Schutt Robert C, Trachtenberg Barry H, Cooke John P, Traverse Jay H, Henry Timothy D, Pepine Carl J, Willerson James T, Perin Emerson C, Ellis Stephen G, Zhao David X M, Bhatnagar Aruni, Johnstone Brian H, Lai Dejian, Resende Micheline, Ebert Ray F, Wu Joseph C, Sayre Shelly L, Orozco Aaron, Zierold Claudia, Simari Robert D, Moyé Lem, Cogle Christopher R, Taylor Doris A
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.).
Circ Res. 2015 Jan 2;116(1):99-107. doi: 10.1161/CIRCRESAHA.116.304710. Epub 2014 Nov 18.
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.
The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction.
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).
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.
http://www.clinicaltrials.gov. Unique identifier: NCT00684021.
尽管骨髓单个核细胞(BMC)治疗缺血性心脏病备受关注,但目前的技术仅带来了有限的益处。然而,部分患者在接受自体BMC治疗后出现了改善,但其相关因素尚不清楚。
本研究旨在确定与ST段抬高型心肌梗死后梗死面积缩小相关的BMC特征。
这项前瞻性研究纳入了连续参加CCTRN TIME(心血管细胞治疗研究网络心肌梗死评估时机)试验且同意在CCTRN生物样本库储存并分析其BMC的患者。通过心脏磁共振成像测量基线(经皮冠状动脉介入治疗后3天)和6个月随访之间梗死面积的变化。获取了101例患者(平均年龄56.5岁;平均筛查射血分数37%;平均基线心脏磁共振成像射血分数45%)的梗死面积测量值以及BMC表型和功能数据。6个月时,75例患者(74.3%)梗死面积缩小(平均变化为-21.0±17.6%)。多元回归分析表明,CD31(+) BMC比例较高的患者梗死面积缩小更明显(P=0.046),在集落形成单位希尔和内皮集落形成细胞功能试验中BMC生长速度较快的患者梗死面积缩小也更明显(分别为P=0.033和P=0.032)。
本研究确定了与ST段抬高型心肌梗死患者更好临床结局相关的BMC特征,并强调了内皮前体细胞活性在梗死心肌再生中的重要性。此外,这表明对于这些ST段抬高型心肌梗死患者,心肌修复更多地依赖于基线BMC特征,而非患者是否接受冠状动脉内BMC移植。