Article: Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial)
| Title | Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial) |
|---|---|
| Authors | Tse, HF2 Thambar, S3 Kwong, YL2 Rowlings, P6 Bellamy, G3 McCrohon, J6 Thomas, P5 Bastian, B3 Chan, JKF7 Lo, G7 Ho, CL7 Chan, WS2 Kwong, RY4 Parker, A1 Hauser, TH1 Chan, J2 Fong, DYT2 Lau, CP2 |
| Keywords | Angiogenesis Bone marrow Coronary artery disease |
| Issue Date | 2007 |
| Publisher | Oxford University Press. The Journal's web site is located at http://eurheartj.oxfordjournals.org/ |
| Citation | European Heart Journal, 2007, v. 28 n. 24, p. 2998-3005 [How to Cite?] DOI: http://dx.doi.org/10.1093/eurheartj/ehm485 |
| Abstract | Aims: 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). Methods and 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 × 106 cells/0.1 mL, n = 9), high dose (2 × 106 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. Conclusion: 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. © The Author 2007. |
| ISSN | 0195-668X 2011 Impact Factor: 10.478 2011 SCImago Journal Rankings: 0.801 |
| DOI | http://dx.doi.org/10.1093/eurheartj/ehm485 |
| ISI Accession Number ID | WOS:000251680600012 |
| References | References in Scopus |
| dc.contributor.author | Tse, HF |
|---|---|
| dc.contributor.author | Thambar, S |
| dc.contributor.author | Kwong, YL |
| dc.contributor.author | Rowlings, P |
| dc.contributor.author | Bellamy, G |
| dc.contributor.author | McCrohon, J |
| dc.contributor.author | Thomas, P |
| dc.contributor.author | Bastian, B |
| dc.contributor.author | Chan, JKF |
| dc.contributor.author | Lo, G |
| dc.contributor.author | Ho, CL |
| dc.contributor.author | Chan, WS |
| dc.contributor.author | Kwong, RY |
| dc.contributor.author | Parker, A |
| dc.contributor.author | Hauser, TH |
| dc.contributor.author | Chan, J |
| dc.contributor.author | Fong, DYT |
| dc.contributor.author | Lau, CP |
| dc.date.accessioned | 2010-10-31T12:30:57Z |
| dc.date.available | 2010-10-31T12:30:57Z |
| dc.date.issued | 2007 |
| dc.description.abstract | Aims: 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). Methods and 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 × 106 cells/0.1 mL, n = 9), high dose (2 × 106 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. Conclusion: 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. © The Author 2007. |
| dc.description.nature | link_to_subscribed_fulltext |
| dc.identifier.citation | European Heart Journal, 2007, v. 28 n. 24, p. 2998-3005 [How to Cite?] DOI: http://dx.doi.org/10.1093/eurheartj/ehm485 |
| dc.identifier.doi | http://dx.doi.org/10.1093/eurheartj/ehm485 |
| dc.identifier.epage | 3005 |
| dc.identifier.hkuros | 174709 |
| dc.identifier.hkuros | 140838 |
| dc.identifier.isi | WOS:000251680600012 |
| dc.identifier.issn | 0195-668X 2011 Impact Factor: 10.478 2011 SCImago Journal Rankings: 0.801 |
| dc.identifier.issue | 24 |
| dc.identifier.openurl | ![]() |
| dc.identifier.pmid | 17984132 |
| dc.identifier.scopus | eid_2-s2.0-37249084757 |
| dc.identifier.spage | 2998 |
| dc.identifier.uri | http://hdl.handle.net/10722/126477 |
| dc.identifier.volume | 28 |
| dc.language | eng |
| dc.publisher | Oxford University Press. The Journal's web site is located at http://eurheartj.oxfordjournals.org/ |
| dc.publisher.place | United Kingdom |
| dc.relation.ispartof | European Heart Journal |
| dc.relation.references | References in Scopus |
| dc.rights | European Heart Journal. Copyright © Oxford University Press. |
| dc.subject.mesh | Acute Disease |
| dc.subject.mesh | Aged |
| dc.subject.mesh | Bone Marrow Transplantation - methods |
| dc.subject.mesh | Coronary Artery Disease - diagnosis - surgery |
| dc.subject.mesh | Exercise Test - methods |
| dc.subject.mesh | Female |
| dc.subject.mesh | Follow-Up Studies |
| dc.subject.mesh | Humans |
| dc.subject.mesh | Magnetic Resonance Angiography - methods |
| dc.subject.mesh | Male |
| dc.subject.mesh | Prospective Studies |
| dc.subject.mesh | Tomography, Emission-Computed, Single-Photon - methods |
| dc.subject | Angiogenesis |
| dc.subject | Bone marrow |
| dc.subject | Coronary artery disease |
| dc.title | Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial) |
| dc.type | Article |
Author Affiliations
- Harvard Medical School
- The University of Hong Kong
- John Hunter Hospital
- Brigham and Women's Hospital
- St George Hospital
- Newcastle Mater Misericordiae Hospital
- Hong Kong Sanatorium and Hospital


