Ex vivo assessment of valve thickness/calcification of patients with calcific aortic stenosis in relation to in vivo clinical outcomes

Abstract

Calcific aortic stenosis (AS) plays a critical role in the risk of cardiovascular disease. This preliminary study examined the relationship between the ex vivo valve thickness/calcification and in vivo clinical outcomes of Chinese patients with calcific AS. Six Chinese patients (3 patients with tricuspid aortic valves (TAV)) and 3 patients with. bicuspid aortic valves (BAV) with calcific AS undergoing heart valve replacement were initially chosen for this study. In vivo medical imaging of these calcific AS patients was evaluated using computed tomography and echocardiography. The ex vivo measurements including the actual thickness, calcified area and components of the calcified aortic values excised were performed by a digimatic caliper, X-ray equipment with a cellSens imaging analysis and portable Raman spectroscopy, respectively. Six patients were diagnosed with symptomatic moderate-to-severe AS. The thickness of noncoronary (N) leaflet in the excised TAV was significantly thicker than left-coronary (L) leaflet (p < 0.01), and right-coronary (R) leaflet was also thicker than L (p < 0.05), but no significant difference occurred between N and R (p > 0.05). The extent of calcification in the excised TAV was a statistically significant difference between N and L (p < 0.01) and between R and L (p < 0.01), respectively. However, there was no significant difference between R and L in both thickness and calcification for the excised BAV (p > 0.05). The patients No. 1–3 were found to be TAV with partial commissural fusion. The patient No. 4 was classified as a type 1 NL-BAV morphotype, but both patients 5 and 6 were found to be true BAV (type 0 lateral-BAV). Each calcified valve leaflet was composed of apatites, proteins (collagen and proteoglycan), and a small amount of β-carotene and cholesterol after Raman spectral determination. The calcified nodules of each valve leaflet were predominately identified to be calcium hydroxyapatite and type-B carbonate apatite. However, octacalcium phosphate was also detected in the protein-rich part of calcified valve leaflets. A positive correlation was observed between thickness and calcification for both excised TAV and BAV after ex vivo examinations. Moreover, a negative relationship was obtained among in vivo AVA index, ex vivo thickness and ex vivo calcification for these calcific AS patients.