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Abstract Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a “digital clinical trial” involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research.

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society describes the current status of mobile health (“mHealth”) technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.

Background: Population-based data on heart failure (HF)-related death in patients with atrial fibrillation (AF) are lacking. We assessed HF-related death in people with AF in the United States over the past 21 years and examined differences by age, sex, race, ethnicity, urbanization, and census region., Methods and Results: Data were extracted from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to determine trends in age-adjusted mortality rates per 100 000 people, due to HF-related death among subjects with AF aged ≥15 years. To calculate nationwide annual trends, we assessed the average annual percent change (AAPC) and annual percent change with relative 95% CIs using joinpoint regression. Between 1999 and 2020, 916 685 HF-related deaths (396 205 men and 520 480 women) occurred among US adults having a concomitant AF. The overall age-adjusted mortality rates increased (AAPC: +4.1% [95% CI, 3.8-4.4]; P <0.001), especially after 2011 (annual percent change, +6.8% [95% CI, 6.2-7.4]; P <0.001) in men (AAPC, +4.8% [95% CI, 4.4-5.1]; P <0.001), in White subjects (AAPC: +4.2% [95% CI, 3.9 to 4.6]; P <0.001) and in subjects aged <65 years (AAPC: +7.5% [95% CI, 6.7-8.4]; P <0.001). The higher percentage of deaths were registered in the South (32.8%). During the first year of the COVID-19 pandemic, a significant excess in HF-related deaths among patients with AF aged >65 years was observed., Conclusions: A worrying increase in the HF-related mortality rate among patients with AF has been observed in the United States over the past 2 decades.

Background: High blood pressure affects approximately 116 million adults in the United States. It is the leading risk factor for death and disability across the world. Unfortunately, over the past decade, hypertension control rates have decreased across the United States. Prediction models and clinical studies have shown that reducing clinician inertia alone is sufficient to reach the target of ≥80% blood pressure control. Digital health tools containing evidence-based algorithms that are able to reduce clinician inertia are a good fit for turning the tide in blood pressure control, but careful consideration should be taken in the design process to integrate digital health interventions into the clinical workflow., Methods: We describe the development of a provider-facing hypertension management platform. We enumerate key steps of the development process, including needs finding, clinical workflow analysis, treatment algorithm creation, platform design and electronic health record integration. We interviewed and surveyed 5 Stanford clinicians from primary care, cardiology, and their clinical care team members (including nurses, advanced practice providers, medical assistants) to identify needs and break down the steps of clinician workflow analysis. The application design and development stage were aided by a team of approximately 15 specialists in the fields of primary care, hypertension, bioinformatics, and software development., Conclusions: Digital monitoring holds immense potential for revolutionizing chronic disease management. Our team developed a hypertension management platform at an academic medical center to address some of the top barriers to adoption and achieving clinical outcomes. The frameworks and processes described in this article may be used for the development of a diverse range of digital health tools in the cardiovascular space.

Competing Interests: Disclosures Dr Pundi reports research grants from the American Heart Association and the American College of Cardiology, as well as consulting fees from Evidently and 100Plus. Dr Marcus reports grant support from the National Institutes of Health (National Institute on Alcohol Abuse and Alcoholism; National Heart, Lung, and Blood Institute; National Institute of Biomedical Imaging and Bioengineering; National Institute on Drug Abuse), the Bill and Melinda Gates Foundation, the Patient Centered Outcomes Research Institute, the Tobacco-Related Disease Research Program, and Baylis Medical; consultant fees from Johnson & Johnson and InCarda; and equity in InCarda. Dr Turakhia reports research grants from Bristol Myers Squibb, the American Heart Association, Apple Inc, Bayer, Gilead Sciences, and the US Food and Drug Administration; consulting fees from Medtronic, Abbott, Biotronik, Sanofi, Pfizer, Myokardia, Johnson & Johnson, and Alivecor; and equity from iRhythm, Connect America, Forward, Evidently, and PocketRN. Dr Turakhia is an employee of iRhythm Technologies Inc, which manufacturers ambulatory electrocardiographic monitors, but this work was not supported by the company and was performed exclusively in his academic role.

Background Cardiovascular procedural treatments were deferred at scale during the COVID-19 pandemic, with unclear impact on patients presenting with non-ST-segment-elevation myocardial infarction (NSTEMI). Methods and Results In a retrospective cohort study of all patients diagnosed with NSTEMI in the US Veterans Affairs Healthcare System from January 1, 2019 to October 30, 2022 (n=67 125), procedural treatments and outcomes were compared between the prepandemic period and 6 unique pandemic phases: (1) acute phase, (2) community spread, (3) first peak, (4) post vaccine, (5) second peak, and (6) recovery. Multivariable regression analysis was performed to assess the association between pandemic phases and 30-day mortality. NSTEMI volumes dropped significantly with the pandemic onset (62.7% of prepandemic peak) and did not revert to prepandemic levels in subsequent phases, even after vaccine availability. Percutaneous coronary intervention and coronary artery bypass grafting volumes declined proportionally. Compared with the prepandemic period, patients with NSTEMI experienced higher 30-day mortality during Phases 2 and 3, even after adjustment for COVID-19-positive status, demographics, baseline comorbidities, and receipt of procedural treatment (adjusted odds ratio for Phases 2 and 3 combined, 1.26 [95% CI, 1.13-1.43], P <0.01). Patients receiving Veterans Affairs-paid community care had a higher adjusted risk of 30-day mortality compared with those at Veterans Affairs hospitals across all 6 pandemic phases. Conclusions Higher mortality after NSTEMI occurred during the initial spread and first peak of the pandemic but resolved before the second, higher peak-suggesting effective adaptation of care delivery but a costly delay to implementation. Investigation into the vulnerabilities of the early pandemic spread are vital to informing future resource-constrained practices.

