Publications
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Backhaus J, Yacoub L, Kambaris A, et al., 2015, The Burundi Heart Centre: From concept to design., Global Cardiology Science and Practice, Vol: 2015, Pages: 22-22, ISSN: 2305-7823
Burundi is one of the world's poorest nations, which is also reflected in its relative lack of cardiac facilities, particularly those catering to young children and adults. The authors discuss current efforts to build "The Burundi Heart Centre" to help address this challenge. In particular, they highlight how the project can act as a case study for a sustainable architecture that involves local people and uses locally available materials in a contemporary and innovative way.
Simry W, Afifi A, Hosny H, et al., 2015, Anatomic correction of ALCAPA in an adult presenting with sudden cardiac death, Global Cardiology Science and Practice, Vol: 2015
We report on a young adult with ALCAPA, who was successfully resuscitated after collapsing in ventricular fibrillation while playing football. This was followed by anatomical correction of the anomaly with a smooth recovery and return to his daily activities. The advantages of this approach are discussed in this brief report.
Marei I, Carubelli I, Reed DM, et al., 2015, The Interaction between Human Blood Endothelial Cells and Polycaprolactone Scaffolds, 4th TERMIS World Congress, Publisher: MARY ANN LIEBERT, INC, Pages: S151-S151, ISSN: 1937-3341
Aguib H, Torii R, Romeih S, et al., 2015, Characterisation of spatiotemporal aortic flow and aortic wall biomechanics in coarctation, Global Cardiology Science and Practice, Vol: 2015
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- Citations: 3
Marei I, Chester A, Carubelli I, et al., 2015, Assessment of Parylene C Thin Films for Heart Valve Tissue Engineering, TISSUE ENGINEERING PART A, Vol: 21, Pages: 2504-2514, ISSN: 1937-3341
Background: Scaffolds are a key component of tissue-engineered heart valves (TEHVs). Several approaches had been adopted in the design of scaffolds using both natural and synthetic resources. We have investigated the suitability of parylene C (PC), a vapor deposited polymeric material, for the use as a scaffold in TEHV.Aims: To evaluate the adsorption of extracellular matrix components onto plasma-activated PC and study the biocompatibility of PC by measuring cellular adhesion, viability, apoptosis, and phenotypic expression of valve endothelial and interstitial cells. Finally, the mechanical properties of PC were compared with those of native aortic valve cusp tissue.Methods: PC slides were plasma activated and then coated with gelatin, type I collagen, or fibronectin. Porcine pulmonary valve endothelial and interstitial cells were then grown on plasma oxidized PC with different types of coatings and their adhesion was observed after 20 h of incubation. Cell viability was tested using the MTS assay, and apoptosis was estimated using TUNEL staining. The mechanical properties of PC and valve tissue were measured using a Bose Mechanical Tester. Finally, cell-seeded PC films were exposed to pulsatile pressure and aortic shear stress, respectively, to test their durability in a dynamic environment.Results: Our findings show that collagen and fibronectin could bind to plasma oxidized PC. Both valve endothelial and interstitial cells adhered to protein-coated ECM. PC had a profile of mechanical stiffness and ultimate tensile strength that were comparable with or in excess of those seen in porcine aortic valve cusps. Cells were still attached to PC films after 3 days of exposure to up to 50 mmHg pulsatile pressure or aortic levels of shear stress.Conclusion: PC is a promising candidate for use as a scaffold in tissue engineering heart valves. Additional studies are required to determine both the durability and long-term performance of cell-seeded PC when in a
Yacoub MH, 2015, In Search of Living Valve Substitutes, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 66, Pages: 889-891, ISSN: 0735-1097
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- Citations: 20
Ibrahim M, Nader A, Yacoub MH, et al., 2015, Manipulation of sarcoplasmic reticulum Ca<SUP>2+</SUP> release in heart failure through mechanical intervention, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 593, Pages: 3253-3259, ISSN: 0022-3751
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- Citations: 10
Yacoub M, 2015, Erratum: Cardiac donation after circulatory death: A time to reflect (Lancet (2015) 385 (2554-56)), The Lancet, Vol: 385, ISSN: 0140-6736
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- Citations: 2
Yacoub M, 2015, Cardiac donation after circulatory death: a time to reflect., Lancet, Vol: 385, Pages: 2554-2556
Latif N, Quillon A, Sarathchandra P, et al., 2015, Modulation of human valve interstitial cell phenotype and function using a fibroblast growth factor 2 formulation, PLOS One, Vol: 10, ISSN: 1932-6203
Latif N, Sarathchandra P, Chester AH, et al., 2015, Expression of smooth muscle cell markers and co-activators in calcified aortic valves, EUROPEAN HEART JOURNAL, Vol: 36, Pages: 1335-1345, ISSN: 0195-668X
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- Citations: 57
Gajendrarao P, Krishnamoorthy N, Selvaraj S, et al., 2015, An Investigation of the Molecular Mechanism of Double cMyBP-C Mutation in a Patient with End-Stage Hypertrophic Cardiomyopathy, JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, Vol: 8, Pages: 232-243, ISSN: 1937-5387
