Objective: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. Methods: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter,0.7 mm) were isolated. Isometric force of contraction was measured in 21 the presence of different concentrations of Ca and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium SR patients contractile force was 10.961.8 mN / mm compared to 3.360.9 mN / mm (n548, P,0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein 1 21 levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na / Ca -exchanger was upregulated by 67% in atria of AF patients. Conclusions: AF-induced atrial contractile dysfunction is not due to b-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced 21 21 cardiomyopathy. Instead, downregulation or altered function of the L-type Ca -channel and an increased Ca extrusion via the 1 21Na / Ca -exchanger seem to be responsible for the depressed contractility in remodeled atria.
Ассоциации ESC: Европейская ассоциация по профилактике и реабили-тации сердечно-сосудистых заболеваний (EACPR), Европейская ассоциа-ция сердечно-сосудистой визуализации (EACVI), Европейская ассоциация сердечного ритма (EHRA), Ассоциация по сердечной недостаточности (HFA).Советы ESC: Совет по сестринскому уходу за больными с сердечно-сосудис тыми заболеваниями и смежным специальностям, Совет по кардио-логической практике, Совет по первичному оказанию помощи больным с сердечно-сосудистыми заболеваниями, Совет специалистов по артери-альной гипертензии. Рабочие группы ESC:Клеточная электрофизиология сердца, Фармакотера-пия сердечно-сосудистых заболеваний, Врожденные пороки сердца у взрос-лых, Тромбоз, Клапанная болезнь сердца.Содержание данных рекомендаций, подготовленных Европейским общест вом кардиологов (European Society of Cardiology, ESC, опубликовано исключи-тельно для использования в личных и образовательных целях. Не допуска ется коммерческое использование содержания рекомендаций. Рекомендации ESC не могут быть переведены на другие языки либо воспроизведены, полно стью или частично, без письменного согласия ESC. Для получения данного согласия письменная заявка должна быть направлена в Oxford University Press -органи-зацию, издающую European Heart Journal и официально упол номоченную ESC, рассматривать подобные заявки.Отказ от ответственности. Рекомендации ESC отражают взгляды ESC и основаны на тщательном анализе научных данных, доступных во время подготовки данных рекомендаций. ESC не несет ответственности в случае противоречий, расхождений и/или неоднозначных моментов между дан-ными рекомендациями и любыми другими официальными рекомендаци-ями или руководствами, изданными действующими организациями здра-воохранения, в особенности в отношении правильного использования стратегий медицинского обслуживания и лечения. Медицинским работни-кам следует придер живаться данных рекомендаций в процессе принятия клинических решений. В то же время, рекомендации не могут заменить личную ответственность медицинских работников при принятии клиниче-ских решений с учетом индивидуальных особенностей и предпочтений пациентов и, при необходимости, предпочтений их опекунов и попечите-лей. Медицинские работники также несут ответственность в отношении дополнительной проверки всех надлежа щих требований и правил перед назначением лекарственных средств и использованием медицинского оборудования. Ключевые слова: клинические рекомендации, фибрилляция предсердий, антикоагулянтный эффект, антагонисты витамина К, пероральные антикоагу-лянты, не являющиеся антагонистами витамина К, окклюзия ушка левого предсердия, контроль частоты сердечных сокращений, кардиоверсия, конт-роль ритма, антиаритмические препараты, upstream терапия, катетерная аблация, хирургическое лечение фибрилляции предсердий, хирургические вмешательства на клапанах сердца, изоляция устьев легочных вен, аблация левого предсердия.
