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Synergistic antiarrhythmic effect of inward rectifier current inhibition and pulmonary vein isolation in a 3D computer model for atrial fibrillation

hal.structure.identifierCenter for Computational Medicine in Cardiology [CCMC]
dc.contributor.authorGHARAVIRI, Ali
hal.structure.identifierCenter for Computational Medicine in Cardiology [CCMC]
dc.contributor.authorPEZZUTO, Simone
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
dc.contributor.authorPOTSE, Mark
hal.structure.identifierCardiocentro Ticino [Lugano]
dc.contributor.authorCONTE, Giulio
hal.structure.identifierDepartment of Physiology [Maastricht]
dc.contributor.authorZEEMERING, Stef
hal.structure.identifierDepartment of Physiology [Maastricht]
dc.contributor.authorSOBOTA, Vladimír
hal.structure.identifierDepartment of Physiology [Maastricht]
dc.contributor.authorVERHEULE, Sander
hal.structure.identifierCenter for Computational Medicine in Cardiology [CCMC]
dc.contributor.authorKRAUSE, Rolf
hal.structure.identifierCardiocentro Ticino [Lugano]
dc.contributor.authorAURICCHIO, Angelo
hal.structure.identifierDepartment of Physiology [Maastricht]
dc.contributor.authorSCHOTTEN, Ulrich
dc.date.accessioned2024-04-04T02:43:52Z
dc.date.available2024-04-04T02:43:52Z
dc.date.created2020-11-23
dc.date.issued2021-03-01
dc.identifier.issn1099-5129
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/191362
dc.description.abstractEnAims: Recent clinical studies showed that antiarrhythmic drug (AAD) treatment and pulmonary vein isolation (PVI) synergistically reduce atrial fibrillation (AF) recurrences after initially successful ablation. Among newly developed atrial-selective AADs, inhibitors of the G-protein-gated acetylcholine-activated inward rectifier current (IKACh) were shown to effectively suppress AF in an experimental model but have not yet been evaluated clinically. We tested in silico whether inhibition of inward rectifier current or its combination with PVI reduces AF inducibility. Methods and results: We simulated the effect of inward rectifier current blockade (IK blockade), PVI, and their combination on AF inducibility in a detailed three-dimensional model of the human atria with different degrees of fibrosis. IK blockade was simulated with a 30% reduction of its conductivity. Atrial fibrillation was initiated using incremental pacing applied at 20 different locations, in both atria. IK blockade effectively prevented AF induction in simulations without fibrosis as did PVI in simulations without fibrosis and with moderate fibrosis. Both interventions lost their efficacy in severe fibrosis. The combination of IK blockade and PVI prevented AF in simulations without fibrosis, with moderate fibrosis, and even with severe fibrosis. The combined therapy strongly decreased the number of fibrillation waves, due to a synergistic reduction of wavefront generation rate while the wavefront lifespan remained unchanged. Conclusion: Newly developed blockers of atrial-specific inward rectifier currents, such as IKAch, might prevent AF occurrences and when combined with PVI effectively supress AF recurrences in human.
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.title.enSynergistic antiarrhythmic effect of inward rectifier current inhibition and pulmonary vein isolation in a 3D computer model for atrial fibrillation
dc.typeArticle de revue
dc.identifier.doi10.1093/europace/euaa413
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologie/Cardiologie et système cardiovasculaire
dc.description.sponsorshipEuropeEU Training Network on Novel Targets and Methods in Atrial Fibrillation
bordeaux.journalEP-Europace
bordeaux.pagei161-i168
bordeaux.volume23
bordeaux.hal.laboratoriesInstitut de Mathématiques de Bordeaux (IMB) - UMR 5251*
bordeaux.issueSupplement_1
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-03452233
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03452233v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=EP-Europace&rft.date=2021-03-01&rft.volume=23&rft.issue=Supplement_1&rft.spage=i161-i168&rft.epage=i161-i168&rft.eissn=1099-5129&rft.issn=1099-5129&rft.au=GHARAVIRI,%20Ali&PEZZUTO,%20Simone&POTSE,%20Mark&CONTE,%20Giulio&ZEEMERING,%20Stef&rft.genre=article


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