1514 results found
Al-Shafai KN, Al-Hashemi M, Manickam C, et al., 2021, Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs, MOLECULAR GENETICS & GENOMIC MEDICINE, ISSN: 2324-9269
Yacoub MH, Afifi A, Hosny H, et al., 2020, A New Technique for Shaping the Aortic Sinuses and Conserving Dynamism in the Remodeling Operation., Ann Thorac Surg
BACKGROUND: Preserving dynamism and recreating the sinuses in the Dacron graft are thought to be important for optimizing results of aortic valve-conserving operations. METHODS: We describe a novel technique that preserves dynamism and recreates the sinotubular junction. In addition, it tailors 3 sinuses of defined longitudinal and transverse curvatures in a straight Dacron tube during the operation. The technique has been used in 6 patients with varied aortic root pathology. We performed preoperative and postoperative multimodality imaging using computerized image analysis as well as 3-dimensional models. RESULTS: There was no early or midterm death. Upon discharge, patients were clinically well, with echocardiographic evidence of minimal (3 patients) or mild (3 patients) aortic regurgitation. Computed tomography and cardiac magnetic resonance imaging with extensive image analysis of the aortic root size, shape, and function showed partial or complete normalization of these parameters. This included the shape and dynamism of the aortic annulus and the size and shape of the geometric (effective) orifice. The 4-dimensional magnetic resonance imaging pattern of flow in the sinuses and ascending aorta showed favorable vortices in the sinuses, right-handed helical flow, and marked diminution of energy loss in the ascending aorta. CONCLUSIONS: The novel technique described here is simple, practical, and cost-effective because it uses a widely available straight Dacron tube. The technique does not use rigid internal or external support. The early results are encouraging. Larger series with longer follow-up are required.
Badran HM, Faheem N, Zidan A, et al., 2020, Effect of Short-Term L-Thyroxine Therapy on Left Ventricular Mechanics in Idiopathic Dilated Cardiomyopathy, JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, Vol: 33, Pages: 1234-1244, ISSN: 0894-7317
Al Kindi HN, Shehata M, Ibrahim AM, et al., 2020, Cor Triatriatum Sinister (Divided Left Atrium): Histopathologic Features and Clinical Management, ANNALS OF THORACIC SURGERY, Vol: 110, Pages: 1380-1386, ISSN: 0003-4975
Allouba M, Aguib Y, Walsh R, et al., 2020, Analysis of HCM in an understudied population reveals a new mechanism of pathogenicity, Publisher: Cold Spring Harbor Laboratory
Hypertrophic Cardiomyopathy (HCM) is an inherited disease characterized by genetic and phenotypic heterogeneity. MYH7 represents one of the main sarcomere-encoding genes associated with HCM. Missense variants in this gene cause HCM through gain-of-function actions, whereby variants produce an abnormal activated protein which incorporates into the sarcomere as a "poison peptide". Here we report a frameshift variant in MYH7, c.5769delG, that is associated with HCM in an Egyptian cohort (3.3%) compared with ethnically-matched controls. This variant is absent from previously published large-scale Caucasian HCM cohorts. We further demonstrate strong evidence of co-segregation of c.5769delG with HCM in a large family (LOD score: 3.01). The predicted sequence of the variant MYH7 transcript shows that the frameshift results in a premature termination codon (PTC) downstream of the last exon-exon junction of the gene that is expected to escape nonsense-mediated decay (NMD). RNA sequencing of myocardial tissue obtained from a patient with the variant during surgical myectomy confirmed the expression of the variant MYH7 transcript. Our analysis reveals a new mechanism of pathogenicity in the understudied Egyptian population whereby distal PTC in MYH7 may lead to the expression of an abnormal protein.
