141 results found
Jabbour R, Owen T, Pandey P, et al., 2021, In vivo grafting of large engineered heart tissue patches for cardiac repair, JCI Insight, Vol: 6, Pages: 1-13, ISSN: 2379-3708
Engineered heart tissue (EHT) strategies, by combining cells within a hydrogel matrix, may be anovel therapy for heart failure. EHTs restore cardiac function in rodent injury models, but more dataare needed in clinically relevant settings. Accordingly, an upscaled EHT patch (2.5 cm × 1.5 cm × 1.5mm) consisting of up to 20 million human induced pluripotent stem cell–derived cardiomyocytes(hPSC-CMs) embedded in a fibrin-based hydrogel was developed. A rabbit myocardial infarctionmodel was then established to test for feasibility and efficacy. Our data showed that hPSC-CMs inEHTs became more aligned over 28 days and had improved contraction kinetics and faster calciumtransients. Blinded echocardiographic analysis revealed a significant improvement in function ininfarcted hearts that received EHTs, along with reduction in infarct scar size by 35%. Vascularizationfrom the host to the patch was observed at week 1 and stable to week 4, but electrical couplingbetween patch and host heart was not observed. In vivo telemetry recordings and ex vivoarrhythmia provocation protocols showed that the patch was not pro-arrhythmic. In summary, EHTsimproved function and reduced scar size without causing arrhythmia, which may be due to the lackof electrical coupling between patch and host heart.
Handa B, Li X, Baxan N, et al., 2021, Ventricular fibrillation mechanism and global fibrillatory organisation are determined by gap junction coupling and fibrosis pattern, Cardiovascular Research, Vol: 117, Pages: 1078-1090, ISSN: 0008-6363
AimsConflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganised multiple-wavelet activation to organised rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.Methods and ResultsOptical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact (CF), diffuse (DiF) and patchy (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum.Enhanced GJ coupling with rotigaptide (n = 10) progressively organised fibrillation in a concentration-dependent manner; increasing FDI (0nM: 0.53±0.04, 80nM: 0.78±0.03, p < 0.001), increasing RA sustained VF time (0nM:44±6%, 80nM: 94±2%, p < 0.001) and stabilised RAs (maximum rotations for a RA; 0nM:5.4±0.5, 80nM: 48.2±12.3, p < 0.001). GJ uncoupling with carbenoxolone progressively disorganised VF; the FDI decreased (0µM: 0.60±0.05, 50µM: 0.17±0.03, p < 0.001) and RA-sustained VF time decreased (0µM: 61±9%, 50µM: 3±2%, p < 0.001).In CF, VF activity was disorganised and the RA-sustained VF time was the lowest (CF: 27±7% versus PF: 75±5%, p < 0.001). Global fibrillatory organisation measured by FDI was highest in PF (PF: 0.67±0.05 versus CF: 0.33±0.03, p < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411&plusm
Pitoulis FG, Nunez-Toldra R, Xiao K, et al., 2021, Remodelling of adult cardiac tissue subjected to physiological and pathological mechanical load in vitro, Cardiovascular Research, ISSN: 0008-6363
Aims:Cardiac remodelling is the process by which the heart adapts to its environment. Mechanical load is a major driver of remodelling. Cardiac tissue culture has been frequently employed for in vitro studies of load-induced remodelling; however, current in vitro protocols (e.g. cyclic stretch, isometric load, and auxotonic load) are oversimplified and do not accurately capture the dynamic sequence of mechanical conformational changes experienced by the heart in vivo. This limits translational scope and relevance of findings.Methods and results:We developed a novel methodology to study chronic load in vitro. We first developed a bioreactor that can recreate the electromechanical events of in vivo pressure–volume loops as in vitro force–length loops. We then used the bioreactor to culture rat living myocardial slices (LMS) for 3 days. The bioreactor operated based on a 3-Element Windkessel circulatory model enabling tissue mechanical loading based on physiologically relevant parameters of afterload and preload. LMS were continuously stretched/relaxed during culture simulating conditions of physiological load (normal preload and afterload), pressure-overload (normal preload and high afterload), or volume-overload (high preload & normal afterload). At the end of culture, functional, structural, and molecular assays were performed to determine load-induced remodelling. Both pressure- and volume-overloaded LMS showed significantly decreased contractility that was more pronounced in the latter compared with physiological load (P < 0.0001). Overloaded groups also showed cardiomyocyte hypertrophy; RNAseq identified shared and unique genes expressed in each overload group. The PI3K-Akt pathway was dysregulated in volume-overload while inflammatory pathways were mostly associated with remodelling in pressure-overloaded LMS.Conclusion:We have developed a proof-of-concept platform and methodology to recreate remodelling under pathophysiol
Mikhail G, Khawaja SA, Mohan P, et al., 2021, COVID-19 and its impact on the cardiovascular system, Open Heart, Vol: 8, Pages: 1-9, ISSN: 2053-3624
Objectives: The clinical impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare NHS Trust, United Kingdom.Methods: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7th March to 7th April 2020. Patient data was collected for baseline demographics, co-morbidities and in-hospital outcomes, especially relating to cardiovascular intervention.Results:Mean age was 67.4±16.1 years and 62.2%(n=310) were male. 64.1%(n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4%(n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%,p<0.001). Only 4 COVID-19 patients had invasive coronary angiography,2 underwent percutaneous coronary intervention and 1 required a permanent pacemaker implantation. 7.0%(n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39,1.31-4.40,p=0.005) and history of hypertension (OR 1.88 ,1.01-3.55,p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for.Conclusion:Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.
Naik M, McNamara C, Jabbour RJ, et al., 2021, Imaging of transcatheter aortic valve replacement complications, CLINICAL RADIOLOGY, Vol: 76, Pages: 27-37, ISSN: 0009-9260
Jabbour RJ, Cook C, Seligman H, et al., 2020, Balloon-Assisted Tracking (BAT) of an Uncrossable Aortic Valve During Transcatheter Aortic Valve Implantation, CARDIOVASCULAR REVASCULARIZATION MEDICINE, Vol: 21, Pages: S33-S35, ISSN: 1553-8389
Malik IS, Jabbour RJ, Ruparelia N, et al., 2020, Rescue Valve-in-Valve-in-Valve TAVR for Acute Transvalvular Aortic Regurgitation, CARDIOVASCULAR REVASCULARIZATION MEDICINE, Vol: 21, Pages: S11-S13, ISSN: 1553-8389
Kalogeras K, Ruparelia N, Kabir T, et al., 2020, Real-world comparison of the last generation main balloon-expandable and self-expanding valves in patients undergoing TAVI. Does the type matter?, Publisher: OXFORD UNIV PRESS, Pages: 1953-1953, ISSN: 0195-668X
Little C, Jabbour R, Kotecha T, et al., 2020, Primary PCI for STEMI During the COVID-19 Pandemic in London: A Systematic Analysis of Pathway Activation and Outcomes, 32nd Annual Transcatheter Cardiovascular Therapeutics Symposium (TCT CONNECT), Publisher: ELSEVIER SCIENCE INC, Pages: B96-B96, ISSN: 0735-1097
Majid QA, Fricker ATR, Gregory DA, et al., 2020, Natural biomaterials for cardiac tissue engineering: a highly biocompatible solution., Frontiers in Cardiovascular Medicine, Vol: 7, Pages: 1-32, ISSN: 2297-055X
Cardiovascular diseases (CVD) constitute a major fraction of the current major global diseases and lead to about 30% of the deaths, i.e., 17.9 million deaths per year. CVD include coronary artery disease (CAD), myocardial infarction (MI), arrhythmias, heart failure, heart valve diseases, congenital heart disease, and cardiomyopathy. Cardiac Tissue Engineering (CTE) aims to address these conditions, the overall goal being the efficient regeneration of diseased cardiac tissue using an ideal combination of biomaterials and cells. Various cells have thus far been utilized in pre-clinical studies for CTE. These include adult stem cell populations (mesenchymal stem cells) and pluripotent stem cells (including autologous human induced pluripotent stem cells or allogenic human embryonic stem cells) with the latter undergoing differentiation to form functional cardiac cells. The ideal biomaterial for cardiac tissue engineering needs to have suitable material properties with the ability to support efficient attachment, growth, and differentiation of the cardiac cells, leading to the formation of functional cardiac tissue. In this review, we have focused on the use of biomaterials of natural origin for CTE. Natural biomaterials are generally known to be highly biocompatible and in addition are sustainable in nature. We have focused on those that have been widely explored in CTE and describe the original work and the current state of art. These include fibrinogen (in the context of Engineered Heart Tissue, EHT), collagen, alginate, silk, and Polyhydroxyalkanoates (PHAs). Amongst these, fibrinogen, collagen, alginate, and silk are isolated from natural sources whereas PHAs are produced via bacterial fermentation. Overall, these biomaterials have proven to be highly promising, displaying robust biocompatibility and, when combined with cells, an ability to enhance post-MI cardiac function in pre-clinical models. As such, CTE has great potential for future clinical solutions and he
Brook J, Kim M-Y, Koutsoftidis S, et al., 2020, Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling, Pflügers Archiv European Journal of Physiology, Vol: 472, Pages: 1435-1446, ISSN: 0031-6768
We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap-junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting Porcine (n=9) and human (n=4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. 1mM of carbenoxolone was administered at 5ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed.We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)max increased between baseline and carbenoxolone (47.9±4.1ms to 67.2±2.7ms) indicating conduction slowing. The features with the largest percentage change between baseline to Carbenoxolone were Fractionation +185.3%, Endpoint amplitude -106.9%, S-Endpoint Gradient +54.9%, S Point, -39.4%, RS Ratio +38.6% and (-dV/dt)max -20.9%.The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically-induced proarrhythmic substrates.
