Robert C Schutt1, Barry H Trachtenberg1, John P Cooke1, Jay H Traverse1, Timothy D Henry1, Carl J Pepine1, James T Willerson1, Emerson C Perin1, Stephen G Ellis1, David X M Zhao1, Aruni Bhatnagar1, Brian H Johnstone1, Dejian Lai1, Micheline Resende1, Ray F Ebert1, Joseph C Wu1, Shelly L Sayre1, Aaron Orozco1, Claudia Zierold1, Robert D Simari1, Lem Moyé2, Christopher R Cogle1, Doris A Taylor1. 1. From the Houston Methodist DeBakey Heart and Vascular Center (R.C.S., B.H.T., J.P.C.) and Houston Methodist Research Institute (R.C.S., B.H.T., J.P.C.), TX; Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (J.H.T.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); University of Florida College of Medicine, Gainesville (C.J.P., C.R.C.); Texas Heart Institute, CHI St. Luke's Health, Houston (J.T.W., E.C.P., M.R., A.O., D.A.T.); University of Minnesota School of Medicine, Minneapolis (C.Z.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest, School of Medicine, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (A.B.); Indiana University School of Medicine, Indianapolis (B.H.J.); The University of Texas Health Science Center, School of Public Health, Houston (D.L., S.L.S., L.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.F.E.); Stanford University, School of Medicine, CA (J.C.W.); and Kansas University Medical Center, School of Medicine, Kansas City (R.D.S.). 2. From the Houston Methodist DeBakey Heart and Vascular Center (R.C.S., B.H.T., J.P.C.) and Houston Methodist Research Institute (R.C.S., B.H.T., J.P.C.), TX; Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (J.H.T.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); University of Florida College of Medicine, Gainesville (C.J.P., C.R.C.); Texas Heart Institute, CHI St. Luke's Health, Houston (J.T.W., E.C.P., M.R., A.O., D.A.T.); University of Minnesota School of Medicine, Minneapolis (C.Z.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest, School of Medicine, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (A.B.); Indiana University School of Medicine, Indianapolis (B.H.J.); The University of Texas Health Science Center, School of Public Health, Houston (D.L., S.L.S., L.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.F.E.); Stanford University, School of Medicine, CA (J.C.W.); and Kansas University Medical Center, School of Medicine, Kansas City (R.D.S.). Lemmoye@msn.com.
Abstract
RATIONALE: Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE: The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction. METHODS AND RESULTS: This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively). CONCLUSIONS: This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.
RCT Entities:
RATIONALE: Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE: The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction. METHODS AND RESULTS: This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively). CONCLUSIONS: This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.
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