patients with valvular AF from January 1, 2013, to March 31, 2019.

Quality indicators for the care and outcomes of adults with atrial fibrillation.

AIMS: To develop quality indicators (QIs) that may be used to evaluate the quality of care and outcomes for adults with atrial fibrillation (AF). METHODS AND RESULTS: We followed the ESC methodology for QI development. This methodology involved (i) the identification of the domains of AF care for the diagnosis and management of AF (by a group of experts including members of the ESC Clinical Practice Guidelines Task Force for AF); (ii) the construction of candidate QIs (including a systematic review of the literature); and (iii) the selection of the final set of QIs (using a modified Delphi method). Six domains of care for the diagnosis and management of AF were identified: (i) Patient assessment (baseline and follow-up), (ii) Anticoagulation therapy, (iii) Rate control strategy, (iv) Rhythm control strategy, (v) Risk factor management, and (vi) Outcomes measures, including patient-reported outcome measures (PROMs). In total, 17 main and 17 secondary QIs, which covered all six domains of care for the diagnosis and management of AF, were selected. The outcome domain included measures on the consequences and treatment of AF, as well as PROMs. CONCLUSION: This document defines six domains of AF care (patient assessment, anticoagulation, rate control, rhythm control, risk factor management, and outcomes), and provides 17 main and 17 secondary QIs for the diagnosis and management of AF. It is anticipated that implementation of these QIs will improve the quality of AF care.

Development of a measure of decision quality for implantable defibrillators.

BACKGROUND: CMS reimbursement guidelines for implantable cardioverter-defibrillators (ICDs) include mandated shared decision making (SDM), but without any manner of assessing the quality of decisions made. We developed and tested a scale meant to assess patients' knowledge of and preferences specific to ICDs. Such a tool would assess these constructs in the clinical environment, targeting resources and support for patients considering a primary prevention ICD. METHODS: Development of the ICD decision quality (ICD-DQ) scale included (1) item creation, (2) content validation using surveys of patients (n = 23) and clinicians (n = 31), and (3) examination of validity and reliability using a survey of patients who previously received an ICD (n = 295, response rate = 72%). RESULTS: The final scale consists of 12 knowledge and 8 preference items. With respect to content validity, clinician and patient respondents agreed on the importance of 19 of 24 candidate knowledge items (79%), and 9 of 11 treatment preference items (81%). Knowledge items exhibited moderate internal validity (α = 0.62, 1 factor), strong test-retest reliability (mean % correct at first administration = 59%, 62% at follow-up, P > .1) and discriminant validity (59% correct for patients, 93% among cardiologists). Short versions of the ICD-DQ were developed for clinical settings, the scores from both of which correlated with the long version in this cohort (11-item (r = 0.90) and a 5-item (r = 0.75)). CONCLUSIONS: The ICD-DQ fills a critical gap in measuring the quality of patients' ICD decisions. They may be used to evaluate the effectiveness of patient decision aids or the quality of SDM in clinical practice.

Development and piloting of four decision aids for implantable cardioverter-defibrillators in different media formats.

BACKGROUND: Using DAs for preference-sensitive decisions is an evidence-based way to improve patient-centered decisions. Reimbursement mandates have increased the need for DAs in ICD care, although none have been formally evaluated. The objectives were to develop and pilot implantable cardioverter-defibrillator (ICD) decision aids (DAs) for patients considering primary prevention ICDs. METHODS: Development Phase: An expert panel, including patients and physicians, iteratively developed four DAs: a one-page Option GridTM conversation aid, a four-page in-depth paper tool, a 17-minute video, and an interactive website. Trial Phase: At three sites, patients with heart failure who were eligible for primary prevention ICDs were randomly assigned 2:1 to intervention (received DAs) or control (usual care). We conducted a mixed-methods evaluation exploring acceptability and feasibility. RESULTS: Twenty-one eligible patients enrolled (15 intervention). Most intervention participants found the DAs to be unbiased (67%), helpful (89%), and would recommend them to others (100%). The pilot was feasible at all sites; however, using clinic staff to identify eligible patients was more efficient than chart review. Although the main goals were to measure acceptability and feasibility, intervention participants trended towards increased concordance between longevity values and ICD decisions (71% concordant vs. 29%, p = .06). Participants preferred the in-depth paper tool and video DAs. Access to a nurse during the decision-making window encouraged questions and improved participant-perceived confidence. CONCLUSIONS: Participants felt the DAs provided helpful, balanced information that they would recommend to other patients. Further exploration of this larger context of DA use and strategies to promote independent use related to electrophysiology (EP) visits are needed.

