From the Department of Cardiology, Lille University Hospital, Lille, France (E.V.B., A.V., F.J., C.H., C.B., N.R., C.D., G.S., D.D.); INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, EGID, Lille, France (E.V.B., A.R., A.V., E.J., F.J., C.B., N.R., C.C., A.E., D.C., A.D., C.Z., G.C., B.S., J.G., B.J., S.S.); Department of Hematology, Transfusion Lille University Hospital, Lille, France (A.R., E.J., C.C., A.E., C.Z., F.M., J.G., B.J., S.S.); INSERM U1176 and UMR_S1176, Univ Paris-Sud, Le Kremlin Bicêtre, France (P.L., P.J.L.); and INSERM UMR 1140, Paris, France (A.G.).
Circ Res. 2015 Mar 27;116(7):1193-201. doi: 10.1161/CIRCRESAHA.116.305046. Epub 2015 Feb 10.
Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures.
To investigate the time course of HMW multimers changes in models and patients with instantaneous induction/reversal of pathological high shear and its related bedside assessment.
We investigated the time course of the induction/recovery of HMW multimers defects under instantaneous changes in shear stress in an aortic stenosis rabbit model and in patients undergoing implantation of a continuous flow left ventricular assist device. We further investigated the recovery of HMW multimers and monitored these changes with PFA-CADP in aortic stenosis patients undergoing transcatheter aortic valve implantation or balloon valvuloplasty. Experiments in the aortic stenosis rabbit model and in left ventricular assist device patients demonstrated that induction/recovery of HMW multimers occurs within 5 minutes. Transcatheter aortic valve implantation patients experienced an acute decrease in shear stress and a recovery of HMW multimers within minutes of implantation which was sustained overtime. In patients with residual high shear or with residual aortic regurgitation, no recovery of HMW multimers was observed. PFA-CADP profiles mimicked HMW multimers recovery both in transcatheter aortic valve implantation patients without aortic regurgitation (correction) and transcatheter aortic valve implantation patients with aortic regurgitation or balloon valvuloplasty patients (no correction).
These results demonstrate that variations in von Willebrand factor multimeric pattern are highly dynamic, occurring within minutes after changes in blood flow. It also demonstrates that PFA-CADP can evaluate in real time the results of transcatheter aortic valve procedures.
经皮主动脉瓣置换术是治疗主动脉瓣狭窄患者的重大突破。残余梯度和残余主动脉瓣反流是经皮主动脉瓣置换术后中期和长期预后的主要预测因素。我们假设：（1）在血流急性变化后，von Willebrand 因子高分子量（HMW）多聚体的诱导/恢复可能是瞬时的；（2）一种床边即时检验（血小板功能分析仪-ADP 封闭时间[PFA-CADP]），反映 HMW 多聚体的变化，可以实时监测经皮主动脉瓣置换术。
研究瞬时诱导/逆转病理性高剪切时 HMW 多聚体变化的时程及其相关床边评估。
我们研究了瞬时剪切应力变化下主动脉瓣狭窄兔模型和植入连续血流左心室辅助装置患者中 HMW 多聚体缺陷的诱导/恢复时程。我们进一步研究了 HMW 多聚体的恢复，并在接受经导管主动脉瓣植入术或球囊瓣膜成形术的主动脉瓣狭窄患者中用 PFA-CADP 监测这些变化。主动脉瓣狭窄兔模型和左心室辅助装置患者的实验表明，HMW 多聚体的诱导/恢复在 5 分钟内发生。经导管主动脉瓣植入术患者在植入后数分钟内经历了剪切应力的急性下降和 HMW 多聚体的恢复，这种恢复持续了很长时间。在残余高剪切或残余主动脉瓣反流的患者中，没有观察到 HMW 多聚体的恢复。PFA-CADP 谱在没有主动脉瓣反流（矫正）的经导管主动脉瓣植入术患者和有主动脉瓣反流或球囊瓣膜成形术患者（未矫正）中模拟了 HMW 多聚体的恢复。
这些结果表明，von Willebrand 因子多聚体模式的变化是高度动态的，在血流变化后几分钟内发生。它还表明，PFA-CADP 可以实时评估经导管主动脉瓣置换术的结果。
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