Comparative effectiveness and healthcare utilization for ambulatory cardiac monitoring strategies in Medicare beneficiaries.

BACKGROUND: Objective data comparing the diagnostic performance of different ambulatory cardiac monitors (ACMs) are lacking. OBJECTIVES: To assess variation in monitoring strategy, clinical outcomes and healthcare utilization in patients undergoing ambulatory monitoring without a pre-existing arrhythmia diagnosis. METHODS: Using the full sample (100%) of Medicare claims data, we performed a retrospective cohort study of diagnostic-naïve patients who received first-time ACM in 2017 to 2018 and evaluated arrhythmia encounter diagnosis at 3-months, repeat ACM testing at 6 months, all-cause 90-day emergency department (ED) and inpatient utilization, and cost of different strategies: Holter; long-term continuous monitor (LTCM); non-continuous, event-based external ambulatory event monitor (AEM); and mobile cardiac telemetry (MCT). We secondarily performed a device-specific analysis by manufacturer, identified from unique claim modifier codes. RESULTS: ACMs were used in 287,789 patients (AEM = 10.3%; Holter = 53.8%; LTCM = 13.3%; MCT = 22.5%). Device-specific analysis showed that compared to Holter, AEM, MCT, or other LTCM manufacturers, a specific LTCM (ZioⓇ XT 14-day patch, iRhythm Technologies, San Francisco, CA) had the highest adjusted odds of diagnosis and lowest adjusted odds of ACM retesting. Findings were consistent for specific arrhythmia diagnoses of ventricular tachycardia, atrioventricular block, and paroxysmal atrial fibrillation. As a category, LTCM was associated with the lowest 1-year incremental health care expenditures (mean Δ$10,159), followed by Holter ($10,755), AEM ($11,462), and MCT ($12,532). CONCLUSIONS: There was large variation in diagnostic monitoring strategy. A specific LTCM was associated with the highest adjusted odds of a new arrhythmia diagnosis and lowest adjusted odds of repeat ACM testing. LTCM as a category had the lowest incremental acute care utilization. Different monitoring strategies may produce different results with respect to diagnosis and care.

Expert opinion on design and endpoints for studies on catheter ablation of atrial fibrillation.

INTRODUCTION: Catheter ablation of atrial fibrillation (AF) is frequently studied in randomized trials, observational and registry studies. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of future clinical studies on catheter ablation of AF, implement lessons learned from previous studies, and promote a higher degree of consistency across studies. BACKGROUND: Studies on catheter ablation of AF may benefit from well-described definitions of endpoints and consistent methodology and documentation of outcomes related to efficacy, safety and cost-effectiveness. The availably of new, innovative technologies warrants further consideration about their application and impact on study design and the choice of endpoints. Moreover, recent insights gained from AF ablation studies suggest a reconsideration of some methodological aspects. METHODS: A panel of clinical experts on catheter ablation of AF and designing and conducting clinical studies developed an expert opinion on the design and endpoints for studies on catheter ablation of AF. Discussions within the expert panel with the aim to reach consensus on predefined topics were based on outcomes reported in the literature and experiences from recent clinical trials. RESULTS: A comprehensive set of recommendations is presented. Key elements include the documentation of clinical AF, medication during the study, repeated ablations and their effect on endpoint assessments, postablation blanking and the choice of rhythm-related and other endpoints. CONCLUSION: This expert opinion provides guidance and promotes consistency regarding design of AF catheter ablation studies and identified aspects requiring further research to optimize study design and methodology. CONDENSED ABSTRACT: Recent insights from studies on catheter ablation of atrial fibrillation (AF) and the availability of new innovative technologies warrant reconsideration of methodological aspects related to study design and the choice and assessment of endpoints. This expert opinion, developed by clinical experts on catheter ablation of AF provides a comprehensive set of recommendations related to these methodological aspects. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of clinical studies, implement lessons learned from previous studies, and promote a higher degree of consistency across studies.

Consumer-Led Screening for Atrial Fibrillation: Frontier Review of the AF-SCREEN International Collaboration.