Background Oral anticoagulation reduces stroke and disability in atrial fibrillation (AF) but is underused. We evaluated the effects of a novel patient-clinician shared decision-making (SDM) tool in reducing oral anticoagulation patient's decisional conflict as compared with usual care. Methods and Results We designed and evaluated a new digital decision aid in a multicenter, randomized, comparative effectiveness trial, ENHANCE-AF (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention). The digital AF shared decision-making toolkit was developed using patient-centered design with clear health communication principles (eg, meaningful images, limited text). Available in English and Spanish, the toolkit included the following: (1) a brief animated video; (2) interactive questions with answers; (3) a quiz to check on understanding; (4) a worksheet to be used by the patient during the encounter; and (5) an online guide for clinicians. The study population included English or Spanish speakers with nonvalvular AF and a CHA 2 DS 2 -VASc stroke score ≥1 for men or ≥2 for women. Participants were randomized in a 1:1 ratio to either usual care or the shared decision-making toolkit. The primary end point was the validated 16-item Decision Conflict Scale at 1 month. Secondary outcomes included Decision Conflict Scale at 6 months and the 10-item Decision Regret Scale at 1 and 6 months as well as a weighted average of Mann-Whitney U -statistics for both the Decision Conflict Scale and the Decision Regret Scale. A total of 1001 participants were enrolled and followed at 5 different sites in the United States between December 18, 2019, and August 17, 2022. The mean patient age was 69±10 years (40% women, 16.9% Black, 4.5% Hispanic, 3.6% Asian), and 50% of participants had CHA 2 DS 2 -VASc scores ≥3 (men) or ≥4 (women). The primary end point at 1 month showed a clinically meaningful reduction in decisional conflict: a 7-point difference in median scores between the 2 arms (16.4 versus 9.4; Mann-Whitney U -statistics=0.550; P =0.007). For the secondary end point of 1-month Decision Regret Scale, the difference in median scores between arms was 5 points in the direction of less decisional regret ( P =0.078). The treatment effects lessened over time: at 6 months the difference in medians was 4.7 points for Decision Conflict Scale ( P =0.060) and 0 points for Decision Regret Scale ( P =0.35). Conclusions Implementation of a novel shared decision-making toolkit (afibguide.com; afibguide.com/clinician) achieved significantly lower decisional conflict compared with usual care in patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096781.

The digital clinical trial is fast emerging as a pragmatic trial that can improve a trial's design including recruitment and retention, data collection and analytics. To that end, digital platforms such as electronic health records or wearable technologies that enable passive data collection can be leveraged, alleviating burden from the participant and study coordinator. However, there are challenges. For example, many of these data sources not originally intended for research may be noisier than traditionally obtained measures. Further, the secure flow of passively collected data and their integration for analysis is non-trivial. The Apple Heart Study was a prospective, single-arm, site-less digital trial designed to evaluate the ability of an app to detect atrial fibrillation. The study was designed with pragmatic features, such as an app for enrollment, a wearable device (the Apple Watch) for data collection, and electronic surveys for participant-reported outcomes that enabled a high volume of patient enrollment and accompanying data. These elements led to challenges including identifying the number of unique participants, maintaining participant-level linkage of multiple complex data streams, and participant adherence and engagement. Novel solutions were derived that inform future designs with an emphasis on data management. We build upon the excellent framework of the Clinical Trials Transformation Initiative to provide a comprehensive set of guidelines for data management of the digital clinical trial that include an increased role of collaborative data scientists in the design and conduct of the modern digital trial.

Background: The COVID-19 pandemic has disrupted routine cardiovascular care, with unclear impact on procedural deferrals and associated outcomes across diverse patient populations., Methods: Cardiovascular procedures performed at 30 hospitals across 6 Western states in 2 large, non-profit healthcare systems (Providence St. Joseph Health and Stanford Healthcare) from December 2018-June 2020 were analyzed for changes over time. Risk-adjusted in-hospital mortality was compared across pandemic phases with multivariate logistic regression., Results: Among 36,125 procedures (69% percutaneous coronary intervention, 13% coronary artery bypass graft surgery, 10% transcatheter aortic valve replacement, and 8% surgical aortic valve replacement), weekly volumes changed in 2 distinct phases after the initial inflection point on February 23, 2020: an initial period of significant deferral (COVID I: March 15-April 11) followed by recovery (COVID II: April 12 onwards). Compared to pre-COVID, COVID I patients were less likely to be female (P = .0003), older (P < .0001), Asian or Black (P = .02), or Medicare insured (P < .0001), and COVID I procedures were higher acuity (P < .0001), but not higher complexity. In COVID II, there was a trend toward more procedural deferral in regions with a higher COVID-19 burden (P = .05). Compared to pre-COVID, there were no differences in risk-adjusted in-hospital mortality during both COVID phases., Conclusions: Significant decreases in cardiovascular procedural volumes occurred early in the COVID-19 pandemic, with disproportionate impacts by race, gender, and age. These findings should inform our approach to future healthcare disruptions., (Published by Elsevier Inc.)

