title: Factors associated with anti-human leukocyte antigen antibodies in patients supported with continuous-flow devices and effect on probability of transplant and post-transplant outcomes.
abstract: BACKGROUND
  One major disadvantage of ventricular assist device (VAD) therapy is the development of human-leukocyte antigen (HLA) antibodies. We aimed to identify factors associated with HLA antibodies during continuous flow (CF)-VAD support and assess the effect on transplant probability and outcomes.
  
  
  METHODS
  We included 143 consecutive heart failure patients who received a CF-VAD as a bridge-to-transplant at 3 institutions. Factors associated with post-VAD peak panel reactive antibodies (PRA) among several measurements were identified using multivariable linear regression. A parametric survival model was used to assess transplant waiting time and probability, risk of rejection, and a composite outcome of rejection, graft failure, and death.
  
  
  RESULTS
  Thirty-six patients (25%) were female; mean age was 47 ± 13 years. Eighty-one patients (57%) had a pre-VAD PRA of 0%, and 16 were highly sensitized (PRA > 80%). Age, female sex, and pre-VAD PRA were independently associated with post-VAD PRA. A 10-year increase in age was associated with a 5% decrease in post-VAD PRA (p = 0.03). Post-VAD PRA was 19% higher in women vs men (p < 0.01). A 10%-increase in pre-VAD PRA was associated with a 4.7% higher post-VAD PRA (p < 0.01). During a mean follow-up of 12 ± 11 months, 90 patients underwent cardiac transplantation. A 20% increase in post-VAD PRA was associated with 13% lower probability of transplant (hazard ratio, 0.87; 95% confidence interval, 0.76-0.99). A high PRA was not associated with adverse post-transplant outcomes.
  
  
  CONCLUSIONS
  Younger age, female sex, and pre-VAD PRA were independent predictors of elevated PRA post-VAD. Higher PRA was significantly associated with lower transplant probability but not increased rejection, graft failure, or death after transplant.
authors: Heart Failure and Transplantation, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: carolina.alba@uhn.ca.
authors: Ana C
authors: AC
authors: Alba
authors: Heart Failure and Transplantation, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Kathryn
authors: K
authors: Tinckam
authors: Heart Failure and Transplantation, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Farid
authors: F
authors: Foroutan
authors: The Heart Centre.
authors: Laerke M
authors: LM
authors: Nelson
authors: The Heart Centre.
authors: Finn
authors: F
authors: Gustafsson
authors: The Heart Centre.
authors: Kam
authors: K
authors: Sander
authors: Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Hellen
authors: H
authors: Bruunsgaard
authors: Advanced Heart Failure and Cardiac Transplant Service, Royal Perth Hospital, Perth, Western Australia, Australia.
authors: Sharon
authors: S
authors: Chih
authors: Advanced Heart Failure and Cardiac Transplant Service, Royal Perth Hospital, Perth, Western Australia, Australia.
authors: Helen
authors: H
authors: Hayes
authors: Heart Failure and Transplantation, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Vivek
authors: V
authors: Rao
authors: Heart Failure and Transplantation, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Diego
authors: D
authors: Delgado
authors: Heart Failure and Transplantation, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Heather J
authors: HJ
authors: Ross
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006333:Heart Failure / Q000601:surgery*; D016027:Heart Transplantation / Q000401:mortality*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014904:Western Australia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D006680:HLA Antigens
keywords: advanced heart failure; human leukocyte antigen; panel reactive antibodies; transplant outcomes; ventricular assist device therapy