Mesenchymal Precursor Cells as Adjunctive Therapy in Recipients of Contemporary Left Ventricular Assist Devices

被引：129

作者：

Ascheim, Deborah D. ^{[1
]}

Gelijns, Annetine C. ^{[1
]}

Goldstein, Daniel ^{[2
]}

Moye, Lemuel A. ^{[3
]}

Smedira, Nicholas ^{[4
]}

Lee, Sangjin ^{[4
]}

Klodell, Charles T. ^{[5
]}

Szady, Anita ^{[5
]}

Parides, Michael K. ^{[1
]}

Jeffries, Neal O. ^{[6
]}

Skerrett, Donna ^{[7
]}

Taylor, Doris A. ^{[8
]}

Rame, Eduardo

Milano, Carmelo ^{[9
]}

Rogers, Joseph G. ^{[9
]}

Lynch, Janine ^{[1
]}

Dewey, Todd ^{[10
]}

Eichhorn, Eric ^{[10
]}

Sun, Benjamin ^{[11
]}

Feldman, David ^{[11
]}

Simari, Robert ^{[12
]}

O'Gara, Patrick T. ^{[13
]}

Taddei-Peters, Wendy C. ^{[6
]}

Miller, Marissa A. ^{[6
]}

Naka, Yoshifumi ^{[14
]}

Bagiella, Emilia ^{[1
]}

Rose, Eric A. ^{[1
]}

Woo, Y. Joseph ^{[15
]}

机构：

[1] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[2] Montefiore Einstein Heart Ctr, Bronx, NY USA

[3] Univ Texas Houston, Houston, TX USA

[4] Cleveland Clin Fdn, Cleveland, OH 44195 USA

[5] Univ Florida, Gainesville, FL USA

[6] NHLBI, NIH, Bethesda, MD 20892 USA

[7] Mesoblast Inc, New York, NY USA

[8] Texas Heart Inst, Houston, TX 77025 USA

[9] Duke Univ, Durham, NC USA

[10] Baylor Hlth Care Syst, Dallas, TX USA

[11] Minneapolis Heart Inst Fdn, Minneapolis, MN USA

[12] Mayo Clin, Rochester, MN USA

[13] Brigham & Womens Hosp, Boston, MA 02115 USA

[14] Columbia Univ, Med Ctr, New York, NY USA

[15] Stanford Univ, Stanford, CA 94305 USA

来源：

CIRCULATION | 2014年 / 129卷 / 22期

基金：

美国国家卫生研究院;

关键词：

heart failure; left ventricular assist device; randomized controlled trial; stem cell; MECHANICAL CIRCULATORY SUPPORT; ACUTE MYOCARDIAL-INFARCTION; FAILING HUMAN HEART; STEM-CELLS; FAILURE; TRANSPLANTATION; IMPLANTATION; RECOVERY; SURVIVAL; CARDIOMYOPATHY;

D O I：

10.1161/CIRCULATIONAHA.113.007412

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Background-Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy. Methods and Results-In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2: 1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (+/- 13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months. Conclusions-In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support.

引用

页码：2287 / +

页数：20

共 43 条

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