A multicenter trial of a shared DECision Support Intervention for Patients offered implantable Cardioverter-DEfibrillators: DECIDE-ICD rationale, design, Medicare changes, and pilot data.

Shared decision making (SDM) facilitates delivery of medical therapies that are in alignment with patients' goals and values. Medicare national coverage decision for several interventions now includes SDM mandates, but few have been evaluated in nationwide studies. Based upon a detailed needs assessment with diverse stakeholders, we developed pamphlet and video patient decision aids (PtDAs) for implantable cardioverter/defibrillator (ICD) implantation, ICD replacement, and cardiac resynchronization therapy with defibrillation to help patients contemplate, forecast, and deliberate their options. These PtDAs are the foundation of the Multicenter Trial of a Shared Decision Support Intervention for Patients Offered Implantable Cardioverter-Defibrillators (DECIDE-ICD), a multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute aimed at understanding the effectiveness and implementation of an SDM support intervention for patients considering ICDs. Finalization of a Medicare coverage decision mandating the inclusion of SDM for new ICD implantation occurred shortly after trial initiation, raising novel practical and statistical considerations for evaluating study end points. METHODS/DESIGN: A stepped-wedge randomized controlled trial was designed, guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) planning and evaluation framework using an effectiveness-implementation hybrid type II design. Six electrophysiology programs from across the United States will participate. The primary effectiveness outcome is decision quality (defined by knowledge and values-treatment concordance). Patients with heart failure who are clinically eligible for an ICD are eligible for the study. Target enrollment is 900 participants. DISCUSSION: Study findings will provide a foundation for implementing decision support interventions, including PtDAs, with patients who have chronic progressive illness and are facing decisions involving invasive, preference-sensitive therapy options.

A risk score model for predicting intraprocedural cardiac injury during implantable cardioverter defibrillator implantation: Insights from the National Cardiovascular Data Registry.

BACKGROUND: Individual risk factors of intraprocedural cardiac injury (cardiac perforation and tamponade) during implantable cardioverter defibrillator (ICD) placement have been documented. However, the prognostic impact of their coexistence has not been explored. OBJECTIVE: To develop a risk score model to identify patients at risk for intraprocedural cardiac injury. METHODS: We identified 438 679 patients from National Cardiovascular Data Registry (NCDR)-ICD who underwent de novo ICD implantation between 2010 and 2015, split randomly into a derivation cohort (n = 220 000) and a validation cohort (n = 218 679). The generalized estimating equations (GEEs) analysis with quasilikelihood under the independence model criterion goodness-of-fit statistics were used to identify the predictors of intraprocedural cardiac injury and a risk scoring model was developed. Model discrimination was assessed by receiver-operator characteristic curve and C-statistic. RESULTS: The risk of intraprocedural cardiac injury in the overall cohort was 0.13%. GEE analysis yielded seven variables (points in parentheses) that were strongly associated with intraprocedural cardiac injury: age, greater than 75 years (1), female gender (1), body mass index, less than 18.5 kg/m 2 (1), hypertension (1), chronic lung disease (1), left bundle branch block (1), and continued warfarin use (1). Only prior history of coronary artery bypass grafting (CABG) (-1) was associated with reduced risk. A risk scoring system was developed that had good discrimination with a C-statistic of 0.72. The risk of intraprocedural cardiac injury increased with the increase in risk score from low risk (0.03%) to high risk (1.37%). CONCLUSION: A practical risk score model can stratify patients into high- and low-risk groups for cardiac perforation or tamponade before undergoing ICD implantation.

Electrophysiologic testing for diagnostic evaluation and risk stratification in patients with suspected cardiac sarcoidosis with preserved left and right ventricular systolic function.

