Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement

Patients with stenotic or regurgitant aortic valve disease appear to cleave multimers of Von Willebrand factor (HMW-multimer), presumably due to high-shear stresses and non-laminar flow. Van Belle and colleagues hypothesized that transcatheter aortic valve replacement (TAVR) would correct this process, but that significant residual paravalvular leak (PVL) following TAVR would abrogate this corrective effect. Moderate to severe PVL has been associated with increased rates of hospitalization, and death compared to mild PVL. Thus, immediate characterization of the degree of PVL post TAVR using echocardiographic, hemodynamic and/or angiographic data is important, though occasionally challenging, particularly if discrepant. In this study, ratios of HMW-multimers and platelet reactivity (CT-ADP) were assessed pre- and post-TAVR in 183 patients receiving the Sapien XT valve at a single center. Among the 137 patients with no regurgitation following TAVR, HMW-multimer ratios and CT-ADP values changed significantly within 15 minutes of the TAVR using point of care testing. Among those with significant PVL, these assays only changed following effective correction of the PVL. These results were unaffected by concomitant use of clopidogrel or pre-existing mitral regurgitation. Using TEE as a reference standard, ROC curves identified a CT-ADP result of ≥180 seconds (AUC = 0.93) and HMW-multimer ratio of ≤ 0.8 (AUC = 0.94) as providing optimal discrimination for significant PVL. In multivariate models, an HMW-ratio < 0.8 or CT-ADP value > 180 seconds at the end of the procedure were both significantly associated with ≥3-fold higher one-year mortality rates.

Conclusions:

Imaging-based techniques to assess PVL post TAVR will undoubtedly remain the primary methodology, but determining the extent and importance of any observed PVL in a quantitative rather than qualitative way may confer an advantage, particularly as TAVR migrates towards lower risk populations, where multiple options for prompt corrective action exist.

 

Van Belle E, Rauch A, Vincent F, Robin E, Kibler M, Labreuche J, Jeanpierre E, Levade M, Hurt C, Rousse N, Dally J-B, Debry N, Dallongeville J, Vincentelli A, Delhaye C, Auffray J-L, Juthier F, Schurtz G, Lemesle G, Caspar T, Morel O, Dumonteil N, Duhamel A, Paris C, Dupont-Prado A, Legendre P, Mouquet F, Marchant B, Hermoire S, Corseaux D, Moussa K, Manchuelle A, Bauchart J-J, Loobuyck V, Caron C, Zawadzki C, Leroy F, Bodart J-C, Staels B, Goudemand J, Lenting PJ, Susen S. Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement. N Engl J Med. 2016;375:335–344.

Authors: Patrick J Goleski, MD and James M McCabe MD