Port, Steven C.

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.

Abstract Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of the most critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHD is discussed. Recommendations for the early identification and monitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed.