Ex Vivo Biomechanics Cast Doubts on Current Diameter-Based Guidelines for Bicuspid Aortic Valve-Associated Proximal Aortic Disease

Objectives: Aortic diameter is accepted as a risk factor for acute aortic dissection, as historical studies have demonstrated a sharp increase in dissection rate once the diameter exceeds 6 cm. Current guidelines recommend an aggressive preemptive replacement of the proximal aorta despite recent research indicating different dissection risk depending on aortic valve pathology—with even higher diameters (> 6.5 cm) in patients with a bicuspid aortic valve (BAV)—but lower diameter in tricuspid aortic valve (TAV) patients (60% of patients dissecting at smaller diameter than recommended for ascending aortic replacement). Due to this contradictory assertions, the biomechanical characteristics of the aorta become focus of attention.

Methods: Sixty-eight ascending aortic samples (33 BAV, 35 TAV) were obtained and divided into convex and concave site. Pieces of 3 × 1 cm were resected, stored at 4°C NaCl, and transferred for biomechanical analysis. The rest of the tissue was partly snap frozen and stored at −80°C and partly fixed in 4% formaldehyde. For ex vivo uniaxial stress testing, aortic samples were clamped in between two pairs of jaws into the tensile stage equipped with a 20N load cell and stretched with a traction speed of 1.5 mm/min until the limit of the tensile stage (20 mm extension or 20 N force) was reached or the aortic samples disrupted. For quantification of elastin, hyaluronic acid (HA) and glycosaminoglycans (GAGs) assays were used. Formaldehyde-fixed aortic cross-sections were processed according to routine histologic protocols, embedded in paraffin, and cut into 3-μm sections for hematoxylin/eosin staining.

Results: Patients with BAV were 8 years younger at the time of surgery, were more often male, and had significantly more often aortic stenosis. In uniaxial testing, the maximum stress the aortic sample could tolerate was significantly higher in BAV patients (convex: 1.26 ± 0.6 vs. 0.97 ± 0.3, p = 0.021; concave: 1.27 ± 0.5 vs. 1.03 ± 0.5, p = 0.097). Elastic modulus was not significantly different between BAV and TAV patients and strain was only significantly different on the convex site being higher in BAV patients (34.29 ± 13.2 vs. 26.64 ± 8.8, p = 0.007). No difference in HA, GAGs, elastin, and collagen between BAV and TAV patient could be seen, but GAGs and HA had significant impact on elastic modulus in multivariable model.

Conclusion: Aortic tissue of BAV patients can tolerate higher maximum stress before disrupting, questioning the current guidelines for aortic replacement in these patients.