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. Keywords: HCM, Aortic wall, lamellae, ECM, PWV ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Science and Technology Development Fund (STDF) government grant (Egypt), Leducq Foundation (11 CVD-01) and Aswan Heart Centre (Magdi Yacoub Heart Foundation). The views expressed in this work are those of the authors and not necessarily those of the funders. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Aswan Heart Centre - Institutional Review Board approved the study and the inclusion of both Hypertrophic Cardiomyopathy and Healthy cohorts; study codes (20130405MYFAHC\_CMR\_20130330) and (20151125MYFAHC\_Hvol\_20161027, respectively]. Informed consents were obtained from HCM patients and healthy subjects prior to their inclusion in the study. Control aortic biopsies were acquired from the Magdi Yacoub Institute UK, upon a material transfer agreement [upon approval from Royal Brompton hospital ethics review board / Brompton and Harefield trust ethics committee (REC approval 10/H0724/18)]. The study is abiding by all the standards of the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All underlying data are available in the article and in its online supplementary materials.