Unlocking the potential of artificial intelligence in electrocardiogram biometrics: age-related changes, anomaly detection, and data authenticity in mobile health platforms.

Aims: Mobile devices such as smartphones and watches can now record single-lead electrocardiograms (ECGs), making wearables a potential screening tool for cardiac and wellness monitoring outside of healthcare settings. Because friends and family often share their smart phones and devices, confirmation that a sample is from a given patient is important before it is added to the electronic health record. Methods and results: We sought to determine whether the application of Siamese neural network would permit the diagnostic ECG sample to serve as both a medical test and biometric identifier. When using similarity scores to discriminate whether a pair of ECGs came from the same patient or different patients, inputs of single-lead and 12-lead medians produced an area under the curve of 0.94 and 0.97, respectively. Conclusion: The similar performance of the single-lead and 12-lead configurations underscores the potential use of mobile devices to monitor cardiac health.

Artificial Intelligence Electrocardiography to Predict Atrial Fibrillation in Patients With Chronic Lymphocytic Leukemia.

Background: The use of an artificial intelligence electrocardiography (AI-ECG) algorithm has demonstrated its reliability in predicting the risk of atrial fibrillation (AF) within the general population. Objectives: This study aimed to determine the effectiveness of the AI-ECG score in identifying patients with chronic lymphocytic leukemia (CLL) who are at high risk of developing AF. Methods: We estimated the probability of AF based on AI-ECG among patients with CLL extracted from the Mayo Clinic CLL database. Additionally, we computed the Mayo Clinic CLL AF risk score and determined its ability to predict AF. Results: Among 754 newly diagnosed patients with CLL, 71.4% were male (median age = 69 years). The median baseline AI-ECG score was 0.02 (range = 0-0.93), with a value ≥0.1 indicating high risk. Over a median follow-up of 5.8 years, the estimated 10-year cumulative risk of AF was 26.1%. Patients with an AI-ECG score of ≥0.1 had a significantly higher risk of AF (HR: 3.9; 95% CI: 2.6-5.7; P < 0.001). This heightened risk remained significant (HR: 2.5; 95% CI: 1.6-3.9; P < 0.001) even after adjusting for the Mayo CLL AF risk score, heart failure, chronic kidney disease, and CLL therapy. In a second cohort of CLL patients treated with a Bruton tyrosine kinase inhibitor (n = 220), a pretreatment AI-ECG score ≥0.1 showed a nonsignificant increase in the risk of AF (HR: 1.7; 95% CI: 0.8-3.6; P = 0.19). Conclusions: An AI-ECG algorithm, in conjunction with the Mayo CLL AF risk score, can predict the risk of AF in patients with newly diagnosed CLL. Additional studies are needed to determine the role of AI-ECG in predicting AF risk in CLL patients treated with a Bruton tyrosine kinase inhibitor.

Sudden Cardiac Death or Ventricular Arrythmia in Patients Taking Levetiracetam or Oxcarbazepine.

BACKGROUND AND OBJECTIVES: Levetiracetam is a widely used antiseizure medication. Recent concerns have been raised regarding the potential prolongation of the QT interval by levetiracetam and increased risk of sudden cardiac death. This could have profound implications for patient safety and for prescribing practice. This study assessed the potential association of levetiracetam with cardiac outcomes related to QT interval prolongation. We compared outcomes of patients taking levetiracetam with those taking oxcarbazepine as a comparator medication that has not been associated with prolongation of the QT interval. METHODS: The sample included patients who were newly prescribed levetiracetam or oxcarbazepine from January 31, 2010, to December 31, 2019, using administrative claims data from the OptumLabs Data Warehouse (OLDW). The analysis focused on a combined endpoint of sudden cardiac death or ventricular arrythmia, which are both linked to QT interval prolongation. We used a new user design and selected oxcarbazepine as an active comparator with levetiracetam to minimize bias. We used propensity score weighting to balance the levetiracetam and oxcarbazepine cohorts and then performed weighted Cox regressions to evaluate the association of levetiracetam with the combined endpoint. RESULTS: We identified 104,655 enrollees taking levetiracetam and 39,596 enrollees taking oxcarbazepine. At baseline, enrollees taking levetiracetam were older, more likely to have diagnosed epilepsy, and more likely to have diagnosed comorbidities including hypertension, cerebrovascular disease, and coronary artery disease. In the main analysis, we found no significant difference between levetiracetam and oxcarbazepine in the rate of the combined endpoint for the Cox proportional hazards model (hazard ratio [HR] 0.79, 95% CI 0.42-1.47) or Cox regression with time-varying characteristics (HR 0.78, 95% CI 0.41-1.50). DISCUSSION: When compared with oxcarbazepine, levetiracetam does not correlate with increased risk of ventricular arrythmia and sudden cardiac death. Our finding does not support the concern for cardiac risk to indicate restriction of levetiracetam use nor the requirement of cardiac monitoring when using it. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that sudden cardiac death and ventricular arrythmia are not more frequent in patients older than 17 years newly prescribed levetiracetam, compared with those prescribed oxcarbazepine.

First-in-man report of transsubclavian venous implantation of the Aveir leadless cardiac pacing system.

INTRODUCTION: Transsubclavian venous implantation of the Aveir leadless cardiac pacemaker (LCP) has not been previously reported. METHODS AND RESULTS: Three cases of transsubclavian implantation of the Aveir LCP are reported. Two cases were postbilateral orthotopic lung transplant, without appropriate femoral or jugular access due to recent ECMO cannulation and jugular central venous catheters. In one case, there was strong patient preference for same-day discharge. Stability testing confirmed adequate fixation and electrical testing confirmed stable parameters in all cases. All patients tolerated the procedure well without significant immediate complications. CONCLUSIONS: We demonstrate the feasibility of transsubclavian implantation of the Aveir LCP.

Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients With Takotsubo Cardiomyopathy.

BACKGROUND: Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TC), but there is no well-established tool for risk stratification. This study sought to evaluate the prognostic value of several artificial intelligence-augmented ECG (AI-ECG) algorithms in patients with TC. METHODS AND RESULTS: This study examined consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. Several previously validated AI-ECG algorithms were used for the estimation of ECG- age, probability of low ejection fraction, and probability of atrial fibrillation. Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events, defined as cardiovascular death, recurrence of TC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. In the final analysis, 305 patients with TC were studied over a median follow-up of 4.8 years. Patients with future major adverse cardiac events were more likely to be older, have a history of hypertension, congestive heart failure, worse renal function, as well as high-risk AI-ECG findings compared with those without. Multivariable Cox proportional hazards analysis indicated that the presence of 2 or 3 high-risk findings detected by AI-ECG remained a significant predictor of major adverse cardiac events in patients with TC after adjustment by conventional risk factors (hazard ratio, 4.419 [95% CI, 1.833-10.66], P=0.001). CONCLUSIONS: The combined use of AI-ECG algorithms derived from a single 12-lead ECG might detect subtle underlying patterns associated with worse outcomes in patients with TC. This approach might be beneficial for stratifying high-risk patients with TC.

Regional differences in outcomes with ablation versus drug therapy for atrial fibrillation: Results from the CABANA trial.

BACKGROUND: The finding of unexpected variations in treatment benefits by geographic region in international clinical trials raises complex questions about the interpretation and generalizability of trial findings. We observed such geographical variations in outcome and in the effectiveness of atrial fibrillation (AF) ablation versus drug therapy in the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. This paper describes these differences and investigates potential causes. METHODS: The examination of treatment effects by geographic region was a prespecified analysis. CABANA enrolled patients from 10 countries, with 1,285 patients at 85 North American (NA) sites and 919 at 41 non-NA sites. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Death and first atrial fibrillation recurrence were secondary endpoints. RESULTS: At least 1 primary endpoint event occurred in 157 patients (12.2%) from NA and 33 (3.6%) from non-NA sites over a median 54.9 and 40.5 months of follow-up, respectively (NA/non-NA adjusted hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.48-3.21, P < .001). In NA patients, 78 events occurred in the ablation and 79 in the drug arm, (HR 0.91, 95% CI 0.66, 1.24) while 11 and 22 events occurred in non-NA patients (HR 0.51, 95% CI 0.25,1.05, interaction P = .154). Death occurred in 53 ablation and 51 drug therapy patients in the NA group (HR 0.96, 95% CI 0.65,1.42) and in 5 ablation and 16 drug therapy patients in the non-NA group (HR 0.32, 95% CI 0.12,0.86, interaction P = .044). Adjusting for baseline regional differences or prognostic risk variables did not account for the regional differences in treatment effects. Atrial fibrillation recurrence was reduced by ablation in both regions (NA: HR 0.54, 95% CI 0.46, 0.63; non-NA: HR 0.44, 95% CI 0.30, 0.64, interaction P = .322). CONCLUSIONS: In CABANA, primary outcome events occurred significantly more often in the NA group but assignment to ablation significantly reduced all-cause mortality in the non-NA group only. These differences were not explained by regional variations in procedure effectiveness, safety, or patient characteristics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0091150; https://clinicaltrials.gov/study/NCT00911508.

Artificial intelligence-enabled ECG for left ventricular diastolic function and filling pressure.

Assessment of left ventricular diastolic function plays a major role in the diagnosis and prognosis of cardiac diseases, including heart failure with preserved ejection fraction. We aimed to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify echocardiographically determined diastolic dysfunction and increased filling pressure. We trained, validated, and tested an AI-enabled ECG in 98,736, 21,963, and 98,763 patients, respectively, who had an ECG and echocardiographic diastolic function assessment within 14 days with no exclusion criteria. It was also tested in 55,248 patients with indeterminate diastolic function by echocardiography. The model was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve, and its prognostic performance was compared to echocardiography. The AUC for detecting increased filling pressure was 0.911. The AUCs to identify diastolic dysfunction grades ≥1, ≥2, and 3 were 0.847, 0.911, and 0.943, respectively. During a median follow-up of 5.9 years, 20,223 (20.5%) died. Patients with increased filling pressure predicted by AI-ECG had higher mortality than those with normal filling pressure, after adjusting for age, sex, and comorbidities in the test group (hazard ratio (HR) 1.7, 95% CI 1.645-1.757) similar to echocardiography and in the indeterminate group (HR 1.34, 95% CI 1.298-1.383). An AI-enabled ECG identifies increased filling pressure and diastolic function grades with a good prognostic value similar to echocardiography. AI-ECG is a simple and promising tool to enhance the detection of diseases associated with diastolic dysfunction and increased diastolic filling pressure.

EDUCATE: An international, randomized controlled trial for teaching electrocardiography.

INTRODUCTION: Despite the critical role of electrocardiograms (ECGs) in patient care, evident gaps exist in ECG interpretation competency among healthcare professionals across various medical disciplines and training levels. Currently, no practical, evidence-based, and easily accessible ECG learning solution is available for healthcare professionals. The aim of this study was to assess the effectiveness of web-based, learner-directed interventions in improving ECG interpretation skills in a diverse group of healthcare professionals. METHODS: In an international, prospective, randomized controlled trial, 1206 healthcare professionals from various disciplines and training levels were enrolled. They underwent a pre-intervention test featuring 30 12-lead ECGs with common urgent and non-urgent findings. Participants were randomly assigned to four groups: (i) practice ECG interpretation question bank (question bank), (ii) lecture-based learning resource (lectures), (iii) hybrid question- and lecture-based learning resource (hybrid), or (iv) no ECG learning resources (control). After four months, a post-intervention test was administered. The primary outcome was the overall change in ECG interpretation performance, with secondary outcomes including changes in interpretation time, self-reported confidence, and accuracy for specific ECG findings. Both unadjusted and adjusted scores were used for performance assessment. RESULTS: Among 1206 participants, 863 (72 %) completed the trial. Following the intervention, the question bank, lectures, and hybrid intervention groups each exhibited significant improvements, with average unadjusted score increases of 11.4 % (95 % CI, 9.1 to 13.7; P<0.01), 9.8 % (95 % CI, 7.8 to 11.9; P<0.01), and 11.0 % (95 % CI, 9.2 to 12.9; P<0.01), respectively. In contrast, the control group demonstrated a non-significant improvement of 0.8 % (95 % CI, -1.2 to 2.8; P=0.54). While no differences were observed among intervention groups, all outperformed the control group significantly (P<0.01). Intervention groups also excelled in adjusted scores, confidence, and proficiency for specific ECG findings. CONCLUSION: Web-based, self-directed interventions markedly enhanced ECG interpretation skills across a diverse range of healthcare professionals, providing an accessible and evidence-based solution.

Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.

