Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement
Selected in The New England Journal of Medicine by R. Dworakowski
E Van Belle, A Rauch, F Vincent, E Robin, M Kibler, J Labreuche, E Jeanpierre, M Levade, C Hurt, N Rousse, JB Dally, N Debry, J Dallongeville, A Vincentelli, C Delhaye, JL Auffray, F Juthier, G Schurtz, G Lemesle, T Caspar, O Morel, N Dumonteil, A Duhamel, C Paris, A Dupont-Prado, P Legendre, F Mouquet, B Marchant, S Hermoire, D Corseaux, K Moussa, A Manchuelle, JJ Bauchart, V Loobuyck, C Caron, C Zawadzki, F Leroy, JC Bodart, B Staels, J Goudemand, P J. Lenting, and S Susen
N Engl J Med 2016; 375:335-344
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What is known
Paravalvular aortic regurgitation (PVR) is a common complication of TAVI and patient outcomes are adversely affected by the degree of PVR that occurs. Usually a degree of PVR is assessed immediately after valve deployment either by echocardiography or using haemodynamic evaluation. None of these techniques are ideal, and all have their limitations. The idea of having a point-of-care additional screening method is thus of great interest. The von Willebrand factor could be used as an endogenous sensor of haemodynamic forces and shear stress as, for instance, in those conditions associated with supra-physiologic shear stress where von Willebrand factor mulitimers undergo rapid degradation, but their distribution normalises very quickly after restoration of normal flow.
In this study published in NEJM, Van Belle et al present the use of a point-of-care haemostatic test. As a method for predicting aortic regurgitation (AR) after TAVI; the authors look at closure time with adenosine diphosphate (CT-ADP) as assessed with the use of a Platelet Function Analyzer 100 along with the presence of defects in high-molecular-weight (HMW) multimers of the von Willebrand factor (vWF). One hundred and eighty-three (183) patients undergoing TAVI were enrolled in this single-centre study. Three qualitative measures of vWF function (including the HMW-multimer ratio) were assessed and a CT-ADP assay was performed at baseline: five and 15 minutes after TAVI implantation; five minutes after additional balloon dilation – and at the end of the procedure – five minutes after removal of the delivery sheath. Forty-six (46) patients were identified as having PVR after TAVI implantation by transoesophageal echocardiography (25%). PVR improved after post-dilatation in 20 patients. A CT-ADP value of less than 180 seconds was both a very sensitive (92.3%), and specific (92.4%), marker of residual PVR. Similarly, the HMW-multimer ratio remained low in cases of persistent AR. The negative predictive value was 98.6%. Even more importantly, these results correlated with one-year mortality.
Based on this, the authors concluded that a CT-ADP test could be a very useful point-of-care test.
Van Belle et al presented a very interesting concept and provided evidence to the effect that a change in the von Willebrand factor and platelet function can be monitored during TAVI, and that there is a correlation with PVR. TOE remains the gold standard in detecting and assessing aortic regurgitation after TAVI. However, increasing numbers of TAVI procedures are performed under conscious sedation without the routine use of TOE. Assessment of AR with TTE might be challenging and difficult. In contrast to echocardiography (TOE/TTE), the CT-ADP test focuses on platelet function status in relation to increased shear stress.
While these results are very promising as well as interesting, they have to be taken with caution before applying routinely in clinical practice. The study was performed on a relatively small group of patients and no correlation has been shown between the degree of PVR and the level of platelet dysfunction. HMW defects are observed in any situation of increased shear stress. Apart from PVR, there are potentially other complications of the TAVI procedure that might result in high-velocity blood flow (for instance: VSD, transvalvular AR, etc.). Paradoxically, severe AR might cause less shear stress than high-velocity mild/moderate AR. Other comorbidities need to be taken into consideration, such as coexisting tricuspid or mitral regurgitation.
Despite these limitations, Van Belle et al have presented a very interesting concept showing that the use of CT-ADP test, in conjunction with imaging, can be a useful, additional tool for PVR assessment.
See the Hot line session on the same topic, presented by E. Van Belle at EuroPCR 2015: Von Willebrand factor, as a highly sensitive sensor of flow and bedside test to detect and monitor aortic regurgitation during TAVI procedure: results from the WiTAVI study