Background: Improving adherence to direct oral anticoagulants (DOAC) is challenging, and simple text messaging reminders have not been effective., Methods: SmartADHERE was a randomized trial that tested a personalized digital and human direct oral anticoagulant adherence intervention compared to usual care. Eligibility required age ≥ 18, newly-prescribed (≤90 days) rivaroxaban for atrial fibrillation (AF), 1 of 4 at-risk criteria for nonadherence, and a smartphone. The intervention consisted of combination of a medication management smartphone app, daily app-based reminders, adaptive text messaging, and phone-based counseling for severe nonadherence. The primary outcome was the proportion of days covered by rivaroxaban (PDC) at 6 months. There were 25 U.S. sites, all cardiology and electrophysiology outpatient practices, activated for a target sample size of 378, but the study was terminated by the sponsor prior to reaching target enrollment., Results: There were 139 participants (age 65±9.6 years, 30% female, median CHA 2 DS 2 -VASc score 3 with IQR 2 to 4, mean total medication burden 7.7±4.4). DOAC adherence was high in both arms with no difference in the primary outcome (PDC 0.86±0.25 intervention vs 0.88±0.25 control, p=0.62) or in secondary outcomes including PDC ≥ 0.80 and medication persistence. Per protocol analyses had similar results. Because of the high overall PDC, the likelihood to answer the primary hypothesis was only 51% even if target enrollment were achieved. There were no study-related adverse events., Conclusions: The use of a centralized digital and human adherence intervention was feasible across multiple sites. Overall adherence was much higher than expected despite prescreening for at-risk individuals. SmartADHERE illustrates the challenges of trials of behavioral and technology interventions, where enrollment itself may lead to selection bias or treatment effects. Pragmatic study designs, such as cluster randomization or stepped-wedge implementation, should be considered to improve enrollment and generalizability., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable; however, current risk stratification tools (CHA 2 DS 2 -VASc) do not include family history or genetic risk. We hypothesized that we could improve ischemic stroke prediction in patients with AF by incorporating polygenic risk scores (PRS)., Methods: Using data from the largest available genome-wide association study in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank, both independently and integrated with clinical risk factors. The integrated PRS and clinical risk factors risk tool had the greatest predictive ability., Results: Compared with the currently recommended risk tool (CHA 2 DS 2 -VASc), the integrated tool significantly improved Net Reclassification Index (2.3% [95% CI, 1.3%-3.0%]) and fit (χ 2 P =0.002). Using this improved tool, >115 000 people with AF would have improved risk classification in the United States. Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (hazard ratio, 1.13 per 1 SD [95% CI, 1.06-1.23]). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson correlation coefficient, -0.018)., Conclusions: In patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors; however, the prediction of stroke remains challenging.

Background: The success of vaccination efforts to curb the COVID-19 pandemic will require broad public uptake of immunization and highlights the importance of understanding factors associated with willingness to receive a vaccine., Methods: U.S. adults aged 65 and older enrolled in the HeartlineTM clinical study were invited to complete a COVID-19 vaccine assessment through the HeartlineTM mobile application between November 6-20, 2020. Factors associated with willingness to receive a COVID-19 vaccine were evaluated using an ordered logistic regression as well as a Random Forest classification algorithm., Results: Among 9,106 study participants, 81.3% (n = 7402) responded and had available demographic data. The majority (91.3%) reported a willingness to be vaccinated. Factors most strongly associated with vaccine willingness were beliefs about the safety and efficacy of COVID-19 vaccines and vaccines in general. Women and Black or African American respondents reported lower willingness to vaccinate. Among those less willing to get vaccinated, 66.2% said that they would talk with their health provider before making a decision. During the study, positive results from the first COVID-19 vaccine outcome study were released; vaccine willingness increased after this report., Conclusions: Even among older adults at high-risk for COVID-19 complications who are participating in a longitudinal clinical study, 1 in 11 reported lack of willingness to receive COVID-19 vaccine in November 2020. Variability in vaccine willingness by gender, race, education, and income suggests the potential for uneven vaccine uptake. Education by health providers directed toward assuaging concerns about vaccine safety and efficacy can help improve vaccine acceptance among those less willing., Trial Registration: Clinicaltrials.gov NCT04276441., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JN, MK, GJW, JW, TS, JS, PB, RZ, NE, JT, RJ are employees of Janssen and Johnson and Johnson. JN, MK, GJW, JW, TS, JS, PB, RZ, NE, JT, RJ are employees of Janssen and Johnson and Johnson. This does not alter our adherence to PLOS ONE policies on sharing data and materials. JS reports personal fees from Amgen, personal fees from Bayer, personal fees from Merck, personal fees from Novartis, personal fees from Janssen, personal fees from Myokardia, personal fees from Blue Cross Blue Shield of Kansas City, outside the submitted work. In addition, Dr. Spertus has a patent Copyright to the KCCQ with royalties paid and Equity in Health Outcomes Sciences. This does not alter my adherence to PLOS ONE policies on sharing data and materials. MT reports grants from Janssen Inc, personal fees from Medtronic Inc, personal fees from Abbott, grants from Boehringer lngelheim, grants and personal fees from Cardiva Medical, personal fees from iRhythm, grants from Bristol Myers Squibb, grants from American Heart Association, grants from SentreHeart, personal fees from Novartis, personal fees from Biotronik, personal fees from Sanofi, personal fees from Pfizer, grants from Apple, grants from Bayer, personal fees from Myokardia, personal fees from Johnson & Johnson, personal fees from Milestone Pharmaceuticals, outside the submitted work; and Dr. Turakhia is an editor for JAMA Cardiology. This does not alter my adherence to PLOS ONE policies on sharing data and materials. LS reports personal fees from J&J, outside the submitted work. This does not alter my adherence to PLOS ONE policies on sharing data and materials. MG receives research grant support from Janssen. This does not alter my adherence to PLOS ONE policies on sharing data and materials. AMN receives consulting fees from Janssen for serving on the steering committee of the Heartline study. In addition, Dr. Navar receives funding for research to her institution from Amgen and Janssen, and honoraria and consulting fees from Amarin, Amgen, Astra Zeneca, BI, Esperion, Lilly, Sanofi, Regeneron, NovoNordisk, Novartis, The Medicines Company, New Amsterdam, Cerner, 89Bio, and Pfizer, outside the scope of this work. This does not alter my adherence to PLOS ONE policies on sharing data and materials.

