Martínez-Dolz Luis, Almenar Luis, Reganon Eldemiro, Vila Virtudes, Chamorro Carlos, Andrés Luis, Martínez-Sales Vicenta, Moro Jose, Agüero Jaime, Sánchez-Lázaro Ignacio, Salvador Antonio
Heart Failure and Transplant Unit, Department of Cardiology, La Fe University Hospital, Valencia, Spain.
J Heart Lung Transplant. 2008 Jul;27(7):760-6. doi: 10.1016/j.healun.2008.04.010. Epub 2008 Jun 6.
Cardiac allograft vasculopathy (CAV) is the major cause of late death in patients undergoing heart transplantation (HT). The most validated method for its diagnosis is intravascular ultrasound (IVUS), and there are no sufficiently reliable non-invasive methods. von Willebrand factor (vWF) is a marker of endothelial dysfunction/activity that is rarely studied in the context of CAV. The purpose of this study was to determine whether patients with higher levels of vWF in the first year post-transplant will develop a greater degree of CAV.
A prospective study of 113 consecutive cardiac transplant recipients was initiated in January 2002. vWF determinations were performed at 1, 2, 4, 6, 9 and 12 months post-transplant, at the same time as biopsies. Coronary arteriography and IVUS were performed on the first and last follow-up visits. Heart-lung transplants, retransplants and pediatric transplants were excluded from the study. Patients who died in the first month and those who refused consent were also excluded. The final analysis included 72 patients and 405 vWF determinations. CAV was defined as an intimal thickening of >or=0.5 mm on follow-up versus baseline IVUS. Patients with CAV (n = 41) and without CAV (n = 31) after 1 year of follow-up were compared.
Patients who developed CAV had a higher prevalence of prior dyslipidemia, ischemic heart disease as the cause of HT, and rate of rejection, as well as higher vWF levels (321 +/- 122 vs 243 +/- 100%, p < 0.05). The receiver-operator characteristic (ROC) curve showed that vWF values of 150% provided a sensitivity of 91%, and values of 400% a specificity of 91% (p < 0.0001). The variables associated with CAV in the multivariate analysis were prior dyslipidemia, rejections and vWF, both linearly and by groups. vWF levels of 300% to 400% increased the probability of developing CAV by 390%, and levels >400% by 500%, versus levels <200%.
vWF levels determined in the first year post-transplant help to distinguish a subgroup of patients with a higher incidence of CAV.
心脏移植血管病变（CAV）是心脏移植（HT）患者晚期死亡的主要原因。其最有效的诊断方法是血管内超声（IVUS），目前尚无足够可靠的非侵入性方法。血管性血友病因子（vWF）是内皮功能障碍/活性的标志物，在CAV背景下很少被研究。本研究的目的是确定移植后第一年vWF水平较高的患者是否会发生更严重的CAV。
2002年1月开始对113例连续的心脏移植受者进行前瞻性研究。在移植后1、2、4、6、9和12个月进行vWF测定，同时进行活检。在首次和最后一次随访时进行冠状动脉造影和IVUS检查。心肺移植、再次移植和儿科移植被排除在研究之外。第一个月内死亡的患者和拒绝同意的患者也被排除。最终分析包括72例患者和405次vWF测定。CAV被定义为随访时内膜增厚≥0.5 mm相对于基线IVUS。比较随访1年后有CAV（n = 41）和无CAV（n = 31）的患者。
发生CAV的患者既往血脂异常、缺血性心脏病作为HT病因以及排斥反应的发生率较高，vWF水平也较高（321±122对243±100%，p < 0.05）。受试者工作特征（ROC）曲线显示，vWF值为150%时敏感性为91%，值为400%时特异性为91%（p < 0.0001）。多变量分析中与CAV相关的变量是既往血脂异常、排斥反应和vWF，包括线性和分组情况。与vWF水平<200%相比，vWF水平为300%至400%时发生CAV的概率增加390%，>400%时增加500%。
移植后第一年测定的vWF水平有助于区分CAV发生率较高的患者亚组。
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