Realtime Diagnosis from Electrocardiogram Artificial Intelligence-Guided Screening for Atrial Fibrillation with Long Follow-Up (REGAL): Rationale and design of a pragmatic, decentralized, randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is associated with increased risks of stroke and dementia. Early diagnosis and treatment could reduce the disease burden, but AF is often undiagnosed. An artificial intelligence (AI) algorithm has been shown to identify patients with previously unrecognized AF; however, monitoring these high-risk patients has been challenging. Consumer wearable devices could be an alternative to enable long-term follow-up. OBJECTIVES: To test whether Apple Watch, used as a long-term monitoring device, can enable early diagnosis of AF in patients who were identified as having high risk based on AI-ECG. DESIGN: The Realtime diagnosis from Electrocardiogram (ECG) Artificial Intelligence (AI)-Guided Screening for Atrial Fibrillation (AF) with Long Follow-up (REGAL) study is a pragmatic trial that will accrue up to 2,000 older adults with a high likelihood of unrecognized AF determined by AI-ECG to reach our target of 1,420 completed participants. Participants will be 1:1 randomized to intervention or control and will be followed up for 2 years. Patients in the intervention arm will receive or use their existing Apple Watch and iPhone and record a 30-second ECG using the watch routinely or if an abnormal heart rate notification is prompted. The primary outcome is newly diagnosed AF. Secondary outcomes include changes in cognitive function, stroke, major bleeding, and all-cause mortality. The trial will utilize a pragmatic, digitally-enabled, decentralized design to allow patients to consent and receive follow-up remotely without traveling to the study sites. SUMMARY: The REGAL trial will examine whether a consumer wearable device can serve as a long-term monitoring approach in older adults to detect AF and prevent cognitive function decline. If successful, the approach could have significant implications on how future clinical practice can leverage consumer devices for early diagnosis and disease prevention. CLINICALTRIALS: GOV: : NCT05923359.

Patient-Level Artificial Intelligence-Enhanced Electrocardiography in Hypertrophic Cardiomyopathy: Longitudinal Treatment and Clinical Biomarker Correlations.

BACKGROUND: Artificial intelligence (AI) applied to 12-lead electrocardiographs (ECGs) can detect hypertrophic cardiomyopathy (HCM). OBJECTIVES: The purpose of this study was to determine if AI-enhanced ECG (AI-ECG) can track longitudinal therapeutic response and changes in cardiac structure, function, or hemodynamics in obstructive HCM during mavacamten treatment. METHODS: We applied 2 independently developed AI-ECG algorithms (University of California-San Francisco and Mayo Clinic) to serial ECGs (n = 216) from the phase 2 PIONEER-OLE trial of mavacamten for symptomatic obstructive HCM (n = 13 patients, mean age 57.8 years, 69.2% male). Control ECGs from 2,600 age- and sex-matched individuals without HCM were obtained. AI-ECG output was correlated longitudinally to echocardiographic and laboratory metrics of mavacamten treatment response. RESULTS: In the validation cohorts, both algorithms exhibited similar performance for HCM diagnosis, and exhibited mean HCM score decreases during mavacamten treatment: patient-level score reduction ranged from approximately 0.80 to 0.45 for Mayo and 0.70 to 0.35 for USCF algorithms; 11 of 13 patients demonstrated absolute score reduction from start to end of follow-up for both algorithms. HCM scores were significantly associated with other HCM-relevant parameters, including left ventricular outflow tract gradient at rest, postexercise, and with Valsalva, and NT-proBNP level, independent of age and sex (all P < 0.01). For both algorithms, the strongest longitudinal correlation was between AI-ECG HCM score and left ventricular outflow tract gradient postexercise (slope estimate: University of California-San Francisco 0.70 [95% CI: 0.45-0.96], P < 0.0001; Mayo 0.40 [95% CI: 0.11-0.68], P = 0.007). CONCLUSIONS: AI-ECG analysis longitudinally correlated with changes in echocardiographic and laboratory markers during mavacamten treatment in obstructive HCM. These results provide early evidence for a potential paradigm for monitoring HCM therapeutic response.

Data-Driven and Technology-Enabled Trial Innovations Toward Decentralization of Clinical Trials: Opportunities and Considerations.

Traditional trial designs have well-recognized inefficiencies and logistical barriers to participation. Decentralized trials and digital health solutions have been suggested as potential solutions and have certainly risen to the challenge during the pandemic. Clinical trial designs are now increasingly data driven. The use of distributed clinical data networks and digitization has helped to fundamentally upgrade existing research systems. A trial design may vary anywhere from fully decentralized to hybrid to traditional on-site. Various decentralization components are available for stakeholders to increase the reach and pace of their trials, such as electronic informed consent, remote interviews, administration, outcome assessment, monitoring, and laboratory and imaging modalities. Furthermore, digital health technologies can be included to enrich study conduct. However, careful consideration is warranted, including assessing verification and validity through usability studies and having various contingencies in place through dedicated risk assessment. Selecting the right combination depends not just on the ability to handle patient care and the medical know-how but also on the availability of appropriate technologic infrastructure, skills, and human resources. Throughout this process, quality of evidence generation and physician-patient relation must not be undermined. Here we also address some knowledge gaps, cost considerations, and potential impact of decentralization and digitization on inclusivity, recruitment, engagement, and retention. Last, we mention some future directions that may help drive the necessary change in the right direction.

Mayo Clinic VT calculator: A practical tool for accurate wide complex tachycardia differentiation.

The discrimination of ventricular tachycardia (VT) versus supraventricular wide complex tachycardia (SWCT) via 12-lead electrocardiogram (ECG) is crucial for achieving appropriate, high-quality, and cost-effective care in patients presenting with wide QRS complex tachycardia (WCT). Decades of rigorous research have brought forth an expanding arsenal of applicable manual algorithm methods for differentiating WCTs. However, these algorithms are limited by their heavy reliance on the ECG interpreter for their proper execution. Herein, we introduce the Mayo Clinic ventricular tachycardia calculator (MC-VTcalc) as a novel generalizable, accurate, and easy-to-use means to estimate VT probability independent of ECG interpreter competency. The MC-VTcalc, through the use of web-based and mobile device platforms, only requires the entry of computerized measurements (i.e., QRS duration, QRS axis, and T-wave axis) that are routinely displayed on standard 12-lead ECG recordings.

Persistence of left atrial thrombus in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: We recently demonstrated that patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM) have an increased risk of left atrial (LA) thrombus. In this study, we aimed to evaluate thrombus management, thrombus persistence, and thromboembolic events for HCM and non-HCM patients with AF and LA thrombus. METHODS: From a cohort of 2,155 AF patients undergoing transesophageal echocardiography (TEE) for any indication, this study included 122 patients with LA thrombus (64 HCM patients and 58 non-HCM controls). RESULTS: There was no difference in mean CHA2DS2-VASc scores between HCM and control patients (3.9 ± 2.2 vs 3.8 ± 2.0, p = 0.88). Ten (16%) and 4 (7%) patients in the HCM and control groups, respectively, were in sinus rhythm at the time of TEE identifying the LA thrombus (p = 0.13). In all patients, the anticoagulation strategy was modified after the LA thrombus diagnosis. A total of 36 (56%) HCM patients and 34 (59%) control patients had follow-up TEE at median 90 and 62 days, respectively, after index TEE. The HCM group had significantly higher 90-day rates of persistent LA thrombus compared to the control group (88% vs 29%; p < 0.001). In adjusted models, HCM was independently associated with LA thrombus persistence. Among patients with LA thrombus, the 5-year cumulative incidence of thromboembolic events was 11% and 2% in HCM and control groups, respectively (p = 0.22). CONCLUSIONS: Among patients with AF with LA thrombus identified by TEE, those with HCM appear to have a higher risk of LA thrombus persistence than non-HCM patients despite anticoagulation.

Physicians' perspectives on percutaneous left atrial appendage occlusion for patients with atrial fibrillation.

BACKGROUND: There has been an increasing uptake of transcatheter left atrial appendage occlusion (LAAO) for stroke reduction in atrial fibrillation. OBJECTIVES: To investigate the perceptions and approaches among a nationally representative sample of physicians. METHODS: Using the American Medical Association Physician Masterfile, we selected a random sample of 500 physicians from each of the specialties: general cardiologists, interventional cardiologists, electrophysiologists, and vascular neurologists. The participants received the survey by mail up to three times from November 9, 2021 to January 14, 2022. In addition to the questions about experiences, perceptions, and approaches, physicians were randomly assigned to 1 of the 4 versions of a patient vignette: white man, white woman, black man, and black woman, to investigate potential bias in decision-making. RESULTS: The top three reasons for considering LAAO were: a history of intracranial bleeding (94.3%), a history of major extracranial bleeding (91.8%), and gastrointestinal lesions (59.0%), whereas the top three reasons for withholding LAAO were: other indications for long-term oral anticoagulation (87.7%), a low bleeding risk (77.0%), and a low stroke risk (65.6%). For the reasons limiting recommendations for LAAO, 59.8% mentioned procedural risks, 42.6% mentioned "limiting efficacy data comparing LAAO to NOAC" and 32.8% mentioned "limited safety data comparing LAAO to NOAC." There was no difference in physicians' decision-making by patients' race, gender, or the concordance between patients' and physicians' race or gender. CONCLUSIONS: In the first U.S. national physician survey of LAAO, individual physicians' perspectives varied greatly, which provided information that will help customize future educational activities for different audiences. CONDENSED ABSTRACT: Although diverse practice patterns of LAAO have been documented, little is known about the reasoning or perceptions that drive these variations. Unlike prior surveys that were directed to Centers that performed LAAO, the current survey obtained insights from individual physicians, not only those who perform the procedures (interventional cardiologists and electrophysiologists) but also those who are closely involved in the decision-making and referral process (general cardiologists and vascular neurologists). The findings identify key evidence gaps and help prioritize future studies to establish a consistent and evidence-based best practice for AF stroke prevention.