INTRODUCTION: While cardiac sarcoidosis (CS) carries a risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD), risk stratification of patients with CS and preserved left ventricular/right ventricular (LV/RV) systolic function remains challenging. We sought to evaluate the role of electrophysiologic testing and programmed electrical stimulation of the ventricle (EPS) in patients with suspected CS with preserved ventricular function. METHODS: One hundred twenty consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function underwent EPS. All patients had either probable CS defined by an abnormal cardiac positron emission tomography or cardiac magnetic resonance imaging, or possible CS with normal advanced imaging but abnormal echocardiogram (ECG), SAECG, Holter, or clinical factors. Patients were followed for 4.5 ± 2.6 years for SCD and VAs. RESULTS: Seven of 120 patients (6%) had inducible ventricular tachycardia (VT) with EPS and received an implantable cardioverter defibrillator (ICD). Three patients (43%) with positive EPS later had ICD therapies for VAs. Kaplan-Meier analysis stratified by EPS demonstrated a significant difference in freedom from VAs and SCD (P = 0.009), though this finding was driven entirely by patients within the cohort with probable CS (P = 0.018, n = 69). One patient with possible CS and negative EPS had unrecognized progression of the disease and unexplained death with evidence of CS at autopsy. CONCLUSIONS: EPS is useful in the risk stratification of patients with probable CS with preserved LV and RV function. A positive EPS was associated with VAs. While a negative EPS appeared to confer low risk, close follow-up is needed as EPS cannot predict fatal VAs related to new cardiac involvement or disease progression.

Esophageal position, measured luminal temperatures, and risk of atrioesophageal fistula with atrial fibrillation ablation.

BACKGROUND: Despite improvement in catheter ablation for atrial fibrillation (AF), ability to recognize and prevent esophageal injury remains challenging. We hypothesized that esophageal course may impact esophageal heating, as measured through ablation, and thereby, risk of injury. METHODS: We evaluated all patients undergoing first-time AF ablation with preprocedural computed tomography (CT) imaging from 2014 to 2016 at our institution, focusing on esophageal position at the left atrial (LA)/pulmonary vein junction. Esophageal luminal temperatures (ELTs) were analyzed by esophageal course. In exploratory work by investigation of published reports of atrioesophageal fistula (AEF), we evaluated for a relationship between esophageal course and risk of AEF. RESULTS: Of 68 patients, 48.5% had midline, 36.8% leftward, and 14.7% rightward esophageal positions. Of 20 patients (29% of cohort) with esophageal confinement-defined as a midline or leftward position relative to the LA, vertebrae, and aorta, with luminal distortion-14 had leftward position. No significant differences in patient or procedure characteristics were noted between confinement and nonconfinement cohorts. The average peak ELT was significantly higher in those with confinement (36.9°C vs 36.2°C, P < 0.05) and confinement with a left-sided esophagus (37.1°C vs 36.2°C, P < 0.05). There was a significant correlation between esophageal confinement and risk of AEF (odds ratio [OR]: 2.7, 95% confidence interval [CI]: 1.2-6.2, P < 0.01). CONCLUSION: Approximately one-third of patients undergoing AF ablation display leftward esophageal course along the ablation zone on preprocedure CT imaging, with a significant portion exhibiting esophageal confinement. In those with confinement, higher peak ELTs are noted with ablation. Esophageal confinement may be a risk factor for development of AEF.

Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

OBJECTIVES: To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. METHODS: MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. RESULTS: Of 3188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. CONCLUSIONS: There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder.

Repeat ablation of refractory ventricular arrhythmias in patients with nonischemic cardiomyopathy: Impact of midmyocardial substrate and role of adjunctive ablation techniques.

INTRODUCTION: Multiple ablations are often necessary to manage ventricular arrhythmias (VAs) in nonischemic cardiomyopathy (NICM) patients. We assessed characteristics and outcomes and role of adjunctive, nonstandard ablation in repeat VA ablation (RAbl) in NICM. METHODS AND RESULTS: Consecutive NICM patients undergoing RAbl were analyzed, with characteristics of the last VA ablations compared between those undergoing 1 versus multiple-repeat ablations (1-RAbl vs. >1RAbl), and between those with or without midmyocardial substrate (MMS). VA-free survival was compared. Eighty-eight patients underwent 124 RAbl, 26 with > 1RAbl, and 26 with MMS. 1-RAbl and > 1-RAbl groups were similar in age (57 ± 16 vs. 57 ± 17 years; P = 0.92), males (76% vs. 69%; P = 0.60), LVEF (40 ± 17% vs. 40 ± 18%; P = 0.96), and amiodarone use (31% vs. 46%, P = 0.22). One-year VA freedom between 1-RAbl vs. > 1RAbl was similar (82% vs. 80%; P = 0.81); adjunctive ablation was utilized more in >1RAbl (31% vs. 11%, P = 0.02), and complication rates were higher (27% vs. 7%, P = 0.01), most due to septal substrate and anticipated heart block. >1-RAbl patients had more MMS (62% vs. 16%, P < 0.01). Although MMS was associated with worse VA-free survival after 1-RAbl (43% vs. 69%, P = 0.01), when >1RAbl was performed, more often with nonstandard ablation, VA-free survival was comparable to non-MMS patients (85% vs. 81%; P = 0.69). More RAbls were required in MMS versus non-MMS patients (2.00 ± 0.98 vs. 1.16 ± 0.37; P < 0.001). CONCLUSION: For NICM patients with recurrent, refractory VAs despite previous ablation, effective arrhythmia control can safely be achieved with subsequent ablation, although >1 repeat procedure with adjunctive ablation is often required, especially with MMS.

