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Stroke and Thromboembolism in Patients With Atrial Fibrillation and Mitral Regurgitation

2019; Lippincott Williams & Wilkins; Volume: 12; Issue: 3 Linguagem: Inglês

10.1161/circep.118.006990

1941-3149

Arnaud Bisson, Anne Bernard, Alexandre Bodin, Nicolas Clémenty, Dominique Babuty, Gregory Y.H. Lip, Laurent Fauchier,

Cardiac Valve Diseases and Treatments

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 12, No. 3Stroke and Thromboembolism in Patients With Atrial Fibrillation and Mitral Regurgitation Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessReview ArticlePDF/EPUBStroke and Thromboembolism in Patients With Atrial Fibrillation and Mitral Regurgitation Arnaud Bisson, MD, Anne Bernard, MD, PhD, Alexandre Bodin, MD, Nicolas Clementy, MD, Dominique Babuty, MD, PhD, Gregory Y.H. Lip, MD and Laurent Fauchier, MD, PhD Arnaud BissonArnaud Bisson Department of Cardiology, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Tours, France (A. Bisson, A. Bernard, A. Bodin, N.C., D.B., L.F.). , Anne BernardAnne Bernard Department of Cardiology, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Tours, France (A. Bisson, A. Bernard, A. Bodin, N.C., D.B., L.F.). , Alexandre BodinAlexandre Bodin Department of Cardiology, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Tours, France (A. Bisson, A. Bernard, A. Bodin, N.C., D.B., L.F.). , Nicolas ClementyNicolas Clementy Department of Cardiology, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Tours, France (A. Bisson, A. Bernard, A. Bodin, N.C., D.B., L.F.). , Dominique BabutyDominique Babuty Department of Cardiology, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Tours, France (A. Bisson, A. Bernard, A. Bodin, N.C., D.B., L.F.). , Gregory Y.H. LipGregory Y.H. Lip Liverpool Centre for Cardiovascular Science, Liverpool Heart & Chest Hospital, University of Liverpool, United Kingdom (G.Y.H.L.). Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.). and Laurent FauchierLaurent Fauchier Laurent Fauchier, MD, PhD, Cardiologie, Centre Hospitalier, Universitaire Trousseau, 37044 Tours, France. Email E-mail Address: [email protected] Department of Cardiology, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Tours, France (A. Bisson, A. Bernard, A. Bodin, N.C., D.B., L.F.). Originally published7 Mar 2019https://doi.org/10.1161/CIRCEP.118.006990Circulation: Arrhythmia and Electrophysiology. 2019;12:e006990A new classification has recently been proposed and validated for atrial fibrillation (AF) patients with valvular heart disease.1,2 Mitral regurgitation (MR) is included in EHRA (European Heart Rhythm Association) Type 2 valvular heart disease, which refers to AF patients with valvular heart disease needing therapy with a vitamin K antagonist or a nonvitamin K antagonist oral anticoagulant, also taking into consideration the CHA2DS2-VASc score.1 It has been suggested that significant MR might actually be protective against left atrial spontaneous echo contrast formation and against stroke in patients with nonrheumatic AF.3 However, the effect of MR on the risk of stroke in patients with AF is still controversial. We, therefore, studied whether or not MR was associated with a lower risk of thromboembolic events in a large series of patients with AF and whether MR may be independently associated with a different risk of thromboembolic events beyond the recognized items of the CHA2DS2-VASc score in AF patients.All patients with AF between 2000 and 2010 seen in the cardiology department in our public institution (academic hospital, tertiary referral center) were retrospectively identified and followed until December 2010.4 We collected information on type of AF, primary diagnoses and coexisting conditions, performed procedures, medication at discharge and in-hospital cardiovascular events and death (1 institution with 4 different sites, all specialties). Patients with prosthetic valve or mitral stenosis were excluded of the analysis, significant left-sided valvular heart diseases were identified (mild, moderate, or severe) and classified as severe or non severe based on the European Society of Cardiology guidelines.5 Severe MR was described by a vena contracta width ≥7 mm, effective regurgitant orifice area ≥40 mm2 and regurgitant volume ≥60 mL/beat calculated on a proximal isovelocity surface area. See the Data Supplement for details related to the methods.Among 8675 patients with AF 838 patients (10%) had MR, among whom 135 (16%) had severe MR. When comparing patients with MR or no MR (Table), patients with MR were older than patients with no MR, had higher CHA2DS2-VASc score, and more frequent permanent AF, heart failure, and vitamin K antagonist use. During a mean follow-up of 2.5 years (median 1.2, interquartile range 4.2), 688 ischemic stroke (IS)/thromboembolic events were recorded. MR was associated with a nonsignificant higher risk for IS/thromboembolic events (hazard ratio, 1.09; 95% CI, 0.86–1.39; P=0.47). After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with MR tended to have a higher all-cause and cardiovascular mortality but had a similar risk of IS/thromboembolic events when compared with patients with no MR (Table; Table in the Data Supplement). Severe MR was also associated with a similar risk for IS/thromboembolic events when compared with other AF patients (adjusted hazard ratio, 0.94; 95% CI, 0.49–1.81; P=0.85). In the 2 groups with MR or no MR, IS/thromboembolic risk increased with higher CHA2DS2-VASc scores. Factors independently associated with an increased risk of IS/thromboembolic events were older age (hazard ratio, 1.25; 95% CI, 1.16–1.34 per 10-year increase; P<0.0001) and a higher CHA2DS2-VASc score (hazard ratio, 1.35; 95% CI, 1.25–1.47; P<0.0001).Table. Characteristics of Patients With a Diagnosis of AF With MR or no MRAF and No MR (n=7837)AF and MR (n=838)P ValueAge, y70±1574±12<0.0001Sex (male)4916 (63%)466 (56%)<0.0001Medical history Heart failure3622 (46%)618 (73%)<0.0001 Hypertension2980 (38%)329 (39%)0.48 Diabetes mellitus1082 (14%)113 (13%)0.80 Prior stroke630 (8%)60 (7%)0.37 Coronary artery disease2209 (28%)249 (30%)0.35 Previous myocardial infarction1048 (13%)149 (18%)0.0004 Renal failure473 (6%)83 (10%)<0.0001 Pulmonary disease665 (8%)63 (8%)0.34 Permanent AF2906 (37%)412 (49%)<0.0001 Aortic regurgitation258 (3%)134 (16%)<0.0001 Aortic stenosis428 (5%)102 (12%)<0.0001 Pacemaker or Implantable cardioverter defibrillator1133 (14%)147 (18%)0.02 Cardiac resynchronization therapy154 (2%)43 (5%)<0.0001 CHA2DS2-VASc score2.9±1.73.5±1.6<0.0001 HAS-BLED score1.5±1.01.7±1.0<0.0001Medications Vitamin K antagonist (n=7863)3932 (56%)488 (63%)<0.0001 Antiplatelet agent (n=7717)2374 (34%)272 (36%)0.38 ACE inhibitor (n=8404)2432 (32%)430 (52%)<0.0001 β-Blocker (n=8500)3298 (43%)376 (45%)0.21 Digoxin (n=8601)1631 (21%)287 (34%)<0.0001 Class III antiarrhythmic agent (n=8593)3030 (39%)347 (42%)0.15 Diuretics (n=7966)2585 (36%)532 (66%)<0.0001Events during follow-up (adjusted hazard ratios) IS/TE (n=688)Reference0.88 (0.69–1.13)0.32 Bleeding events (n=743)Reference1.28 (1.03–1.59)0.02 Cardiovascular death (n=675)Reference1.17 (0.92–1.47)0.20 All-cause death (n=1254)Reference1.16 (0.97–1.38)0.10ACE indicates angiotensin-converting enzyme; AF, atrial fibrillation; IS, ischemic stroke; MR, mitral regurgitation; and TE, thromboembolic event.In a small series of patients with nonrheumatic AF seen in the 1990s, it was found that MR might be protective against stroke, especially in those patients with LA enlargement.3 A general concept is that MR may play the role of a washing machine effect in the left atrium and might be associated with a lower risk of IS/thromboembolic, but this has not been robustly demonstrated. In this large real-life cohort study, we found that AF patients with MR had a higher CHA2DS2-VASc score but a similar risk of IS/thromboembolic than other AF patients. Importantly, MR was neither an independent additional risk nor a protective factor for IS/thromboembolic when applying the CHA2DS2-VASc score.Our study has some limitations. The data set had a limited size and may not be large enough to demonstrate some possible differences although it is by far the largest focusing on this issue. There may be residual confounding between groups that could not be accounted for despite adjustments. Some of the echocardiography criteria were not widely applied in the early 2000s, and all the quantitative parameters were not available for each patient. However, our findings indicate that in patients with AF neither MR nor severe MR seems independently associated with a different risk of IS/thromboembolic events. The perceived protective effect of MR against the risk of thromboembolic events is not relevant in AF patients when using a contemporary risk stratification scheme, the CHA2DS2-VASc score.DisclosuresDr Clementy has received consulting honoraria from Boston Scientific, Medtronic, St Jude Medical, and Sorin-LivaNova. Dr Babuty has received clinical study support from Biotronik, Boston Scientific, Medtronic, St Jude Medical, and Sorin-LivaNova. Dr Lip has served as a speaker or consultant for Bayer/Janssen, Astellas, Merck, Sanofi, BMS/Pfizer, Biotronik, Medtronic, Portola, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo. Dr Fauchier has served as a speaker or consultant for Bayer, BMS/Pfizer, Boehringer Ingelheim, Medtronic, and Novartis. The other authors report no conflicts.FootnotesThe Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCEP.118.006990.Laurent Fauchier, MD, PhD, Cardiologie, Centre Hospitalier, Universitaire Trousseau, 37044 Tours, France. Email [email protected]univ-tours.frReferences1. Lip GYH, Collet JP, Caterina R, Fauchier L, Lane DA, Larsen TB, Marin F, Morais J, Narasimhan C, Olshansky B, Pierard L, Potpara T, Sarrafzadegan N, Sliwa K, Varela G, Vilahur G, Weiss T, Boriani G, Rocca B; ESC Scientific Document Group. Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).Europace. 2017; 19:1757–1758. doi: 10.1093/europace/eux240MedlineGoogle Scholar2. Bisson A, Bodin A, Clementy N, Bernard A, Babuty D, Lip GYH, Fauchier L. Stroke, thromboembolism and bleeding in patients with atrial fibrillation according to the EHRA valvular heart disease classification.Int J Cardiol. 2018; 260:93–98. doi: 10.1016/j.ijcard.2018.03.017CrossrefMedlineGoogle Scholar3. Nakagami H, Yamamoto K, Ikeda U, Mitsuhashi T, Goto T, Shimada K. Mitral regurgitation reduces the risk of stroke in patients with nonrheumatic atrial fibrillation.Am Heart J. 1998; 136:528–532.CrossrefMedlineGoogle Scholar4. Philippart R, Brunet-Bernard A, Clementy N, Bourguignon T, Mirza A, Babuty D, Angoulvant D, Lip GY, Fauchier L. Prognostic value of CHA2DS2-VASc score in patients with 'non-valvular atrial fibrillation' and valvular heart disease: the Loire Valley Atrial Fibrillation Project.Eur Heart J. 2015; 36:1822–1830. doi: 10.1093/eurheartj/ehv163CrossrefMedlineGoogle Scholar5. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schäfers H-J, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012).Eur Heart J. 2012; 33:2451–2496. doi: 10.1093/eurheartj/ehs109CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Melduni R, Nkomo V, Wysokinski W, Gersh B, Deshmukh A, Padang R, Greene E, Oh J and Lee H (2021) Risk of left atrial appendage thrombus and stroke in patients with atrial fibrillation and mitral regurgitation, Heart, 10.1136/heartjnl-2020-317659, 108:1, (29-36), Online publication date: 1-Jan-2022. Nishi H, Oishi N, Ogawa H, Natsue K, Doi K, Kawakami O, Aoki T, Fukuda S, Akao M and Tsukahara T (2021) Predicting cerebral infarction in patients with atrial fibrillation using machine learning: The Fushimi AF registry, Journal of Cerebral Blood Flow & Metabolism, 10.1177/0271678X211063802, 42:5, (746-756), Online publication date: 1-May-2022. Van Laer S, Verreyen S, Winkler K, Miljoen H, Sarkozy A, Heuten H, Saenen J, Van Herck P, Van de Heyning C, Heidbuchel H and Claeys M (2021) Effect of Mitral Regurgitation on Thrombotic Risk in Patients With Nonrheumatic Atrial Fibrillation: A New CHA2DS2-VASc Score Risk Modifier?, The American Journal of Cardiology, 10.1016/j.amjcard.2021.01.006, 145, (69-76), Online publication date: 1-Apr-2021. Melgaard L, Overvad T, Jensen M, Lip G, Larsen T and Nielsen P (2020) Thromboembolism and bleeding complications in anticoagulated patients with atrial fibrillation and native aortic or mitral valvular heart disease: a descriptive nationwide cohort study, European Heart Journal - Cardiovascular Pharmacotherapy, 10.1093/ehjcvp/pvaa008, 7:FI1, (f101-f110), Online publication date: 9-Apr-2021. 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Melgaard L, Jensen M, Overvad T, Larsen T, Lip G and Nielsen P (2020) Thromboembolic and bleeding outcomes in patients with atrial fibrillation and valvular heart disease: A descriptive nationwide cohort study, International Journal of Clinical Practice, 10.1111/ijcp.13589, 74:10, Online publication date: 1-Oct-2020. Gue Y, Bisson A, Bodin A, Herbert J, Lip G and Fauchier L (2021) Season of Birth and Cardiovascular Mortality in Atrial Fibrillation: A Population-Based Cohort Study, Journal of Cardiovascular Development and Disease, 10.3390/jcdd8120177, 8:12, (177) Huang H, Cai C, Hua W, Zhang N, Niu H, Chen X, Wang J, Jia Y, Chu J, Tang M and Zhang S (2022) Mitral Regurgitation and Body Mass Index Increase the Predictability of Perioperative Bleeding in Anticoagulated Patients With Nonvalvular Atrial Fibrillation, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.846590, 9 March 2019Vol 12, Issue 3 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.118.006990PMID: 30841722 Originally publishedMarch 7, 2019 Keywordsatrial fibrillationheart diseasesanticoagulantsdiagnosisheart failurePDF download Advertisement SubjectsArrhythmiasIschemic Stroke