经导管主动脉瓣置换术中的血管性血友病因子多聚体。
Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.
机构信息
From the Departments of Cardiology (E.V.B., F.V., C.H., J.-B.D., N. Debry, C.D., J.-L.A., G.S., G.L., B.M., K.M., A.M., J.-J.B., F.L., J.-C.B.), Hematology and Transfusion (A.R., E.J., C.P., A.D.-P., S.H., C.C., C.Z., B.S., J.G., S.S.), and Cardiac Surgery (E.R., N.R., A.V., F.J., V.L.), Centre Hospitalier Universitaire (CHU) Lille, INSERM Unité 1011 (E.V.B., A.R., F.V., E.R., N.R., A.V., F.J., C.P., A.D.-P., F.M., B.M., D.C., C.Z., B.S., J.G., S.S.), Université Lille, INSERM Unité 1011 - European Genomic Institute for Diabetes (E.V.B., A.R., F.V., E.R., N.R., A.V., F.J., C.P., A.D.-P., F.M., B.M., D.C., C.Z., J.G., S.S.), INSERM Unité 1167 (J.D.), Institut Pasteur de Lille (E.V.B., A.R., F.V., E.R., N.R., J.D., A.V., F.J., C.P., A.D.-P., F.M., B.M., D.C., C.Z., J.G., S.S.), and Université Lille, CHU Lille, Equipe d'accueil 2694 - Santé Publique: Epidemiologie et Qualité des Soins (J.L., A.D.), Lille, Pole d'Activité Médico-chirurgicale Cardio-vasculaire, Nouvel Hôpital Civil, CHU, Université de Strasbourg, Strasbourg (M.K., T.C., O.M.), INSERM Unité 1048 and Université Toulouse III (J.L., A.D.), Institut des Maladies Métaboliques et Cardiovasculaires (M.L., N. Dumonteil), and Laboratoire d'Hematologie (M.L.), and Service de Cardiologie (N. Dumonteil), CHU de Toulouse, Toulouse, Unité Mixte de Recherche (UMR), Centre Nationale de la Recherche Scientifique 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch (O.M.), and INSERM UMR-S Unité 1176, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre (P.L., P.J.L.) - all in France.
出版信息
N Engl J Med. 2016 Jul 28;375(4):335-44. doi: 10.1056/NEJMoa1505643.
BACKGROUND
Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR.
METHODS
We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation.
RESULTS
After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year.
CONCLUSIONS
The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).
背景
经导管主动脉瓣置换术（TAVR）治疗主动脉瓣狭窄后，10%至 20%的患者会发生术后主动脉瓣反流。我们假设，高相对分子质量（HMW）von Willebrand 因子多聚体缺陷评估或即时止血评估可用于 TAVR 期间监测主动脉瓣反流。
方法
我们纳入了 183 例行 TAVR 的患者。通过经食管超声心动图确定初始植入后存在主动脉瓣反流的患者，接受了额外的球囊扩张以纠正主动脉瓣反流。在 TAVR 各个步骤前后 5 分钟，评估 HMW 多聚体和二磷酸腺苷（ADP）诱导的血小板聚集时间（CT-ADP），后者是即时止血的一种检测手段。评估 1 年死亡率。另一组（201 例患者）用于验证 CT-ADP 检测在识别主动脉瓣反流患者中的应用。
结果
在初始植入后，无主动脉瓣反流的患者（137 例）的 HMW 多聚体恢复正常。在 46 例主动脉瓣反流患者中，20 例经额外球囊扩张成功的患者 HMW 多聚体恢复正常，但 26 例持续存在主动脉瓣反流的患者未恢复正常。CT-ADP 也观察到类似的变化序列。CT-ADP 值大于 180 秒时，对主动脉瓣反流的敏感性、特异性和阴性预测值分别为 92.3%、92.4%和 98.6%，在验证队列中也得到了类似的结果。多变量分析显示，TAVR 结束时 HMW 多聚体和 CT-ADP 的值与 1 年死亡率相关。
结论
HMW 多聚体缺陷和即时止血检测 CT-ADP 值升高，均与 TAVR 后主动脉瓣反流的发生相关，且与术后 1 年死亡率相关。（由里尔第二大学等资助；ClinicalTrials.gov 编号，NCT02628509。）
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