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Background— The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Methods and Results— Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow–derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P =0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P =0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group ( P Conclusions— Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00279175.

Background Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction. Methods In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy. Results At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [±SD] increase, 5.5±7.3% vs. 3.0±6.5%; P = 0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P = 0.01). Conclusions Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Largescale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality. (ClinicalTrials.gov number, NCT00279175.)

We sought to investigate the association of the EAT with CMR parameters of ventricular remodelling and left ventricular (LV) dysfunction in patients with non-ischemic dilated cardiomyopathy (DCM).One hundred and fifty subjects (112 consecutive patients with DCM and 48 healthy controls) underwent CMR examination. Function, volumes, dimensions, the LV remodelling index (LVRI), the presence of late gadolinium enhancement (LGE) and the amount of EAT were assessed.Compared to healthy controls, patients with DCM revealed a significantly reduced indexed EAT mass (31.7 ± 5.6 g/m(2) vs 24.0 ± 7.5 g/m(2) , p0.0001). There was no difference in the EAT mass between DCM patients with moderate and severe LV dysfunction (23.5 ± 9.8 g/m(2) vs 24.2 ± 6.6 g/m(2) , P = 0.7). Linear regression analysis in DCM patients showed that with increasing LV end-diastolic mass index (LV-EDMI) (r = 0.417, P0.0001), increasing LV end-diastolic volume index (r = 0.251, P = 0.01) and increasing LV end-diastolic diameter (r = 0.220, P = 0.02), there was also a significantly increased amount of EAT mass. However, there was no correlation between the EAT and the LV ejection fraction (r = 0.0085, P = 0.37), right ventricular ejection fraction (r = 0.049, P = 0.6), LVRI (r = 0.116, P = 0.2) and the extent of LGE % (r = 0.189, P = 0.1). Among the healthy controls, the amount of EAT only correlated with increasing age (r = 0.461, P = 0.001), BMI (r = 0.426, P = 0.003) and LV-EDMI (r = 0.346, P = 0.02).In patients with DCM the amount of EAT is decreased compared to healthy controls irrespective of LV function impairment. However, an increase in LV mass and volumes is associated with a significantly increase in EAT in patients with DCM.

Increased platelet reactivity may contribute to the development of coronary artery disease and myocardial infarction. The aim of the present study was to assess platelet adhesiveness in different stages of coronary artery disease using the platelet adhesion assay (PADA). In addition, the acute effect of coronary angiography and stent implantation on platelet adhesiveness was examined.85 patients with stable coronary artery disease (SAP - stable angina pectoris) and 19 patients with acute myocardial infarction (AMI) were enrolled in the study. 35 volunteers served as controls. Blood sampling in SAP and AMI patients was done before coronary angiography to measure the adhesion index (AI) using the PADA. In 33 patients additional blood was drawn at the end of coronary angiography. In 6 patients blood samples were drawn also after stent implantation.In blood samples from patients with an AMI the AI was significantly higher than in blood samples from the SAP group (p0.01) and the control group (p0.01). Coronary angiography and stent implantation did not result in significant acute changes in mean AI however results show an interindividual variability in initial values as well as in AI changes during procedures.This is the first study to show that PADA, a quick and simple laboratory method for the quantitative determination of platelet adhesiveness, is able to detect platelet hyper-adhesiveness in patients with AMI.

Thrombogenicitiy of drug-eluting stents is a matter of controversial debate. The aim of this study was to evaluate the thrombogenicity of sirolimus-eluting stents (SES) compared to bare metal stents (BMS) in a standardised in vitro model.Nine SES and nine BMS were implanted in tubing loops and nine loops without stent served as controls. Initially and after 90 minutes of blood circulation in a modified chandler loop model, thrombin-antithrombin III complex (TAT), PMN-elastase, factor XIIa, SC5b-9, sP-selectin and platelet count were measured. Expression of CD62P, CD45/41 and PAC-1 on platelets were determined by flow cytometry.After 90 minutes, platelet count decreased significantly in the loops with BMS and SES (p0.05). Levels of TAT, PMN-elastase and SC5b-9 were significantly elevated after 90 minutes in all loops (p0.05). sP-selectin significantly increased in the loops with BMS and SES after 90 minutes. No significant changes occurred in any flow cytometric data. Platelet count, sP-selectin, TAT, PMN-elastase, SC5b-9, CD62P, CD41/CD45 and PAC-1 showed no significant difference between BMS and SES.These data provide evidence that there is no difference in thrombogenicity of BMS and SES in the in vitro model.

Expression of cellular adhesion molecules on leukocytes plays a key role in coronary artery disease (CAD). The aim of the present study was to assess whether atorvastatin therapy has an impact on the expression of cellular adhesion molecules on leukocytes in patients with normocholesterolemic CAD.In 54 patients with CAD and atorvastatin treatment and 54 CAD patients without atorvastatin therapy, expression of CD40L, CD11a, CD11b, CD54, CD62L and CD41 on leukocytes was measured using flow cytometry. All patients were normocholesterolemic.Atorvastatin treatment led to a significantly lower expression of CD40L, CD11b and CD54 on monocytes (p0.05) and neutrophils (p0.05). Expression of CD11a was significantly lower on monocytes (p0.05) in atorvastatin-treated patients.The present results indicate that atorvastatin apparently improves chronic inflammation and may have a beneficial effect on hemostasis by reducing the expression of cellular adhesion molecules on leukocytes.