Background: Calcific aortic stenosis (CAS) is driven by progressive inflammatory and fibro-calcific processes regulated by infiltration of circulating peripheral monocytes. The impact of monocytes on disease progression and local valvular inflammation and mineralization is presently unknown.

Methods: We prospectively enrolled 338 consecutive patients with severe symptomatic CAS with clinical need for valve replacement. 174 patients underwent surgical aortic valve replacement (AVR) whereas 164 underwent transcatheter aortic valve implantation (TAVI). Cardiac workup included physical examination, echocardiography, and blood sampling for laboratory parameters. For phenotyping of monocytes, we performed flow cytometry analysis of patient blood samples pre-surgery and a follow-up of 3-6 months.

Results: Classical, intermediate and non-classical monocytes display different surface expression pattern of established markers of adhesion, migration, and T cell activation. The pro-inflammatory chemokine CXCL12 is significantly increased in all three monocyte subsets in patients with TAVI compared to patients with AVR (p<0.05). Moreover, important markers regulating leukocyte adhesion and migration and mediating inflammation like CD11b are significantly elevated in patients with TAVI (p<0.001). CD80, an important marker for modulation of T-cell immune functions, is significantly decreased in TAVI patients compared to AKR patients (p<0.01), whereas the costimulatory protein CD40 is significantly increased on all monocyte subsets in TAVI patients (p<0.05). Further, CD54 which facilitate leukocyte endothelial transmigration is less expressed on monocytes in TAVI patients (p<0.05). A similar increased expression on monocytes in TAVI patients was observed for CX3CR1, which plays a critical role in monocyte survival (p<0.05). In addition, analyzing the surface marker expression on monocytes before the AKE or TAVI and a follow-up of 3-6 months display huge differences in their expression indicating an altered phenotype of monocytes after a follow-up of 3-6 months between AKE and TAVI patients.

Conclusion: Our findings indicate an altered phenotype of circulating peripheral monocytes between patients undergoing surgical valve replacement or transcatheter aortic valve implantation and after a follow-up of up to 6 months.