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The detection of underlying atrial fibrillation (AF) has become increasingly possible by insertable cardiac monitoring (ICM). During hospitalization for cryptogenic stroke, factors related to the early and late development of AF have not been studied. CHALLENGE ESUS/CS is a multicenter registry of cryptogenic stroke patients undergoing transesophageal echocardiography. Twelve-lead electrocardiogram, continuous cardiac monitoring, and 24-h Holter electrocardiogram were all used for the detection of AF. Early and late detection of AF was determined with an allocation ratio of 1:1 among patients with AF. A total of 677 patients (68.7 ± 12.8 years; 455 men) were enrolled, and 64 patients developed AF during hospitalization. Four days after admission was identified as the approximate median day to classify early and late phases to detect AF: ≤ 4 days, 37 patients; > 4 days, 27 patients. Multiple logistic regression analysis showed that spontaneous echo contrast (SEC) (OR 5.91; 95% CI 2.19–15.97; p < 0.001) was associated with AF ≤ 4 days, whereas a large infarction > 3 cm in diameter (OR 3.28; 95% CI 1.35–7.97; p = 0.009) was associated with AF > 4 days. SEC and large infarctions were important predictors of in-hospital AF detection, particularly in the early and late stages, respectively; thus, they could serve as indications for recommending ICM. [ABSTRACT FROM AUTHOR]

Background: Cryptogenic stroke encompasses diverse emboligenic mechanisms and pathogeneses. Cerebral microbleeds (CMBs) occur differently among stroke subtypes. The association of CMBs with cryptogenic stroke is essentially unknown. Methods: CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for ESUS/CS) is a multicenter registry with comprehensive data including gradient-echo T2*-weighted magnetic resonance imaging of cryptogenic stroke patients who underwent transesophageal echocardiography. Patients' clinical characteristics were compared according to the presence and location of CMBs. Results: A total of 661 patients (68.7 ± 12.7 years; 445 males) were enrolled, and 209 (32%) had CMBs. Age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00–1.04, p = 0.020), male sex (OR 1.85, 95% CI 1.18–2.91, p = 0.007), hypertension (OR 1.71, 95% CI 1.03–2.86, p = 0.039), chronic kidney disease (OR 1.64, 95% CI 1.11–2.43, p = 0.013), deep and subcortical white matter hyperintensity (OR 1.82, 95% CI 1.16–2.85, p = 0.009), and periventricular hyperintensity (OR 2.18, 95% CI 1.37–3.46, p = 0.001) were independently associated with the presence of CMBs. Aortic complicated lesions (OR 1.78, 95% CI 1.12–2.84, p = 0.015) were associated with deep and diffuse CMBs, whereas prior anticoagulant therapy (OR 7.88, 95% CI, 1.83–33.9, p = 0.006) was related to lobar CMBs. Conclusions: CMBs were common, and age, male sex, hypertension, chronic kidney disease, and cerebral white matter diseases were related to CMBs in cryptogenic stroke. Aortic complicated lesions were associated with deep and diffuse CMBs, while prior anticoagulant therapy was related to lobar CMBs. [ABSTRACT FROM AUTHOR]

• Characteristics of high-risk patent foramen ovale (PFO) in elderly are unclear. • High-risk PFO had specific clinical characteristics and mechanistic associations. • This trend was consistent among CS patients aged ≥60 years. High-risk patent foramen ovale (PFO) could be pathological in cryptogenic stroke (CS), but its clinical characteristics have not been fully studied, especially in elderly patients. Patients with CS were enrolled in the CHALLENGE ESUS/CS registry, a multicenter registry of CS patients undergoing transesophageal echocardiography. Clinical characteristics were compared among three groups: high-risk PFO group, large shunt PFO (≥25 microbubbles) or PFO with atrial septal aneurysm (ASA); right-to-left shunt (RLS) group, RLS including PFO with <25 microbubbles or without ASA; and no-RLS group. In total, 654 patients were analyzed: 91, 221, and 342 in the high-risk PFO, RLS, and no-RLS groups, respectively. In multinomial logistic regression analysis, the male sex (odds ratio [OR] 1.825 [1.067–3.122]) was independently associated with high-risk PFO, but hypertension (OR, 0.562 [0.327–0.967]), multiple infarctions (OR, 0.601 [0.435–0.830]), and other cardioaortic embologenic risks (OR, 0.514 [0.294–0.897]) were inversely associated with high-risk PFO compared with non-RLS. In 517 patients aged ≥60 years, multiple infarctions (OR, 0.549 [0.382–0.788]) and other cardioaortic embologenic risks (OR, 0.523 [0.286–0.959]) were inversely associated with high-risk PFO. High-risk PFO had specific clinical characteristics and possible mechanistic associations, and this trend was consistent among CS patients aged ≥60 years. http://www.umin.ac.jp/ctr/ (UMIN000032957). [ABSTRACT FROM AUTHOR]

Background: Mobile or ulcerated aortic plaques (MUAPs) on transesophageal echocardiography (TEE) can cause aortogenic brain embolism. Aortic arch calcification (AoAC) on chest X-ray represents systemic atherosclerosis. This study focused on AoAC on chest X-ray and its link with atheromatous aortic plaques (AAPs) on TEE in stroke patients. The aim of the present study was to assess the relationship between AoAC and AAPs in unexplained stroke patients. Methods: A total of 178 patients (mean age: 64 ± 15 years; 115 males) with ischemic stroke who underwent TEE were enrolled. The patients were classified based on TEE findings: (1) AAPs <4 mm; (2) AAPs ≥4 mm, and (3) MUAPs. The extent of AoAC on chest X-ray was divided into 4 grades (0-3). Clinical characteristics including AoAC were compared among the 3 groups. Multiple logistic regression analysis was performed to identify the independent factors associated with MUAPs. An original diagnostic criterion was defined as a potential indicator of MUAPs in unexplained stroke patients. Results: 104 (58%) patients had AAPs <4 mm, 46 (26%) had AAPs ≥4 mm, and 28 (16%) had MUAPs. Older age (OR: 1.14; 95% CI: 1.06-1.24; p = 0.001), AoAC (OR: 2.35; 95% CI: 1.30-4.24; p = 0.005), and multiple infarctions in multiple vascular territories (VTs) demonstrated on diffusion-weighted imaging (DWI) (OR: 2.58; 95% CI: 1.35-4.92; p = 0.004) were independently associated with MUAPs. The CAM score was defined as consisting of the degree of AoAC (0-3 points), age (≥70 years: 1 point), and DWI findings (multiple infarctions in 1 VT: 1 point; 2 VTs: 2 points; more than 3 VTs: 3 points). The prevalence of MUAPs was substantially increased in patients with medium risk (CAM score 3-4, OR: 7.68; 95% CI: 2.89-20.44; p < 0.001) and high risk (CAM score 5-7, OR: 20.63; 95% CI: 5.12-83.06; p < 0.001). Conclusions: Older age, advanced AoAC, and multiple infarctions in multiple VTs are associated with aortogenic brain embolism. The CAM score can be useful for the diagnosis of aortogenic brain embolism. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Ulcerative aortic plaques (UAPs) are considered a major source of brain embolism. However, whether UAPs contribute to a specific stroke mechanism remains unknown. Methods: Three consecutive patients with recurrent embolic stroke underwent repeated transesophageal echocardiography (TEE) examinations after their initial and recurrent strokes. Results: All 3 patients had UAPs. Between TEEs, different morphologies of UAPs were found in cases 1 and 2, and case 3 maintained advanced UAPs with no significant morphological alteration. Case 3 underwent repeated contrast-enhanced computed tomographic examinations after each stroke event, which showed newly developed, uneven, ulcerative plaques in the aortic arch after recurrent stroke. Conclusions: Repeated TEE showed dynamic changes of UAPs in recurrent stroke patients and supported the diagnosis of aortogenic brain embolism. [Copyright &y& Elsevier]

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. 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 CHADS 2 and CHA 2 DS 2 -VASc scores (0–1 vs. ≥2, respectively). This study was registered at http://www.umin.ac.jp/ctr/ (UMIN000032957). 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 CHADS 2 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 CHA 2 DS 2 -VASc score ≥2. 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 CHADS 2 and CHA 2 DS 2 -VASc scores, and represented important embolic sources in cryptogenic stroke. Image 1 • 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 CHADS 2 and CHA 2 DS 2 -VASc scores. • Paroxysmal atrial fibrillation was linked to CHADS 2 and CHA 2 DS 2 -VASc scores. • Right-to-left shunt was inversely associated with CHA 2 DS 2 -VASc score. [ABSTRACT FROM AUTHOR]

