Correlations between genetic mutations, biomolecular patterns and elastic properties of the aorta in patients with bicuspid aortic valve.

Background. Bicuspid aortic valve (BAV), one of the most common congenital heart diseases, is frequently associated with alterations of aortic wall. A range of biomarkers stemming from the aortic extracellular matrix such as soluble elastin fragments (SEF) have been associated with increased risk of aortic dissection.Purpose. We aim to detect any correlation between the aortic elasticity [studied by M-mode and speckle tracking echocardiography (STE)] and genetic and biomolecular patterns of elastin. Methods. We enrolled 47 patients (mean age: 38±17.05) and 13 age-matched subjects (mean age:33±9.67) with tricuspid aortic valve (TAV). All measurements of aortic diameters [sinus of Valsalva, sinu-tubular (ST) junction and ascending aorta (AA)] were indexed to BSA. On M-mode images, aortic stiffness was derived through the formula: ln (SBP/DBP )/[( Dmax - Dmin )/Dmin ]. Longitudinal strain (LS) of AA was estimated as the average between anterior and posterior aortic walls strain values by STE. The genomic DNA was extracted from the whole blood and PCR reactions were used for the evaluation of a specific polymorphism (Eln G1663A), responsible for an amino acid substitution, leading to a misfolding of elastin. The SEF were detected in plasma and serum using the specific antibodies (ELISA). Results. Aortic dimensions were signicantly higher in BAV than in TAV: Valsalva sinus (p= 0.004), ST junction (p=0.013) and AA (p<0.001). Aortic stiffness was higher in BAV than in TAV (10.4±9.9 vs. 3.5±1.8, p=0.002). The LS of AA was lower in BAV than in TAV (39.3± 12vs 43±15%, p=0.04), particularly at posterior wall (35±16vs41.3±16%, p=0.004). Pts with BAV type I had lower LS (33.3 ± 12%) than those with BAV type II (41.8±11%, p=0.02). LS of AA negatively correlated with AA stiffness (r =-0.40; p=0.02) and aortic dimension ( r=-0.36;p=0.009).Results from ANOVA with post-hoc Bonferroni test for comparing pts with genotype mutated (AA, n=10) with those heterozigous (GA, n=21) and the wild-types (GG, n=14) revealed that pts with genotype mutated had: 1) an increased amount of SEF (GG=56.9±6.7 ng/mL, GA=58.6±6.3 ng/mL, AA=64±4 ng/mL; p=0.010 GG vs GA ; p=0.035 GA vs AA), 2) larger dimension of AA (GG= 29±2.8 mm, GA= 33±4.5 mm, AA= 36±4.7 mm; p= 0.019 GG vs GA; p=0.001 GG vs AA and, 3) lower LS (GG= 42±21 %, GA=49±17%, AA=29±13%; p= 0.032 GG-GA vs AA). Moreover, pts with enlarged AA showed higher amount of SEF (63.2±4.8ng/mL vs 55±7 ng/mL; p=0.001), higher AA stiffness (15.6±13 vs 6±4.2, p=0.037) and lower LS of AA (29±17% vs 52±15%, p=0.001) compared to those with normal AA dimension. In addition, SEF had significant correlations with: genotype (?=0.42; p=0.04), AA stiffness (r=0.51; p=0.003), the LS of AA (r=-0.44; p=0.006), aortic dimension (r=0.48 ;p=0.002) and the presence of AA dilatation (?=0.53; p<0.001).Conclusions Our results show a close correlation between genetic and biomolecular patterns of elastin and mechanical properties of the aorta in pts with BAV.