The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

Research Opportunities in Stroke Prevention for Atrial Fibrillation: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Association of CHA2DS2-VASc and HAS-BLED to frailty and frail outcomes: From the TREAT-AF study.

BACKGROUND: Morbidity and mortality associated with high CHA2DS2-VASc and HAS-BLED scores is not specific to atrial fibrillation (AF). Frailty could be an important contributor to this morbidity and mortality while being mechanistically independent from AF. We sought to evaluate the association of stroke and bleeding risk to noncardiovascular frail events and the association of stroke prevention therapy to outcomes in frail patients with AF. METHODS: Using the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the Veterans Health Administration, we identified patients with newly diagnosed AF from 2004 to 2014. Baseline frailty was identified using a previously validated claims-based index requiring ≥2 of 12 ICD-9 diagnoses. Logistic regressions modeled the association between CHA2DS2-VASc and modified HAS-BLED and frailty. Cox proportional hazard regressions were used to evaluate the association between CHA2DS2-VASc and modified HAS-BLED and a composite of noncardiovascular frail events (fractures, urinary tract infections, bacterial pneumonia, or dehydration). We also evaluated the association of oral anticoagulant (OAC) use with stroke, bleeding, and 1-year mortality in frail patients and non-frail patients. RESULTS: In 213,435 patients (age 70 ± 11; 98% male; CHA2DS2-VASc 2.4 ± 1.7) with AF, 8,498 (4%) were frail. CHA2DS2-VASc > 0 and HAS-BLED > 0 were strongly associated with frailty (odds ratio [OR] 13.3 (95% CI: 11.6-15.2) for CHA2DS2-VASc 4+ and OR 13.4 (10.2-17.5) for HAS-BLED 3+). After adjusting for covariates, CHA2DS2-VASc, and HAS-BLED > 0 were associated with higher risk of non-cardiovascular frail events (hazard ratio [HR] 2.1 (95% CI: 2.0-2.2) for CHA2DS2-VASc 4+ and HR 1.4 (95% CI: 1.3-1.5) for HAS-BLED 3+). In frail patients, OAC use was associated with significantly lower risk of 1-year mortality (HR 0.82; 95% CI 0.72-0.94, P = .0031) but did not reach significance for risk of stroke (HR 0.80; 95% CI 0.55-1.18, P = .26) or major bleeding (HR 1.08; 95% CI 0.93-1.25, P = .34). CONCLUSIONS: High CHA2DS2-VASc and HAS-BLED scores are strongly associated with frailty. However, in frail patients, OAC use was associated with reduction in 1-year mortality. For this challenging clinical population with competing risks of frailty and frail events, focused prospective studies are needed to support clinical decision-making. Until then, careful evaluation of frailty should inform shared decision-making.

Does early detection of atrial fibrillation reduce the risk of thromboembolic events? Rationale and design of the Heartline study.

BACKGROUND: The impact of using direct-to-consumer wearable devices as a means to timely detect atrial fibrillation (AF) and to improve clinical outcomes is unknown. METHODS: Heartline is a pragmatic, randomized, and decentralized application-based trial of US participants aged ≥65 years. Two randomized cohorts include adults with possession of an iPhone and without a history of AF and those with a diagnosis of AF taking a direct oral anticoagulant (DOAC) for ≥30 days. Participants within each cohort are randomized (3:1) to either a core digital engagement program (CDEP) via iPhone application (Heartline application) and an Apple Watch (Apple Watch Group) or CDEP alone (iPhone-only Group). The Apple Watch Group has the watch irregular rhythm notification (IRN) feature enabled and access to the ECG application on the Apple Watch. If an IRN notification is issued for suspected AF then the study application instructs participants in the Apple Watch Group to seek medical care. All participants were "watch-naïve" at time of enrollment and have an option to either buy or loan an Apple Watch as part of this study. The primary end point is time from randomization to clinical diagnosis of AF, with confirmation by health care claims. Key secondary endpoint are claims-based incidence of a 6-component composite cardiovascular/systemic embolism/mortality event, DOAC medication use and adherence, costs/health resource utilization, and frequency of hospitalizations for bleeding. All study assessments, including patient-reported outcomes, are conducted through the study application. The target study enrollment is approximately 28,000 participants in total; at time of manuscript submission, a total of 26,485 participants have been enrolled into the study. CONCLUSION: The Heartline Study will assess if an Apple Watch with the IRN and ECG application, along with application-facilitated digital health engagement modules, improves time to AF diagnosis and cardiovascular outcomes in a real-world environment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276441.

Research Priorities in Atrial Fibrillation Screening: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.

Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation.

BACKGROUND: Optical sensors on wearable devices can detect irregular pulses. The ability of a smartwatch application (app) to identify atrial fibrillation during typical use is unknown. METHODS: Participants without atrial fibrillation (as reported by the participants themselves) used a smartphone (Apple iPhone) app to consent to monitoring. If a smartwatch-based irregular pulse notification algorithm identified possible atrial fibrillation, a telemedicine visit was initiated and an electrocardiography (ECG) patch was mailed to the participant, to be worn for up to 7 days. Surveys were administered 90 days after notification of the irregular pulse and at the end of the study. The main objectives were to estimate the proportion of notified participants with atrial fibrillation shown on an ECG patch and the positive predictive value of irregular pulse intervals with a targeted confidence interval width of 0.10. RESULTS: We recruited 419,297 participants over 8 months. Over a median of 117 days of monitoring, 2161 participants (0.52%) received notifications of irregular pulse. Among the 450 participants who returned ECG patches containing data that could be analyzed - which had been applied, on average, 13 days after notification - atrial fibrillation was present in 34% (97.5% confidence interval [CI], 29 to 39) overall and in 35% (97.5% CI, 27 to 43) of participants 65 years of age or older. Among participants who were notified of an irregular pulse, the positive predictive value was 0.84 (95% CI, 0.76 to 0.92) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular pulse notification and 0.71 (97.5% CI, 0.69 to 0.74) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular tachogram. Of 1376 notified participants who returned a 90-day survey, 57% contacted health care providers outside the study. There were no reports of serious app-related adverse events. CONCLUSIONS: The probability of receiving an irregular pulse notification was low. Among participants who received notification of an irregular pulse, 34% had atrial fibrillation on subsequent ECG patch readings and 84% of notifications were concordant with atrial fibrillation. This siteless (no on-site visits were required for the participants), pragmatic study design provides a foundation for large-scale pragmatic studies in which outcomes or adherence can be reliably assessed with user-owned devices. (Funded by Apple; Apple Heart Study ClinicalTrials.gov number, NCT03335800.).

Achievement and quality measure attainment in patients hospitalized with atrial fibrillation: Results from The Get With The Guidelines - Atrial Fibrillation (GWTG-AFIB) registry.

BACKGROUND: The Get With The Guidelines - Atrial Fibrillation (GWTG-AFIB) Registry uses achievement and quality measures to improve the care of patients with atrial fibrillation (AF). We sought to evaluate overall and site-level variation in attainment of these measures among sites participating in the GWTG-AFIB Registry. METHODS: From the GWTG-AFIB registry, we included patients with AF admitted between 1/3/2013 and 6/30/2019. We described patient-level attainment and variation in attainment across sites of 6 achievement measures with 1) defect-free scores (percent of patients with all eligible measures attained), and 2) composite opportunity scores (percent of all eligible patient measures attained). We also described attainment of 11 quality measures at the patient-level. RESULTS: Among 80,951 patients hospitalized for AF (age 70±13 years, 47.0% female; CHA2DS2-VASc 3.6±1.8) at 132 sites. Site-level defect-free scores ranged from 4.7% to 85.8% (25th, 50th, 75th percentile: 32.7%, 52.1%, 64.4%). Composite opportunity scores ranged from 39.4% to 97.5% (25th, 50th, 75th: 68.1%, 80.3%, 87.1%). Attainment was notably low for the following quality measures: 1) aldosterone antagonist prescription when ejection fraction ≤35% (29% of those eligible); and 2) avoidance of antiplatelet therapy with OAC in patients without coronary/peripheral artery disease (81% of those eligible). CONCLUSIONS: Despite high overall attainment of care measures across GWTG-AFIB registry sites, large site variation was present with meaningful opportunities to improve AF care beyond OAC prescription, including but not limited to prescription of aldosterone antagonists in those with AF and systolic dysfunction and avoidance of non-indicated adjunctive antiplatelet therapy.

Wearables, telemedicine, and artificial intelligence in arrhythmias and heart failure: Proceedings of the European Society of Cardiology Cardiovascular Round Table.

Digital technology is now an integral part of medicine. Tools for detecting, screening, diagnosis, and monitoring health-related parameters have improved patient care and enabled individuals to identify issues leading to better management of their own health. Wearable technologies have integrated sensors and can measure physical activity, heart rate and rhythm, and glucose and electrolytes. For individuals at risk, wearables or other devices may be useful for early detection of atrial fibrillation or sub-clinical states of cardiovascular disease, disease management of cardiovascular diseases such as hypertension and heart failure, and lifestyle modification. Health data are available from a multitude of sources, namely clinical, laboratory and imaging data, genetic profiles, wearables, implantable devices, patient-generated measurements, and social and environmental data. Artificial intelligence is needed to efficiently extract value from this constantly increasing volume and variety of data and to help in its interpretation. Indeed, it is not the acquisition of digital information, but rather the smart handling and analysis that is challenging. There are multiple stakeholder groups involved in the development and effective implementation of digital tools. While the needs of these groups may vary, they also have many commonalities, including the following: a desire for data privacy and security; the need for understandable, trustworthy, and transparent systems; standardized processes for regulatory and reimbursement assessments; and better ways of rapidly assessing value.

Association of kidney function and atrial fibrillation progression to clinical outcomes in patients with cardiac implantable electronic devices.

BACKGROUND: Kidney function may promote progression of AF. OBJECTIVE: We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED). METHODS: We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). All devices had atrial leads and at least 75% of remote monitoring transmission coverage. Patients were included at the date of the first AF episode lasting ≥6 minutes, and followed until the occurrence of persistent AF in the first year, defined as ≥7 consecutive days with continuous AF. We used Cox regression analyses with persistent AF as a time-varying covariate to examine the association to stroke, myocardial infarction, heart failure and death. RESULTS: Of, 10,323 eligible patients, 1,771 had a first CIED-detected AF (mean age 69 ± 10 years, 1.2% female). In the first year 355 (20%) developed persistent AF. Kidney function was not associated with persistent AF after multivariable adjustment including CHA2DS2-VASc variables and prior medications. Only higher age increased the risk (HR: 1.37 per 10 years; 95% CI:1.22-1.54). Persistent AF was associated to higher risk of heart failure (HR: 2.27; 95% CI: 1.88-2.74) and death (HR: 1.60; 95% CI: 1.30-1.96), but not stroke (HR: 1.28; 95% CI: 0.62-2.62) or myocardial infarction (HR: 1.43; 95% CI: 0.91-2.25). CONCLUSION: Kidney function was not associated to AF progression, whereas higher age was. Preventing AF progression could reduce the risk of heart failure and death.

Patient characteristics, care patterns, and outcomes of atrial fibrillation associated hospitalizations in patients with chronic kidney disease and end-stage renal disease.

