Although clinical trials of autologous whole bone marrow for cardiac repair demonstrate promising results, many practical and mechanistic issues regarding this therapy remain highly controversial. Here, we report the results of a randomized study of bone-marrow-derived mesenchymal stem cells, administered to pigs, which offer several new insights regarding cellular cardiomyoplasty. First, cells were safely injected by using a percutaneous-injection catheter 3 d after myocardial infarction. Second, cellular transplantation resulted in long-term engraftment, profound reduction in scar formation, and near-normalization of cardiac function. Third, transplanted cells were preprepared from an allogeneic donor and were not rejected, a major practical advance for widespread application of this therapy. Together, these findings demonstrate that the direct injection of cellular grafts into damaged myocardium is safe and effective in the periinfarct period. The direct delivery of cells to necrotic myocardium offers a valuable alternative to intracoronary cell injections, and the use of allogeneic mesenchymal stem cells provides a valuable strategy for cardiac regenerative therapy that avoids the need for preparing autologous cells from the recipient.

ContextThe worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among persons with diabetes. The independent effect of diabetes on mortality following acute coronary syndromes (ACS) is uncertain.Objective To evaluate the influence of diabetes on mortality following ACS using a large database spanning the full spectrum of ACS. Design, Setting, and PatientsA subgroup analysis of patients with diabetes enrolled in randomized clinical trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62 036 patients (46 577 with ST-segment elevation myocardial infarction [STEMI] and 15 459 with unstable angina/ non-STEMI [UA/NSTEMI]), of whom 10 613 (17.1%) had diabetes. A multivariable model was constructed to adjust for baseline characteristics, aspects of ACS presentation, and treatments for the ACS event.Main Outcome Measures Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes.

Recent developments in cancer therapeutics have improved outcomes but have also been associated with cardiovascular complications. Therapies harnessing the immune system have been associated with an immune mediated myocardial injury described as myocarditis. Immune checkpoint inhibitors (ICI) are one such therapy with an increasing number of case and cohort reports describing a clinical syndrome of ICI-associated myocarditis. While the full spectrum of ICI-associated cardiovascular disease still needs to be fully defined, described cases of myocarditis range from more "smoldering" to fatal ones. These observations in the clinic setting stand in contrast to outcomes from randomized clinical trials where myocarditis is a rare event that is investigator reported and lacking in a specific case definition. The complexities associated with diagnosis, as well as the heterogeneous clinical presentation of ICI-associated myocarditis, have made ascertainment and identification of myocarditis with high specificity challenging in clinical trials and other data sets, limiting the ability to better understand the incidence, outcomes and predictors of these rare events. Therefore, establishing a uniform definition of myocarditis for application in clinical trials of cancer immunotherapies will enable greater understanding of these events. We propose an operational definition of cancer therapy associated myocarditis characterizing a broad spectrum of disease to facilitate improved case ascertainment and in turn incidence, outcomes and risk factors. Bonaca et al.