Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices

Deborah D. Ascheim, Annetine C. Gelijns, Daniel J. Goldstein, Lemuel A. Moye, Nicholas Smedira, Sangjin Lee, Charles T. Klodell, Anita Szady, Michael K. Parides, Neal O. Jeffries, Donna Skerrett, Doris A. Taylor, J. Eduardo Rame, Carmelo Milano, Joseph G. Rogers, Janine Lynch, Todd Dewey, Eric Eichhorn, Benjamin Sun, David Feldman & 8 others Robert Simari, Patrick T. O'Gara, Wendy C. Taddei-Peters, Marissa A. Miller, Yoshifumi Naka, Emilia Bagiella, Eric A. Rose, Y. Joseph Woo

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

BACKGROUND - : Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contrib ute 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.

Original languageEnglish (US)
Pages (from-to)2287-2296
Number of pages10
JournalCirculation
Volume129
Issue number22
DOIs
StatePublished - Jun 3 2014

Fingerprint

Heart-Assist Devices
Random Allocation
Therapeutics
Weaning
Safety
Stroke Volume
Ventricular Function
Myocarditis
Rupture
Hypersensitivity
Tissue Donors
Transplants
Injections

Keywords

  • heart failure
  • left ventricular assist device
  • randomized controlled trial
  • stem cell

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. / Ascheim, Deborah D.; Gelijns, Annetine C.; Goldstein, Daniel J.; Moye, Lemuel A.; Smedira, Nicholas; Lee, Sangjin; Klodell, Charles T.; Szady, Anita; Parides, Michael K.; Jeffries, Neal O.; Skerrett, Donna; Taylor, Doris A.; Rame, J. Eduardo; Milano, Carmelo; Rogers, Joseph G.; Lynch, Janine; Dewey, Todd; Eichhorn, Eric; Sun, Benjamin; Feldman, David; Simari, Robert; O'Gara, Patrick T.; Taddei-Peters, Wendy C.; Miller, Marissa A.; Naka, Yoshifumi; Bagiella, Emilia; Rose, Eric A.; Woo, Y. Joseph.

In: Circulation, Vol. 129, No. 22, 03.06.2014, p. 2287-2296.

Research output: Contribution to journalArticle

Ascheim, DD, Gelijns, AC, Goldstein, DJ, Moye, LA, Smedira, N, Lee, S, Klodell, CT, Szady, A, Parides, MK, Jeffries, NO, Skerrett, D, Taylor, DA, Rame, JE, Milano, C, Rogers, JG, Lynch, J, Dewey, T, Eichhorn, E, Sun, B, Feldman, D, Simari, R, O'Gara, PT, Taddei-Peters, WC, Miller, MA, Naka, Y, Bagiella, E, Rose, EA & Woo, YJ 2014, 'Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices', Circulation, vol. 129, no. 22, pp. 2287-2296. https://doi.org/10.1161/CIRCULATIONAHA.113.007412
Ascheim, Deborah D. ; Gelijns, Annetine C. ; Goldstein, Daniel J. ; Moye, Lemuel A. ; Smedira, Nicholas ; Lee, Sangjin ; Klodell, Charles T. ; Szady, Anita ; Parides, Michael K. ; Jeffries, Neal O. ; Skerrett, Donna ; Taylor, Doris A. ; Rame, J. Eduardo ; Milano, Carmelo ; Rogers, Joseph G. ; Lynch, Janine ; Dewey, Todd ; Eichhorn, Eric ; Sun, Benjamin ; Feldman, David ; Simari, Robert ; O'Gara, Patrick T. ; Taddei-Peters, Wendy C. ; Miller, Marissa A. ; Naka, Yoshifumi ; Bagiella, Emilia ; Rose, Eric A. ; Woo, Y. Joseph. / Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. In: Circulation. 2014 ; Vol. 129, No. 22. pp. 2287-2296.
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T1 - Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices

AU - Ascheim, Deborah D.

AU - Gelijns, Annetine C.

AU - Goldstein, Daniel J.

AU - Moye, Lemuel A.

AU - Smedira, Nicholas

AU - Lee, Sangjin

AU - Klodell, Charles T.

AU - Szady, Anita

AU - Parides, Michael K.

AU - Jeffries, Neal O.

AU - Skerrett, Donna

AU - Taylor, Doris A.

AU - Rame, J. Eduardo

AU - Milano, Carmelo

AU - Rogers, Joseph G.

AU - Lynch, Janine

AU - Dewey, Todd

AU - Eichhorn, Eric

AU - Sun, Benjamin

AU - Feldman, David

AU - Simari, Robert

AU - O'Gara, Patrick T.

AU - Taddei-Peters, Wendy C.

AU - Miller, Marissa A.

AU - Naka, Yoshifumi

AU - Bagiella, Emilia

AU - Rose, Eric A.

AU - Woo, Y. Joseph

PY - 2014/6/3

Y1 - 2014/6/3

N2 - BACKGROUND - : Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contrib ute 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.

AB - BACKGROUND - : Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contrib ute 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.

KW - heart failure

KW - left ventricular assist device

KW - randomized controlled trial

KW - stem cell

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