Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.

Background Despite restoration of epicardial flow following primary percutaneous coronary intervention (PPCI), microvascular reperfusion as reflected by ST-elevation resolution (ST-ER) resolution remains variable and its pathophysiology remains unclear. Methods and Results Using principal component analyses, we explored associations between 91 serum biomarkers drawn before PPCI clustered into 14 pathobiologic processes (including NT-proBNP [N-terminal pro-B-type natriuretic peptide] as an independent cluster), and (1) ST-ER resolution ≥50% versus <50%; and (2) 90-day composite of death, shock, and heart failure. Network analyses were performed to understand interbiomarker relationships between the ST-ER groups. Among the 1160 patients studied, 861 (74%) had ST-ER ≥50% at a median 40 (interquartile range, 23-70) minutes following PPCI, yet both groups had comparable post-PPCI TIMI (Thrombolysis in Myocardial Infarction) grade 3 flow (86.6% versus 82.9%; P=0.25). ST-ER ≥50% was associated with significantly lower pre-PPCI concentrations of platelet activation cluster (particularly P-selectin, von Willebrand factor, and platelet-derived growth factor A) and NT-proBNP, including after risk adjustment. Across both ST-ER groups, strong interbiomarker relationships were noted between pathways indicative of myocardial stretch, platelet activation, and inflammation, whereas with ST-ER <50% correlations between iron homeostasis and inflammation were observed. Of all 14 biomarker clusters, only NT-proBNP was significantly associated with the 90-day clinical composite. Conclusions Suboptimal ST-ER is common despite achieving post-PPCI TIMI grade 3 flow. The cluster of platelet activation proteins and NT-proBNP were strongly correlated with suboptimal ST-ER and NT-proBNP was independently associated with 90-day outcomes. This analysis provides insights into the pathophysiology of microvascular reperfusion in ST-segment-elevation myocardial infarction and suggests novel pre-PPCI risk targets potentially amenable to enhancing tissue-level reperfusion following PPCI.

Patients with age-related macular degeneration (ARMD) begin with non-neovascular (NNV) phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV) ARMD, but precise timing of this event is unknown. Developing a clinical test predicting impending conversion to NV-ARMD is necessary to prevent vision loss. Endothelial progenitor cells (EPCs), defined as CD34(+)VEGR2(+) using traditional fluorescence activated cell sorting (FACS), are rare cell populations known to be elevated in patients with NV-ARMD compared to NNV-ARMD. FACS has high inter-observer variability and subjectivity when measuring rare cell populations precluding development into a diagnostic test. We hypothesized that automated rare cell analysis (ARCA), a validated and FDA-approved technology for reproducible rare cell identification, can enumerate EPCs in ARMD patients more reliably. This pilot study serves as the first step in developing methods for reproducibly predicting ARMD phenotype conversion.

This study aims to explore long-term clinical outcomes of cardiopoiesis-guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial.