title: Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: the CELLWAVE randomized clinical trial.
abstract: OBJECTIVE
  The modest effects of clinical studies using intracoronary administration of autologous bone marrow-derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs.
  
  
  OBJECTIVE
  To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure.
  
  
  METHODS
  The CELLWAVE double-blind, randomized, placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt, Germany, between 2006 and 2011.
  
  
  METHODS
  Single-blind low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the left ventricular anterior wall. Twenty-four hours later, patients receiving shock wave pretreatment were randomized to receive double-blind intracoronary infusion of BMCs or placebo, and patients receiving placebo shock wave received intracoronary infusion of BMCs.
  
  
  METHODS
  Primary end point was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion vs shock wave + BMCs; secondary end points included regional left ventricular function assessed by magnetic resonance imaging and clinical events.
  
  
  RESULTS
  The primary end point was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2% [95% CI, 2.0% to 4.4%]), compared with the shock wave + placebo infusion group (1.0% [95% CI, -0.3% to 2.2%]) (P = .02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6% [95% CI, 2.0% to 5.2%]) but not in the shock wave + placebo infusion group (0.5% [95% CI, -1.2% to 2.1%]) (P = .01). Overall occurrence of major adverse cardiac events was significantly less frequent in the shock wave + BMCs group (n = 32 events) compared with the placebo shock wave + BMCs (n = 18) and shock wave + placebo infusion (n = 61) groups (hazard ratio, 0.58 [95% CI, 0.40-0.85]; P = .02).
  
  
  CONCLUSIONS
  Among patients with postinfarction chronic heart failure, shock wave-facilitated intracoronary administration of BMCs vs shock wave treatment alone resulted in a significant, albeit modest, improvement in LVEF at 4 months. Determining whether the increase in contractile function will translate into improved clinical outcomes requires confirmation in larger clinical end point trials.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00326989.
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Germany
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmus
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Walter
authors.forename: Florian H
authors.initials: FH
authors.lastname: Seeger
authors.forename: David M
authors.initials: DM
authors.lastname: Leistner
authors.forename: Julia
authors.initials: J
authors.lastname: Steiner
authors.forename: Ina
authors.initials: I
authors.lastname: Ziegler
authors.forename: Andreas
authors.initials: A
authors.lastname: Lutz
authors.forename: Walaa
authors.initials: W
authors.lastname: Khaled
authors.forename: Jens
authors.initials: J
authors.lastname: Klotsche
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000628:therapy*; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications; D016037:Single-Blind Method; D013318:Stroke Volume; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left