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Large aortic arch plaques correlate with CHADS2 and CHA2DS2-VASc scores in cryptogenic stroke

      Highlights

      • CHALLENGE ESUS/CS registry is a large transesophageal echocardiography (TEE) registry for cryptogenic stroke patients.
      • CHALLENGE ESUS/CS registry clarified potential embolic sources.
      • Large aortic arch plaques were closely related to CHADS2 and CHA2DS2-VASc scores.
      • Paroxysmal atrial fibrillation was linked to CHADS2 and CHA2DS2-VASc scores.
      • Right-to-left shunt was inversely associated with CHA2DS2-VASc score.

      Abstract

      Background and aims

      Current trends have suggested covert atrial fibrillation as a mechanism of cryptogenic stroke. However, etiological heterogeneity regarding the underlying embolic sources remains a critical issue in cryptogenic stroke.

      Methods

      CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke) is a multicenter observational registry of cryptogenic stroke patients admitted to participating hospitals, who underwent transesophageal echocardiography between April 2014 and December 2016. We obtained baseline characteristics, radiological and laboratory data, and echocardiographic findings, especially for embolic sources demonstrated on transesophageal echocardiography, and conducted comparisons according to CHADS2 and CHA2DS2-VASc scores (0–1 vs. ≥2, respectively). This study was registered at http://www.umin.ac.jp/ctr/(UMIN000032957).

      Results

      The study comprised 677 patients (age, 68.7 ± 12.8 years; 455 males; median National Institutes of Health Stroke Scale score, 2) with cryptogenic stroke. On multiple logistic regression analysis, large aortic arch plaque ≥4 mm (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.51–3.36; p < 0.001), with ulcerative or mobile components (OR, 2.37; 95%CI, 1.38–4.06; p = 0.002), was associated with CHADS2 score ≥2. Large aortic arch plaque ≥4 mm (OR, 3.88; 95%CI, 2.07–7.27; p < 0.001) and ulcerative or mobile components (OR, 3.25; 95%CI, 1.44–7.34; p = 0.005) were linked to CHA2DS2-VASc score ≥2.

      Conclusions

      The CHALLENGE ESUS/CS registry is a large TEE registry, and clarifies potential embolic etiologies of cryptogenic stroke using TEE. Large aortic arch plaques were associated with high CHADS2 and CHA2DS2-VASc scores, and represented important embolic sources in cryptogenic stroke.

      Graphical abstract

      Keywords

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      References

        • Hart R.G.
        • Diener H.C.
        • Coutts S.B.
        • Easton J.D.
        • Granger C.B.
        • O'Donnell M.J.
        • et al.
        Embolic strokes of undetermined source: the case for a new clinical construct.
        Lancet Neurol. 2014; 13: 429-438
        • Amarenco P.
        • Cohen A.
        • Tzourio C.
        • Bertrand B.
        • Hommel M.
        • Besson G.
        • et al.
        Atherosclerotic disease of the aortic arch and the risk of ischemic stroke.
        N. Engl. J. Med. 1994; 331: 1474-1479
        • Homma S.
        • Sacco R.L.
        • Di Tullio M.R.
        • Sciacca R.R.
        • Mohr J.P.
        • Investigators PFOiCSS.
        Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in cryptogenic stroke study.
        Circulation. 2002; 105: 2625-2631
        • Di Tullio M.R.
        • Russo C.
        • Jin Z.
        • Sacco R.L.
        • Mohr J.P.
        • Homma S.
        • et al.
        Aortic arch plaques and risk of recurrent stroke and death.
        Circulation. 2009; 119: 2376-2382
        • Mas J.L.
        • Arquizan C.
        • Lamy C.
        • Zuber M.
        • Cabanes L.
        • Derumeaux G.
        • et al.
        Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both.
        N. Engl. J. Med. 2001; 345: 1740-1746
        • Sanna T.
        • Diener H.C.
        • Passman R.S.
        • Di Lazzaro V.
        • Bernstein R.A.
        • Morillo C.A.
        • et al.
        Cryptogenic stroke and underlying atrial fibrillation.
        N. Engl. J. Med. 2014; 370: 2478-2486
        • Gladstone D.J.
        • Spring M.
        • Dorian P.
        • Panzov V.
        • Thorpe K.E.
        • Hall J.
        • et al.
        Atrial fibrillation in patients with cryptogenic stroke.
        N. Engl. J. Med. 2014; 370: 2467-2477
        • Ntaios G.
        • Papavasileiou V.
        • Milionis H.
        • Makaritsis K.
        • Manios E.
        • Spengos K.
        • et al.
        Embolic strokes of undetermined source in the Athens stroke registry: a descriptive analysis.
        Stroke. 2015; 46: 176-181
        • Hart R.G.
        • Sharma M.
        • Mundl H.
        • Kasner S.E.
        • Bangdiwala S.I.
        • Berkowitz S.D.
        • et al.
        Rivaroxaban for stroke prevention after embolic stroke of undetermined source.
        N. Engl. J. Med. 2018; 378: 2191-2201
        • Diener H.C.
        • Easton J.D.
        • Granger C.B.
        • Cronin L.
        • Duffy C.
        • Cotton D.
        • et al.
        Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS).
        Int. J. Stroke. 2015; 10: 1309-1312
        • Kasner S.E.
        • Swaminathan B.
        • Lavados P.
        • Sharma M.
        • Muir K.
        • Veltkamp R.
        • et al.
        Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial.
        Lancet Neurol. 2018; 17: 1053-1060
        • Ueno Y.
        • Yamashiro K.
        • Tanaka Y.
        • Watanabe M.
        • Miyamoto N.
        • Shimada Y.
        • et al.
        Rosuvastatin may stabilize atherosclerotic aortic plaque: transesophageal echocardiographic study in the EPISTEME trial.
        Atherosclerosis. 2015; 239: 476-482
        • Stroke G.
        • Amarenco P.
        • Cohen A.
        • Hommel M.
        • Moulin T.
        • Leys D.
        • et al.
        Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke.
        N. Engl. J. Med. 1996; 334 (French Study of Aortic Plaques in): 1216-1221
        • Ueno Y.
        • Yamashiro K.
        • Tanaka R.
        • Kuroki T.
        • Hira K.
        • Kurita N.
        • et al.
        Emerging risk factors for recurrent vascular events in patients with embolic stroke of undetermined source.
        Stroke. 2016; 47: 2714-2721
        • Kirchhof P.
        • Benussi S.
        • Kotecha D.
        • Ahlsson A.
        • Atar D.
        • Casadei B.
        • et al.
        ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.
        Eur. Heart J. 2016; 37 (2016): 2893-2962
        • Gage B.F.
        • Waterman A.D.
        • Shannon W.
        • Boechler M.
        • Rich M.W.
        • Radford M.J.
        Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation.
        J. Am. Med. Assoc. 2001; 285: 2864-2870
        • Ntaios G.
        • Vemmos K.
        • Lip G.Y.
        • Koroboki E.
        • Manios E.
        • Vemmou A.
        • et al.
        Risk stratification for recurrence and mortality in embolic stroke of undetermined source.
        Stroke. 2016; 47: 2278-2285
        • Shimada Y.
        • Ueno Y.
        • Tanaka Y.
        • Okuzumi A.
        • Miyamoto N.
        • Yamashiro K.
        • et al.
        Aging, aortic arch calcification, and multiple brain infarcts are associated with aortogenic brain embolism.
        Cerebrovasc. Dis. 2013; 35: 282-290
        • Katsanos A.H.
        • Bhole R.
        • Frogoudaki A.
        • Giannopoulos S.
        • Goyal N.
        • Vrettou A.R.
        • et al.
        The value of transesophageal echocardiography for embolic strokes of undetermined source.
        Neurology. 2016; 87: 988-995
        • Knebel F.
        • Masuhr F.
        • von Hausen W.
        • Walde T.
        • Dreger H.
        • Raab V.
        • et al.
        Transesophageal echocardiography in patients with cryptogenic cerebral ischemia.
        Cardiovasc. Ultrasound. 2009; 7: 15
        • Lamy C.
        • Giannesini C.
        • Zuber M.
        • Arquizan C.
        • Meder J.F.
        • Trystram D.
        • et al.
        Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: the PFO-ASA Study. Atrial Septal Aneurysm.
        Stroke. 2002; 33: 706-711
        • Handke M.
        • Harloff A.
        • Olschewski M.
        • Hetzel A.
        • Geibel A.
        Patent foramen ovale and cryptogenic stroke in older patients.
        N. Engl. J. Med. 2007; 357: 2262-2268
        • Kasner S.E.
        • Lavados P.
        • Sharma M.
        • Wang Y.
        • Wang Y.
        • Davalos A.
        • et al.
        Characterization of patients with embolic strokes of undetermined source in the NAVIGATE ESUS randomized trial.
        J. Stroke Cerebrovasc. Dis. 2018; 27: 1673-1682
        • Olesen J.B.
        • Torp-Pedersen C.
        • Hansen M.L.
        • Lip G.Y.
        The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort study.
        Thromb. Haemostasis. 2012; 107: 1172-1179
        • Kim T.H.
        • Yang P.S.
        • Kim D.
        • Yu H.T.
        • Uhm J.S.
        • Kim J.Y.
        • et al.
        CHA2DS2-VASc score for identifying truly low-risk atrial fibrillation for stroke: a Korean nationwide cohort study.
        Stroke. 2017; 48: 2984-2990
        • Ntaios G.
        • Lip G.Y.
        • Makaritsis K.
        • Papavasileiou V.
        • Vemmou A.
        • Koroboki E.
        • et al.
        CHADS(2), CHA(2)S(2)DS(2)-VASc, and long-term stroke outcome in patients without atrial fibrillation.
        Neurology. 2013; 80: 1009-1017
        • Ueno Y.
        • Kimura K.
        • Iguchi Y.
        • Shibazaki K.
        • Inoue T.
        • Hattori N.
        • et al.
        Mobile aortic plaques are a cause of multiple brain infarcts seen on diffusion-weighted imaging.
        Stroke. 2007; 38: 2470-2476
        • Hagen P.T.
        • Scholz D.G.
        • Edwards W.D.
        Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts.
        Mayo Clin. Proc. 1984; 59: 17-20
        • Liao J.
        • Khalid Z.
        • Scallan C.
        • Morillo C.
        • O'Donnell M.
        Noninvasive cardiac monitoring for detecting paroxysmal atrial fibrillation or flutter after acute ischemic stroke: a systematic review.
        Stroke. 2007; 38: 2935-2940
        • Yaghi S.
        • Elkind M.S.
        Cryptogenic stroke: a diagnostic challenge.
        Neurol. Clin. Pract. 2014; 4: 386-393