Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation

Spronk, Henri M. H.; Jong, Anne Margreet De; Verheule, Sander; Boer, Hetty C. de; Maass, Alexander H.; Lau, Dennis H.; Rienstra, Michiel; Hunnik, Arne van; Kuiper, Marion; Lumeij, Stijn; Zeemering, Stef; Linz, Dominik; Kamphuisen, Pieter Willem; Cate, Hugo Ten; Crijns, Harry J.; Gelder, Isabelle C. Van; Zonneveld, Anton Jan van; Schotten, Ulrich

doi:10.1093/eurheartj/ehw119

Cited by 134 publications

(110 citation statements)

References 39 publications

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“…Several recent studies [14,20,[23][24][25] have demonstrated that DOACs can directly modulate the mechanical and electrophysiological properties of the LA and PVs and suggest that DOACs may have a beneficial effect of anti-AF actions via preventing AF progression in addition to their anti-thrombotic action. Therefore, DOACs may affect the natural course of AF progression causing a transition from a paroxysmal to persistent form.…”

Section: Resultsmentioning

confidence: 99%

“…Spronk et al investigated the effects of hypercoagulability and its suppression of AF remodeling using several animal models [23]. In isolated rat atria preparations, the authors found that thrombin enhances the expression of the pro-fibrotic factor, transforming growth factor β1, and pro-inflammatory substance monocyte chemoattractant protein-1, and also increases the incorporation of 3H-proline, suggesting an increased collagen synthesis by fibroblasts.…”

Section: Beneficial Effects Of Doacs On the Electrophysiological Propmentioning

confidence: 99%

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Possible Benefits of Direct Oral Anticoagulants for the Electrophysiological Substrate Properties of Atrial Fibrillation: Can these New Agents have Antiatrial Fibrillation Actions?

Higa¹,

Yj²,

Sa³

2017

Cardiovasc Pharm Open Access

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Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia, and is associated with thromboembolic events. Previous studies also have shown a close relationship between AF and heart failure, and heart failure can be one of the most important risk factors for AF. Therefore, heart failure animal models have been established to investigate the structural and electrical remodeling for AF substrates and suggested that the structural and/or electrical remodeling caused by heart failure may play an important role in AF genesis. Several recent studies have demonstrated that Direct Oral Anticoagulants (DOACs) can directly modulate the mechanical and electrophysiological properties of the Left Atrium (LA) and Pulmonary Veins (PVs) and suggest that DOACs may have a beneficial effect of anti-AF actions via preventing AF progression in addition to their anti-thrombotic action. Therefore, DOACs may affect the natural course of AF progression causing a transition from a paroxysmal to persistent form. Although, many clinical studies need to be conducted to evaluate the additional effects of DOACs, it would have a great impact on clinical practice. In this manuscript, I will focus on recent studies regarding: The effects of thrombin, factor Xa, and its inhibitors on tissue inflammation and fibrosis. The beneficial effects of thrombin inhibitors on the AF substrate in a heart failure animal model. The role of the PV myocardium on AF arrhthmogenesis in a heart failure animal model. The beneficial effects of DOACs on the electrophysiological properties of the atrium and PVs.Finally, I will discuss about the significant impact of AF progression and the possible benefits of DOACs on the clinical outcomes of catheter ablation of AF and the future direction of clinical research to evaluate the beneficial effects of DOACs on AF substrates.

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Section: Resultsmentioning

confidence: 99%

Section: Beneficial Effects Of Doacs On the Electrophysiological Propmentioning

confidence: 99%

Possible Benefits of Direct Oral Anticoagulants for the Electrophysiological Substrate Properties of Atrial Fibrillation: Can these New Agents have Antiatrial Fibrillation Actions?

Higa¹,

Yj²,

Sa³

2017

Cardiovasc Pharm Open Access

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“…A PF idején fennálló ischaemia aktiválja az alvadási faktorokat, amelyek proteáz aktiválta receptorokat (PARs) stimulálva szívizomsejt-hypertrophiát, gyulladásos reakciót, valamint fibroblastaktiváció talaján pitvari fibrosist idéznek elő. A fokozott alvadékonyság által aktivált folyamatok a pitvarok strukturális remodellációját előidéz-ve megzavarják a szívizomrostok közötti ingerületveze-tést, és ezáltal a PF szubsztrátjául szolgálnak [5,43].…”

Section: Fokozott Alvadékonyságunclassified

“…Mindezek az adatok arra utalnak, hogy a fokozott alvadékonysággal járó állapotok-nak szerepük lehet a PF-szubsztrát kialakulásában. A NOAC-ok eredményesen gátolják a pitvari fibroticus folyamatokat és a PF szubsztrátjának kialakulását, ezáltal késleltethetik a PF progresszióját, továbbá a pitvari thrombusképződést és a következményes stroke kialakulását [43].…”

Section: Fokozott Alvadékonyságunclassified

Új felismerések a pitvarfibrilláció genezisében és fenntartásában: az egyénre szabott kezelés lehetőségei

