TY - JOUR
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
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
UR - http://www.scopus.com/inward/record.url?scp=84901952623&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.113.007412
DO - 10.1161/CIRCULATIONAHA.113.007412
M3 - Article
C2 - 24682346
AN - SCOPUS:84901952623
SN - 0009-7322
VL - 129
SP - 2287
EP - 2296
JO - Circulation
JF - Circulation
IS - 22
ER -