Background Clinical characteristics are important for determining the etiologies of embolic stroke, including patent foramen ovale and complex aortic plaques demonstrated on transesophageal echocardiography (TEE). This study sought to analyze the clinical signs of cryptogenic stroke (CS) without such embolic etiologies and to examine the association between CS and brain natriuretic peptide (BNP), which is currently unknown. Methods Patients with CS after routine examinations who underwent TEE were included in this single-center observational study. Patients were classified into the potential embolic sources (PES) group (patients having PES on TEE) and the no potential embolic source (NPES) group. Patients were also categorized according to the tertile of BNP. Results A total of 158 patients (age, 64.0 ± 13.9 years; 119 males) with CS were enrolled. The PES group had 108 (68%) patients, and the NPES group had 50 (32%). Hypertension was more common, and glucose, D-dimer, and BNP were higher in the NPES than in the PES group ( p < 0.05). NPES was independently associated with high-BNP tertile (OR: 5.61; 95% CI: 1.91 to 16.44; p = 0.002). Conclusions BNP, an indicator of cardioembolism, was closely associated with NPES. Cardiogenic mechanisms may be implicated in the etiology of CS without potential embolic etiologies on TEE. [ABSTRACT FROM AUTHOR]

Objective Large atheromatous aortic plaques (AAPs) have been associated with ischemic stroke. There is little evidence to guide the therapeutic strategy for ischemic stroke associated with large AAPs. This study sought to analyze the temporal profile of AAPs after rosuvastatin therapy in Japanese patients with acute ischemic stroke. Methods The Efficacy of Post-stroke Intensive Rosuvastatin Treatment for aortogenic Embolic stroke (EPISTEME) trial was a prospective, randomized, open-label study. Acute ischemic stroke patients with dyslipidemia and AAPs ≥4-mm-thick on transesophageal echocardiography (TEE) were enrolled and randomly allocated to either the group treated with 5 mg/day rosuvastatin or the control group. The primary endpoint was the changes in volume and composition of AAPs on repeat TEE after 6 months. High-echoic plaque area was analyzed using binary images. Results A total of 24 Japanese patients (rosuvastatin 12; control 12) were included in the primary analysis. Rosuvastatin substantially reduced low-density lipoprotein cholesterol (LDL-C) compared to control (−42.1% vs. 1.4%, P < 0.001). Percent changes of high-echoic plaque areas were significantly increased in the rosuvastatin group, while they were decreased in the control group (65.8% vs −14.7%, P < 0.001). There was a significant linear correlation between percent increase in high-echoic plaque area and LDL-C decrease (r = −0.434, P = 0.002). Conclusion Treatment with 5-mg rosuvastatin for 6 months might induce atheromatous aortic plaque stabilization together with marked LDL-C reduction in Japanese patients with ischemic stroke, which could provide evidence on which to base the therapeutic strategy for aortogenic brain embolism. [ABSTRACT FROM AUTHOR]

Abstract: The ratio of low- (LDL-C) to high- (HDL-C) density lipoprotein cholesterol serves as a positive predictor of atherosclerosis including coronary artery disease. We assessed the contribution of the LDL-C/HDL-C ratio to atheromatous aortic plaques (AAPs) in patients with unexplained ischemic stroke. One hundred thirty-seven patients (age, 65±14years; 87 male) with ischemic stroke underwent transesophageal echocardiography (TEE) and enrolled to the study. Patients were classified based on TEE findings: (1) AAPs<4mm in thickness; (2) AAPs≥4mm; and (3) mobile or ulcerated aortic plaques (MUAPs). We assessed clinical characteristics and biochemical findings, and investigated the relationship between AAPs and the LDL-C/HDL-C ratio of stroke patients. 84 (61%) patients had AAPs<4mm, 29 (21%) had AAPs≥4mm, and 24 (18%) had MUAPs. Older age (OR: 1.18; 95% CI: 1.08 to 1.30; p=0.001), and LDL-C/HDL-C ratio (OR: 2.94; 95% CI: 1.10 to 7.87; p=0.032) were significantly associated with MUAPs. The incidence of MUAPs substantially increased in patients with LDL-C/HDL-C ratios of >2.23 (p<0.001) when the ratios were divided into quartiles. The LDL-C/HDL-C ratio was closely associated with MUAPs. An elevated LDL-C/HDL-C ratio could be a positive predictor of aortogenic brain embolism. [Copyright &y& Elsevier]