Ahmed Kharabish

Mucopolysaccharidoses (MPS) are rare lysosomal storage diseases characterized by multiorgan involvement and shortened longevity. Due to advances in therapies such as enzyme replacement therapy and haematopoietic stem cell therapy, life expectancy has increased posing newer challenges to patients and health professionals. One such challenge is cardiovascular manifestations of MPS, which can be life limiting and cause reduction in quality of life. Any cardiovascular intervention mandates comprehensive, multi-systemic work-up by specialist teams to optimize outcome. We highlight the importance of multidisciplinary evaluation of adult MPS patients requiring cardiovascular intervention. Clinical assessments and investigations are discussed, with a focus on the cardiac, anesthetic, airway, respiratory, radiological and psychosocial factors.

OBJECTIVES: To evaluate a systolic ECG-gated high-pitch aortoiliac computed tomography (CT) angiography for planning transcatheter aortic valve implantation (TAVI).

METHODS: Patients referred for TAVI underwent a combined CT imaging with retrospective, multiphasic ECG-gating of the heart and systolic ECG-gated high-pitch aortoiliac CT angiography. Consecutive patients were retrospectively included in this study group. Heart rate (HR) and heart rate variability (HRV) were assessed during the high-pitch ECG prediction phase. Aortic annulus area (AAA) was planimetrically quantified on both datasets. While only one moment of cardiac cycle was available for measurements in the high-pitch CT, the point of time in the multiphasic CT was chosen, where AAA yielded maximum size. Hypothetical prosthesis sizing was compared between multiphasic vs. high-pitch CT.

RESULTS: Among 61 patients (44.2 % men, mean age: 83.3 ± 5.5 years) average heart rate and HRV were 71.0 ± 13.4 bpm and 7.3 ± 8.5 bpm. 20 patients (32.7 %) had atrial fibrillation at the time of image acquisition. There was a strong correlation of AAA as derived from multiphasic vs. the high-pitch CT (r = 0.98). The difference in AAA was 10.5 ± 17.1mm (455.1 ± 83.0 mm for multiphasic vs. 444.5 ± 87.2 mm for high-pitch CT) and did not reach statistical significance (p = 0.08). Hypothetical prosthesis sizing showed an agreement in 55 of 61 patients (90.2 %). A sizing based on the high-pitch CT resulted in smaller prosthesis choice in 6 patients, all of them suffering from atrial fibrillation. Mean effective radiation dose was 10.9 ± 6.1 mSv for cardiac CTA and 4.1 ± 1.0 mSv for high-pitch CTA.

CONCLUSION: For patients with sinus rhythm, systolic high-pitch aortoiliac CTA provides adequate prosthesis size selection as compared with multiphasic ECG-gated cardiac CTA and may result in significantly reduced radiation exposition.

The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities toward advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations, such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac magnetic resonance imaging (MRI), and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions. We identified 1262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is known to impact the subepicardial layer of the myocardium through chronic inflammation. Recent animal studies have shown predominant subendocardial involvement in rats with DMD. The primary outcome parameter was to determine by cardiovascular MRI (CMR) if two differential patterns of myocardial involvements exist in DMD; the secondary outcome parameters were to correlate the observed pattern with metabolic markers such as insulin resistance measures.

METHODS: Forty patients with DMD were screened using CMR to determine which of them had predominantly subendocardial dysfunction (SENDO group), or subepicardial/midmyocardial involvement (SEPMI group). Patients were subjected to body mass index measurement, serum creatinine kinase, serum lactate dehydrogenase enzyme, fasting glucose-insulin ratio (FGIR), full lipid profile, left ventricular ejection fraction (LVEF), left ventricle E/E´ ratio (the ratio of early mitral inflow velocity to average early diastolic velocities of the basal septum and mitral annulus) for left ventricle diastolic function, and myocardial layer strain discriminating echocardiography (MLSD-STE). Results: 26 patients displayed SENDO while 34 displayed SEPMI. SENDO group displayed overt insulin resistance; (FGIR (SENDO: 7 ± 1 vs. SEPMI: 5 ± 1,  < 0.001). FGIR was negatively correlated with Subendocardial Global Longitudinal Strain (ENDO-LS) with  = -0.75.

CONCLUSION: DMD does not seem to influence the heart uniformly; DMD cardiomyopathy probably has two separate phenotypes with different mechanisms. Insulin resistance might be implicated in its pathogenesis and its reversal may help to slow disease progression.