Elevated regional wall shear stress in the ascending aorta of BAV patients was associated with greater medial elastin degradation (p=0.01) and ECM dysregulation compared to adjacent normal WSS regions.
Observational (n=20)
Does elevated wall shear stress correlate with extracellular matrix dysregulation in the ascending aorta of patients with bicuspid aortic valves?
Elevated wall shear stress measured by 4D flow CMR correlates with extracellular matrix dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, suggesting hemodynamics contribute to aortopathy.
p-value: p=0.01
BACKGROUND Suspected genetic causes for extracellular matrix (ECM) dysregulation in the ascending aorta in patients with bicuspid aortic valves (BAV) has influenced strategies and thresholds for surgical resection of BAV aortopathy. Using 4-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we have documented increased regional wall shear stress (WSS) in the ascending aorta of BAV patients. OBJECTIVES We assessed the relationship between WSS and regional aortic tissue remodeling in BAV patients to determine the influence of regional WSS on the expression of ECM dysregulation. METHODS BAV patients (n = 20) undergoing ascending aortic resection underwent preoperative 4D flow CMR to regionally map WSS. Paired aortic wall samples (i.e., within-patient samples obtained from regions of elevated and normal WSS) were collected and compared for medial elastin degeneration by histology and ECM regulation by protein expression. RESULTS Regions of increased WSS showed greater medial elastin degradation compared to adjacent areas with normal WSS: decreased total elastin (p = 0.01) with thinner fibers (p = 0.00007) that were farther apart (p = 0.001). Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (p = 0.04), matrix metalloproteinase (MMP)-1 (p = 0.03), MMP-2 (p = 0.06), MMP-3 (p = 0.02), and tissue inhibitor of metalloproteinase-1 (p = 0.04) in elevated WSS regions, indicating ECM dysregulation in regions of high WSS. CONCLUSIONS Regions of increased WSS correspond with ECM dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, implicating valve-related hemodynamics as a contributing factor in the development of aortopathy. Further study to validate the use of 4D flow CMR as a noninvasive biomarker of disease progression and its ability to individualize resection strategies is warranted.
“Abnormalities in systolic WSS were shown to be associated with colocalized medial elastin degradation, decreased elastic aortic wall fiber thickness, and progressive dilation, while scan-rescan studies showed good reproducibility, positioning this biomarker as top priority for its introduction in clinical care.”
Guzzardi et al. (Sat,) conducted a observational in Bicuspid aortic valves (BAV) aortopathy (n=20). Elevated regional wall shear stress (WSS) vs. Adjacent areas with normal WSS was evaluated on Medial elastin degradation (total elastin) (p=0.01). Elevated regional wall shear stress in the ascending aorta of BAV patients was associated with greater medial elastin degradation (p=0.01) and ECM dysregulation compared to adjacent normal WSS regions.