Mazzarotto F, Hawley M, Beltrami M, et al., 2020, The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases, Publisher: bioRxiv
Rationale: Left ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. Objective: To investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies. Methods and Results: We performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases. We observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes. Conclusions: We demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVN
Kalman JM, Lavandero S, Mahfoud F, et al., 2019, Looking back and thinking forwards-15 years of cardiology and cardiovascular research, NATURE REVIEWS CARDIOLOGY, Vol: 16, Pages: 651-660, ISSN: 1759-5002
Al Kindi HN, Yacoub MH, 2019, Transection and Relocation of Anomalous Left Coronary Artery After Aborted Sudden Cardiac Death, ANNALS OF THORACIC SURGERY, Vol: 108, Pages: E25-E28, ISSN: 0003-4975
Cavigli L, Fumagalli C, Maurizi N, et al., 2018, Timing of invasive septal reduction therapies and outcome of patients with obstructive hypertrophic cardiomyopathy, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 273, Pages: 155-161, ISSN: 0167-5273
Mazine A, El-Hamamsy I, Verma S, et al., 2018, Ross Procedure in Adults for Cardiologists and Cardiac Surgeons JACC State-of-the-Art Review, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 72, Pages: 2761-2777, ISSN: 0735-1097
Zilla P, Bolman RM, Yacoub MH, et al., 2018, The Cape Town Declaration on access to cardiac surgery in the developing world, JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, Vol: 156, Pages: 2206-2209, ISSN: 0022-5223
Yacoub MH, McLeod C, 2018, The expanding role of implantable devices to monitor heart failure and pulmonary hypertension, NATURE REVIEWS CARDIOLOGY, Vol: 15, Pages: 770-779, ISSN: 1759-5002
Yu JK, Sarathchandra P, Chester A, et al., 2018, Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program, Scientific Reports, Vol: 8, ISSN: 2045-2322
Cardiac regeneration post-injury is a tantalizing feature of many lower vertebrates such as fishes and urodeles, but absent in adult humans. Restoration of pumping function is a key endpoint of cardiac regeneration, but very little is known about the biomechanical remodeling process. Here, we quantify and compare the evolution of cellular composition and mechanical stiffness of the zebrafish ventricular myocardium during maturation and following cryoinjury during regeneration to better understand the dynamics of biomechanical remodeling during these two processes. With increasing age, normal myocardial trabecular density and cardiomyocyte fraction increased, while non-myocyte cell fractions decreased. Cell density remained constant during maturation. Cardiomyocyte sarcomeres shortened to a minimum reached at 7.5 months of age, but lengthened with additional age. Concomitantly, ventricular wall stiffness increased up until 7.5 months before plateauing with additional age. Endothelial, myofibroblast/smooth muscle, and cardiomyocyte cell fractions were disrupted following cryoinjury, but were progressively restored to age-specific natural norms by 35 days post infarct (DPI). Infarcted myocardium stiffened immediately following cryoinjury and was a 100-fold greater than non-infarcted tissue by 3 DPI. By 14 DPI, stiffness of the infarcted myocardium had fallen below that of 0 DPI and had completely normalized by 35 DPI. Interestingly, cardiomyocyte sarcomere length increased until 14 DPI, but subsequently shortened to lengths below age-specific natural norms, indicating recovery from a volume overloaded condition. These observations are consistent with the view that regenerating myocardium requires biomechanical stimulation (e.g. strain) to rescue from a volume overloaded condition. Intriguingly, the biomechanical progression of the infarcted adult myocardial wall mirrors that of normal remodeling during aging. The biomechanical progression of the infarcted myocardium ta
Watkins DA, Beaton AZ, Carapetis JR, et al., 2018, Rheumatic Heart Disease Worldwide JACC Scientific Expert Panel, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 72, Pages: 1397-1416, ISSN: 0735-1097
Zilla P, Bolman RM, Yacoub MH, et al., 2018, The Cape Town Declaration on Access to Cardiac Surgery in the Developing World., Asian Cardiovasc Thorac Ann, Vol: 26, Pages: 535-539
Zilla P, Bolman RM, Yacoub MH, et al., 2018, The Cape Town Declaration on Access to Cardiac Surgery in the Developing World, ANNALS OF THORACIC SURGERY, Vol: 106, Pages: 930-933, ISSN: 0003-4975
Kaniewska-Bednarczuk E, Kutryb-Zajac B, Sarathchandra P, et al., 2018, CD39 and CD73 in the aortic valve-biochemical and immunohistochemical analysis in valve cell populations and its changes in valve mineralization, CARDIOVASCULAR PATHOLOGY, Vol: 36, Pages: 53-63, ISSN: 1054-8807
Yacoub MH, Aguib H, Abou Gamrah M, et al., 2018, Aortic root dynamism, geometry, and function after the remodeling operation: Clinical relevance, JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, Vol: 156, Pages: 951-+, ISSN: 0022-5223
Zilla P, Bolman RM, Yacoub MH, et al., 2018, The Cape Town declaration on access to cardiac surgery in the developing world, EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol: 54, Pages: 407-410, ISSN: 1010-7940
Zilla P, Bolman RM, Yacoub MH, et al., 2018, The Cape Town Declaration on Access to Cardiac Surgery in the Developing World, SAMJ SOUTH AFRICAN MEDICAL JOURNAL, Vol: 108, Pages: 702-704, ISSN: 0256-9574
Rich S, Haworth SG, Hassoun PM, et al., 2018, Pulmonary hypertension: the unaddressed global health burden, LANCET RESPIRATORY MEDICINE, Vol: 6, Pages: 577-579, ISSN: 2213-2600
Zilla P, Bolman RM, Yacoub MH, et al., 2018, The Cape Town Declaration on Access to Cardiac Surgery in the Developing World, CARDIOVASCULAR JOURNAL OF AFRICA, Vol: 29, Pages: 256-259, ISSN: 1995-1892
Mongkoldhumrongkul N, Latif N, Yacoub MH, et al., 2018, Effect of side-specific valvular shear stress on the content of extracellular matrix in aortic valves, Cardiovascular Engineering and Technology, Vol: 9, Pages: 151-157, ISSN: 1869-4098
Responses of valve endothelial cells (VECs) to shear stresses are important for the regulation of valve durability. However, the effect of flow patterns subjected to VECs on the opposite surfaces of the valves on the production of extracellular matrix (ECM) has not yet been investigated. This study aims to investigate the response of side-specific flow patterns, in terms of ECM synthesis and/or degradation in porcine aortic valves. Aortic and ventricular sides of aortic valve leaflets were exposed to oscillatory and laminar flow generated by a Cone-and-Plate machine for 48 h. The amount of collagen, GAGs and elastin was quantified and compared to samples collected from the same leaflets without exposing to flow. The results demonstrated that flow is important to maintain the amount of GAGs and elastin in the valve, as compared to the effect of static conditions. Particularly, the laminar waveform plays a crucial role on the modulation of elastin in side-independent manner. Furthermore, the ability of oscillatory flow on the aortic surface to increase the amount of collagen and GAGs cannot be replicated by exposure of an identical flow pattern on the ventricular side of the valve. Side-specific responses to the particular patterns of flow are important to the regulation of ECM components. Such understanding is imperative to the creation of tissue-engineered heart valves that must be created from the “appropriate” cells that can replicate the functions of the native VECs to regulate the different constituents of ECM.
Yacoub MH, Hosny H, Romeih S, et al., 2018, MID-TERM OUTCOME OF A MODIFIED MUSTARD OPERATION FOR NEGLECTED TRANSPOSITION OF THE GREAT ARTERIES, 67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 591-591, ISSN: 0735-1097
Haikal RR, Hua C, Perry JJ, et al., 2017, Controlling the Uptake and Regulating the Release of Nitric Oxide in Microporous Solids, ACS APPLIED MATERIALS & INTERFACES, Vol: 9, Pages: 43520-43528, ISSN: 1944-8244
You AYF, Bergholt MS, St-Pierre JP, et al., 2017, Raman spectroscopy imaging reveals interplay between atherosclerosis and medial calcification in human aorta, Science Advances, Vol: 3, ISSN: 2375-2548
Medial calcification in the human aorta accumulates during aging and is known to be aggravated in several diseases. Atherosclerosis, another major cause of cardiovascular calcification, shares some common aggravators. However, the mechanisms of cardiovascular calcification remain poorly understood. To elucidate the relationship between medial aortic calcification and atherosclerosis, we characterized the cross-sectional distributions of the predominant minerals in aortic tissue, apatite and whitlockite, and the associated extracellular matrix. We also compared the cellular changes between atherosclerotic and nonatherosclerotic human aortic tissues. This was achieved through the development of Raman spectroscopy imaging methods that adapted algorithms to distinguish between the major biomolecules present within these tissues. We present a relationship between apatite, cholesterol, and triglyceride in atherosclerosis, with the relative amount of all molecules concurrently increased in the atherosclerotic plaque. Further, the increase in apatite was disproportionately large in relation to whitlockite in the aortic media directly underlying a plaque, indicating that apatite is more pathologically significant in atherosclerosis-aggravated medial calcification. We also discovered a reduction of β-carotene in the whole aortic intima, including a plaque in atherosclerotic aortic tissues compared to nonatherosclerotic tissues. This unprecedented biomolecular characterization of the aortic tissue furthers our understanding of pathological and physiological cardiovascular calcification events in humans.
Kotit S, Said K, ElFaramawy A, et al., 2017, Prevalence and prognostic value of echocardiographic screening for rheumatic heart disease, OPEN HEART, Vol: 4, ISSN: 2053-3624
Yacoub MH, Bonow RO, 2017, Editors' page., Glob Cardiol Sci Pract, Vol: 2017, Pages: e201716-e201716, ISSN: 2305-7823
Krishnamoorthy N, Tseng Y-T, Gajendrarao P, et al., 2017, A Strategy to Enhance Secretion of Extracellular Matrix Components by Stem Cells: Relevance to Tissue Engineering., Tissue Engineering: Parts A, B, and C, Vol: 24, Pages: 145-156, ISSN: 1937-3341
The ability of cells to secrete extracellular matrix proteins is an important property in the repair, replacement, and regeneration of living tissue. Cells that populate tissue-engineered constructs need to be able to emulate these functions. The motifs, KTTKS or palmitoyl-KTTKS (peptide amphiphile), have been shown to stimulate production of collagen and fibronectin in differentiated cells. Molecular modeling was used to design different forms of active peptide motifs to enhance the efficacy of peptides to increase collagen and fibronectin production using terminals KTTKS/SKTTK/SKTTKS connected by various hydrophobic linkers, V4A3/V4A2/A4G3. Molecular dynamic simulations showed SKTTKS-V4A3-SKTTKS (P3), with palindromic (SKTTKS) motifs and SKTTK-V4A2-KTTKS (P5), maintained structural integrity and favorable surface electrostatic distributions that are required for functionality. In vitro studies showed that peptides, P3 and P5, showed low toxicity to human adipose-derived stem cells (hADSCs) and significantly increased the production of collagen and fibronectin in a concentration-dependent manner compared with the original active peptide motif. The 4-day treatment showed that stem cell markers of hADSCs remained stable with P3. The molecular design of novel peptides is a promising strategy for the development of intelligent biomaterials to guide stem cell function for tissue engineering applications.
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