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/ Heart Rhythm Society/ European Heart Rhythm Association/ Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored., (This article has been co-published with the permission of Annals of Noninvasive Electrocardiology, Cardiovascular Digital Health Journal, Circulation: Arrhythmia and Electrophysiology, European Heart Journal - Digital Health and Journal of Arrhythmia. All rights reserved. © 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals Inc. on behalf of the International Society for Holter and Noninvasive Electrocardiology / Cardiovascular Digital Health Journal published by Elsevier Inc. on behalf of the Heart Rhythm Society / Circulation: Arrhythmia and Electrophysiology published by Wolters Kluwer Health, Inc. on behalf of the American Heart Association, Inc. / European Heart Journal - Digital Health published by Oxford University Press on behalf of the European Society of Cardiology / Journal of Arrhythmia published by Wiley and Sons Australia Ltd on behalf of the Japanese Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. This article is published under the Creative Commons CC-BY license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.)

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology / Heart Rhythm Society / European Heart Rhythm Association / Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a "digital clinical trial" involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research., Competing Interests: Competing interestsM.T. reports grants from Janssen Inc, personal fees from Medtronic Inc, grants from AstraZeneca, other from AliveCor, personal fees from Abbott, grants from Boehringer Ingelheim, personal fees from Precision Health Economics, personal fees from iBeat Inc, grants and personal fees from Cardiva Medical, personal fees from iRhythm, grants from Bristol Myers Squibb, grants from American Heart Association, grants from SentreHeart, personal fees from Novartis, personal fees from Biotronik, personal fees from Sanofi-Aventis, personal fees from Pfizer, grants from Apple, outside the submitted work; and Dr. M.T. is an editor for JAMA Cardiology. B. Spring is on the Scientific Advisory Board for Actigraph. O.T.I. is a Scientific Advisor for Physiowave, Inc. and a Co-Founder and Scientific Advisor for Cardiosense, has research funding for his lab from Hill-Rom Services, Inc. and Murata Americas, and has IP licensed by Physiowave, TandemLaunch, and Cardiosense. Dr. K.D.M.’s research lab receives philanthropic support from Eli Lily and he has consulted on using real world evidence for Merck. M.J.P. is supported by the NIH to develop and maintain a research platform to support digital trials and mHealth data collection. S.R.S. has served as a medical advisor for Janssen, Otsuka, Livongo, DynoSense, BioSense, and Spry Health. H.R. has received donations of OCT catheters for a research study from Abbott Vascular and telemetry monitors from BioTelemetry, Inc. Dr. Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs; was a recipient of a research grant, through Yale, from Medtronic and the Food and Drug Administration to develop methods for post-market surveillance of medical devices; was a recipient of a research grant with Medtronic and is the recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin/Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the co-founder of HugoHealth, a personal health information platform, and co-founder of Refactor Health, an enterprise healthcare AI-augmented data management company.R.C. reports employment with Verily Life Sciences and Google Health, board membership at Cytokinetics, and status of former commissioner of the US FDA., (© The Author(s) 2020.)

Background: Many digital health technologies capable of atrial fibrillation (AF) detection are directly available to patients. However, adaptation into clinical practice by heart rhythm healthcare practitioners (HCPs) is unclear., Objective: To examine HCP perspectives on use of commercial technologies for AF detection and management., Methods: We created an electronic survey for HCPs assessing practice demographics and perspectives on digital devices for AF detection and management. The survey was distributed electronically to all members of 3 heart rhythm professional societies., Results: We received 1601 responses out of 73,563 e-mails sent, with 43.6% from cardiac electrophysiologists, 12.8% from fellows, and 11.6% from advanced practice practitioners. Most respondents (62.3%) reported having recommended patient use of a digital device for AF detection. Those who did not had concerns about their accuracy (29.6%), clinical utility of results (22.8%), and integration into electronic health records (19.8%). Results from a 30-second single-lead electrocardiogram were sufficient for 42.7% of HCPs to recommend oral anticoagulation for patients at high risk for stroke. Respondents wanted more data comparing the accuracy of digital devices to conventional devices for AF monitoring (64.9%). A quarter (27.3%) of HCPs had no reservations recommending digital devices for AF detection, and most (53.4%) wanted guidelines from their professional societies providing guidance on their optimal use., Conclusion: Many HCPs have already integrated digital devices into their clinical practice. However, HCPs reported facing challenges when using digital technologies for AF detection, and professional society recommendations on their use are needed., (© 2020 The Authors.)

Aims: Manual compression (MC), widely used to achieve venous access haemostasis, needs prolonged immobilization and extended time-to-haemostasis. Vascular closure devices (VCD) have been reported to have significantly shorter time to haemostasis and ambulation in arterial access-site management. The current study aimed to evaluate the safety and efficacy as well as rate of urinary tract complications in patients receiving MC vs. VCD for venous access-site closure., Methods and Results: A total of 803 consecutive patients undergoing catheter ablation or left atrial appendage closure were classified into the VCD (n = 304) and the MC (n = 499) group, based on the methods used for haemostasis at the venous access site. Foley catheter was used for bladder-emptying in all MC cases and 15 VCD patients. At one site, VCD group patients with experience of MC in prior ablations were asked to describe their overall satisfaction level after comparing the past experience with the present. Haemostasis was achieved effectively in both populations. No VCD cases required >2 h bed rest, whereas 7 (1.4%) patients in the MC group needed prolonged immobilization (P = 0.04). Significantly higher incidence of access-site haematoma (P = 0.004) and urinary complications (P < 0.05) were observed in the MC group. Majority of VCD patients (68%) with prior experience of MC for haemostasis expressed satisfaction over the early ambulation and ability to void urine without bladder catheterization., Conclusion: Vascular closure devices provided effective haemostasis, while reducing the access-site complications, ambulation time, and urinary complications., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Antiarrhythmic drugs used in atrial fibrillation (AF) cause QT prolongation and are associated with torsades de pointes, a deadly ventricular arrhythmia. No consensus exists on the optimal method of QT measurement or correction in AF. Therefore, we compared common methods to measure and correct QT in AF to identify the most accurate approach. We identified patients who had electrocardiograms done at Stanford Hospital (Stanford, California) between January 2014 and October 2016 with conversion from AF to sinus rhythm (SR) within a 24-hour period. QT intervals were determined using different measurement methods and corrected using the Bazett's, Framingham, Fridericia, or Hodges formulas for heart rate (HR). Comparisons were made between QT in a patient's last instance of AF to SR. Computerized measurements were taken from 715 patients. Manual measurements were taken from a 50-patient subset. Bazett's formula produced the longest corrected QT in AF compared with other formulas (p <0.005). Measuring QT as an average over multiple beats resulted in a smaller difference between AF and SR than choosing a single beat. Determining QT from a 5-beat average resulted in a QTc that was 19.0 ms higher (interquartile range 0.30 to 43.7) in AF than SR. After correcting for residual effect of HR on QTc, there was not a significant difference between QTc in AF to SR. In conclusion, measuring QT over multiple beats produces a more accurate measurement of QT in AF. Differences between QTc in AF and SR exist because of imperfect HR correction formula and not due to an independent effect of AF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Efforts to improve prescription of oral anticoagulation (OAC) drugs in patients with atrial fibrillation have had limited success in improving guideline adherence., Methods: We evaluated adherence to the American College of Cardiology/American Heart Association performance measures for OAC in eligible patients with a CHA 2 DS 2 -VASc score ≥2 and trends in prescription over time in the American Heart Association's Get With The Guidelines-AFIB (atrial fibrillation) registry. Adjusted associations with in-hospital outcomes were also determined. The cohort included 33 235 patients with a CHA 2 DS 2 -VASc score ≥2 who were admitted for atrial fibrillation and were enrolled at 115 sites between January 1, 2013, and September 31, 2017., Results: The median (25th, 75th percentile) age was 73 years (65, 81 years); 51% were female; and the median (25th, 75th percentile) CHA 2 DS 2 -VASc score was 4 (3, 5). At admission, 16 206 (59.5%) of 27 221 patients with a previous diagnosis of atrial fibrillation were taking OAC agents, and OAC drug use at admission was associated with a lower adjusted odds of in-hospital ischemic stroke (odds ratio, 0.38; 95% CI, 0.24-0.59; P<0.0001). At discharge, prescription of OAC in eligible patients (no contraindications) was 93.5% (n=25 499 of 27 270). In a sensitivity analysis, when excluding only strict contraindications (4.6%, n=1497 of 32 806), OAC prescription at discharge was 80.3%. OAC prescription at discharge was higher in those aged ≤75 years, men, those with heart failure, those with previous atrial fibrillation ablation, and those with rhythm control ( P<0.0001 for all). OAC use was lowest in Hispanic patients (90.2%, P<0.0001). Prescription of OAC at discharge in eligible patients improved over time from 79.9% to 96.6% ( P<0.0001)., Conclusions: Among hospitals participating in the GWTG-AFIB quality improvement program, OAC prescription at discharge in eligible guideline-indicated patients increased significantly and improved consistently over time. These data confirm that high-level adherence to guideline-recommended stroke prevention is achievable.

Aims: Atrial fibrillation (AF) is associated with increased mortality, but the temporal relationship between AF burden (AFB) and death among patients with cardiac implanted electronic devices is unknown. We sought to characterize the timing and progression of AFB before death., Methods and Results: Using Merlin.netTM remote monitoring (RM) data, we analysed weekly AFB in patients age ≥55 years implanted with dual-chamber pacemaker, implantable cardioverter-defibrillator, or cardiac resynchronization therapy devices whose death was verified in the Social Security Death Index and who had continuous RM from 1 year to 4 weeks preceding death. Atrial fibrillation burden was defined as amount of time per week atrial rate exceeded a set threshold of 180 b.p.m. Case-crossover analysis was used to compare the AFB at every week to 6 control weeks at the start of the year before death. There were 3131 patients meeting analysis criteria (age at death 76 ± 8 years, 70% men). Weekly increase in AFB >6 h was associated with increased odds of death, which was greatest at 4 weeks before death [odds ratio (OR) 2.30, 95% confidence interval (CI) 2.09-2.53; P < 0.001]. Atrial fibrillation progression week-to-week >24 h was associated with the greatest odds of death (OR 12.95, 95% 8.72-19.22; P < 0.001). A combination of AFB >6 h per week and activity <0.5 h per day was associated with an increased odds of death., Conclusion: In this large patient cohort, AFB progression accelerated in the weeks leading to death. Continuous monitoring of AFB may help identify device patients who may be at risk for adverse outcomes, including death., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: The risk of stroke is heterogeneous across different groups of patients with atrial fibrillation (AF), being dependent on the presence of various stroke risk factors. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios., Methods: Systematic literature reviews were conducted to identify relevant articles published from the last formal search perfomed for the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). The overall quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted, voted on, and revised until consensus was reached., Results: For patients with AF without valvular heart disease, including those with paroxysmal AF, who are at low risk of stroke (eg, CHA 2 DS 2 -VASc [congestive heart failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)] score of 0 in males or 1 in females), we suggest no antithrombotic therapy. The next step is to consider stroke prevention (ie, oral anticoagulation therapy) for patients with 1 or more non-sex CHA 2 DS 2 -VASc stroke risk factors. For patients with a single non-sex CHA 2 DS 2 -VASc stroke risk factor, we suggest oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel; and for those at high risk of stroke (eg, CHA 2 DS 2 -VASc ≥ 2 in males or ≥ 3 in females), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest using a non-vitamin K antagonist oral anticoagulant drug rather than adjusted-dose vitamin K antagonist therapy. With the latter, it is important to aim for good quality anticoagulation control with a time in therapeutic range > 70%. Attention to modifiable bleeding risk factors (eg, uncontrolled BP, labile international normalized ratios, concomitant use of aspirin or nonsteroidal antiinflammatory drugs in an anticoagulated patient, alcohol excess) should be made at each patient contact, and HAS-BLED (hypertension, abnormal renal/liver function [1 point each], stroke, bleeding history or predisposition, labile international normalized ratio, elderly (0.65), drugs/alcohol concomitantly [1 point each]) score used to assess the risk of bleeding where high risk patients (≥ 3) should be reviewed and followed up more frequently., Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF with ≥1 non-sex CHA 2 DS 2 -VASc stroke risk factor(s)., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Atrial fibrosis appears to be a key factor in the genesis and/or perpetuation of atrial fibrillation (AF). The pathological distribution of atrial fibrosis is geographically consistent with the attachments between the posterior left atrium and the pericardium along the reflections where wall stiffness is increased and structural changes are found. While there is a wide range of complex etiological factors and electrophysiological mechanisms in AF, there is evidence for a common pathophysiological pathway that could account for deliberate substrate formation and progression of AF. Anatomical stresses along the atrium, mediated by the elastic modulus mismatch between atrial tissue and the pericardium, result in inflammatory and fibrotic changes which create the substrate for atrial fibrillation. This may explain the anatomical predominance of pulmonary vein triggers earlier in the development of atrial fibrillation and the increasing involvement of the atrium as the disease progresses. Ablative treatments that address the progressive nature of atrial fibrillation and fibrosis may yield improved success rates.

Objective: Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring may predispose patients to non-persistence. Limited information is available on NOAC non-persistence rates and related clinical outcomes in clinical practice., Methods: We conducted a retrospective cohort study using administrative data from Ontario, Canada, from January 1998 to March 2014 of patients with AF who were dispensed dabigatran or rivaroxaban. Non-persistence was defined as a gap in dabigatran or rivaroxaban prescriptions ≥14 days. A multivariable Cox proportional hazards model was used to estimate the primary composite outcome of stroke, transient ischaemic attack (TIA) and mortality associated with non-persistence., Results: The cohort consisted of 15 857 dabigatran (age 80.7±6.7 year) and 10 119 rivaroxaban users (age 77.0±7.1 year) with women comprising 52% of each medication group. At 6 months, 36.4% of patients were non-persistent to dabigatran, while 31.9% of patients were non-persistent to rivaroxaban. Stroke/TIA/death was significantly higher for those non-persistent to dabigatran (HR 1.76 (95% CI 1.60 to 1.94); p<0.0001) or rivaroxaban (HR 1.89 (95% CI 1.64 to 2.19); p<0.0001) compared with those who were persistent. Risk of stroke/TIA was markedly higher in non-persistent patients to dabigatran (HR 3.75 (95% CI 2.59 to 5.43); p<0.0001) and rivaroxaban (HR 6.25 (95% CI 3.37 to 11.58); p<0.0001) than those persistent., Conclusions: NOAC non-persistence rates are high in clinical practice, with approximately one in three patients becoming non-persistent to dabigatran or rivaroxaban within 6 months after drug initiation. Non-persistence with either dabigatran or rivaroxaban is significantly associated with worse clinical outcomes of stroke/TIA/death., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Use of the CHA 2 DS 2 -VASc score instead of the CHADS 2 score for thromboembolic risk stratification and initiation of oral anticoagulation (OAC) was recommended in the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society atrial fibrillation (AF) guidelines. We sought to define the proportion of patients with AF qualifying for and receiving OAC in contemporary practice by applying the CHA 2 DS 2 -VASc score to patients with a low CHADS 2 score., Methods and Results: Among patients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry's outpatient Practice Innovation and Clinical Excellence registry (2008-2014) CHADS 2 score of 0 or 1, we calculated the impact of adoption of the CHA 2 DS 2 -VASc score on the proportion of patients with an indication for OAC. We examined trends in prescription of OAC overall, direct OAC (dabigatran/rivaroxaban/apixaban), and multivariable associations between clinical characteristics and OAC use. Of 346 068 patients with AF aged 65±12 years, 61% were men and 65% were white. In total, 24% of those with CHADS 2 =0 and 81% of those with a CHADS 2 =1 were reclassified as having a definite indication for OAC (CHA 2 DS 2 -VASc score ≥2). OAC use increased from 37% to 48% during the study period, and direct OAC use increased from 5% to 30%. Increasing CHA 2 DS 2 -VASc score (odds ratio, 2.07; 95% confidence interval, 1.97-2.19 for score of 4 versus 0) and rhythm control strategy (odds ratio, 1.34; 95% confidence interval, 1.30-1.39) were associated with increased OAC use., Conclusions: Adoption of the CHA 2 DS 2 -VASc score reclassifies 64.5% of patients with AF with low CHADS 2 scores into a class I indication for OAC prescription. Overall OAC prescription increased between 2011 and 2014., (© 2017 American Heart Association, Inc.)