2018

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A pitvarfibrilláció prevalenciája a felnőttkorosztályban körülbelül három százalék. A ritmuskontroll céljából alkalmazott katéterablatiós terápia alapját jelenleg a pulmonalis vénák izolációja képezi, amelynek egyéves sikeraránya azonban többszöri beavatkozással sem emelhető 70% fölé. A beavatkozás hosszú távú eredményességét a pitvarokban bekövetkező elektromos és strukturális remodelláció korlátozza, amely az arrhythmia tartós fennmaradásához vezet. Az epicardialis zsírszöveti akkumuláció, a pitvari fibrosis, az autonóm idegrendszeri hatások, valamint a különféle arrhythmogen gócok lehetséges szerepét számos tanulmány elemezte. A pitvari epicardialis zsírszövet mennyisége, gyulladás indukálta fibroticus átalakulása és a myocardium zsíros infiltrációja, például obesitas esetén, pitvarfibrilláció fellépésére hajlamosít. Az autonóm szabályozás egyensúlyának megváltozása, például rendszeres sporttevékenység hatására, a triggerelt aktivitás fokozódása, valamint a pitvari refrakter periódus csökkenése révén indukálhat ritmuszavart. Hatékony terápia a lehetséges arrhythmogen trigger és szubsztrátmechanizmusok egyénre szabott komplex befolyásolása által valósulhat meg. A fibroticus folyamatok a renin-angiotenzin-aldoszteron rendszer gátlása révén lassíthatók. A neuromodulációs lehetőségek magukban foglalják a renalis denervációt, illetve a ganglionablatiót, és az antikoaguláns terápia pitvari remodellációt gátló hatásáról is ismertek adatok. A katéterablatiós beavatkozások lehetséges új irányait a jobb és bal pitvari lineáris laesiók alkalmazása, a heges területek homogenizálása mellett a komplex frakcionált pitvari elektrogramok, rotorok és az ectopiás fókuszok ablatiója képezik. Mindezek mellett kiemelt fontosságú a fennálló rizikófaktorok, úgymint obesitas, hyperlipidaemia, hypertonia, diabetes mellitus és obstruktív alvá-si apnoe hosszú távú, tervezett kezelése. Orv Hetil. 2018; 159(28): 1135-1145.Kulcsszavak: pitvarfibrilláció, pitvari remodelláció, zsírszövet, autonóm idegrendszer, egyénre szabott kezelés Novel mechanisms in the initiation and maintenance of atrial fibrillation: tailored individual treatmentAtrial fibrillation affects approximately three percent of the adults. Ablation strategies targeting the isolation of the pulmonary veins are the up-to-date cornerstones for atrial fibrillation ablations. However, a one-year success rate of repeated interventions is not more than 70%. Long-term efficacy of catheter ablation is presumably limited by electrical and structural remodeling of the atria, which results in a progressive increase in the duration of atrial fibrillation to become sustained. The potential pathophysiological importance of the epicardial adipose tissue, atrial fibrosis, autonomic nervous system and arrhythmogenic foci are documented by several studies. Increased volume, inflammation induced transformation to fibrosis and myocardial infiltration of atrial subepicardial fat in obese patients result in higher risk of atrial fibrillation development. Changes in atrial autonomic innervation und...

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“…26 New anticoagulant therapy can inhibit PAR1 activation and through it can prevent the development of a substrate for AF. 27 A CHADS2 and CHA2DS2-VASC score of 0 may be insufficient to avoid thromboembolism events in patients with AF. 28 More information about thromboembolic risk can be obtain by determination of the level of troponin I, CRP, and NT-pro BNP.…”

Section: Introductionmentioning

confidence: 99%

Imaging-derived Biomarkers Associated with Atrial FIBROsis, Structural Remodeling and the Risk of Cardioembolic Events in Patients with Atrial Fibrillation – the FIBROS Study

Oltean-Péter

Korodi

Benedek

et al. 2017

Journal of Interdisciplinary Medicine

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Recent studies demonstrated that despite restoration of the sinus rhythm, patients with a positive history of atrial fibrillation (AF) are still at risk of thromboembolic events. The primary objective of this study is to identify new imaging-derived biomarkers provided by modern imaging technologies, such as cardiac computed tomography angiography, delayed enhancement magnetic resonance imaging, or speckle tracking echocardiography, as well as hematological biomarkers, associated with the risk of intracavitary thrombosis in patients with AF, in order to identify the imaging-derived characteristics associated with an increased risk of cardioembolic events. Imaging data collected will be post-processed using advanced techniques of computational modeling, in order to fully characterize the degree of structural remodeling and the amount of atrial fibrosis. The primary endpoint of the study is represented by the rate of thromboembolic events. The rate of cardiovascular death, the rate of major adverse cardiovascular events, and the rate of AF recurrence will also be determined in relation to the degree of structural remodeling and atrial fibrosis.

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Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation

Cited by 134 publications

References 39 publications

Possible Benefits of Direct Oral Anticoagulants for the Electrophysiological Substrate Properties of Atrial Fibrillation: Can these New Agents have Antiatrial Fibrillation Actions?

Possible Benefits of Direct Oral Anticoagulants for the Electrophysiological Substrate Properties of Atrial Fibrillation: Can these New Agents have Antiatrial Fibrillation Actions?

Új felismerések a pitvarfibrilláció genezisében és fenntartásában: az egyénre szabott kezelés lehetőségei

Imaging-derived Biomarkers Associated with Atrial FIBROsis, Structural Remodeling and the Risk of Cardioembolic Events in Patients with Atrial Fibrillation – the FIBROS Study

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