BACKGROUND: Chronic Kidney Disease (CKD) and end-stage renal disease (ESRD) are associated with poor outcomes in patients with cardiovascular disease. There is a paucity of contemporary data on in-hospital outcomes and care patterns of atrial fibrillation (AF) associated hospitalizations CKD and ESRD. METHODS: Outcomes and care patterns were evaluated in GWTG-AFIB database (Jan 2013-Dec 2018), including in-hospital mortality, use of a rhythm control strategy, and oral anticoagulation (OAC) prescription at discharge among eligible patients. Generalized logistic regression models with generalized estimating equations were used to ascertain differences in outcomes. Hospital-level variation in OAC prescription and rhythm control was also evaluated. RESULTS: Among 50,154 patients from 105 hospitals the median age was 70 years (interquartile range 61-79) and 47.3% were women. The prevalence of CKD was 36.0% while that of ESRD was 1.6%. Among eligible patients, discharge OAC prescription rates were 93.6% for CKD and 89.1% for ESRD. After adjustment, CKD and ESRD were associated with higher in-hospital mortality (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.57-6.03 for ESRD and OR 2.02, 95% CI 1.52-2.67 for CKD), lower odds of OAC prescription at discharge (OR 0.59, 95% CI 0.44-0.79 for ESRD and OR 0.84, 95% CI 0.75-0.94 for CKD) compared with normal renal function. CKD was associated with lower utilization of rhythm control strategy (OR 0.92, 95% CI 0.87-0.98) with no significant difference between ESRD and normal renal function (OR 1.32, 95% CI 0.79-1.11). There was large hospital-level variation in OAC prescription at discharge (MOR 2.34, 95% CI 2.05-2.76) and utilization of a rhythm control strategy (MOR 2.69, 95% CI 2.34-3.21). CONCLUSIONS: CKD/ESRD is associated with higher in-hospital mortality, less frequent rhythm control, and less OAC prescription among patients hospitalized for AF. There is wide hospital-level variation in utilization of a rhythm control strategy and OAC prescription at discharge highlighting potential opportunities to improve care and outcomes for these patients, and better define standards of care in this patient population.

Procedure characteristics and outcomes of atrial fibrillation ablation procedures using cryoballoon versus radiofrequency ablation: A report from the GWTG-AFIB registry.

INTRODUCTION: Cryoballoon ablation (CBA) is an alternative to radiofrequency ablation (RFA) for ablation of atrial fibrillation (AF) and real-world comparisons of this strategy are lacking. As such, we sought to compare patient and periprocedural characteristics and outcomes of CBA versus RFA in the Get With the Guidelines AFIB Registry. METHODS: Categorical variables were compared via the χ2 test and continuous variables were compared via the Wilcoxon rank-sum test. Adjusted analyses were performed using overlap weighting of propensity scores. RESULTS: A total of 5247 (1465 CBA, 3782 RFA) ablation procedures were reported from 33 sites. Those undergoing CBA more often had paroxysmal AF (60.0% vs. 48.8%) and no prior AF ablation (87.5% vs. 73.8%). CHA2 DS2 -VASc scores were similar. Among de novo ablations, most ablations involved intracardiac echocardiography and electroanatomic mapping, but both were less common with CBA (87.3% vs. 93.9%, p < .0001, and 87.7% vs. 94.6%, p < .0001, respectively). CBA was associated with shorter procedures (129 vs. 179 min, p < .0001), increased fluoroscopy use (19 vs. 11 min, p < .0001), and similar ablation times (27 vs. 35 min, p = .15). Nonpulmonary vein ablation was common with CBA: roof line 38.6%, floor line 20.4%, cavotricuspid isthmus 27.7%. RFA was associated with more total complications compared to CBA (5.4% vs. 2.3%, p < .0001), due to more volume overload and "other" events, although phrenic nerve injury was more common with CBA (0.9% vs 0.1%, p = .0001). In the adjusted model, any complication was less common among CBA cases (odds ratio, 0.45; confidence interval, 0.25-0.79, p = .0056). CONCLUSION: CBA was associated with fewer complications, and shorter procedure times, and greater fluoroscopy times, compared to RFA. Nonpulmonary vein ablation and electroanatomic mapping system use was common with CBA.

Practice Variation in Anticoagulation Prescription and Outcomes After Device-Detected Atrial Fibrillation.