Aims Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. Methods and results This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Conclusions Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.
developing kidney, gut, and vasculature. Morpholino (MO)-based knockdown of TFPI resulted in coagulopathy and disordered vascular development (Abstract 141 figure 2. left column: green endothelial Fli1GFP, right column: red erythrocytes. AB: uninjected controls. CD: MO controls. EeP: TFPI knockdown). Abnormally targetted (ie, vessels sprouting from normal site but growing in abnormal direction; grey arrows) and extra vessels (ie, superfluous vessels not seen in controls; white arrows in Abstract 141 figure 2EFHIK&L) were seen by 48hpf. TFPI MO induced coagulopathy (a spontaneous clot or bleed; white arrows Abstract 141 figure 2GJMP Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with altered nitric oxide (NO)-redox balance. The molecular mechanisms and implications of this phenomenon in the management of patients with AF are poorly understood. Statins improve NO-redox imbalance and decrease the occurrence of postoperative AF but are less effective in the secondary prevention of AF, suggesting that the sources of reactive oxygen species might vary with the substrate and duration of AF. Methods and ResultsWe investigated atrial tissue from 130 patients undergoing cardiac surgery (26 with permanent AF, 32 who developed AF post-operatively and 72 who were in normal sinus rhythm before and after surgery), and from goats in sinus rhythm (SR, n¼19) with or without atrial structural remodelling secondary to surgical AV block (AVB, n¼10) or after 2 weeks (2W, n¼15) or 6 months (6M, n¼10) of pacing-induced AF. Atrial NADPH oxidase activity (chemiluminescence and 2-OH ethidium, Abstract 142 figures 1 and 2), NOX2 & p22phox protein level were increased after 2W-AF and in patients who developed AF post-operatively (n¼32). In contrast, the increased superoxide production in atrial tissue from goats with AVB or 6M-AF was exclusively driven by mitochondrial oxidases and uncoupled NOS (secondary to a reduction in atrial BH4 level and an increase in arginase activity). These findings were recapitulated in the right atrial appendage of patients. Increase in basal superoxide production in postoperative AF was associated with an apocynin-reversible increase in NADPH oxidase activity and protein level of the NOX2 and p22phox subunits. NOS activity remained coupled despite the increase in superoxide production. In line with this, atrial BH4 content was unaltered. In contrast, in patients with permanent AF, increased superoxide production was not reversed by apocynin, and was maintained by mitochondrial oxidases and uncoupled NOS (secondary to BH4 deplition). Ex-vivo
Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk-factors, including heart failure, hypertension, obesity and coronary artery disease. We also discuss the potential antiarrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.
ObjectiveAtrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF.MethodsIn this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression.ResultsMean age was 65 (58–71) years, 179 (43%) were female. Follow-up was 2.2 (1.6–2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression.ConclusionIn patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed.Trial registration numberNCT02726698.
Aims In atrial fibrillation (AF) patients, untreated sleep-disordered breathing (SDB) is associated with lower success rates of rhythm control strategies and as such structured SDB testing is recommended. Herein, we describe the implementation of a virtual SDB management pathway in an AF outpatient clinic and examine the utility and feasibility of this new approach. Methods and results Prospectively, consecutive AF patients accepted for AF catheter ablation procedures without previous diagnosis of SDB were digitally referred to a virtual SDB management pathway and instructed to use WatchPAT-ONE (ITAMAR) for one night. Results were automatically transferred to a virtual sleep laboratory, upon which a teleconsultation with a sleep physician was planned. Patient experience was measured using surveys. SDB testing was performed in 119 consecutive patients scheduled for AF catheter ablation procedures. The median time from digital referral to finalization of the sleep study report was 18 [11–24] days. In total, 65 patients (55%) were diagnosed with moderate-to-severe SDB. Patients with SDB were prescribed more cardiovascular drugs and had higher body mass indices (BMI, 29 ± 3.3 vs. 27 ± 4.4kg/m2, P < 0.01). Patients agreed that WatchPAT-ONE was easy to use (91%) and recommended future use of this virtual pathway in AF outpatient clinics (86%). Based on this remote SDB testing, SDB treatment was recommended in the majority of patients. Conclusion This novel virtual AF management pathway allowed remote SDB testing in AF outpatient clinics with a short time to diagnosis and high patient satisfaction. Structured SDB testing results in a high detection of previously unknown SDB in AF patients scheduled for AF ablation.
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