Immunologic sensitization in recipients of left ventricular assist devices.
OBJECTIVE
Left ventricular assist device implantation is associated with an increased risk of development of circulating anti-HLA class I and II antibodies (sensitization). We investigated the impact of sensitization on posttransplantation outcomes in 105 consecutive left ventricular assist device recipients.


METHODS
Five hundred twenty-one consecutive adult cardiac allograft recipients between 1992 and 1999 were retrospectively studied. Of these, 105 were supported with a left ventricular assist device. Pretransplantation and posttransplantation antibody production, time to transplantation after listing, rejection, freedom from transplant coronary artery disease, and survival were evaluated by Kaplan-Meier analysis. Among sensitized left ventricular assist device recipients, 26 were treated with a pretransplantation immunomodulatory regimen consisting of intravenous immunoglobulin and cyclophosphamide.


RESULTS
There were no significant differences between left ventricular assist device recipients and nonbridged recipients with respect to pretransplantation demographic characteristics and ABO and HLA matching. Among left ventricular assist device recipients, 66% (69/105) were sensitized before transplantation; in contrast, only 6% (24/399) of nonbridged recipients were sensitized (P <.001). Sensitized untreated left ventricular assist device recipients had both a prolongation of waiting time to transplantation and an increased risk of acute rejection. Pretransplantation immunomodulatory therapy reduced both the increased waiting time and the increased risk of acute rejection. However, sensitization or the use of immunomodulatory therapy in left ventricular assist device-bridged recipients did not influence posttransplantation survival relative to nonbridged recipients.


CONCLUSIONS
Left ventricular assist device recipients have survival outcomes similar to those of nonbridged recipients after cardiac transplantation, despite their significantly higher immunologic risk. The reduced rate of transplantation and the increased incidence of rejection observed in sensitized left ventricular assist device recipients are prevented by immunomodulatory therapy. Sensitization will remain an important issue with increased use of left ventricular assist devices, and improved understanding of this is essential to achieve better outcomes in the management of patients with end-stage heart failure.
John
Ranjit
R
Department of Surgery Cardiology, Columbia University College of Physicians and Surgeons, New York, NY, USA. ranjitj@pol.net
Lietz
Katherine
K
Schuster
Michael
M
Naka
Yoshifumi
Y
Rao
Vivek
V
Mancini
Donna M
DM
Rose
Eric A
EA
Smith
Craig R
CR
Oz
Mehmet C
MC
Edwards
Niloo M
NM
Itescu
Silviu
S
D000206:Actuarial Analysis; D000208:Acute Disease; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D003327:Coronary Disease / Q000175:diagnosis / Q000209:etiology; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005549:Foreign-Body Reaction / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology*; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000401:mortality; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013256:Steroids; D016019:Survival Analysis; D013997:Time Factors; D014850:Waiting Lists
D000893:Anti-Inflammatory Agents; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D013256:Steroids; D003520:Cyclophosphamide; D001379:Azathioprine