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Aims: Autologous CD34+ (auto-CD34+) cells represent an attractive option for the treatment of refractory angina. Three double-blinded randomized trials (n = 304) compared intramyocardial (IM) auto-CD34+ cells with IM placebo injections to affect total exercise time (TET), angina frequency (AF), and major adverse cardiac events (MACE). Patient-level data were pooled from the Phase I, Phase II ACT-34, ACT-34 extension, and Phase III RENEW trials to determine the efficacy and safety of auto-CD34+ cells., Methods and Results: Treatment effects for TET were analysed using an analysis of covariance mixed-effects model and for AF using Poisson regression in a log linear model with repeated measures. The Kaplan-Meier rate estimates for MACE were compared using the log-rank test. Autologous CD34+ cell therapy improved TET by 46.6 s [3 months, 95% confidence interval (CI) 13.0 s-80.3 s; P = 0.007], 49.5 s (6 months, 95% CI 9.3-89.7; P = 0.016), and 44.7 s (12 months, 95% CI - 2.7 s-92.1 s; P = 0.065). The relative frequency of angina was 0.78 (95% CI 0.63-0.98; P = 0.032), 0.66 (0.48-0.91; P = 0.012), and 0.58 (0.38-0.88; P = 0.011) at 3-, 6- and 12-months in auto-CD34+ compared with placebo patients. Results remained concordant when analysed by treatment received and when confined to the Phase III dose of 1 × 105 cells/kg. Autologous CD34 + cell therapy significantly decreased mortality (12.1% vs. 2.5%; P = 0.0025) and numerically reduced MACE (38.9% vs. 30.0; P = 0.14) at 24 months., Conclusion: Treatment with auto-CD34+ cells resulted in clinically meaningful durable improvements in TET and AF at 3-, 6- and 12-months, as well as a reduction in 24-month mortality in this patient-level meta-analysis.

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

Aims: Red blood cell transfusion is associated with increased mortality among patients with acute coronary syndromes, but little is known about the consequences of transfusion in a contemporary setting of ST-segment elevation myocardial infarction. We describe the association between transfusion and 90-day mortality among patients with acute myocardial infarction treated with primary percutaneous coronary intervention., Methods and Results: Analyses were performed on 5532 patients with ST-elevation myocardial infarction from the Assessment of Pexelizumab in Acute Myocardial Infarction trial. The primary objective of this analysis was to ascertain the relation between red blood cell transfusion and 90-day mortality in patients with recent myocardial infarction. We initially determined the baseline and in-hospital predictors of transfusion (multivariable logistic regressions) and subsequently assessed the association between transfusion and mortality using a series of Cox proportional hazards regression combined to a landmark analyses. A total of 213 patients (3.9%) received a transfusion. Transfusion remained significantly associated with mortality [hazards ratio = 2.16 (1.20-3.88)], despite adjustment for baseline characteristics, in-hospital co-interventions, and for propensity of receiving a transfusion. Among patients who survived to hospital discharge, however, the hazard of death was not different in patients treated with transfusion., Conclusion: Transfusion is associated with 90-day mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. Although transfusion may be causally related to mortality, it is likely that at least part of the association is due to confounding. This association illustrates the complex relationship between transfusion, bleeding, and mortality and underscores the need for further research to understand the relationship between transfusion and clinical outcomes.