Tsampasian V, Panoulas V, Jabbour RJ, et al., 2020, Left ventricular speckle tracking echocardiographic evaluation before and after TAVI, ECHO RESEARCH AND PRACTICE, Vol: 7, Pages: 29-38, ISSN: 2055-0464
Kalogeras K, Ruparelia N, Kabir T, et al., 2020, Comparison of the self-expanding Evolut-PRO transcatheter aortic valve to its predecessor Evolut-R in the real world multicenter ATLAS registry, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 310, Pages: 120-125, ISSN: 0167-5273
Jabbour RJ, Owen TJ, Pandey P, et al., 2020, IN-VIVO GRAFTING OF LARGE ENGINEERED HEART TISSUE PATCHES FOR CARDIAC REPAIR, Publisher: BMJ PUBLISHING GROUP, Pages: A111-A112, ISSN: 1355-6037
Jabbour RJ, Colombo A, Latib A, 2020, Looking Toward the Post-TAVR Period and Keeping Options Open for Easy Coronary Access, JACC-CARDIOVASCULAR INTERVENTIONS, Vol: 13, Pages: 951-953, ISSN: 1936-8798
Little CD, Kotecha T, Candilio L, et al., 2020, COVID-19 pandemic and STEMI: pathway activation and outcomes from the pan-London heart attack group, OPEN HEART, Vol: 7, ISSN: 2053-3624
Jabbour RJ, Owen TJ, Pandey P, et al., 2019, Future potential of engineered heart tissue patches for repairing the damage caused by heart attacks, EXPERT REVIEW OF MEDICAL DEVICES, Vol: 17, Pages: 1-3, ISSN: 1743-4440
Tanaka A, Jabbour RJ, Colombo A, 2019, What are the remaining lessons to be learnt from 1st-generation bioresorbable scaffolds?, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 293, Pages: 103-104, ISSN: 0167-5273
Kalogeras K, Jabbour RJ, Ruparelia N, et al., 2019, Comparison of warfarin versus DOACs in patients with concomitant indication for oral anticoagulation undergoing TAVI; results from the ATLAS registry, JOURNAL OF THROMBOSIS AND THROMBOLYSIS, Vol: 50, Pages: 82-89, ISSN: 0929-5305
Handa BS, Li X, Mansfield CA, et al., 2019, Ventricular fibrosis spatial distribution and quantity is a key mechanistic determinant of ventricular fibrillation mechanisms, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 896-896, ISSN: 0195-668X
Jabbour R, Owen T, Reinsch M, et al., 2019, Development and preclinical testing of upscaled engineered heart tissue for use in translational studies, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 3273-3273, ISSN: 0195-668X
Harding S, Jabbour R, 2019, Tissue engineering for cardiovascular repair, Annual Conference of the British-Society-for-Gene-and-Cell-Therapy, Publisher: MARY ANN LIEBERT, INC, Pages: A8-A8, ISSN: 1043-0342
Jabbour RJ, Latib A, 2019, The changing landscape of interventional cardiology, AGING-US, Vol: 11, Pages: 2914-2915, ISSN: 1945-4589
Watson S, Duff J, Bardi I, et al., 2019, Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro, Nature Communications, Vol: 10, ISSN: 2041-1723
Adult cardiac tissue undergoes a rapid process of dedifferentiation when cultured outside the body. The in vivo environment, particularly constant electromechanical stimulation, is fundamental to the regulation of cardiac structure and function. We investigated the role of electromechanical stimulation in preventing culture-induced dedifferentiation of adult cardiac tissue using rat, rabbit and human heart failure myocardial slices. Here we report that the application of a preload equivalent to sarcomere length (SL) = 2.2 μm is optimal for the maintenance of rat myocardial slice structural, functional and transcriptional properties at 24 h. Gene sets associated with the preservation of structure and function are activated, while gene sets involved in dedifferentiation are suppressed. The maximum contractility of human heart failure myocardial slices at 24 h is also optimally maintained at SL = 2.2 μm. Rabbit myocardial slices cultured at SL = 2.2 μm remain stable for 5 days. This approach substantially prolongs the culture of adult cardiac tissue in vitro.
Handa B, Li X, Mansfield C, et al., 2019, MYOCARDIAL FIBROSIS AND THE DEGREE OF GAP JUNCTION COUPLING DIRECTLY MODIFIES THE UNDERLYING MECHANISM OF FIBRILLATION, Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A179-A180, ISSN: 1355-6037
Tanaka A, Jabbour RJ, Testa L, et al., 2019, Incidence, Technical Safety, and Feasibility of Coronary Angiography and Intervention Following Self-expanding Transcatheter Aortic Valve Replacement, CARDIOVASCULAR REVASCULARIZATION MEDICINE, Vol: 20, Pages: 371-375, ISSN: 1553-8389
Jabbour R, Owen T, Reinsch M, et al., 2019, DEVELOPMENT AND PRECLINICAL TESTING OF A LARGE HEART MUSCLE PATCH, Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A157-A158, ISSN: 1355-6037
Jabbour RJ, Mikhail GW, 2019, Valve durability - is this the Achilles' heel of TAVI?, EUROINTERVENTION, Vol: 14, Pages: E1544-E1547, ISSN: 1774-024X
Jabbour RJ, Latib A, 2019, The "new" syndrome of delayed coronary obstruction after transcatheter aortic valve replacement, CARDIOVASCULAR REVASCULARIZATION MEDICINE, Vol: 20, Pages: 81-83, ISSN: 1553-8389
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