To gain more insight into the phenomenon of Tako-Tsubo cardiomyopathy (TTC), the purpose of the present study was to investigate the myocardial structure in the acute phase of TTC and after functional recovery. We studied eight patients presenting with TTC diagnosed by coronary angiography, ventriculography, magnetic resonance imaging, and echocardiography. Serial myocardial biopsies were taken during the phase of severely impaired left ventricular function and after functional recovery. Specimens were examined by light and electron microscope as well as immunohistochemistry. Additionally, specific methods detecting different types of cell death and measurements of virus titer were performed. All patients showed the typical contractile pattern of TTC and complete functional recovery within 12 ± 3 days. In ‘acute’ biopsies, many vacuoles of different size were found contributing to cellular hypertrophy. PAS staining revealed intracellular accumulation of glycogen. Additionally, structural deteriorations characterized by disorganization of contractile and cytoskeletal proteins could be detected. The extracellular matrix proteins were increased. Signs of oncotic and apoptotic cell death were absent. After functional recovery, all described alterations showed a nearly complete reversibility. TTC is accompanied by severe morphological alterations potentially resulting from catecholamine excess followed by microcirculatory dysfunction and direct cardiotoxicity. However, the affected myocardium represents a high potential of structural reconstitution which correlates with the rapid functional recovery.

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 <0.001). 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.

An important goal in cardiology is to minimize myocardial necrosis and to support a discrete but resilient scar formation after myocardial infarction (MI). Macrophages are a type of cells that influence cardiac remodelling during MI. Therefore, the goal of the present study was to investigate their transcriptional profile and to identify the type of activation during scar tissue formation. Ligature of the left anterior descending coronary artery was performed in mice. Macrophages were isolated from infarcted tissue using magnetic cell sorting after 5 days. The total RNA of macrophages was subjected to microarray analysis and compared with RNA from MI and LV‐control. mRNA abundance of relevant targets was validated by quantitative real‐time PCR 2, 5 and 10 days after MI (qRT‐PCR). Immunohistochemistry was performed to localize activation type‐specific proteins. The genome scan revealed 68 targets predominantly expressed by macrophages after MI. Among these targets, an increased mRNA abundance of genes, involved in both the classically (tumour necrosis factor α, interleukin 6, interleukin 1β) and the alternatively (arginase 1 and 2, mannose receptor C type 1, chitinase 3‐like 3) activated phenotype of macrophages, was found 5 days after MI. This observation was confirmed by qRT‐PCR. Using immunohistochemistry, we confirmed that tumour necrosis factor α, representing the classical activation, is strongly transcribed early after ligature (2 days). It was decreased after 5 and 10 days. Five days after MI, we found a fundamental change towards alternative activation of macrophages with up‐regulation of arginase 1. Our results demonstrate that macrophages are differentially activated during different phases of scar tissue formation after MI. During the early inflammatory phase, macrophages are predominantly classically activated, whereas their phenotype changes during the important transition from inflammation to scar tissue formation into an alternatively activated type.