Wall Shear Stress in the Middle Cerebral Artery of HM II Patients - A Prospective, Mechanistic Study Using Vector Flow Mapping

Purpose It has been proposed that the high prevalence of bleeding events in continuous-flow left ventricular assist device (CF-LVAD) patients may be lowered by increasing von Willebrand factor-release via augmented peripheral pulsatility (PI). However, the hemostatic effects of increased PI may be offset by concomitant increases in local wall shear stress (WSS) - which is known to stimulate the endothelial release of anti-thrombotic factors (NO, prostacyclin, thrombomodulin). Hypothesis Higher pulsatility in the middle cerebral artery of CF-LVAD patients will be significantly associated with increased local WSS. Methods Video loops of color Doppler recordings from the middle cerebral artery were obtained in 8 HeartMate II (HM II) patients and 8 healthy controls. Data were analyzed offline with validated vector flow mapping software. WSS was calculated as: viscosity*(du/dy), according to Newton's law. Viscosity was corrected by using individuals’ hematocrit. Importantly, we determined not only peak WSS but also WSS per beat (area under the curve) and WSS/min (WSS/beat * heart rate). PI was measured from angle-corrected pulsed-wave Doppler velocities. Results Peak WSS and WSS/beat were lower in HM II ( P  = 0.05) but WSS/min was not different ( P > 0.05). Supporting our hypothesis, WSS and pulsatility index (PI) were strongly correlated non-linearly in HM II patients (r 2  = 0.94) and shared a common linear slope with healthy controls between a PI of ∼0.45 and ∼0.90 (Fig. 1). Conclusion In CF-LVAD patients, a strong curvilinear relationship was noted between cerebral PI and WSS, with linear increases in WSS shown above a PI of ∼0.45. These data suggest a threshold for PI and its interaction with endothelium-dependent hemostatic and anti-thrombotic activity. Future work is warranted to investigate whether alteration of the PI-WSS relationship will influence the release of hemostatic or anti-thrombotic factors and reduce cerebral bleeding in CF-LVAD patients.