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- Citations: 13
Sanoudou D, Kolokathis F, Arvanitis D, et al., 2015, Genetic modifiers to the PLN L39X mutation in a patient with DCM and sustained ventricular tachycardia?, Global Cardiology Science and Practice, Vol: 2015, ISSN: 2305-7823
Raafat II, Azab NA, Khorshied MM, et al., 2015, Signal transducer and activator of transcription 4 (STAT4) G/T gene polymorphism in Egyptian systemic lupus erythematosus female patients, EGYPTIAN RHEUMATOLOGIST, Vol: 37, Pages: 75-80, ISSN: 1110-1164
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- Citations: 6
Yacoub MH, 2015, Bridge to Recovery and Myocardial Cell Division A Paradigm Shift?, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 65, Pages: 901-903, ISSN: 0735-1097
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- Citations: 3
Cartledge JE, Kane C, Dias P, et al., 2015, Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by soluble mediators, CARDIOVASCULAR RESEARCH, Vol: 105, Pages: 260-270, ISSN: 0008-6363
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- Citations: 110
El-Sherbiny IM, El-Baz NM, Yacoub MH, 2015, Inhaled nano- and microparticles for drug delivery, Global Cardiology Science and Practice, Vol: 2015, ISSN: 2305-7823
The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems.
Roberts AM, Ware JS, Herman DS, et al., 2015, Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease, Science Translational Medicine, Vol: 7, Pages: 270ra6-270ra6, ISSN: 1946-6234
The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms (using the TTN transcript annotations available at http://cardiodb.org/titin), and demonstrate that these data, coupled with the position of the TTNtv, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause of DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses, we provide evidence for a length-dependent mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings.
Roberts AM, Ware JS, Herman DS, et al., 2015, What Happens When Titins Are Trimmed?, SCIENCE TRANSLATIONAL MEDICINE, Vol: 7, ISSN: 1946-6234
Aguib H, Chapron J, Donya M, et al., 2015, 3D modelling of atrial and ventricular shape and function in a patient following the new modified Mustard operation, Global Cardiology Science and Practice, Vol: 2015
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- Citations: 2
Badran HM, Ibrahim WA, Faheem N, et al., 2015, Provocation of left ventricular outflow tract obstruction using nitrate inhalation in hypertrophic cardiomyopathy: Relation to electromechanical delay, Global Cardiology Science and Practice, Vol: 2015
Background: Left ventricular outflow tract obstruction (LVOT) is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). It is of major importance that the provocation modalities used are validated against each other. Aim: To define the magnitude of LVOT gradients provocation during both isosorbide dinitrate (ISDN) inhalation and treadmill exercise in non-obstructive HCM and analyze the correlation to the electromechanical delay using speckle tracking. Methods: We studied 39 HCM pts (64% males, mean age 38±13 years) regional LV longitudinal strain and electromechanical delay (TTP) was analyzed at rest using speckle tracking. LVOT gradient was measured at rest and after ISDN then patients underwent a treadmill exercise echocardiography (EE) and LVOT gradient was measured at peak exercise. Results: The maximum effect of ISDN on LVOT gradient was obtained at 5 minutes, it increased to a significant level in 12 (31%) patients, and in 14 (36%) patients using EE, with 85.6% sensitivity & 100% specificity. Patients with latent obstruction had larger left atrial volume and lower E/A ratio compared to the non-obstructive group (p<0.01). LVOTG using ISDN was significantly correlated with that using EE (p<0.0001), resting LVOTG (p<0.0001), SAM(p<0.0001), EF%(p<0.02) and regional electromechanical delay but not related to global LV longitudinal strain. Using multivariate regression, resting LVOTG (p=0.006) & TTP mid septum (p=0.01) were found to be independent predictors of latent LVOT obstruction using ISDN. Conclusion: There is a comparable diagnostic value of nitrate inhalation to exercise testing in provocation of LVOT obstruction in HCM. Latent obstruction is predominantly dependent on regional electromechanical delay.
Yacoub M, ElGuindy A, 2015, Towards 'eternal youth' of cardiac and skeletal muscle, Global Cardiology Science and Practice, Vol: 2015
Donya M, Radford M, ElGuindy A, et al., 2014, Radiation in medicine: Origins, risks and aspirations., Global Cardiology Science and Practice, Vol: 2014, Pages: 437-448, ISSN: 2305-7823
The use of radiation in medicine is now pervasive and routine. From their crude beginnings 100 years ago, diagnostic radiology, nuclear medicine and radiation therapy have all evolved into advanced techniques, and are regarded as essential tools across all branches and specialties of medicine. The inherent properties of ionizing radiation provide many benefits, but can also cause potential harm. Its use within medical practice thus involves an informed judgment regarding the risk/benefit ratio. This judgment requires not only medical knowledge, but also an understanding of radiation itself. This work provides a global perspective on radiation risks, exposure and mitigation strategies.
