Weintraub, Neal L.

Background: Refractory angina(Ang) effects 150 –250,000 pts in the US alone. These individuals have exhausted options for revasc and continue to have lifestyle limiting ang despite optimal medical Rx. Pre-clinical studies provided evidence that human CD34+ cells(CD34) can stimulate new blood vessel formation in ischemic myocardium(Myo), improving perfusion and function. We performed a phase 2 study of intraMyo injection of autologous CD34 in pts with CCS Class 3 and 4 Ang to obtain evidence for feasibility, safety and bioactivity. Methods: A phase 2 randomized, double-blind, placebo-controlled clinical trial was performed at 26 centers in the United States. There were 3 treatment groups: placebo, low dose (1×10^5 CD34/kg body wt) and high dose (5×10^5 CD34/kg). All pts underwent mobilization with GCSF 5 mcg/kg/day SC for 5 d, followed by apheresis on d5 to collect mononuclear cells. On day 6 CD34 were purified from the collected cells using the Isolex 300i device. After lot release testing, CD34 were injected endocardially at 10 locations in the ischemic Myo using the Myostar catheter following NOGA mapping. Placebo injections consisted of identical volumes of the diluent only. Results: A total of 167 pts were randomized and completed the injection procedure and 162 completed the 6 mo evaluation. The mean age of subjects was 61.0±8.9, there were 22 female and 145 male subjects. Trop was elevated in 26 pts at baseline and in 71 at some point following GCSF or injection. At 6 mo CD34 treated pts showed more reduction in ang frequency (−8.6 placebo vs 14.2 low dose) and improved ETT time (+69 sec placebo vs. +138 low dose). At 12m CD34 treated continue to show more reduction in angina (−8.2 placebo vs. −15.0 low dose) and improved ETT (+58 sec placebo vs. + 139 sec low dose). For key endpoints the high dose group results were inferior to low dose. The 12m data set has been locked and is being analyzed and the results of the completed analysis will be presented. Conclusions: Autologous CD34 cell therapy was associated with improved exercise tolerance and reduced angina in no-option pts with intractable angina. Ongoing analysis will determine endpoints, sample size and suitability of this therapy for a phase III study in no-option pts with refractory angina.

314 Background: Prostate cancer patients (PC) face an elevated risk of both developing atherosclerotic cardiovascular disease (ASCVD). The American College of Cardiology Pooled Cohort Equations (PCE) for ASCVD predictions may lack accuracy. Methods: Males ≥18 years, diagnosed with PC between 2005-2012 at a hybrid academic-community practice were included. Using XGBoost algorithm we developed using a training subset of the cohort (50% train + 25% test), ranked 33 covariates (including demographic, treatment-related and social determinants of health (SDOH) information) for ASCVD prediction using SHAP (Shapley additive explanations) values. The top 10 predictors were transformed in a predictive equation using logistic regression models. This equation was tested in the cohort validation subset (25%), and subsequently compared to the PCE risk score. Results: We included 1,506 patients, with a median age of 67 (IQR 60-74) years, 13.8% had advanced stage disease (TNM III-IV), 1.5% had high risk PC (Gleason 8-10), and 20.5% received androgen deprivation therapy (ADT). Of those, 10.4% had a 10-year ASCVD risk. The PCE had an area under the curve (AUC)=0.61 and underestimated ASCVD in 0.9% (mean risk=20.1% [95% CI 17.2-23.0] vs. mean predicted risk=19.2% [95% CI 18.6-19.8]). The equation pooled from the top-10 predictors of the ML algorithm (C-index=0.78 [95% CI 0.75-0.81]) achieved an AUC=0.71 (Table). Conclusions: Conventional PCE tend to underestimate ASCVD risk in males with PC. A cancer-specific model inclusive of SDOH exhibits good performance for predicting ASCVD risk in this population. [Table: see text]