Atrial fibrillation (AF) is an arrhythmia that can occur as the result of numerous different pathophysiological processes in the atria. Some aspects of the morphological and electrophysiological ...alterations promoting AF have been studied extensively in animal models. Atrial tachycardia or AF itself shortens atrial refractoriness and causes loss of atrial contractility. Aging, neurohumoral activation, and chronic atrial stretch due to structural heart disease activate a variety of signaling pathways leading to histological changes in the atria including myocyte hypertrophy, fibroblast proliferation, and complex alterations of the extracellular matrix including tissue fibrosis. These changes in electrical, contractile, and structural properties of the atria have been called "atrial remodeling." The resulting electrophysiological substrate is characterized by shortening of atrial refractoriness and reentrant wavelength or by local conduction heterogeneities caused by disruption of electrical interconnections between muscle bundles. Under these conditions, ectopic activity originating from the pulmonary veins or other sites is more likely to occur and to trigger longer episodes of AF. Many of these alterations also occur in patients with or at risk for AF, although the direct demonstration of these mechanisms is sometimes challenging. The diversity of etiological factors and electrophysiological mechanisms promoting AF in humans hampers the development of more effective therapy of AF. This review aims to give a translational overview on the biological basis of atrial remodeling and the proarrhythmic mechanisms involved in the fibrillation process. We pay attention to translation of pathophysiological insights gained from in vitro experiments and animal models to patients. Also, suggestions for future research objectives and therapeutical implications are discussed.
Around the world there are 33.5 million patients suffering from atrial fibrillation (AF) with an annual increase of 5 million cases. Most AF patients have an established form of an atrial ...cardiomyopathy. The concept of atrial cardiomyopathy was introduced in 2016. Thus, therapy of underlying diseases and atrial tissue changes appear as a cornerstone of AF therapy. Furthermore, therapy or prevention of atrial endocardial changes has the potential to reduce atrial thrombogenesis and thereby cerebral stroke. The present manuscript will summarize the underlying pathophysiology and remodeling processes observed in the development of an atrial cardiomyopathy, thrombogenesis, and atrial fibrillation. In particular, the impact of oxidative stress, inflammation, diabetes, and obesity will be addressed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary Background An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring ...function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. Methods We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II–III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov , number NCT00538356. Findings We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43–0·90). Ten versus 27 patients died during follow-up. Interpretation Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. Funding Biotronik SE & Co. KG.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Approximately one fifth of patients diagnosed with atrial fibrillation (AF) undergo a percutaneous coronary intervention (PCI). Current guidelines recommend different combinations and ...durations of triple or dual antithrombotic therapy for these patients but data on the implementation of these recommendations in clinical routine are scarce. ENCOURAGE-AF is a prospective, non-interventional, non-comparative, multicentre study. Approximately 720 patients will be consecutively enrolled from 70 participating sites across Germany. Patients with non-valvular AF treated with edoxaban, who have undergone successful PCI, have no planned elective cardiac intervention during the study period, have capability, availability, and willingness for follow-up by telephone interview during the study, are aged ≥ 18 years with life expectancy ≥ 1 year, and provide written informed consent, will be included. Eligible patients will be enrolled between 4- and 72-h after completing a successful PCI. Duration of exposure to and dosing regimens of edoxaban, antiplatelet agents and other concomitant medications of interest will be monitored in line with the clinical practice. Physician- and patient-reported clinical events, adverse drug reactions, patient quality of life (EQ-5D-5L) and health resource utilisation (HRU) parameters will be evaluated at 30 days and 1-year post-PCI. The ENCOURAGE-AF non-interventional study will provide insights into the patterns of edoxaban usage in combination with antiplatelet treatment and other concomitant medications in AF patients with a successful PCI over a 1-year time period during routine clinical practice in Germany. The effectiveness and safety of edoxaban in this patient population, as well as patients’ quality of life and HRU will be evaluated.
Trial registration
: Clinicaltrial.gov NCT04519944, registered on 20 August 2020.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Covid-19 pandemic during its early phases posed significant psychological threats particularly for medical frontline personal. It is unclear whether the medical workforce with the passage of time ...has adapted to these threats or have generalized to wider medical settings. An online survey was conducted reaching 1476 physicians in Germany with valid data from 1327 participants. Depression and anxiety were screened with the PHQ-2 and the GAD-2. Among a subtotal of 1139 (86.6%) physicians reporting personal treatment experiences with Covid-19 patients, 553 (84.8%) worked in a private practice (PP) and 586 (88.3%) in a hospital (HP). Covid-19 provoked profound conflicts between professional and ethical values: more physicians in PPs than HPs reported external constraints on their medical care being in conflict with the code of medical ethics (39.1 vs. 34.4%, p < 0.002) and significantly more HPs failed to maintain the dignity of their patients during the pandemic (48 vs. 27%, p < 0.0001). Comparison with reference groups among physicians with comparable size and settings during the first wave of Covid-19 revealed a significant increase in the prevalence of depression (23.0%) and anxiety (24.16%). Feelings of helplessness (63.3% in HPs and 53.4% in PPs) were associated with female sex, minor years of medical experience, sleeping problems and being encountered to unsettling events. Exposure to unsettling events and helplessness was significantly mediated by sleep disturbances (ß = 0.29, SE = 0.03, p < 0.0001). Covid-19 induced stress job content issues have broadened to medical disciplines beyond frontline workers. Emotional perturbations among physicians have attained a critical magnitude.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Atrial fibrillation (AF) is associated with increased inward-rectifier current activity that may stabilize atrial rotors maintaining the arrhythmia. Left atrial (LA) structures are important for AF ...maintenance, but previous studies have mostly evaluated changes in the right atrium. MicroRNA-1 (miR-1) reciprocally regulates inwardly rectifying potassium channel (Kir)2.1 expression in coronary disease, contributing to arrhythmogenesis.
This study sought to evaluate changes in miR-1 and Kir2 subunit expression in relation to I(K1) alterations in LA of patients with persistent AF.
Atrial tissue was obtained from 62 patients (31 with AF) undergoing mitral valve repair or bypass grafting. Currents were recorded from isolated cells. Proteins were quantified from immunoblots. mRNA and miR-1 levels were measured with real-time polymerase chain reaction. Immunohistochemistry was applied to localize connexin (Cx) 43.
I(K1) density was increased in LA cells from patients with AF (at -100 mV: -5.9 +/- 1.3 vs. -2.7 +/- 0.7 sinus rhythm, P <.05). There was a corresponding increase in Kir2.1 protein expression, but no change in other Kir or Cx proteins. Expression of inhibitory miR-1 was reduced by approximately 86% in tissue samples of AF patients. Kir2.1 mRNA was significantly increased. No change in Cx43 localization occurred. Ex vivo tachystimulation of human atrial slices up-regulated Kir2.1 and down-regulated miR-1, suggesting a primary role of atrial rate in miR-1 down-regulation and I(K1) up-regulation.
miR-1 levels are greatly reduced in human AF, possibly contributing to up-regulation of Kir2.1 subunits, leading to increased I(K1). Because up-regulation of inward-rectifier currents is important for AF maintenance, these results provide potential new insights into molecular mechanisms of AF with potential therapeutic implications.
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