title: Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial).
abstract: OBJECTIVE
  Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD).
  
  
  RESULTS
  We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation.
  
  
  CONCLUSIONS
  Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.
authors.affiliation: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong. hftse@hkucc.hku.hk
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Sukumaran
authors.initials: S
authors.lastname: Thambar
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.forename: Philip
authors.initials: P
authors.lastname: Rowlings
authors.forename: Greg
authors.initials: G
authors.lastname: Bellamy
authors.forename: Jane
authors.initials: J
authors.lastname: McCrohon
authors.forename: Paul
authors.initials: P
authors.lastname: Thomas
authors.forename: Bruce
authors.initials: B
authors.lastname: Bastian
authors.forename: John K F
authors.initials: JK
authors.lastname: Chan
authors.forename: Gladys
authors.initials: G
authors.lastname: Lo
authors.forename: Chi-Lai
authors.initials: CL
authors.lastname: Ho
authors.forename: Wing-Sze
authors.initials: WS
authors.lastname: Chan
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Kwong
authors.forename: Anthony
authors.initials: A
authors.lastname: Parker
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hauser
authors.forename: Jenny
authors.initials: J
authors.lastname: Chan
authors.forename: Daniel Y T
authors.initials: DY
authors.lastname: Fong
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
mesh_terms: D000208:Acute Disease; D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000601:surgery*; D005080:Exercise Test / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D011446:Prospective Studies; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods