Immunologic effects of continuous-flow left ventricular assist devices before and after heart transplant.
Immune allosensitization can be triggered by continuous-flow left ventricular assist devices (CF LVAD). However, the effect of this type of allosensitization on post-transplant outcomes remains controversial. This study examined the post-transplant course in a contemporary cohort of patients undergoing transplantation with and without LVAD bridging.



We included consecutive patients who were considered for cardiac transplant from 2006 to 2015. Serum alloantibodies were detected with single-antigen beads on the Luminex platform (One Lambda Inc., Canoga Park, CA). Allosensitization was defined as calculated panel reactive antibody (cPRA) > 10%. cPRA was determined at multiple times. LVAD-associated allosensitization was defined as development of cPRA > 10% in patients with cPRA ≤ 10% before LVAD implantation. Post-transplant outcomes of interest were acute cellular rejection (ACR), antibody-mediated rejection (AMR), and survival.



Allosensitization status was evaluated in 268 patients (20% female). Mean age was 52 ± 12 years, and 132 (49.3%) received CF LVADs. After LVAD implant, 30 patients (23%) became newly sensitized, and the level of sensitization appeared to diminish in many of these patients while awaiting transplant. During the study period, 225 of 268 patients underwent transplant, and 43 did not. A CF LVAD was used to bridge 50% of the transplant recipients. Compared with patients without new sensitization or those already sensitized at baseline, the patients with LVAD-associated sensitization had a higher risk of ACR (p = 0.049) and higher risk of AMR (p = 0.018) but a similar intermediate-term post-transplant survival. The patients who did not receive a transplant had higher level of allosensitization, with a baseline cPRA of 20% vs 6% in those who received an allograft and a high risk (40%) of death during follow-up.



New allosensitization takes place in > 20% of patents supported with CF LVADs. Among patients who undergo transplant, this results in a higher risk of ACR and AMR, but survival remains favorable, likely due to the efficacy of current management after transplant. However, mortality in sensitized patients who do not reach transplant remains high, and new approaches are necessary to meet the needs of this group of patients.
Division of Cardiovascular Disease, University of Utah Health Sciences Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Byung-Soo
BS
Ko
Division of Cardiovascular Disease, University of Utah Health Sciences Center, Salt Lake City, Utah; George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Stavros
S
Drakos
Division of Cardiovascular Disease, Intermountain Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Abdallah G
AG
Kfoury
Department of Pathology, University of Utah Health Sciences Centers, Salt Lake City, Utah.
Denise
D
Hurst
Division of Clinical Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah.
Gregory J
GJ
Stoddard
Division of Cardiovascular Disease, Intermountain Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Carrie A
CA
Willis
Department of Pathology, University of Utah Health Sciences Centers, Salt Lake City, Utah.
Julio C
JC
Delgado
Department of Pathology, University of Utah Health Sciences Centers, Salt Lake City, Utah; Department of Pathology, Intermountain Medical Center, Salt Lake City, Utah.
Elizabeth H
EH
Hammond
Division of Cardiovascular Disease, University of Utah Health Sciences Center, Salt Lake City, Utah; George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Edward M
EM
Gilbert
Division of Cardiovascular Disease, Intermountain Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Rami
R
Alharethi
Department of Pathology, University of Utah Health Sciences Centers, Salt Lake City, Utah.
Monica P
MP
Revelo
Division of Cardiovascular Disease, University of Utah Health Sciences Center, Salt Lake City, Utah; George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Jose
J
Nativi-Nicolau
Division of Cardiothoracic Surgery, Intermountain Medical Center, Salt Lake City, Utah.
Bruce B
BB
Reid
Division of Cardiothoracic Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah.
Stephen H
SH
McKellar
Division of Cardiovascular Disease, University of Utah Health Sciences Center, Salt Lake City, Utah; George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Omar
O
Wever-Pinzon
Department of Pathology, Intermountain Medical Center, Salt Lake City, Utah.
Dylan V
DV
Miller
Department of Pathology, University of Utah Health Sciences Centers, Salt Lake City, Utah.
David D
DD
Eckels
Division of Cardiovascular Disease, University of Utah Health Sciences Center, Salt Lake City, Utah; George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
James C
JC
Fang
Division of Cardiothoracic Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah.
Craig H
CH
Selzman
Division of Cardiovascular Disease, University of Utah Health Sciences Center, Salt Lake City, Utah; George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah; Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, Utah.
Josef
J
Stehlik
D005260:Female; D006084:Graft Rejection; D006333:Heart Failure; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006801:Humans; D007518:Isoantibodies; D008297:Male; D008875:Middle Aged
D007518:Isoantibodies
acute cellular rejection; allosensitization; antibody-mediated rejection; continuous-flow left ventricular assist device; transplant outcome