Impact of repetitive episodes of antibody-mediated or cellular rejection on cardiovascular mortality in cardiac transplant recipients: defining rejection patterns.
BACKGROUND
In our previously published work dealing with antibody-mediated (vascular) rejection (AMR), we defined patterns of rejection (AMR and cellular rejection [CR]) based on a review of biopsy diagnoses taken in the first 6 to 12 weeks post-transplant. We have shown the significance of these pattern designations in relation to patient and allograft outcome in five outcome analyses. The current retrospective analysis was done to determine whether our previous criteria for pattern designations provided the greatest degree of discrimination between AMR and CR.


METHODS
Six hundred sixty-five patients from the U.T.A.H. Cardiac Transplant Program were included in our study. Patients induced with OKT3 immunosuppression were excluded. We analyzed the relationship of a number of either AMR or CR episodes to cardiovascular mortality. We constructed Kaplan-Meier survival curves to assess the impact of incremental numbers of AMR or CR episodes on cardiovascular mortality.


RESULTS
Three or more episodes of AMR resulted in a statistically significant increase in cardiovascular mortality. By contrast, CR episodes did not increase the risk of cardiovascular mortality.


CONCLUSIONS
Based on our findings, we believe that clinical trials should be designed to test treatments based on predominant rejection patterns and that end-points for trials should be defined by number of biopsies positive for either CR or AMR. This approach may lead to improved patient and allograft survival.
Kfoury
Abdallah G
AG
LDS Hospital, Intermountain Health Care, Salt Lake City, Utah 84143, USA.
Stehlik
Josef
J
Renlund
Dale G
DG
Snow
Gregory
G
Seaman
James T
JT
Gilbert
Edward M
EM
Stringham
James S
JS
Long
James W
JW
Hammond
M Elizabeth H
ME
D000328:Adult; D001706:Biopsy / Q000379:methods; D023381:Endpoint Determination; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology / Q000401:mortality*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D014180:Transplantation / Q000401:mortality* / Q000473:pathology; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome