Clerkin Kevin J, Restaino Susan W, Zorn Emmanuel, Vasilescu Elena R, Marboe Charles C, Mancini Donna M
Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, New York.
J Heart Lung Transplant. 2016 Sep;35(9):1059-66. doi: 10.1016/j.healun.2016.04.007. Epub 2016 May 6.
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.
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.
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.
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.
抗体介导的排斥反应（AMR）与死亡风险增加及心脏移植血管病变（CAV）相关。早期研究表明，晚期AMR很少与移植物功能障碍相关，而近期报告显示其与死亡率增加有关。我们调查了AMR的发生时间及其与移植物功能障碍、死亡和CAV的关联。
这项回顾性队列研究纳入了2004年至2013年在哥伦比亚大学医学中心接受原位心脏移植（OHT）的所有成年受者（N = 689）。共有68例AMR原发性病例，根据早期（OHT后<1年）或晚期（OHT后>1年）AMR进行分层。采用多变量逻辑回归和Cox比例风险回归进行Kaplan-Meier生存分析和建模。
从2004年1月1日至2015年10月1日，43例患者发生早期AMR（OHT后中位时间23天），25例发生晚期AMR（OHT后中位时间1084天）。与晚期AMR相比，早期AMR时移植物功能障碍较少见（25.6%对56%，p = 0.01）。晚期AMR患者AMR后的生存率低于早期AMR患者（1年：80%对93%，5年：51%对73%，p < 0.05）。按移植物功能障碍分层时，只有晚期AMR且伴有移植物功能障碍的患者生存率较差（30天：79%，1年：64%，5年：36%；p < 0.006）。无论年龄、性别、供者特异性抗体、是否使用左心室辅助装置、OHT原因及移植物功能恢复情况，这种关联均存在。同样，晚期AMR且伴有移植物功能障碍的患者新发CAV进展加速（1年时为50%；风险比为5.42；p = 0.009），而所有其他组与一般移植人群相似。
晚期AMR常与移植物功能障碍相关。当晚期AMR出现移植物功能障碍时，尽管积极治疗，死亡风险仍早期且持续增加，新发CAV迅速进展。
