A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy.
BACKGROUND
Intracoronary administration of bone marrow-derived progenitor cells (BMC) was shown to improve coronary microvascular function in ischemic heart disease. Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy (DCM), we investigated the effects of intracoronary BMC administration in patients with DCM.


RESULTS
Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter. Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms. Coronary hemodynamics were determined by intracoronary Doppler wire measurements. After 3 months, regional wall motion of the target area (contractility from -1.08 + or - 0.39 to -0.97 + or - 0.47 SD/chord, P=0.029) and global left ventricular ejection fraction (from 30.2 + or - 10.9 to 33.4 + or - 11.5%, P<0.001) were improved. Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity. Minimal vascular resistance index was significantly reduced in the BMC-treated vessel after 3 months (from 1.53 + or - 0.63 to 1.32 + or -0.61 mm Hg x s/cm; P=0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60 + or - 0.45 to 1.49 + or - 0.45 mm Hg x s/cm; P=0.133, n=13). Twelve months after BMC infusion, N-terminal prohormone brain natriuretic peptide (NT-proBNP) serum levels were decreased, suggesting a beneficial effect on left ventricular remodeling processes (from 1610 + or - 993 to 1473 + or - 1147 pg/mL; P=0.038 for logNT-proBNP, n=26).


CONCLUSIONS
Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM. Thus, randomized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM.
Fischer-Rasokat
Ulrich
U
Cardiology and Molecular Cardiology, Department of Medicine III, Goethe University of Frankfurt, Frankfurt/Main, Germany.
Assmus
Birgit
B
Seeger
Florian H
FH
Honold
Jörg
J
Leistner
David
D
Fichtlscherer
Stephan
S
Schächinger
Volker
V
Tonn
Torsten
T
Martin
Hans
H
Dimmeler
Stefanie
S
Zeiher
Andreas M
AM
D000368:Aged; D015415:Biomarkers / Q000097:blood; D016026:Bone Marrow Transplantation / Q000379:methods; D006328:Cardiac Catheterization; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D002404:Catheterization; D049109:Cell Proliferation; D003326:Coronary Circulation; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D011446:Prospective Studies; D020127:Recovery of Function; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain