{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:19:36Z","timestamp":1790911176343,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2011,8,5]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1\u00d710\n              <jats:sup>5<\/jats:sup>\n              or 5\u00d710\n              <jats:sup>5<\/jats:sup>\n              cells\/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8\u00b11.1 versus 10.9\u00b11.2,\n              <jats:italic>P<\/jats:italic>\n              =0.020) and 12 months (6.3\u00b11.2 versus 11.0\u00b11.2,\n              <jats:italic>P<\/jats:italic>\n              =0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139\u00b1151 versus 69\u00b1122 seconds,\n              <jats:italic>P<\/jats:italic>\n              =0.014; 12 months: 140\u00b1171 versus 58\u00b1146 seconds,\n              <jats:italic>P<\/jats:italic>\n              =0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10\n              <jats:sup>5<\/jats:sup>\n              cells\/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.111.245993","type":"journal-article","created":{"date-parts":[[2011,7,8]],"date-time":"2011-07-08T15:17:00Z","timestamp":1310138220000},"page":"428-436","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":426,"title":["Intramyocardial, Autologous CD34+ Cell Therapy for Refractory Angina"],"prefix":"10.1161","volume":"109","author":[{"given":"Douglas W.","family":"Losordo","sequence":"first","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Henry","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Davidson","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon","family":"Sup Lee","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Costa","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Bass","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrell","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. David","family":"Fortuin","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J.","family":"Pepine","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay H.","family":"Traverse","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Amrani","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M.","family":"Ewenstein","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Riedel","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Story","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Barker","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Povsic","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Schatz","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL (D.W.L., C.D.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (T.D.H., J.H.T.); University of Pittsburgh Medical Center, Pittsburgh, PA (J.S.L.); University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH (M.A.C.); Shands Jacksonville Medical Center, Jacksonville, FL (T.B.); Center for Therapeutic Angiogenesis, Birmingham, AL (F..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ACT34-CMI Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2001.2706"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2007.12.004"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2007.12.005"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.098"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192667"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00387-2"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcnurse.2006.01.003"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.671545"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.200386"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5302.964"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.644518"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.541268"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.687376"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(02)00072-8"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.11.1116"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.18.1837"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.20.2708"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.09.011"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.187397"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08937-7"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm485"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.685"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.08.010"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ccd.21345"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcp005"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.10.044"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-130179"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.12.068"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.842302"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.57.121304.131306"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.10.066"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032691"},{"key":"e_1_3_5_34_2","first-page":"1427","article-title":"Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of pet identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects","volume":"46","author":"Johnson NP","year":"2005","unstructured":"Johnson NP, Gould KL. Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of pet identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects. 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