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. 2016 Sep;35(9):1059-66.
doi: 10.1016/j.healun.2016.04.007. Epub 2016 May 6.

The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection

Kevin J Clerkin  1 , Susan W Restaino  1 , Emmanuel Zorn  2 , Elena R Vasilescu  3 , Charles C Marboe  3 , Donna M Mancini  4
Affiliations

The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection

Kevin J Clerkin et al. J Heart Lung Transplant. 2016 Sep.

Abstract

Background: Antibody-mediated rejection (AMR) has been associated with increased death and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction, whereas recent reports have demonstrated an association with increased mortality. We investigated the timing of AMR and its association with graft dysfunction, death, and CAV.

Methods: This retrospective cohort study identified all adult orthotopic heart transplant (OHT) recipients (N = 689) at Columbia University Medical Center from 2004 to 2013. There were 68 primary cases of AMR, which were stratified by early (< 1 year post-OHT) or late (> 1 year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression.

Results: From January 1, 2004, through October 1, 2015, early AMR (median 23 days post-OHT) occurred in 43 patients and late AMR (median 1,084 days post-OHT) occurred in 25. Graft dysfunction was less common with early compared with late AMR (25.6% vs 56%, p = 0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1 year: 80% vs 93%, 5 years: 51% vs 73%, p < 0.05). When stratified by graft dysfunction, only those with late AMR and graft dysfunction had worse survival (30 days: 79%, 1 year: 64%, 5 years: 36%; p < 0.006). The association remained irrespective of age, sex, donor-specific antibodies, left ventricular assist device use, reason for OHT, and recovery of graft function. Similarly, those with late AMR and graft dysfunction had accelerated development of de novo CAV (50% at 1 year; hazard ratio, 5.42; p = 0.009), whereas all other groups were all similar to the general transplant population.

Conclusions: Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR, there is an early and sustained increased risk of death and rapid development of de novo CAV despite aggressive treatment.

Keywords: antibody-mediated rejection; cardiac allograft vasculopathy; donor specific antibodies; graft dysfunction; mortality.

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Figures

Figure 1
Figure 1
A. Freedom from death or retransplant after OHT stratified by timing of AMR B. Freedom from death or retransplant after AMR stratified by timing of AMR
Figure 2
Figure 2
Freedom from death or retransplant stratified by timing of AMR and graft dysfunction
Figure 3
Figure 3
Freedom from CAV after AMR, stratified by timing and presence of graft dysfunction. Patients with pre-existing CAV were censored.
See this image and copyright information in PMC

Comment in

References

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