Objectives The aim of this study was to explore post-MI myocardial inflammation. Background Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease, however; clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the non-ischemic remote zone recruits monocytes. Methods Acute inflammation was followed in mice with coronary ligation by 18FDG PET/MRI, FACS, PCR and histology. Results Gd-DTPA enhanced infarcts showed high 18FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b+ cells had 4-fold higher 18FDG uptake than the infarct tissue from which they were isolated (P<0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (~104/mg myocardium, 5.6-fold increase, P<0.01), a finding mirrored by macrophage infiltration in remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative PCR showed robust increase of recruiting adhesion molecules and chemokines in remote myocardium (e.g. 12-fold increase of MCP-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in non-infarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post MI dilation. Conclusion These studies shed light on the innate inflammatory response in remote myocardium after myocardial infarction.

SUMMARY Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlate closely with mortality. The origin of these myeloid cells, and the response of hematopoietic stem and progenitor cells (HSPCs) to MI, however, is unclear. Here, we identify a CCR2+CD150+CD48− LSK hematopoietic subset as the most upstream contributor to emergency myelopoiesis after ischemic organ injury. CCR2+ HSPC have fourfold higher proliferation rates than CCR2−CD150+CD48− LSK cells, display a myeloid differentiation bias, and dominate the migratory HSPC population. We further demonstrate the myeloid translocation gene 16 (Mtg16) regulates CCR2+ HSPC emergence. Mtg16−/− mice have decreased levels of systemic monocytes and infarct-associated macrophages and display compromised tissue healing and post-MI heart failure. Together, these data provide insights into regulation of emergency hematopoiesis after ischemic injury, and identify potential therapeutic targets to modulate leukocyte output after MI.

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.

Deep learning has the potential to improve automatic interpretation of MPI as compared with current clinical methods.