Adherence and outcomes to direct oral anticoagulants among patients with atrial fibrillation: findings from the veterans health administration.

BACKGROUND: The direct oral anticoagulants (DOACs) reduce the risk of stroke in moderate to high-risk patients with non-valvular atrial fibrillation (AF). Yet, concerns remain regarding its routine use in real world practice. We sought to describe adherence patterns and the association between adherence and outcomes to the DOACs among outpatients with AF. METHODS: We performed a retrospective cohort study of patients in the VA Healthcare System who initiated pharmacotherapy with dabigatran, rivaroxaban, or apixaban between November 2010 and January 2015 for non-valvular AF with CHA2DS2-VASc score ≥ 2. Adherence was determined using pharmacy refill data and estimated by the proportion of days covered (PDC) over the first year of therapy. Clinical outcomes, including all-cause mortality and stroke, were measured at 6 months and used to assess measures of adherence for each DOAC. RESULTS: A total of 2882 patients were included. Most were prescribed dabigatran (72.7%), compared with rivaroxaban (19.8%) or apixaban (7.5%). The mean PDC was 0.84 ± 0.20 for dabigatran, 0.86 ± 0.18 for rivaroxaban, and 0.89 ± 0.14 for apixaban (p < 0.01). The proportion of non-adherent patients, PDC <0.80, was 27.6% for all and varied according DOAC. Lower adherence to dabigatran was associated with higher risk of mortality and stroke (HR 1.07; 1.03-1.12 per 0.10 decline in PDC). CONCLUSIONS: In a real-world VA population being prescribed anticoagulation for AF, more than one quarter had sub-optimal adherence. Lower adherence was associated with a higher risk of mortality and stroke. Efforts identifying non-adherent patients, and targeted adherence interventions are needed to improve outcomes.

Central Sleep-disordered Breathing Predicts Incident Atrial Fibrillation in Older Men.

RATIONALE: Although research supports a sleep-disordered breathing and atrial fibrillation association, prospective data examining sleep-disordered breathing predicting incident atrial fibrillation are lacking. OBJECTIVES: To investigate sleep-disordered breathing indices as predictors of incident atrial fibrillation. METHODS: A cohort (n = 843) of ambulatory older men without prevalent atrial fibrillation was assessed for baseline sleep indices: apnea-hypopnea index, central sleep apnea (central apnea index, ≥5 vs. <5), central sleep apnea or Cheyne-Stokes respiration, obstructive apnea-hypopnea index, and percentage of sleep time with less than 90% oxygen saturation. Incident clinically symptomatic adjudicated or self-reported atrial fibrillation outcome was ascertained (mean follow-up, 6.5 ± 0.7 yr). We used logistic regression models adjusted for age, race, body mass index, cardiopulmonary disease, alcohol use, pacemaker, cholesterol, cardiac medications, and alternate apnea type for obstructive and central apnea. Age interaction terms and median age-stratified analyses were performed. MEASUREMENTS AND MAIN RESULTS: Central sleep apnea (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.18-5.66) and Cheyne-Stokes respiration with central sleep apnea (OR, 2.27; 95% CI, 1.13-4.56), but not obstructive apnea or hypoxemia, predicted incident atrial fibrillation. Central apnea, Cheyne-Stokes respiration, and sleep-disordered breathing-age interaction terms were significant (P < 0.05). Unlike the case with younger participants, among participants aged 76 years or older (albeit with small atrial fibrillation counts), atrial fibrillation was related to central apnea (OR, 9.97; 95% CI, 2.72-36.50), Cheyne-Stokes respiration with central apnea (OR, 6.31; 95% CI, 1.94-20.51), and apnea-hypopnea index (OR, 1.22; 95% CI, 1.08-1.39 [per 5-unit increase]). CONCLUSIONS: In older men, central apnea and Cheyne-Stokes respiration predicted increased atrial fibrillation risk, with findings being strongest in older participants in whom overall sleep-disordered breathing also increased atrial fibrillation risk.