Yacoub M, ElGuindy A, Afifi A, et al., 2014, Taking cardiac surgery to the people., J Cardiovasc Transl Res, Vol: 7, Pages: 797-802
Cardiovascular disease (CVD) is currently the leading cause of mortality in the world, and it is estimated that 80% of the disease burden is encountered in low- and middle-income countries (LMICs). While numerous wake-up calls have been issued in the recent years to face this emerging epidemic, little has been achieved. One particularly deficient area is cardiac surgery. This article aims to address the challenges and barriers to establishing cardiac surgery programs in LMICs and some of the existing efforts to overcome them, focusing on a center in Aswan, Egypt, as an example.
Yacoub M, El-Hamamsy I, 2014, The Ross operation in infants and children, when and how?, Heart, Vol: 100, Pages: 1905-1906
Yacoub MH, 2014, DECADE IN REVIEW-CARDIOMYOPATHIES Cardiomyopathy on the move, NATURE REVIEWS CARDIOLOGY, Vol: 11, Pages: 628-629, ISSN: 1759-5002
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- Citations: 10
El-Sherbiny IM, Elkholi IE, Yacoub MH, 2014, Tissue plasminogen activator-based clot busting: Controlled delivery approaches., Global Cardiology Science and Practice, Vol: 2014, Pages: 336-349, ISSN: 2305-7823
Cardiovascular diseases are the leading cause of death worldwide. Thrombosis, the formation of blood clot (thrombus) in the circulatory system obstructing the blood flow, is one of the main causes behind various ischemic arterial syndromes such as ischemic stroke and myocardial infarction, as well as vein syndromes such as deep vein thrombosis, and consequently, pulmonary emboli. Several thrombolytic agents have been developed for treating thrombosis, the most common being tissue plasminogen activator (tPA), administrated systemically or locally via IV infusion directly proximal to the thrombus, with the aim of restoring and improving the blood flow. TPA triggers the dissolution of thrombi by inducing the conversion of plasminogen to protease plasmin followed by fibrin digestion that eventually leads to clot lysis. Although tPA provides powerful thrombolytic activity, it has many shortcomings, including poor pharmacokinetic profiles, impairment of the reestablishment of normal coronary flow, and impairment of hemostasis, leading to life-threatening bleeding consequences. The bleeding consequence is ascribed to the ability of tPA to circulate throughout the body and therefore can lysis all blood clots in the circulation system, even the good ones that prevent the bleeding and promote injury repair. This review provides an overview of the different delivery approaches for tPA including: liposomes, ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged-tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches.
Colazzo F, Alrashed F, Saratchandra P, et al., 2014, Shear stress and VEGF enhance endothelial differentiation of human adipose-derived stem cells, GROWTH FACTORS, Vol: 32, Pages: 139-149, ISSN: 0897-7194
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- Citations: 40
Navaratnarajah M, Siedlecka U, Ibrahim M, et al., 2014, Impact of Combined Clenbuterol and Metoprolol Therapy on Reverse Remodelling during Mechanical Unloading, PLOS One, Vol: 9, ISSN: 1932-6203
Background: Clenbuterol (Cl), a b2 agonist, is associated with enhanced myocardial recovery during left ventricular assistdevice (LVAD) support, and exerts beneficial remodelling effects during mechanical unloading (MU) in rodent heart failure(HF). However, the specific effects of combined Cl+b1 blockade during MU are unknown.Methods and Results: We studied the chronic effects (4 weeks) of b2-adrenoceptor (AR) stimulation via Cl (2 mg/kg/day)alone, and in combination with b1-AR blockade using metoprolol ((Met), 250 mg/kg/day), on whole heart/cell structure,function and excitation-contraction (EC) coupling in failing (induced by left coronary artery (LCA) ligation), and unloaded(induced by heterotopic abdominal heart transplantation (HATx)) failing rat hearts. Combined Cl+Met therapy displayedfavourable effects in HF: Met enhanced Cl’s improvement in ejection fraction (EF) whilst preventing Cl-induced hypertrophyand tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MUinducedmyocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Metmono-therapy, but these benefits, together with Cl’s enhancement of sarcomeric contraction speed, and MU-inducedrecovery of Ca2+ spark frequency, disappeared during combined therapy.Conclusions: Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appearsinferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined b2-AR simulation +b1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective asmono-therapy in enhancing myocardial recovery during LVAD support.
Carr C, Sanoudou D, Dilawar M, et al., 2014, Whole exome sequencing of a family with 3 sibling affected by bicuspid aortic valve disease, Annual Meeting of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 950-951, ISSN: 0195-668X
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