Predictive Value of Circulating Progenitor Cell Apoptosis on Bioprosthetic Aortic Valve Degeneration

Background:
Bioprosthetic valves are composed of altered biological tissue that may undergo degenerative processes. Endothelial progenitor cells (EPCs) are mainly found in degenerative native aortic valves (AV) and degenerative bioprosthesis. Enhanced apoptosis as well as increased senescence of EPCs is seen in degenerative AV. We recently reported high levels of circulating EPCs in patients with aortic stenosis. However the correlation between circulating EPCs, Progenitor cells (PC) and apoptotic PCs and bioprosthetic aortic valve degeneration (BAVD) is not known.

Aim: To determine the predictive value of circulating apoptotic EPC and PC level in BAVD.

Patients and Methods:
The study included 88 patients (mean age 77±9 years, 55 male) before aortic valve replacement (AVR). Patients underwent clinical and echocardiographic assessment before, immediately after and every 6 months after AVR. The number of PCs (CD34+), EPCs (CD34+KDR+), apoptotic PCs (annexin positive) and late apoptotic PCs (7-AAD positive) was determined by flow cytometry. Patients were divided into a group with and a group without BAVD. BAVD was defined as an increase of 10mmhg in mean gradient or an increase of at least one level of valve regurgitation.

Results:
During median follow up of 34 month, degeneration of bioprosthesis was observed in 21 (24%) patients. There were no significant changes in baseline characteristics between the groups. Patients with BAVD had significantly higher levels of circulating apoptotic PCs as compared to patients with no BAVD ( p=0.019, Table). In addition, the percent of late apoptotic PCs was also significantly higher in patients with BAVD (p=0.028).There was no difference in the levels of PCs and EPCs between the 2 groups.

Conclusions:
Patients with BAVD have significantly higher level of circulating apoptotic PCs before AVR. This finding suggests that extravalvular apoptotic PCs are related to bioprosthesis degeneration and may provide an insight into the mechanism of BAVD.