Atrial fibrillation (AF) is associated with a high risk of thromboembolic events, and its prevalence is projected to increase because of population aging. 17 Indeed, the thromboembolic complications of AF are an important cause of morbidity and mortality. The CHADS 2 and CHA 2 DS 2 -VASc scores are useful for thromboembolic risk stratification. 18,19 Background-Coronary artery embolism (CE) is recognized as an important nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical features, and prognosis remain insufficiently characterized. Methods and Results-We screened 1776 consecutive patients who presented with de novo acute myocardial infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing histological, angiographic, and other diagnostic imaging findings. The prevalence, clinical characteristics, treatment strategies, in-hospital outcomes, and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and the median international normalized ratio was 1.42 (range, 0.95-1.80). Eighteen of the 30 CE patients with nonvalvular atrial fibrillation had a CHADS 2 score of 0 or 1. When those patients were reevaluated using CHA 2 DS 2 -VASc, 61% were reassigned to a higher risk category. During a median follow-up of 49 months, CE and thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of major adverse cardiac and cerebrovascular events was 27.1%. In the propensity score-matched cohorts (n=45 each), Kaplan-Meier analysis showed a significantly higher incidence of cardiac death in the CE group than in the non-CE group (hazard ratio, 9.29; 95% confidence interval, 1.13-76.5; P<0.001). Correspondence to Teruo Noguchi, MD, PhD, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, 565-8565, Japan. E-mail tnoguchi@hsp. The present study was designed to evaluate the prevalence, clinical characteristics, and initial management of CE, and early and late outcomes, as well, in a large consecutive series of patients. We also propose new diagnostic criteria for CE based on histological, angiographic, and other diagnostic imaging findings. Conclusions-Atrial Methods Study Population and PCI ProcedureWe retrospectively analyzed a total of 2135 consecutive patients with AMI from January 2001 to December 2013 in the National Cerebral and Cardiovascular Center AMI database. We excluded 359 patients with a history of previous myocardial infarction (n=241), PCI (n=90), coronary artery bypass grafting (n=18), or both PCI and coronary artery bypass grafting (n=10), resulting in a total of 1776 patients with de novo AMI that were ultimately analyzed in this study (Figure 1). All study patients under...

Background-Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34-and CD133-positive cells present in peripheral blood, in maintenance of the vasculature and neovascularization. Immature populations, including CD34-positive cells, have been shown to contribute to vascular homeostasis, not only as a pool of endothelial progenitor cells but also as a source of growth/angiogenesis factors at ischemic loci. We hypothesized that diminished numbers of circulating immature cells might impair such physiological and reparative processes, potentially contributing to cerebrovascular dysfunction. Methods and Results-The level of circulating immature cells, CD34-, CD133-, CD117-, and CD135-positive cells, in patients with a history of atherothrombotic cerebral ischemic events was analyzed to assess possible correlations with the degree of carotid atherosclerosis and number of cerebral infarctions. There was a strong inverse correlation between numbers of circulating CD34-and CD133-positive cells and cerebral infarction. In contrast, there was no correlation between the degree of atherosclerosis and populations of circulating immature cells. Analysis of patients with cerebral artery occlusion revealed a significant positive correlation between circulating CD34-and CD133-positive cells and regional blood flow in areas of chronic hypoperfusion. Key Words: cerebral infarction Ⅲ cerebral ischemia Ⅲ antigens, CD34 Ⅲ stem cells A lthough it had traditionally been assumed that replacement of damaged endothelium resulted only from outgrowth of preexisting vasculature, recent studies have identified endothelial progenitor cells (EPCs) that appear to contribute to vascular homeostasis and repair. 1 Clinical trials to assess the therapeutic potential of bone marrow-derived mononuclear cells, a rich source of immature cells including EPCs, in hind-limb 2,3 and cardiac ischemia 4 have been initiated and have, thus far, provided promising results. Furthermore, immature cells, including CD34-positive (CD34 ϩ ) cells, have been shown to contribute to maintenance of the vasculature, not only as a pool of EPCs but also as the source of growth/angiogenesis factors. 5 Bone marrow-derived immature cells have also been shown to participate in neovascularization of ischemic brain after experimental stroke. 6 On the basis of these results, we hypothesized that levels of circulating immature cells might be proportional to the resilience of the cerebral circulation to ischemic stress; ie, lower numbers of circulating immature cells might be associated with cerebral ischemia and infarction. Conclusions-These MethodsThe institutional review board of the National Cardiovascular Center approved this study. All subjects provided informed consent. Circulating CD34 ϩ cells in 50 L of peripheral blood were quantified according to the manufacturer's protocol (ProCOUNT, Becton Dickinson Biosciences). To minimize intersample variation for measurements of CD34 ϩ cells, several methods were used: A nucleic ...

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665.

Subcortical white matter (WM) is a frequent target of ischemic injury and extensive WM lesions are important substrates of vascular cognitive impairment (VCI) in humans. However, ischemic stroke rodent models have been shown to mainly induce cerebral infarcts in the gray matter, while cerebral hypoperfusion models show only WM rarefaction without infarcts. The lack of animal models consistently replicating WM infarct damage may partially explain why many neuroprotective drugs for ischemic stroke or VCI have failed clinically, despite earlier success in preclinical experiments. Here, we report a novel animal model of WM infarct damage with cognitive impairment can be generated by surgical implantation of different devices to the right and left common carotid artery (CCA) in C57BL/6J mice. Implantation of an ameroid constrictor to the right CCA resulted in gradual occlusion of the vessel over 28 d, whereas placement of a microcoil to the left CCA induced ϳ50% arterial stenosis. Arterial spin labeling showed a gradual reduction of cerebral blood flow over 28 d post operation. Such reductions were more marked in the right, compared with the left, hemisphere and in subcortical, rather than the cortical, areas. Histopathological analysis showed multiple infarct damage in right subcortical regions, including the corpus callosum, internal capsule, hippocampal fimbria, and caudoputamen, in 81% of mice. Mice displaying such damage performed significantly poorer in locomotor and cognitive tests. The current mouse model replicates the phenotypes of human subcortical VCI, including multiple WM infarcts with motor and cognitive impairment.