von Willebrand Factor as a Biological Sensor of Blood Flow to Monitor Percutaneous Aortic Valve Interventions
Rationale: Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis (AS). Residual gradient and residual aortic-regurgitation (AR) are major predictors of mid-term 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 (VWF) defect, could be instantaneous after acute changes in blood flow, 2) a bedside point-of-care assay (PFA-CADP), reflecting HMW-multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures.
Objective: 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.
Methods and Results: We investigated the time course of the induction/recovery of HMW-multimers defects under instantaneous changes in shear stress in an AS-rabbit model and in patients undergoing implantation of a continuous-flow Left-Ventricular Assist-Device (LVAD). We further investigated the recovery of HMW-multimers and monitored these changes with PFA-CADP in AS-patients undergoing transcatheter-aortic-valve implantation (TAVI) or balloon valvuloplasty (BAV). Experiments in the AS-rabbit model and in LVAD-patients demonstrated that induction/recovery of HMW-multimers occurs within 5 minutes. TAVI-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-AR, no recovery of HMW-multimers was observed. PFA-CADP profiles mimicked HMW-multimers recovery both in TAVI-patients without-AR (correction) and TAVI-patients with-AR or BAV-patients (no correction).
Conclusions:: These results demonstrate that variations in VWF 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.
- bedside monitoring
- aortic stenosis
- von Willebrand factor
- blood flow
- left ventricular assist device
- transcatheter aortic valve implantation
- Received August 18, 2014.
- Revision received February 2, 2015.
- Accepted February 10, 2015.