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...

In patients with fulminant myocarditis, percutaneous ECMO is a highly effective form of a haemodynamic support. Once a patient recovers from inflammatory myocardial damage, the subsequent clinical outcome is favourable, similar to that observed in patients with acute non-fulminant myocarditis.

Factors secreted by the heart, referred to as "cardiokines," have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial hypertrophy and heart failure. The aim of this study was to investigate the role of cardiac Fstl1 in the remodeling response to pressure overload. Cardiac myocyte-specific Fstl1-KO mice were constructed and subjected to pressure overload induced by transverse aortic constriction (TAC). Although Fstl1-KO mice displayed no detectable baseline phenotype, TAC led to enhanced cardiac hypertrophic growth and a pronounced loss in ventricular performance by 4 wk compared with control mice. Conversely, mice that acutely or chronically overexpressed Fstl1 were resistant to pressure overload-induced hypertrophy and cardiac failure. Fstl1-deficient mice displayed a reduction in TAC-induced AMP-activated protein kinase (AMPK) activation in heart, whereas Fstl1 overexpression led to increased myocardial AMPK activation under these conditions. In cultured neonatal cardiomyocytes, administration of Fstl1 promoted AMPK activation and antagonized phenylephrine-induced hypertrophy. Inhibition of AMPK attenuated the antihypertrophic effect of Fstl1 treatment. These results document that cardiac Fstl1 functions as an autocrine/paracrine regulatory factor that antagonizes myocyte hypertrophic growth and the loss of ventricular performance in response to pressure overload, possibly through a mechanism involving the activation of the AMPK signaling axis.TSC-36 | angiogenesis

BackgroundThere is little known about whether the clinical and pathological characteristics and incidence of cardiac rupture (CR) in patients with acute myocardial infarction (AMI) have changed over the years.Methods and ResultsThe incidence and clinical characteristics of CR were investigated in patients with AMI, who were divided into 3 cohorts: 1977–1989, 1990–2000, and 2001–2011. Of a total of 5699 patients, 144 were diagnosed with CR and 45 survived. Over the years, the incidence of CR decreased (1977–1989, 3.3%; 1990–2000, 2.8%; 2001–2011, 1.7%; P=0.002) in association with the widespread adoption of reperfusion therapy. The mortality rate of CR decreased (1977–1989, 90%; 1990–2000, 56%; 2001–2011, 50%; P=0.002) in association with an increase in the rate of emergent surgery. In multivariable analysis, first myocardial infarction, anterior infarct, female sex, hypertension, and age >70 years were significant risk factors for CR, whereas impact of hypertension on CR was weaker from 2001 to 2011. Primary percutaneous coronary intervention (PPCI) was a significant protective factor against CR. In 64 autopsy cases with CR, myocardial hemorrhage occurred more frequently in those who underwent PPCI or fibrinolysis than those who did not receive reperfusion therapy (no reperfusion therapy, 18.0%; fibrinolysis, 71.4%; PPCI, 83.3%; P=0.001).ConclusionsWith the development of medical treatment, the incidence and mortality rate of CR have decreased. However, first myocardial infarction, anterior infarct, female sex, and old age remain important risk factors for CR. Adjunctive cardioprotection against reperfusion‐induced myocardial hemorrhage is emerging in the current PPCI era.

FSTL1 is an extracellular glycoprotein whose functional significance in physiological and pathological processes is incompletely understood. Recently, we have shown that FSTL1 acts as a muscle-derived secreted factor that is up-regulated by Akt activation and ischemic stress and that FSTL1 exerts favorable actions on the heart and vasculature. Here, we sought to identify the receptor that mediates the cellular actions of FSTL1. We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. DIP2A was present on the cell surface of endothelial cells, and knockdown of DIP2A by small interfering RNA reduced the binding of FSTL1 to cells. In cultured endothelial cells, knockdown of DIP2A by small interfering RNA diminished FSTL1-stimulated survival, migration, and differentiation into network structures and inhibited FSTL1-induced Akt phosphorylation. In cultured cardiac myocytes, ablation of DIP2A reduced the protective actions of FSTL1 on hypoxia/ reoxygenation-induced apoptosis and suppressed FSTL1-induced Akt phosphorylation. These data indicate that DIP2A functions as a novel receptor that mediates the cardiovascular protective effects of FSTL1.FSTL1 (follistatin-like 1; also referred to TSC36) is a secreted extracellular glycoprotein that was initially identified from a mouse osteoblast cell line as a transforming growth factor-␤ (TGF-␤) 2 -regulated gene (1). Prior studies have shown that FSTL1 can have antiproliferative effects on cells (2, 3) and that it can exert anti-inflammatory (4, 5) or pro-inflammatory (6) actions in animal models. Recently, we have found that FSTL1 is up-regulated in the myocardium in response to Akt1-induced hypertrophic growth and myocardial stress, including pressure overload, ischemia-reperfusion, and myocardial infarction (7). Systemic delivery of FSTL1 protects the heart from ischemiareperfusion injury in mice, which is accompanied by reduced myocyte apoptosis. More recently, we have shown that FSTL1 is up-regulated and secreted in skeletal muscle in response to Akt-mediated growth and ischemic injury (8). FSTL1 promotes endothelial cell function in vitro and accelerates ischemia-induced revascularization in vivo. Thus, we proposed that FSTL1 functions as an injury-induced secreted protein that protects against ischemic damage. However, the molecular mechanisms by which FSTL1 promotes cardiovascular cell protection and function are incompletely understood.FSTL1 possesses extracellular calcium-binding and follistatin-like domains and is categorized as the follistatin family member of proteins (9). Other members of the follistatin family act through their ability to function as extracellular binding partners of TGF-␤ superfamily proteins and antagonize the binding of these ligands to the receptors (10). However, it has never been documented that FSTL1 modulates cell function by binding members of the TGF-␤ superfamily, as do follistatin and FSTL3 (11...

The presence of CAE predicted future cardiac events in patients with acute MI. Our findings suggest that acute MI patients with CAE are a high-risk subset who might benefit from a pharmacological approach to controlling the coagulation cascade.

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Appropriate anticoagulation therapy may decrease the incidence of embolic events without increasing the incidence of bleeding events in patients with first AMI complicated by LV thrombus.