BACKGROUND: Device-detected atrial fibrillation (AF) is associated with increased risk of stroke; however, there are no clearly defined thresholds of AF burden at which to initiate oral anticoagulation (OAC). We sought to describe OAC prescription practice variation in response to new device-detected AF and the association with outcomes. METHODS: We performed a retrospective cohort study using data from the Veterans Health Administration linked to remote monitoring data that included day-level AF burden. We included patients with cardiac implantable electronic devices and remote monitoring from 2011 to 2014, CHA2DS2-VASc score ≥2, and no prior stroke or OAC receipt in the preceding 2 years. We determined the proportion of patients prescribed OAC within 90 days after new device-detected AF across a range of AF thresholds (≥6 minutes to >24 hours) and examined site variation in OAC prescription. We used multivariable Cox proportional hazards regressions to determine the association of OAC prescription with stroke by device-detected AF burden. RESULTS: Among 10 212 patients with cardiac implantable electronic devices, 4570 (45%), 3969 (39%), 3263 (32%), and 2469 (24%) had device-detected AF >6 minutes, >1 hour, >6 hours, and >24 hours, respectively. For device-detected AF >1 hour, 1712 patients met inclusion criteria (72±10 years; 1.5% female; CHA2DS2-VASc score 4.0±1.4; HAS-BLED score 2.6±1.1). The proportion receiving OAC varied based on device-detected AF burden (≥6 minutes: 272/2101 [13%]; >1 hour: 273/1712 [16%]; >6 hours: 263/1279 [21%]; >24 hours: 224/818 [27%]). Across 52 sites (N=1329 patients), there was substantial site-level variation in OAC prescription after device-detected AF >1 hour (median, 16%; range, 3%-67%; median odds ratio, 1.56 [95% credible interval, 1.49-1.71]). In adjusted models, OAC prescription after device-detected AF >24 hours was associated with reduced stroke risk (hazard ratio, 0.28; 95% CI, 0.10-0.81; P=0.02), although the propensity-adjusted model was significant when AF lasted at least 6 minutes. CONCLUSIONS: Among veterans with cardiac implantable electronic devices, device-detected AF is common. There is large practice variation in 90-day OAC initiation after new device-detected AF, with low rates of treatment overall, even for episodes that last >24 hours. The strongest association of OAC with reduction in stroke was observed after device-detected AF >24 hours. Randomized trials are needed to confirm these observational findings.

Technology-Enabled Clinical Trials: Transforming Medical Evidence Generation.

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.

Termination of persistent atrial fibrillation by ablating sites that control large atrial areas.

AIMS: Persistent atrial fibrillation (AF) has been explained by multiple mechanisms which, while they conflict, all agree that more disorganized AF is more difficult to treat than organized AF. We hypothesized that persistent AF consists of interacting organized areas which may enlarge, shrink or coalesce, and that patients whose AF areas enlarge by ablation are more likely to respond to therapy. METHODS AND RESULTS: We mapped vectorial propagation in persistent AF using wavefront fields (WFF), constructed from raw unipolar electrograms at 64-pole basket catheters, during ablation until termination (Group 1, N = 20 patients) or cardioversion (Group 2, N = 20 patients). Wavefront field mapping of patients (age 61.1 ± 13.2 years, left atrium 47.1 ± 6.9 mm) at baseline showed 4.6 ± 1.0 organized areas, each separated by disorganization. Ablation of sites that led to termination controlled larger organized area than competing sites (44.1 ± 11.1% vs. 22.4 ± 7.0%, P < 0.001). In Group 1, ablation progressively enlarged unablated areas (rising from 32.2 ± 15.7% to 44.1 ± 11.1% of mapped atrium, P < 0.0001). In Group 2, organized areas did not enlarge but contracted during ablation (23.6 ± 6.3% to 15.2 ± 5.6%, P < 0.0001). CONCLUSION: Mapping wavefront vectors in persistent AF revealed competing organized areas. Ablation that progressively enlarged remaining areas was acutely successful, and sites where ablation terminated AF were surrounded by large organized areas. Patients in whom large organized areas did not emerge during ablation did not exhibit AF termination. Further studies should define how fibrillatory activity is organized within such areas and whether this approach can guide ablation.

Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association.

Our understanding of the risk factors and complications of atrial fibrillation (AF) is based mostly on studies that have evaluated AF in a binary fashion (present or absent) and have not investigated AF burden. This scientific statement discusses the published literature and knowledge gaps related to methods of defining and measuring AF burden, the relationship of AF burden to cardiovascular and neurological outcomes, and the effect of lifestyle and risk factor modification on AF burden. Many studies examine outcomes by AF burden classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively, AF burden can be defined by longest duration, number of AF episodes during a monitoring period, and the proportion of time an individual is in AF during a monitoring period (expressed as a percentage). Current guidelines make identical recommendations for anticoagulation regardless of AF pattern or burden; however, a review of recent evidence suggests that higher AF burden is associated with higher risk of stroke. It is unclear whether the risk increases continuously or whether a threshold exists; if a threshold exists, it has not been defined. Higher burden of AF is also associated with higher prevalence and incidence of heart failure and higher risk of mortality, but not necessarily lower quality of life. A structured and comprehensive risk factor management program targeting risk factors, weight loss, and maintenance of a healthy weight appears to be effective in reducing AF burden. Despite this growing understanding of AF burden, research is needed into validation of definitions and measures of AF burden, determination of the threshold of AF burden that results in an increased risk of stroke that warrants anticoagulation, and discovery of the mechanisms underlying the weak temporal correlations of AF and stroke. Moreover, developments in monitoring technologies will likely change the landscape of long-term AF monitoring and could allow better definition of the significance of changes in AF burden over time.

Secular trends in success rate of catheter ablation for atrial fibrillation: The SMASH-AF cohort.

BACKGROUND: Approaches, tools, and technologies for atrial fibrillation (AF) ablation have evolved significantly since its inception. We sought to characterize secular trends in AF ablation success rates. METHODS: We performed a systematic review and meta-analysis of AF ablation from January 1, 1990, to August 1, 2016, searching PubMed, Scopus, and Cochrane databases. Major exclusion criteria were insufficient outcome reporting and ablation strategies that were not prespecified and uniform. We stratified treatment arms by AF type (paroxysmal AF; nonparoxysmal AF) and analyzed single-procedure outcomes. Multivariate meta-regressions analyzed effects of study, patient, and procedure characteristics on success rate trends. Registered in PROSPERO (CRD42016036549). RESULTS: A total of 180 trials and observational studies with 28,118 patients met inclusion. For paroxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 73.1% in 2003 to 77.1% in 2016, increasing by 0.9%/year (95% CI 0.4%-1.4%; P = .001; I2 = 90%). After controlling for study design and patient demographics, rate of improvement in success rate summary estimate increased (1.6%/year; 95% CI 0.9%-2.2%; P = .001; I2 = 87%). For nonparoxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 70.0% in 2010 to 64.3% in 2016 (1.1%/year; 95% CI -1.3% to 3.5%; P = .37; I2 = 85%), with no improvement in multivariate analyses. CONCLUSIONS: Despite substantial research investment and health care expenditure, improvements in AF ablation success rates have been incremental. Meaningful improvements may require major paradigm or technology changes, and evaluation of clinical outcomes such as mortality and quality of life may prove to be important going forward.

Rationale and design of a large-scale, app-based study to identify cardiac arrhythmias using a smartwatch: The Apple Heart Study.

BACKGROUND: Smartwatch and fitness band wearable consumer electronics can passively measure pulse rate from the wrist using photoplethysmography (PPG). Identification of pulse irregularity or variability from these data has the potential to identify atrial fibrillation or atrial flutter (AF, collectively). The rapidly expanding consumer base of these devices allows for detection of undiagnosed AF at scale. METHODS: The Apple Heart Study is a prospective, single arm pragmatic study that has enrolled 419,093 participants (NCT03335800). The primary objective is to measure the proportion of participants with an irregular pulse detected by the Apple Watch (Apple Inc, Cupertino, CA) with AF on subsequent ambulatory ECG patch monitoring. The secondary objectives are to: 1) characterize the concordance of pulse irregularity notification episodes from the Apple Watch with simultaneously recorded ambulatory ECGs; 2) estimate the rate of initial contact with a health care provider within 3 months after notification of pulse irregularity. The study is conducted virtually, with screening, consent and data collection performed electronically from within an accompanying smartphone app. Study visits are performed by telehealth study physicians via video chat through the app, and ambulatory ECG patches are mailed to the participants. CONCLUSIONS: The results of this trial will provide initial evidence for the ability of a smartwatch algorithm to identify pulse irregularity and variability which may reflect previously unknown AF. The Apple Heart Study will help provide a foundation for how wearable technology can inform the clinical approach to AF identification and screening.