Abstract 13050: Cardiac Extracorporal Shock Wave Application to Enhance the Efficiency of Intracoronary Cell Therapy in Chronic Heart Failure - Final Results of the Randomized, Double-Blind, Placebo-Controlled CELLWAVE Trial
Introduction: The modest effects of early clinical studies using intracoronary administration of autologous bone marrow-derived mononuclear cells (BMC) in patients (pts) with chronic post-infarction heart failure (CHF) has been attributed to impaired homing of the applied BMC to the target area. Extracorporal shockwave (SW) treatment (tx) was experimentally shown to increase the homing factors like SDF-1 in the target tissue, resulting in enhanced homing and neovascularization of applied BMC. Therefore, we performed the randomized, double-blind, Placebo-controlled CELLWAVE trial to demonstrate improved recovery of LVEF by combining targeted SW application with subsequent BMC application in pts with CHF.
Methods: Pts were randomized to receive low-dose (n=39), high-dose (n=43) or Placebo (n=21) SW (Biotripter, Dornier) targeted to the LV anterior wall. 24 hours after SW application, pts with SW pretreatment were further randomized to either administration of BMC or Placebo-medium, whereas pts with Placebo-SW pretreatment received intracoronary BMC application.
Results: A total of 103 pts with stable advanced CHF and at least 3 months old previous anterior MI (time from last AMI 5.7±6.1 years) were randomized. The primary efficacy endpoint, absolute change in global LVEF at 4 months, was significantly improved in pts receiving SW tx and BMC infusion (abs. delta LVEF +3.2±3.2%; n=37) compared to pts with SW tx only (LVEF +1.0±4.0%; n=32; p=0.01). Likewise, NYHA class improved significantly from 2.3±0.6 to 2.0±0.7 (p=0.03) in the SW & BMC group, but not in the SW only treated pts (NYHA from 2.1±0.6 to 2.2±0.8, p=0.16). This effect persisted until 12 months follow-up. Most importantly, adverse cardiovascular events including death, rehospitalization for CHF, re-MI, VT, any revascularization and stroke were significantly (p=0.04) less frequent in the SW & BMC group compared to the BMC and SW & Placebo group.
Conclusion: Shock wave-facilitated intracoronary BMC administration in pts with chronic post-infarction heart failure is safe and associated with significant persistent improvements in NYHA class, contractile function and reduction of major adverse clinical events during extended clinical follow-up. (clinicaltrials.gov: NCT00326989).
- © 2012 by American Heart Association, Inc.