Clinical Effects of CD34+ Cell Transplantation in Non-Ischemic Dilated Cardiomyopathy Correlate with Myocardial Cell Engraftment

Abstract

Purpose In pre-clinical models of stem cell therapy, early myocardial cell engraftment predicted late cardiac functional recovery. We sought to analyze the effect of myocardial homing of CD34 + cells on clinical outcome in patients with non-ischemic dilated cardiomyopathy (DCM). Methods and Materials In 94 patients with non-ischemic DCM, stem cells were mobilized by daily subcutaneous injections of filgrastim. CD34 + cells were collected via apheresis and labeled with technetium. Cells were injected intracoronary in the artery supplying segments of reduced myocardial viability (n=53), or transendocardially in the target areas defined by electro-anatomical mapping (n=41). Nuclear imaging for quantitation of myocardial homing was performed 18 hours after the procedure.Good homing was predefined as measured activity greater than median value of general activity.Patients were followed for 1 year. Results At baseline, patients with good (>median, group A) and poor (≤median, group B) homing did not differ in age, gender, LVEF, or plasma levels of creatinine or NT-proBNP. The number of mobilized CD34 + cells used for injection was comparable in both groups (98±56 x 10 6 in group A vs. 101±38 x 10 6 in group B, P=0.73). Transendocardial cell injection was more frequent in group A (62%) than in group B (32%, P=0.01). At year 1, LVEF improved more in group A (+6.2±2.8 %) than group B (+2.7±1.7 %, P=0.01). The same was true for 6-minute walk test distance (+101±21 m in group A vs. +46±11 m in group B, P=0.01) and levels of NT-proBNP (−733±2411 pg/ml vs. −115±123 pg/ml, P=0.006). In both groups, we found no significant change in LVEDD (-0.08±0.16 cm in group A vs. -0.06±0.10 cm in group B, P=0.70). Conclusions In patients with non-ischemic DCM, higher myocardial CD34 + cell homing is associated with superior improvement in ventricular function, NT proBNP levels, and exercise capacity. This suggests that early myocardial cell engraftment translates into long-term clinical benefit in this patient cohort.