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result(s) for
"Akar, Joseph G."
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Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes
2017
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. Several risk factors promote AF, among which diabetes mellitus has emerged as one of the most important. The growing recognition that obesity, diabetes and AF are closely intertwined disorders has spurred major interest in uncovering their mechanistic links. In this article we provide an update on the growing evidence linking oxidative stress and inflammation to adverse atrial structural and electrical remodeling that leads to the onset and maintenance of AF in the diabetic heart. We then discuss several therapeutic strategies to improve atrial excitability by targeting pathways that control oxidative stress and inflammation.
Journal Article
Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation
by
Cacheux, Marine
,
Guerrera, Nicole
,
Wu, Xiaohong
in
AMP-activated protein kinase
,
AMP-Activated Protein Kinases - metabolism
,
Animals
2022
Metabolic stress is an important cause of pathological atrial remodeling and atrial fibrillation. AMPK is a ubiquitous master metabolic regulator, yet its biological function in the atria is poorly understood in both health and disease. We investigated the impact of atrium-selective cardiac AMPK deletion on electrophysiological and structural remodeling in mice. Loss of atrial AMPK expression caused atrial changes in electrophysiological properties and atrial ectopic activity prior to the onset of spontaneous atrial fibrillation. Concomitant transcriptional downregulation of connexins and atrial ion channel subunits manifested with delayed left atrial activation and repolarization. The early molecular and electrophysiological abnormalities preceded left atrial structural remodeling and interstitial fibrosis. AMPK inactivation induced downregulation of transcription factors (Mef2c and Pitx2c) linked to connexin and ion channel transcriptional reprogramming. Thus, AMPK plays an essential homeostatic role in atria, protecting against adverse remodeling potentially by regulating key transcription factors that control the expression of atrial ion channels and gap junction proteins.
Journal Article
Aggregating multiple real-world data sources using a patient-centered health-data-sharing platform
by
Caldwell, Brittany
,
Chow, Wing
,
Dykhoff, Hayley J.
in
631/114/2400
,
631/114/2401
,
Biomedicine
2020
Real-world data sources, including electronic health records (EHRs) and personal digital device data, are increasingly available, but are often siloed and cannot be easily integrated for clinical, research, or regulatory purposes. We conducted a prospective cohort study of 60 patients undergoing bariatric surgery or catheter-based atrial fibrillation ablation at two U.S. tertiary care hospitals, testing the feasibility of using a patient-centered health-data-sharing platform to obtain and aggregate health data from multiple sources. We successfully obtained EHR data for all patients at both hospitals, as well as from ten additional health systems, which were successfully aggregated with pharmacy data obtained for patients using CVS or Walgreens pharmacies; personal digital device data from activity monitors, digital weight scales, and single-lead ECGs, and patient-reported outcome measure data obtained through surveys to assess post-procedure recovery and disease-specific symptoms. A patient-centered health-data-sharing platform successfully aggregated data from multiple sources.
Journal Article
Observational study protocol for an arrhythmia notification feature
by
Garg, Kanika
,
Weinstein, Jason
,
Lee, Victoria
in
Adult
,
Algorithms
,
Arrhythmias, Cardiac - diagnosis
2024
IntroductionScreening for atrial fibrillation (AF) in the general population may help identify individuals at risk, enabling further assessment of risk factors and institution of appropriate treatment. Algorithms deployed on wearable technologies such as smartwatches and fitness bands may be trained to screen for such arrhythmias. However, their performance needs to be assessed for safety and accuracy prior to wide-scale implementation.Methods and analysisThis study will assess the ability of the WHOOP strap to detect AF using its WHOOP Arrhythmia Notification Feature (WARN) algorithm in an enriched cohort with a 2:1 distribution of previously diagnosed AF (persistent and paroxysmal) and healthy controls. Recruited participants will collect data for 7 days with the WHOOP wrist-strap and BioTel ePatch (electrocardiography gold-standard). Primary outcome will be participant level sensitivity and specificity of the WARN algorithm in detecting AF in analysable windows compared with the ECG gold-standard. Similar analyses will be performed on an available epoch-level basis as well as comparison of these findings in important subgroups.Ethics and disseminationThe study was approved by the ethics board at the study site. Participants will be enrolled after signing an online informed consent document. Updates will be shared via clinicaltrials.gov. The data obtained from the conclusion of this study will be presented in national and international conferences with publication in clinical research journals.Trial registration number NCT05809362.
Journal Article
Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT)
by
Choucair, Wassim K.
,
Lip, Gregory Y.H.
,
Wathen, Mark
in
Administration, Oral
,
Aged
,
Anticoagulants
2016
Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist–treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR.
