Objective: The neonatal arterial switch operation is currently the procedure of choice for patients with transposition of the great arteries. However, a large number of patients present too late for the arterial switch operation and are best managed with the atrial switch operation. Methods:We have used the Mustard operation in its original form or following a new modification designed to enhance the atrial functions and filling of the left ventricle in an attempt to improve long-term results.From the

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Hypertrophic cardiomyopathy (HCM) is the most common inherited heart muscle disease, with a prevalence of at least 1 in 500 in the general population. The disease is pleiotropic and is characterized by an increased stiffness of the myocardium, partly due to changes in the extracellular matrix (ECM), with elevated levels of interstitial fibrosis. Myocardial fibrosis is linked to impaired diastolic function and possibly phenotypic heterogeneity of HCM. The ECM consists of a very large number of proteins, which actively interact with each other as well as with myocardial cells. The role of other multiple components of the ECM in HCM has not been defined. Fibulin-2 is a glycoprotein component of the ECM, which plays an important role during embryogenesis of the heart; however, its role in adult myocardium has not been adequately studied. We here describe, for the first time, abnormal expression of fibulin-2 in the myocardium in patients with HCM as compared to normal controls. This abnormal expression was localized in the cytoplasm of myocardial cells and in the interstitial fibroblasts. In addition, fibulin-2 levels, measured by ELISA, were significantly elevated in the serum of patients with HCM as compared to normal controls.

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

Introduction Changes in the Extracellular Matrix (ECM) in Hypertrophic Cardiomyopathy (HCM) is thought to involve the myocardium as well as extracardiac tissues. The extent and significance of extra-myocardial changes has not been adequately studied. Purpose To describe the structural, molecular, and functional changes in the aorta of HOCM patients. Methods The structural and molecular changes in the aortic wall were studied in a cohort of 102 consecutive patients with hypertrophic obstructive cardiomyopathy undergoing myectomy. The biopsies were examined histologically, immunohistochemically and by Electron microscopy. The findings were compared to 10 normal controls obtained from the homograft bank of the Harefield hospital, following IRB guidelines. Changes in expression were quantified using morphometry and western blotting. For aortic stiffness, pulse wave velocity [PWV] was measured using Cardiac Magnetic Resonance (CMR), in the 102 HCM patients as well as age-matched 166 normal controls. Results Specimens from HCM aortas showed a misalignment in collagen and elastin fibres. There was a significant reduction in smooth muscle cells [SMCs] markers; integrin beta1 and smooth muscle actin, and an increase in an apoptosis marker, Caspase3. In addition, there was a significant decrease in the number of lamellae and an increase in the interlamellar distance in HCM aortas. FBLNs 1, 2 and 5 showed a reduction in expression in tunica intima and tunica media of HCM biopsies. PWV was significantly higher in HCM patients compared to healthy controls with the highest levels in patients with LV fibrosis. Conclusion This study illustrates the link between functional abnormalities in the aorta of HCM patients with structural and molecular changes. These findings can have a potential value in risk stratification and identify new therapeutic targets in HCM. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): STDF-EgyptMagdi Yacoub Foundation