The role of stress concentration in calcified bicuspid aortic valve

Abstract

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in the aging population, and is now believed to be a slow, progressive, yet actively regulated process. The disease progression can be divided into two phases: initiation phase associated with lipid deposition and inflammation response, and the later propagation phase with active calcification growth. It has been hypothesized that elevated mechanical stress plays a major role in both phases of disease progression. In order to identify a direct link between leaflet stress and calcification development, we performed patient-specific finite-element (FE) analyses of six bicuspid aortic valves (BAV), where the leaflets, raphe and calcifications were all considered. The results showed that during the initiation phase, calcium buildup is likely to occur along the leaflet-root attachment curve (ATC), and the commissures, which are subject to the most drastic changes in stress during the cardiac cycle. During the propagation phase, the presence of calcification would lead to local stress concentration along its boundary, hence further calcification growth. Three patterns of calcification formation were identified on BAV leaflets: 'radial', which extended radially from ATC into the leaflet belly region; 'commissure to commissure', which extended circumferentially along the coaptation; and 'raphe', which located in the vicinity of the raphe. Furthermore, we found a strong correlation between regions with a high risk of calcium buildup and regions with elevated mechanical stress. The high-risk regions predicted at diastole on the non-calcified leaflet from FE models agreed reasonably well with the in vivo calcification locations, which indicates that patient-specific FE modelling could help us to evaluate the potential risk of calcification formation in the early stage of CAVD.