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Observational Study
. 2023 Apr 1;30(4):377-389.
doi: 10.5551/jat.63267. Epub 2022 Jun 12.

Evaluating the Potential Pathology and Short-Term Outcomes of Cryptogenic Stroke Using the Etiological Classification System

Takahiro Shimizu  1 , Yuji Ueno  2 , Yohei Tateishi  3 , Ryosuke Doijiri  4 , Ayako Kuriki  5 , Muneaki Kikuno  6   7 , Hidehiro Takekawa  8 , Yoshiaki Shimada  9 , Kodai Kanemaru  6   7 , Yuki Kamiya  5 , Eriko Yamaguchi  4 , Masatoshi Koga  7 , Masafumi Ihara  10 , Akira Tsujino  3 , Koichi Hirata  8 , Yasuhiro Hasegawa  1 , Nobutaka Hattori  2 , Takao Urabe  9
Affiliations
Observational Study

Evaluating the Potential Pathology and Short-Term Outcomes of Cryptogenic Stroke Using the Etiological Classification System

Takahiro Shimizu et al. J Atheroscler Thromb. .

Abstract

Aim: Various embolic sources and pathogenetic mechanisms underlie cryptogenic stroke (CS). We investigated the association of etiological diversity with short-term outcomes in patients with CS using a modified atherosclerosis (A), small-vessel disease (S), cardiac pathology (C), other causes (O), and dissection (D) (ASCOD) system.

Methods: Patients with CS who underwent transesophageal echocardiography were registered in this multicenter, observational study. In the modified classification system, O and D were inapplicable and thus excluded. Instead, atherosclerosis, small-vessel disease, cardiac pathology-CS classification was specifically constructed for the etiological diagnosis of CS. We utilized this system to explore the mechanism of CS by grading each pathology and evaluated its association with poorer modified Rankin Scale scores of 3-6 at hospital discharge.

Results: A total of 672 patients (68.7±12.8 years, 220 females) were analyzed. In the multiple logistic regression model, female sex (odds ratio [OR], 1.87 [1.15-3.04]; P =0.012), body mass index (OR, 0.93 [0.88-0.99]; P =0.025), National Institute of Health Stroke Scale score (OR, 1.16 [1.12-1.21]; P＜0.001), CHADS2 score (OR, 1.56 [1.30-1.86]; P＜0.001), D-dimer (OR, 1.04 [1.01-1.08]; P =0.015), diffusion-weighted image (DWI) lesion size (OR, 1.44 [1.10-1.89]; P =0.009), and S＋C score (OR, 1.26 [1.03-1.56]; P =0.029) were associated with poor functional outcome at discharge whereas the S＋C score was marginally associated with poor functional outcome after excluding 137 patients with a premorbid modified Rankin Scale score of ≥ 3.

Conclusions: The coexistence of small-vessel disease and cardiac pathology might be associated with poor in-hospital functional outcome in CS.

Keywords: Cryptogenic stroke; Embolic stroke of undetermined source; Etiology; Transesophageal echocardiography.

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Conflict of interest statement

YU received personal fees from OHARA Pharmaceutical Co., Ltd. and grants from Bristol-Myers Squibb outside the submitted work. HT received grants from Pfizer Japan Inc. and Daiichi Sankyo Co., Ltd. outside the submitted work. YK received personal fees from Daiichi Sankyo Co., Ltd. and grants from Bristol-Myers Squibb Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. outside the submitted work. MK received honoraria from Bayer Pharmaceutical Co. and Daiichi Sankyo Co., Ltd.; consultant fees from Ono Pharmaceutical Co., Ltd.; and research funds from Takeda, Daiichi Sankyo, Nippon Boeringer Ingelheim, Astellas, and Shionogi. MI received grants from Shimadzu Corporation, Otsuka Pharmaceutical, and Panasonic Corporation and personal fees from Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., and Bayer Pharmaceutical Co. outside the submitted work. KH received personal fees from MSD Co., Ltd., Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., Novartis Pharma K.K, AbbVie GK, Kyowa Hakko-Kirin Co., Eli Lilly Japan K.K, Amgen K.K., and Lundbeck Japan K.K. and grants from Eisai Co., Ltd., Pfizer Japan Inc., Novartis Pharma K.K., Takeda Pharmaceutical Co., Ltd., TAIYO Co., Ltd., Kyowa Minami Hospital, Shirasawa Hospital, Shiobara Onsen Hospital, Utsunomiya Chuo Hospital, Nishikata Hospital, and Moka Hospital outside the submitted work. YH received personal fees from Bayer Pharmaceutical Co. and Nippon Boehringer Ingelheim, Co., Ltd. during the conduct of the study. NH was an advisory member of Dai-Nippon Sumitomo Pharma Co., Ltd., Hisamitsu Pharmaceutical Co., Inc, and Biogen Idec Japan Ltd.; received lecture fees from Dai-Nippon Sumitomo Pharma Co., Ltd., Otsuka Pharmaceutical, Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Hakko-Kirin Co., Ltd., FP Pharmaceutical Corporation, Eisai Co., Ltd., Novartis Pharma K.K., and AbbVie; and received departmental endowments by commercial entities from Kyowa Hakko-Kirin Co., Ltd., Nippon Boehringer Ingelheim, Co., Ltd., AbbVie GK, FP Pharmaceutical Corporation, Otsuka Pharmaceutical, Co., Ltd., Dai-Nippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., Nihon Medi-physics Co., Ltd., Asahi Kasei Medical Co., Ltd., Ono Pharmaceutical Co., Ltd., MiZ Co., Ltd., AbbVie GK, OHARA Pharmaceutical Co., Ltd., Nihon Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Boston Scientific Corporation, and Medtronic Inc. TU received lecture fees from Daiichi Sankyo Co., Ltd., Boehringer Ingelheim, Otsuka Pharmaceutical Co., Ltd., Bayer Pharmaceutical Co., and AstraZeneca K.K. and research funds from Otsuka Pharmaceutical Co., Ltd. and AbbVie GK.

Figures

Fig.1. Sole and complex pathology in cryptogenic stroke
Fig.1. Sole and complex pathology in cryptogenic stroke
Venn diagram of the A (atherosclerosis), S (small-vessel disease), and C (cardiac pathology) phenotypes of all study subjects and patients with modified Rankin Scale scores of 0–2 and 3–6.
Fig.2. Comparison of scores in ASC-CS classification
Fig.2. Comparison of scores in ASC-CS classification
Dot plots and bar graph showing mean＋standard deviation for A, S, C, A＋S, S +C, A＋C, and A＋S＋C in patients with modified Rankin Scale scores of 0–2 and 3–6.
See this image and copyright information in PMC

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