Published online before print July 29, 2009, doi: 10.1161/CIRCHEARTFAILURE.109.855023
Original Articles |
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
From the Cardiology and Molecular Cardiology (U.F.-R., B.A., F.H.S., J.H., D.L., S.F., V.S., S.D., A.M.Z.), Department of Medicine III, Goethe University of Frankfurt, Frankfurt/Main, Germany; Institute for Transfusion Medicine and Immunohematology (T.T.), Red Cross Blood Donor Service Baden-Württemberg-Hessen, Frankfurt/Main, Germany; and Institute of Hematology (H.M.), Department of Medicine II, Goethe University of Frankfurt, Frankfurt/Main, Germany.
Correspondence to Andreas M. Zeiher, MD, Cardiology and Molecular Cardiology, Department of Medicine III, Goethe University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail zeiher{at}em.uni-frankfurt.de
Received August 26, 2008; accepted June 24, 2009.
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.
Methods and 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±0.39 to –0.97±0.47 SD/chord, P=0.029) and global left ventricular ejection fraction (from 30.2±10.9 to 33.4±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±0.63 to 1.32±0.61 mm Hg · s/cm; P=0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60±0.45 to 1.49±0.45 mm Hg · 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±993 to 1473±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.
Key Words: cardiomyopathy • cells • congestive heart failure • myocardial contraction • regional blood flow