Morphological Changes in the Mitral Valve of Pathogenic Gene Mutation Carriers of Familial Hypertrophic Cardiomyopathy

Background: The shape of the mitral valve is remodeled as heart function changes, even before cardiac decompensation and obvious clinical symptoms appear. How does the early mitral valve morphology change in carriers of pathogenic gene mutation in hypertrophic cardiomyopathy(HCM)? Methods: Whole exome sequencing was performed on the probands of 258 families affected by HCM. Ninety-one families with definite pathogenic gene mutations. Sanger sequencing of families with definitive diseasecausing gene mutations was performed to verify the genotype, which was divided into the HCM group (G+/LVH+, n = 167); pathogenic gene mutationcarrying group (G+/LVH-, n = 149); and non-pathogenic gene mutationcarrying group (G-/LVH-, n = 189). Two-dimensional and three-dimensional ultrasound images were acquired from all family members, and mitral valve morphology parameters were analyzed and compared among the groups. Results: The results showed that the anteroposterior diameter and annulus height of G+/LVH+ were higher than those of G+/LVH- and G-/LVH-. The anterolateral-posteromedial diameter and sphericity index of G+/LVH+ and G+/LVH- differed significantly from those of G-/LVH-. The annulus circumference (3D), annulus area (2D), and annulus area (3D) of G+/LVH- were significantly lower than those of G+/LVH+ and G-/LVH-. The leaflets tenting volume, tenting height, commissural diameter, and annular height-to-commissural width ratio (AHCWR) (%) of G+/LVH- were significantly lower than those of G-/LVH- (1.4 ± 1.2 vs. 1.9 ± 0.9, p < 0.001) (7.7 ± 2.4 vs. 8.2 ± 2.0, p < 0.05), (2.8 ± 0.5 vs. 3.3 ± 0.3, p < 0.001), (23.1 ± 7.1 vs. 25.9 ± 6.5, p < 0.05). The angle between the mitral annulus plane and aortic valve annulus plane of G+/LVH+ was lower than that of G-/LVH- (134.4 ± 16.4 vs. 138.4 ± 13.4). Further studies revealed that mitral valve morphology parameters in the MYBPC3+/LVHgroup were significantly reduced compared with G-/LVH- group, whereas those parameters in the MYH7+/LVH- group showed no significant differences. Conclusions: Mitral valve morphological parameters show early deformation with a flatter appearance in pathogenic gene mutation carriers. They can be used as sensitive parameters to detect abnormal cardiac function in carriers of HCM, particularly in the carriers of MYBPC3 gene mutations. Funding Statement: This study was supported by grant no. 81671685 from the National Science Foundation of China and grant no. 17411954400 from the Science and Technology Committee Foundation of Shanghai. Declaration of Interests: The authors stated: None. Ethics Approval Statement: The study was approved by the Ethics Committee of Zhongshan Hospital, affiliated to Fudan University (no. 2016-16B), and all subjects gave informed consent.