In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2

by Jieyun Bai, Andy Lo, Patrick A. Gladding, Martin K. Stiles, Vadim V. Fedorov, Jichao Zhao Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a major cause of stroke and morbidity. Recent genome-wide association studies have shown that paired-like homeodomain transcription factor 2 (Pitx2) to be strongly associated with AF. However, the mechanisms underlying Pitx2 modulated arrhythmogenesis and variable effectiveness of antiarrhythmic drugs (AADs) in patients in the presence or absence of impaired Pitx2 expression remain unclear. We have developed multi-scale computer models, ranging from a single cell to tissue level, to mimic control and Pitx2-knocko ut atria by incorporating recent experimental data on Pitx2-induced electrical and structural remodeling in humans, as well as the effects of AADs. The key findings of this study are twofold. We have demonstrated that shortened action potential duration, slow conduction and triggered activity occur due to electrical and structural remodelling under Pitx2 deficiency conditions. Notably, the elevated function of calcium transport ATPase increases sarcoplasmic reticulum Ca2+ concentration, thereby enhancing susceptibility to triggered activity. Furthermore, heterogeneity is further elevated due to Pitx2 deficiency: 1) Electrical heterogeneity between left and right atria increases; and 2) Increased fibrosis and decreased cell-cell coupling due to structural remodelling slow electrical propagation an...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research

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Tatjana PS Abstract Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of death, stroke and heart failure. The prevalence and incidence of AF is increasing due to better overall medical treatment, longer survival and increasing incidence of cardiometabolic and lifestyle risk factors. Treatment of AF and AF-related complications significantly increase health-care costs. In addition, use of conventional rhythm control strategies (i.g. antiarrhyhtmic drugs and catheter-ablation) is associated with limited efficacy for sinus rhythm maintenance and serious adverse effe...
Source: Polish Heart Journal - Category: Cardiology Authors: Tags: Kardiol Pol Source Type: research
mmittee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Lifestyle and Cardiometabolic Health Abstract Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with substantial morbidity, mortality, and healthcare use. Great strides have been made in stroke prevention and rhythm control strategies, yet reducing the incidence of AF has been slowed by the increasing incidence and prevalence of AF risk factors, including obesity, physical inactivity, sleep apnea, diabetes melli...
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
New Brunswick, NJ, February 25, 2020 — Johnson &Johnson (NYSE: JNJ) today announced that the Janssen Pharmaceutical Companies of Johnson &Johnson, in collaboration with Apple, opened enrollment for the Heartline™ Study. The study is designed to explore if the Heartline™ Study app on iPhone and heart health features on Apple Watch can improve health outcomes, including reducing the risk of stroke, with earlier detection of atrial fibrillation (AFib). AFib, a common form of irregular heart rhythm, is a leading cause of stroke in the U.S. To enroll in the Heartline™ Study, individuals must be a...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
;li B Abstract BACKGROUND: Long-term ECG recording is a commonly used test. However, there are no clear guidelines on who should be examined using this method, and we lack an overview of the results of testing and their therapeutic implications. MATERIAL AND METHOD: All long-term ECG recordings performed at Sørlandet Hospital Arendal in the period 2017-18 were included in the study. The tests were identified by searching the medical records system for relevant procedure codes, and all medical records related to the test were subsequently reviewed. Patient characteristics, referrer, indication, results,...
Source: Tidsskrift for den Norske Laegeforening - Category: General Medicine Authors: Tags: Tidsskr Nor Laegeforen Source Type: research
This study is an extremely important step in assessing the Amplatzer Amulet as an effective non-prescription drug alternative for patients with AFib who are at an increased risk for ischemic stroke." In an email sent to MD+DI, Abbott wrote, “We already have an Amulet IDE trial underway that is intended to support our submission for approval in the U.S. for Amplatzer Amulet. The newly announced CATALYST trial will support our submission for an expanded indication for Amulet as a safe and effective alternative to NOAC drugs for patients with atrial fibrillation and at risk of stroke.”...
Source: MDDI - Category: Medical Devices Authors: Tags: Cardiovascular Regulatory and Compliance Source Type: news
ConclusionsThis study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data.
Source: IJC Heart and Vasculature - Category: Cardiology Source Type: research
Abstract Atrial fibrillation is the most common cardiac arrhythmia in western society affecting more than 35 million individuals worldwide annually. It is a common postoperative complication and may also occur spontaneously during general and local anesthesia administration. Aging, diabetes mellitus, hypertension, and cardiovascular diseases including cardiomyopathies, congenital cardiac anomalies, heart failure, myocardial ischemia, pericarditis, previous cardiac surgery, vascular disease, and valvular heart disease are some correlated factors. Beyond age, increased incidence of atrial fibrillation has been corre...
Source: Annals of Cardiac Anaesthesia - Category: Anesthesiology Authors: Tags: Ann Card Anaesth Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med. 2019 Dec 03;171(11):828-836 Authors: Burns RB, Zimetbaum P, Lubitz SA, Smetana GW Abstract Atrial fibrillation (AFib) is the most common type of cardiac arrhythmia, affecting 2.7 million to 6.1 million persons in the United States. Although some persons with AFib have no symptoms, others do. For those without symptoms, AFib may be detected by 12-lead electrocardiogram (ECG), single-lead monitors (such as ambulatory blood pressure monitors and pulse oximeters), or consumer devices (such as wearable monitors and smartphones). Pulse pa...
Source: Annals of Internal Medicine - Category: Internal Medicine Authors: Tags: Ann Intern Med Source Type: research
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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