Valentin Loobuyck

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement

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.).

A new case of Mycoplasma hominis mediastinitis and sternal osteitis after cardiac surgery.

We report a case of nosocomial mediastinitis and sternal osteitis due to M. hominis after open-heart surgery in an immuno-competent patient. This infection has been diagnosed by incubating the culture media for an extended period of time, and sequencing 16S rDNA directly from the clinical samples.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support

BACKGROUND The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied. OBJECTIVES The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS. METHODS We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS. RESULTS We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF. CONCLUSIONS We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.

von Willebrand Factor for Aortic Valve Intervention: From Bench to Real-Time Bedside Assessment

VWF (von Willebrand factor ) is a circulating multimeric blood glycoprotein. VWF plays a major role in primary hemostasis by promoting the adhesion of platelets to subendothelial collagen at sites of vascular damage and thereby promoting platelet aggregation. VWF is synthesized in endothelial cells and megakaryocytes. The VWF units dimerize and are transported into the Golgi apparatus, where disulfide bonds are formed leading to formation of VWF multimers. This large subunit combination is required to support its hemostatic function. VWF has the unique features to be circulating in an inactive coiled form, hiding binding domains for platelet receptors and subendothelial collagen. At the site of vascular injury, VWF binds to the exposed collagen and unfolds. Once VWF is unfolded, the VWF A1 domain is exposed allowing the binding of platelets via GP Ib (glycoprotein IB) receptor. After platelet activation, GP IIb/IIIa (glycoprotein IIb/IIIa) receptor becomes able to bind VWF C1 domain. The VWF conformation and activity is intimately related to shear conditions and blood flow. At high shear rate (beyond 10–15 pN), it becomes unfolded exposing binding sites but also the cleavage site in VWF A2 domain for ADAMTS13 (adisintegrin-like and metalloprotease thrombospondin) protease that conducts to its proteolysis. Overall, these environmental changes generate the modification of the conformation of VWF …