In the United States (U.S.), atrial fibrillation (AF) is the second-most common cardiovascular condition after hypertension, affecting four million Americans each year. Individuals with AF are three times more likely to be hospitalized over the span of a year when compared to medically matched control groups. The considerably large clinical population of individuals with AF mandates that the cost-effectiveness and efficacy of current treatment regimens for AF have egregious implications for health care spending and public health. Unfortunately, catheter ablation for AF treatment has been shown to make only modest gains in quality-adjusted life years, has yet to demonstrate cost-utility advantages over conventional therapies for AF, and has a reported rate of recurrence for AF that is notably high. Thus, there is a major unmet clinical need for a therapeutic option to treat AF that produces more consistent and efficacious results that are cost-effective. Cardiac radiosurgery as a therapy for AF has the potential to be remarkably cost-effective and produce robust patient outcomes. CyberHeart Inc. has developed the world's first-ever cardiac radiosurgery (CRS) system designed to ablate the heart non-invasively. Procedures that ablate the heart utilizing the Cyberheart CRS system are anticipated to allow higher efficacy and more consistent results than current techniques such as catheter ablation. The aim of this study is to present the current healthcare utilization and expenditures in AF treatment, report the cost-effectiveness of catheter ablation for AF, and project the potential cost-effectiveness of cardiac radiosurgery for the treatment of AF., Competing Interests: T. Fogarty serves on the board of CyberHeart Inc.

Background: Sleep disordered breathing (SDB) such as sleep apnea is associated with cardiovascular disease in the general population. However, little is known about the cardiovascular risks of SDB in patients with end-stage renal disease (ESRD)., Methods: We identified Medicare fee-for-service beneficiaries aged ≥67 years initiating dialysis between 2004 and 2009. Outcomes of interest included all-cause mortality, incident myocardial infarction, ischemic stroke, and atrial fibrillation. We compared patients with and without diagnosed SDB using Cox proportional hazards regression., Results: Between 2004 and 2009, 184,217 older patients developed ESRD, of whom 15,121 (8.2 %) were previously diagnosed with SDB. Patients diagnosed with SDB were younger, more likely to be male and Caucasian, less Medicaid eligible, had more non-Nephrology clinic visits, higher body mass index, and more comorbidity. In analyses adjusting for demographics and BMI, diagnosed SDB was associated with higher risk of death and atrial fibrillation, but not associated with myocardial infarction or ischemic stroke risk. After further adjustment for all baseline characteristics, diagnosed SDB was associated with slightly lower risks of death (hazard ratio [HR]: 0.93, 95 % confidence interval [CI]: 0.91-0.96), myocardial infarction (HR: 0.92, CI: 0.87-0.98), and ischemic stroke (HR: 0.90, 95 % CI: 0.82-0.98), and not associated with atrial fibrillation (HR: 1.02, CI: 0.98-1.07)., Conclusions: In older patients initiating dialysis in the U.S., diagnosed SDB was weakly associated with lower risks of death and important cardiovascular outcomes, thus adding to the list of established risk factors that are paradoxically associated with cardiovascular outcomes in the ESRD population.

One of the provisions of the health care reform legislation in 2010 was for funding pragmatic clinical trials or large observational studies for comparing the effectiveness of different approved medical treatments, involving broadly representative patient populations. After reviewing pragmatic clinical trials and the issues and challenges that have made them just a small fraction of comparative effectiveness research (CER), we focus on a recent development that uses point-of-care (POC) clinical trials to address the issue of "knowledge-action gap" in pragmatic CER trials. We give illustrative examples of POC-CER trials and describe a trial that we are currently planning to compare the effectiveness of newly approved oral anticoagulants. We also develop novel stage-wise designs of information-rich POC-CER trials under competitive budget constraints, by using recent advances in adaptive designs and other statistical methodologies., (Published by Elsevier Inc.)

Aims: Metabolic syndrome has been associated with increased risk of cardiovascular disease. We aimed to determine the effectiveness of a community-based screening program in identifying cardiovascular risk factors in healthy young South Asian population., Materials and Methods: Between 2006 and 2011, 3314 patients of all ages were recruited as a part of a prospective cohort study investigating cardiovascular risk in South Asians. We analyzed 1537 patients between the ages of 18 and 40. Demographic and baseline characteristics including baseline laboratory markers and blood pressures were obtained at initial visit., Results: The total cohort of 1537 patients was 66.5% male, and the mean age was 35±5 years. Among participants who denied a history of hypercholesterolemia, 62% had elevated LDL-C (>100 mg/dL), and 8% had markedly elevated LDL-C (>160 mg/dL). Overall, diabetes was present in 4%, hypertension was present in 12% and hyperlipidemia was present in 46%. Low HDL-C (50% of men, 52% of women) and elevated triglycerides (44% of men, 18% of women) were the most prevalent components of metabolic syndrome. Metabolic syndrome was present in 14% of men and 8% of women and one-third (30%) of men and one-fifth (19%) of women had at least two component risk factors., Conclusions: This is the largest study to date assessing effectiveness of a community based screening program aiming to identify cardiovascular risk in young South Asians. We note significant modifiable risk at a young age. Such community based interventions can be effective at detecting and managing risk factors early in this vulnerable population., (Published by Elsevier Ltd.)

Background: One sixth of US dialysis patients 65 years of age have been diagnosed with atrial fibrillation/flutter (AF). Little is known, however, about the incidence of AF in this population., Methods and Results: We identified 258 605 older patients (≥67 years of age) with fee-for-service Medicare initiating dialysis in 1995 to 2007, who had not been diagnosed with AF within the previous 2 years. Patients were followed for newly diagnosed AF. Multivariable proportional hazard regression was used to examine temporal trends and associations of race and ethnicity with incident AF. We also studied temporal trends in the mortality and risk of ischemic stroke after new AF. Over 514 395 person-years of follow-up, 76 252 patients experienced incident AF for a crude AF incidence rate of 148/1000 person-years. Incidence of AF increased by 11% (95% confidence interval, 5-16) from 1995 to 2007. Compared with non-Hispanic whites, blacks (-30%), Asians (-19%), Native Americans (-42%), and Hispanics (-29%) all had lower rates of incident AF. Mortality after incident AF decreased by 22% from 1995 to 2008. Even more pronounced reductions were seen for incident ischemic stroke during these years., Conclusions: The incidence of AF is high in older patients initiating dialysis in the United States and has been increasing over the 13 years of study. Mortality declined during that time but remained >50% during the first year after newly diagnosed AF. Because data on warfarin use were not available, we were unable to study whether trends toward better outcomes could be explained by higher rates of oral anticoagulation.

Background: Determination of the defibrillation safety margin (DSM) is the most common method of testing device effectiveness at the time of implantation of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRTD). Low DSM remains a problem in clinical practice., Objective: The purpose of this study is to ascertain the incidence and clinical predictors of low DSM and the treatment strategies for low DSM in ICD or CRTD recipients., Methods: Selected ICD or CRTD recipients from January 2006 to May 2008 who underwent DSM test at the time of implantation were included. Low DSM patients were defined as patients who had a DSM within 10 J of the maximum delivered energy of the device. These patients were compared to patients who had DSM > 10 J., Results: This study included 243 patients. Of these, 13 (5.3%) patients had low DSM, and 230 patients had adequate DSM. Patients with low DSM had a high prevalence of amiodarone use (69% vs 13%, p < 0.01), secondary prevention indications (69% vs 30%, p < 0.01), and a trend toward younger age (51 ± 18 vs 58 ± 15 years, p = 0.08). After adjustment for age and sex, amiodarone use was significantly associated with low DSM. All low DSM patients except one obtained adequate DSM after taking additional steps, including discontinuing amiodarone and starting sotalol, RV lead repositioning, adding a subcutaneous array or shock coil, changing single-coil to dual-coil lead, and upgrading to a high output device., Conclusion: The incidence of low DSM patients is low with high-energy devices. Amiodarone use is associated with low DSM, and its discontinuation or substitution with sotalol is one of a variety of available options for low DSM patients.

Introduction: Although recent case reports and one small single-year observational study report a substantially increased rate of perforation with the St. Jude Riata series defibrillator lead, these results have not been externally validated., Methods and Results: From 2004 to 2007, 593 implantable cardioverter-defibrillator (ICD) implants were performed by six faculty and 13 fellows at four University of California, San Francisco, CA, USA and affiliate hospitals. An electronic medical records system was systematically searched to identify clinically significant cases of ICD lead dislodgment or perforation. Of 307 (56%) St. Jude leads (all Riata series 6.3- and 7.3-French leads), 188 (29%) Medtronic leads (including 99 Sprint Fidelis 6.6 French leads), and 98 (15%) Guidant/Boston Scientific leads, there were three perforations in 593 cases (0.51%). One perforation occurred with a Medtronic Sprint Fidelis 6949 lead (0.53%), and two with a St. Jude Riata 1581 lead (0.65%). There were no statistically significant differences in perforation or dislodgement rates between manufacturers or lead models (p = NS for all). In both cases of perforation with the St. Jude Riata leads, the lead tip perforated through the pericardium into the pleural space., Conclusions: In our 4-year series of ICD implants, perforation and dislodgement rates were low, similar across all lead makes and models, and well below published and accepted complication rates. Our findings contradict previously-reported higher rates of perforation with the Riata lead. Registry and product performance reports should also classify complications by severity and outcome to provide a more complete assessment of product safety.

Background: Remote magnetic catheter navigation (RCN) is gaining acceptance in clinical cardiac electrophysiology, but details regarding how RCN affects procedure execution are not well characterized., Methods: From January 1, 2005, to November 30, 2007, 721 cases were retrospectively analyzed and compared. Of these, 127 used RCN and 594 used manual catheter navigation (MCN). Data including procedure time, fluoroscopy time, ablation catheter, procedural success, and complications were extracted from our procedure database and compared between RCN and MCN., Results: RCN use significantly decreased fluoroscopy time for atrial fibrillation (AF) ablation (-29 minutes, P < 0.001), atrioventricular nodal reentrant tachycardia ablation (-14 minutes, P < 0.001), and atrioventricular reentrant tachycardia ablation (-18 minutes, P = 0.045). While RCN significantly increased mean procedure time for AF (+36 minutes, P = 0.003) and atypical atrial flutter cases (+116 minutes, P = 0.016), RCN AF procedure time diminished with increasing number of cases performed. Two cases of tamponade occurred during AF ablation using MCN (2.2%, 2 of 91 cases). No tamponade occurred during all 75 AF ablations with RCN., Conclusion: RCN can reduce fluoroscopy time and may reduce complications during catheter ablation. While it may increase total procedure duration, procedure times decrease with increasing operator experience. (PACE 2008; 31:1399-1404).

The transcriptional modulator Cited2 is induced by various biological stimuli including hypoxia, cytokines, growth factors, lipopolysaccharide (LPS) and flow shear. In this study, we report that Cited2 is required for mouse fetal liver development. Cited2(-/-) fetal liver displays hypoplasia with higher incidence of cell apoptosis, and exhibits disrupted cell-cell contact, disorganized sinusoidal architecture, as well as impaired lipid metabolism and hepatic gluconeogenesis. Furthermore, we demonstrated the physical and functional interaction of Cited2 with liver-enriched transcription factor HNF4alpha. Chromatin immunoprecipitation (ChIP) assays further confirmed the recruitment of Cited2 onto the HNF4alpha-responsive promoters and the reduced HNF4alpha binding to its target gene promoters in the absence of Cited2. Taken together, this study suggests that fetal liver defects in mice lacking Cited2 result, at least in part, from its defective coactivation function for HNF4alpha.