Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

被引：173

作者：

Bartunek, Jozef ^{[1
]}

Terzic, Andre ^{[2
]}

Davison, Beth A. ^{[3
]}

Filippatos, Gerasimos S. ^{[4
]}

Radovanovic, Slavica ^{[5
]}

Beleslin, Branko ^{[6
]}

Merkely, Bela ^{[7
]}

Musialek, Piotr ^{[8
]}

Wojakowski, Wojciech ^{[9
]}

Andreka, Peter ^{[10
]}

Horvath, Ivan G. ^{[11
]}

Katz, Amos ^{[12
]}

Dolatabadi, Dariouch ^{[13
]}

El Nakadi, Badih ^{[13
]}

Arandjelovic, Aleksandra ^{[14
,34
]}

Edes, Istvan ^{[15
]}

Seferovic, Petar M. ^{[16
]}

Obradovic, Slobodan ^{[17
]}

Vanderheyden, Marc ^{[1
]}

Jagic, Nikola ^{[18
]}

Petrov, Ivo ^{[19
]}

Atar, Shaul ^{[20
,21
]}

Halabi, Majdi ^{[21
]}

Gelev, Valeri L. ^{[19
]}

Shochat, Michael K. ^{[22
]}

Kasprzak, Jaroslaw D. ^{[23
]}

Sanz-Ruiz, Ricardo ^{[24
]}

Heyndrickx, Guy R. ^{[1
]}

Nyolczas, Noemi ^{[25
]}

Legrand, Victor ^{[26
]}

Guedes, Antoine ^{[27
]}

Heyse, Alex ^{[28
]}

Moccetti, Tiziano ^{[29
]}

Fernandez-Aviles, Francisco ^{[24
]}

Jimenez-Quevedo, Pilar ^{[30
]}

Bayes-Genis, Antoni ^{[31
]}

Maria Hernandez-Garcia, Jose ^{[32
]}

Ribichini, Flavio ^{[33
]}

Gruchala, Marcin ^{[34
]}

Waldman, Scott A. ^{[35
]}

Teerlink, John R. ^{[36
]}

Gersh, Bernard J. ^{[2
]}

Povsic, Thomas J. ^{[37
]}

Henry, Timothy D. ^{[38
]}

Metra, Marco ^{[39
]}

Hajjar, Roger J. ^{[40
]}

Tendera, Michal ^{[9
]}

Behfar, Atta ^{[2
]}

Alexandre, Bertrand ^{[41
]}

Seron, Aymeric ^{[41
]}

机构：

[1] Onze Lieve Vrouwziekenhuis OLV Hosp, Ctr Cardiovasc, Moorselbaan 164, B-9300 Aalst, Belgium

[2] Mayo Clin, Ctr Regenerat Med, Dept Cardiovasc Dis, 200 First St SW, Rochester, MI USA

[3] Momentum Res Inc, Durham, NC USA

[4] Univ Athens, Attikon Univ Hosp, Sch Med, Athens, Greece

[5] Univ Hosp, Ctr Bezanijska Kosa, Belgrade, Serbia

[6] Univ Belgrade, Sch Med, Cardiol Clin, Clin Ctr Serbia, Belgrade, Serbia

[7] Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary

[8] Jagiellonian Univ, John Paul Hosp 2, Dept Cardiac & Vasc Dis, Krakow, Poland

[9] Med Univ Silesia, Div Cardiol 3, Katowice, Poland

[10] Gottsegen Gyorgy Hungarian Inst Cardiol, Budapest, Hungary

[11] Univ Pecs, Inst Heart, Pecs, Hungary

[12] Ben Gurion Univ Negev, Israel Fac Hlth Sci, Barzilai Med Ctr, Dept Cardiol, Beer Sheva, Israel

[13] Ctr Hosp Univ Charleroi, Div Cardiol, Charleroi, Belgium

[14] Clin Hosp Zvezdara, Dept Cardiol, Belgrade, Serbia

[15] Univ Debrecen, Dept Cardiol, Debrecen, Hungary

[16] Univ Belgrade, Med Ctr, Sch Med, Belgrade, Serbia

[17] Univ Def, Mil Med Acad, Sch Med, Clin Emergency Med, Belgrade, Serbia

[18] Clin Ctr Kragujevac, Kragujevac, Serbia

[19] Univ Sofia, City Clin Heart & Vasc Inst, Dept Cardiol Angiol & Electrophysiol, Sofia, Bulgaria

[20] Galilee Med Ctr, Dept Cardiol, Nahariyya, Israel

[21] Bar Ilan Univ, Fac Med Galilee, Safed, Israel

[22] Inst Heart, Hillel Yaffe Med Ctr, Hadera Rappaport Sch Med, Haifa, Israel

[23] Med Univ Lodz, Dept Cardiol, Lodz, Poland

[24] Univ Gregorio Maranon, Gen Hosp, Madrid, Spain

[25] Med Ctr, Hungarian Def Forces, Budapest, Hungary

[26] Ctr Hosp Univ Liege, Dept Cardiol, Liege, Belgium

[27] Catholic Univ Louvain, Dept Cardiol, CHU UcL Namur, Yvoir, Belgium

[28] AZ Glorieux, Dept Cardiol, Ronse, Belgium

[29] Cardioctr Ticino, Lugano, Switzerland

[30] Hosp Clin San Carlos, Dept Cardiol, Madrid, Spain

[31] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Barcelona, Spain

[32] Hosp Clinico Univ Virgen Victoria, Malaga, Spain

[33] Univ Verona, Dept Cardiol, I-37100 Verona, Italy

[34] Med Univ Gdansk, Dept Cardiol, Gdansk, Poland

[35] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA USA

[36] Univ Calif San Francisco & Sect Cardiol, San Francisco Vet Affairs Med Ctr, Sch Med, San Francisco, CA USA

[37] Duke Clin Res Inst & Duke Med, Durham, NC USA

[38] Cedars Sinai Heart Inst, Los Angeles, CA USA

[39] Univ & Spedali Civili, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Cardiol, Brescia, Italy

[40] Mt Sinai Sch Med, New York, NY USA

[41] Celyad, Mont St Guibert, Belgium

[42] Campbell Univ Coll Pharm & Hlth Sci, Dept Clin Res & Pharm Practice, Cary, NC USA

[43] Natl Univ Ireland Galway & Saolta Univ Healthcare, Lambe Inst Translat Med & Curam, Galway, Ireland

来源：

EUROPEAN HEART JOURNAL | 2017年 / 38卷 / 09期

关键词：

Regenerative medicine; Cardiopoiesis; Cardiovascular disease; Stem cell; Target population; Disease severity; Marker; Precision medicine; MESENCHYMAL STEM-CELLS; BONE-MARROW; EUROPEAN-SOCIETY; PREDICTORS; MORTALITY; DELIVERY; DISEASE;

D O I：

10.1093/eurheartj/ehw543

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Aims Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. Methods and results This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n= 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving> 24 million mesenchymal stem cells (n= 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n= 157) or sham procedure (n= 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n= 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value> 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. Conclusion The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

引用

页码：648 / 660

页数：13

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