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J Heart Lung Transplant. 2016 May 6. pii: S1053-2498(16)30110-3. doi: 10.
1016/j.healun.2016.04.007. [Epub ahead of print]
The effect of timing and graft dysfunction on survival and cardiac allograft
vasculopathy in antibody-mediated rejection.
Clerkin KJ1, Restaino SW1, Zorn E2, Vasilescu ER3, Marboe CC3, Mancini DM4.
Author information
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.
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