Journal Article
Heart Watch Study: protocol for a pragmatic randomised controlled trial
by
Shah, Nilay D
,
Hu, Tiffany
,
Bartlett, Victoria
in
Accuracy
,
adult cardiology
,
Atrial Fibrillation - epidemiology
2021
IntroductionPersonal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation.Methods and analysisWe are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings.Ethics and disseminationThe Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals.Trial registration numberNCT04468321
Journal Article
Feasibility of using real-world data in the evaluation of cardiac ablation catheters: a test-case of the National Evaluation System for Health Technology Coordinating Center
2021
ObjectivesTo determine the feasibility of using real-world data to assess the safety and effectiveness of two cardiac ablation catheters for the treatment of persistent atrial fibrillation and ischaemic ventricular tachycardia.DesignRetrospective cohort.SettingThree health systems in the USA.ParticipantsPatients receiving ablation with the two ablation catheters of interest at any of the three health systems.Main outcome measuresFeasibility of identifying the medical devices and participant populations of interest as well as the duration of follow-up and positive predictive values (PPVs) for serious safety (ischaemic stroke, acute heart failure and cardiac tamponade) and effectiveness (arrhythmia-related hospitalisation) clinical outcomes of interest compared with manual chart validation by clinicians.ResultsOverall, the catheter of interest for treatment of persistent atrial fibrillation was used for 4280 ablations and the catheter of interest for ischaemic ventricular tachycardia was used 1516 times across the data available within the three health systems. The duration of patient follow-up in the three health systems ranged from 91% to 97% at ≥7 days, 89% to 96% at ≥30 days, 77% to 90% at ≥6 months and 66% to 84% at ≥1 year. PPVs were 63.4% for ischaemic stroke, 96.4% for acute heart failure, 100% at one health system for cardiac tamponade and 55.7% for arrhythmia-related hospitalisation.ConclusionsIt is feasible to use real-world health system data to evaluate the safety and effectiveness of cardiac ablation catheters, though evaluations must consider the implications of variation in follow-up and endpoint ascertainment among health systems.
Journal Article
Catheter-related complications and mortality of atrial fibrillation ablation following introduction of contact force-sensing technology
2020
ObjectivesContact force-sensing catheters allow real-time catheter-tissue contact force monitoring during atrial fibrillation. These catheters were rapidly adopted into clinical practice following market introduction in 2014, but concerns have been raised regarding collateral damage such as esophageal injury. We sought to examine whether the introduction of force-sensing catheters was associated with a change in short-term and intermediate-term acute care use, complications and mortality following atrial fibrillation ablation.DesignRetrospective cohort analysis. We used inverse probability treatment weight matching to account for the differences in baseline characteristics between groups.SettingWe examined patients included in the OptumLabs Data Warehouse who underwent ablation for atrial fibrillation before (2011–2013) and after (2015–2017) the market introduction of contact force-sensing catheters.Main outcome measuresWe examined 30-day and 90-day rates of all-cause acute care use, including hospitalizations and emergency department visits, as well as death and hospitalization for catheter-related complications, including atrioesophageal fistula, pericarditis, cardiac tamponade/perforation and stroke/transient ischemic attack.ResultsOur sample included 3470 and 5772 patients who underwent atrial fibrillation (AF) ablation before and after market introduction of contact force-sensing catheters, respectively. Complication rates were low and did not differ between the two periods (p>0.10 for each outcome). The 30-day and 90-day mortality was 0.1% and 0.3%, respectively after market introduction and unchanged from prior to 2014. The 90-day rates of all-cause acute care use decreased, from 27.0% in 2011–2013 to 23.9% in 2015–2017 (p<0.001).ConclusionsAF ablation-related catheter complications and mortality are low and there has been no significant change following the introduction of force-sensing catheters.
Journal Article
Regulation of ion channels and arrhythmias in the ischemic heart
2007
Ventricular arrhythmias in the setting of ischemic heart disease is a leading cause of mortality in the United States. A better understanding of the complex changes associated with ischemic injury is likely to improve our ability to design better treatment strategies for patients who have coronary events. A major difficulty in treating those patients arises from the complexity of the electrophysiological changes that occur with varying time courses during the ischemic episode and the reperfusion phase. Here, we discuss some of the key cellular and network electrophysiological changes that are associated with ischemic injury and highlight the link between alterations in the energetic/metabolic substrate of the heart and electrical dysfunction.
Journal Article
2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary
by
Gerstenfeld, Edward P.
,
Di Biase, Luigi
,
Marchlinski, Francis E.
in
Ablation
,
Ablation (Surgery)
,
antiarrhythmic drug
2017
Reflecting both the worldwide importance of AF, as well as the worldwide performance of AF ablation, this document is the result of a joint partnership between the HRS, EHRA, ECAS, the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Society of Cardiac Stimulation and Electrophysiology (Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología [SOLAECE]). The purpose of this 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group, convened by these five international societies. The writing group is composed of 60 experts representing 11 organizations: HRS, EHRA, ECAS, APHRS, SOLAECE, STS, ACC, American Heart Association (AHA), Canadian Heart Rhythm Society (CHRS), Japanese Heart Rhythm Society (JHRS), and Brazilian Society of Cardiac Arrhythmias (Sociedade Brasileira de Arritmias Cardíacas [SOBRAC]). Rather, the ultimate judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all the circumstances presented by that patient.
Journal Article