Abstract 18617: Development of Aortic Root Dilation is Accompanied by Increased Vascular Expression of Proinflammatory Adhesion Molecules VCAM, ICAM and E-Selectin in Patients with Advanced Heart Failure Following Left Ventricular Assist Device Placement

Abstract

Background Left ventricular assist devices (LVADs) are increasingly used for patients with advanced heart failure. Continuous flow LVADs (cfLVADs) have replaced older pulsatile LVADs (pLVADs); however, effects of attenuated pulse pressure waveforms are largely unknown. We compared vascular histomorphometric and molecular changes in patients on cfLVADs compared to pLVADs. Methods Clinical and echocardiographic data was collected from electronic medical records for 28 LVAD patients (12 pLVAD vs. 16 cfLVAD). Endothelial van Willebrand stores, markers of aortic wall thickness, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at LVAD placement and at explantation during heart transplant. Expression of adhesion molecules was quantified by Western blot. Results Age (55±13 vs. 62±9 yrs) and duration of LVAD support (279±191 vs. 201±114 days) were similar in both groups. Aortic root dilation was only observed in cfLVAD patients (change in root diameter: +0.32±0.29 in cfLVAD vs. -0.20±0.61 in pLVAD; p<0.05). Decellularization of the aorta (tunica media and adventitia) was observed in cfLVAD patients (media: 22.8±7.1 vs. 48.0±8.0 cells/µm 2 in pLVAD; adventitia: 21.0±9.3 vs. 46.8±11.3 cells/µm 2 in pLVAD; both p<0.01). Decreased media thickness developed only in cfLVAD patients (-0.44±0.01 vs. 0.047±0.006 µm/BMI in pLVAD; p<0.05). Inflammation was higher in cfLVAD patients (T-cells: 5.2±3.2 vs. 8.2±4.2 cells/µm 2 in cfLVAD; macrophages: 5.2±2.6 vs. 6.86±3.3 cells/µm 2 in cfLVAD). Both device types showed an increase in vascular E-selectin, ICAM and VCAM levels following LVAD placement (E-selectin: +39.6% vs. +29.0% in pLVAD, ICAM: +24.42% vs. +19.6% in pLVAD, VCAM: +30.6% vs. +34.0% in pLVAD; all p<0.05). Endothelial vWF stores were preserved in pLVAD patients with near complete depletion in cfLVAD patients. Conclusion LVAD implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on cfLVADs and associated with aortic media decellularization and endothelial vWF depletion. These findings help to explain the progressive aortic root dilation seen in patients following cfLVAD placement.