Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy

Background and aims Changes in the phenotype and genotype in Hypertrophic Obstructive Cardiomyopathy (HOCM) are thought to involve the myocardium as well as extracardiac tissues. The extent and significance of extra-myocardial changes has not been adequately studied. We here describe the structural and functional changes in the ascending aorta of HOCM patients. Methods Changes in the aortic wall were studied in a cohort of 102 consecutive HOCM patients undergoing myectomy, and 10 normal controls. Biopsies were examined histologically, immunohistochemically and by electron microscopy. Changes in protein expression were quantified using morphometry and western blotting. Pulse wave velocity (PWV) was measured using Cardiac Magnetic Resonance (CMR), in 86 HCM patients compared to 166 age-matched normal controls. Results In HCM, the number of medial lamellar units (MLU) was significantly decreased, associated with an increase in the interlamellar distance and a preserved thickness of the aortic wall, as compared to controls. Electron microscopy showed an altered lamellar structure with disorientation of elastin fibers from the circumferential direction. There was an altered composition and orientation of smooth muscle cells. In addition, there was a significant decrease in alpha-smooth muscle actin, smooth muscle myosin, smooth muscle 22 and integrin beta1, and a significant increase in calponin and caspase3. Fibulins 1, 2 and 5, had a reduced expression in HOCM aortic biopsies. Functionally, PWV was significantly higher in HOCM patients compared to healthy controls. Conclusion In HOCM patients, specific molecular and structural changes in the composition and organisation of the arterial wall have been identified. This was associated with increased stiffness of the arterial wall. Translational Perspective This study sheds light for the first time on the altered lamellar organization in the aorta of Hypertrophic Obstructive Cardiomyopathy (HOCM), in addition to the Smooth muscle cells and Extracellular Matrix abnormalities, to explain the increased wall stiffness associated with patients clinical phenotype. The data provide insights on extra-myocardial targets that can have potential value for risk stratification and personalized therapeutics for HOCM patients.