Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure -: Results of the TOPCARE-CHD registry

被引:162
作者
Assmus, Birgit
Fischer-Rasokat, Ulrich
Honold, Joerg
Seeger, Florian H.
Fichtlscherer, Stephan
Tonn, Torsten
Seifried, Erhard
Schaechinger, Volker
Dimmeler, Stefanie
Zeiher, Andreas M.
机构
[1] Goethe Univ Frankfurt, Dept Med 3, D-60590 Frankfurt, Germany
[2] Red Cross Donor Serv Baden Wurttemberg Hessen, Inst Transfus Med & Immunohematol, Frankfurt, Germany
关键词
progenitors cells; ischemic cardiomyopathy; NT-proBNP;
D O I
10.1161/01.RES.0000264508.47717.6b
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although intracoronary administration of bone marrow-derived mononuclear progenitor cells (BMCs) may be associated with improved cardiac function in patients with chronic postinfarction heart failure, the impact on prognosis and clinical outcome of these patients is unknown. To identify potential predictors for a favorable clinical outcome, we assessed natriuretic peptide serum levels as objective markers of heart failure and the occurrence of cardiac death in relation to functional capacity of the infused cells in a consecutive series of 121 patients with chronic ischemic heart disease treated with intracoronary infusion of BMCs. Our analyses show that both N-terminal pro-brain natriuretic peptide (NT-proBNP) and N-terminal pro-atrial natriuretic peptide (NT-proANP) serum levels were significantly reduced in patients with established postinfarction heart failure 3 months after transcoronary progenitor cell administration. NT-proBNP serum levels greater than or equal to median (735 pg/mL) at baseline and a high number of infused progenitor cells with colony-forming capacity were the only independent predictors of a favorable response 3 months after intracoronary administration of BMCs. During extended clinical follow-up (577 +/- 442 days), a total of 14 deaths occurred in the overall patient population. Kaplan-Meier curves for both all cause and cardiac mortality showed that patients receiving a higher number of colony-forming cells were significantly less likely to die than those patients receiving low numbers of colony-forming cells (P=0.01). Most importantly, infusion of a high number of cells with colony-forming capacity was associated with a complete abrogation of increased mortality in patients with elevated NT-proBNP serum levels (>= 735 pg/mL; median) at baseline (P<0.001). Taken together, our results show that patients with objective evidence of postinfarction heart failure demonstrate a significant reduction of both NT-proBNP and NT-proANP serum levels within 3 months following intracoronary infusion of BMCs. Importantly, infusion of progenitor cells with a high functional capacity is associated with a significantly lower mortality during further follow-up.
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页码:1234 / 1241
页数:8
相关论文
共 24 条
[1]   Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells [J].
Aicher, A ;
Heeschen, C ;
Mildner-Rihm, C ;
Urbich, C ;
Ihling, C ;
Technau-Ihling, K ;
Zeiher, AM ;
Dimmeler, S .
NATURE MEDICINE, 2003, 9 (11) :1370-1376
[2]   Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction -: (TOPCARE-AMI) [J].
Assmus, B ;
Schächinger, V ;
Teupe, C ;
Britten, M ;
Lehmann, R ;
Döbert, N ;
Grünwald, F ;
Aicher, A ;
Urbich, C ;
Martin, H ;
Hoelzer, D ;
Dimmeler, S ;
Zeiher, AM .
CIRCULATION, 2002, 106 (24) :3009-3017
[3]   Transcoronary transplantation of progenitor cells after myocardial infarction [J].
Assmus, Birgit ;
Honold, Joerg ;
Schaechinger, Volker ;
Britten, Martina B. ;
Fischer-Rasokat, Ulrich ;
Lehmann, Ralf ;
Teupe, Claudius ;
Pistorius, Katrin ;
Martin, Hans ;
Abolmaali, Nasreddin D. ;
Tonn, Torsten ;
Dimmeler, Stefanie ;
Zeiher, Andreas M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (12) :1222-1232
[4]   Unchain my heart: the scientific foundations of cardiac repair [J].
Dimmeler, S ;
Zeiher, AM ;
Schneider, MD .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (03) :572-583
[5]   Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure - A substudy of the carvedilol prospective randomized cumulative survival (COPERNICUS) trial [J].
Hartmann, F ;
Packer, M ;
Coats, AJS ;
Fowler, MB ;
Krum, H ;
Mohacsi, P ;
Rouleau, JL ;
Tendera, M ;
Castaigne, A ;
Anker, SD ;
Amann-Zalan, I ;
Hoersch, S ;
Katus, HA .
CIRCULATION, 2004, 110 (13) :1780-1786
[6]   Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease [J].
Heeschen, C ;
Lehmann, R ;
Honold, J ;
Assmus, B ;
Aicher, A ;
Walter, DH ;
Martin, H ;
Zeiher, AM ;
Dimmeler, S .
CIRCULATION, 2004, 109 (13) :1615-1622
[7]  
Hunt SA, 2005, CIRCULATION, V112, pE154, DOI [10.1161/CIRCULATIONAHA.105.167586, 10.1161/CIRCULATIONAHA.105.167587]
[8]   The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study [J].
Januzzi, JL ;
Camargo, CA ;
Anwaruddin, S ;
Baggish, AL ;
Chen, AA ;
Krauser, DG ;
Tung, R ;
Cameron, R ;
Nagurney, JT ;
Chae, CU ;
Lloyd-Jones, DM ;
Brown, DF ;
Foran-Melanson, S ;
Sluss, PM ;
Lee-Lewandrowski, EL ;
Lewandrowski, KB .
AMERICAN JOURNAL OF CARDIOLOGY, 2005, 95 (08) :948-954
[9]   Medical progress: Heart failure [J].
Jessup, M ;
Brozena, S .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (20) :2007-2018
[10]  
KISSEL C, IN PRESS J AM COLL C