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). Conclusions—: Atrial fibrillation is the most frequent cause of CE. Patients with CE represent a high-risk subgroup of patients with acute myocardial infarction and require close follow-up.

Background—: Inflammation and immune responses are integral components in the healing process after myocardial infarction. We previously reported dendritic cell (DC) infiltration in the infarcted heart; however, the precise contribution of DC in postinfarction healing is unclear. Methods and Results—: Bone marrow cells from CD11c-diphtheria toxin receptor/green fluorescent protein transgenic mice were transplanted into lethally irradiated wild-type recipient mice. After reconstitution of bone marrow–derived cells, the recipient mice were treated with either diphtheria toxin (DC ablation) or vehicle (control), and myocardial infarction was created by left coronary ligation. CD11c ⁺ green fluorescent protein–positive DCs expressing CD11b and major histocompatibility complex class II were recruited into the heart, peaking on day 7 after myocardial infarction in the control group. Mice with DC ablation for 7 days showed deteriorated left ventricular function and remodeling. The DC-ablated group demonstrated enhanced and sustained expression of inflammatory cytokines such as interleukin-1β, interleukin-18, and tumor necrosis factor-α, prolonged extracellular matrix degradation associated with a high level of matrix metalloproteinase-9 activity, and diminished expression level of interleukin-10 and endothelial cell proliferation after myocardial infarction compared with the control group. In vivo analyses revealed that DC-ablated infarcts had enhanced monocyte/macrophage recruitment. Among these cells, marked infiltration of proinflammatory Ly6C ^high monocytes and F4/80 ⁺ CD206 ⁻ M1 macrophages and, conversely, impaired recruitment of anti-inflammatory Ly6C ^low monocytes and F4/80 ⁺ CD206 ⁺ M2 macrophages in the infarcted myocardium were identified in the DC-ablated group compared with the control group. Conclusions—: These results suggest that the DC is a potent immunoprotective regulator during the postinfarction healing process via its control of monocyte/macrophage homeostasis.

Background Pump failure after acute myocardial infarction (AMI) can be predicted by several indices that estimate infarct size. However, there are few indices that predict infarct expansion and cardiac rupture. We focused on the prognostic significance of serum C-reactive protein (CRP) after AMI. Methods and Results Serum CRP levels were measured every 24 hours in 220 patients with a first Q-wave AMI. In-hospital complications, predischarge left ventriculographic findings, and long-term prognosis were assessed in relation to peak CRP levels. Peak levels of both CRP and creatine kinase (CK) were higher in patients with pump failure than in those without pump failure. In patients with cardiac rupture, peak CRP levels were higher than in those without rupture ( P =.001); peak CK levels were not predictive. Higher CRP levels were found in patients with left ventricular aneurysm ( P =.001 versus those without), aggravated heart failure ( P =.03 versus those without), and cardiac death ( P <.0001 versus survivors) during the first year after AMI. Multivariate analysis confirmed that an elevation of the peak CRP level ≥20 mg/dL was an independent predictor of cardiac rupture (relative risk, 4.72; P =.004), left ventricular aneurysmal formation (relative risk, 2.11; P =.03), and 1-year cardiac death (relative risk, 3.44; P <.0001). Conclusions Cardiac rupture, left ventricular aneurysmal formation, and 1-year cardiac death were associated with an elevation of serum CRP early after AMI, suggesting that elevation of CRP levels after AMI may predict infarct expansion.

Background: There 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 Results: The 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). Conclusions: With 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.

High-mobility group box 1 protein (HMGB1) is one of the recently defined damage-associated molecular pattern molecules derived from necrotic cells and activated macrophages. We investigated clinical implications of serum HMGB1 elevation in patients with acute myocardial infarction (MI). Then, we evaluated the effect of HMGB1 blockade on post-MI left ventricular (LV) remodelling in a rat MI model. Serum HMGB1 levels were examined in patients with ST-elevation MI (n = 35). A higher peak serum HMGB1 level was associated with pump failure, cardiac rupture, and in-hospital cardiac death. Then, an experimental MI model was induced in male Wistar rats. The mRNA and protein expression of HMGB1 were increased in the infarcted area compared with those values observed in sham-operated rats. We administered neutralizing anti-HMGB1 antibody (MI/anti-H) or control antibody (MI/C) to MI rats subcutaneously for 7 days. The mRNA levels of tumour necrosis factor-α and interleukin-1β and the number of macrophages in the infarcted area were reduced on day 3 in MI/anti-H rats compared with MI/C rats. Interestingly, HMGB1 blockade resulted in thinning and expansion of the infarct scar and marked hypertrophy of the non-infarcted area on day 14. Elevated serum HMGB1 levels were associated with adverse clinical outcomes in patients with MI. However, HMGB1 blockade in a rat MI model aggravated LV remodelling, possibly through impairment of the infarct-healing process. HMGB1, a novel predictor of adverse clinical outcomes after MI, may have an essential role in the appropriate healing process after MI.