Publications
308 results found
Miragoli M, Sanchez Alonso JL, Bhargava A, et al., 2015, Microtubule-dependent mitochondria alignment regulates calcium release in response to nanomechanical stimulus in heart myocytes, Cell Reports, Vol: 14, Pages: 140-151, ISSN: 2211-1247
Arrhythmogenesis during heart failure is a major clinical problem. Regional electrical gradients produce arrhythmias, and cellular ionic transmembrane gradients are its originators. We investigated whether the nanoscale mechanosensitive properties of cardiomyocytes from failing hearts have a bearing upon the initiation of abnormal electrical activity. Hydrojets through a nanopipette indent specific locations on the sarcolemma and initiate intracellular calcium release in both healthy and heart failure cardiomyocytes, as well as in human failing cardiomyocytes. In healthy cells, calcium is locally confined, whereas in failing cardiomyocytes, calcium propagates. Heart failure progressively stiffens the membrane and displaces sub-sarcolemmal mitochondria. Colchicine in healthy cells mimics the failing condition by stiffening the cells, disrupting microtubules, shifting mitochondria, and causing calcium release. Uncoupling the mitochondrial proton gradient abolished calcium initiation in both failing and colchicine-treated cells. We propose the disruption of microtubule-dependent mitochondrial mechanosensor microdomains as a mechanism for abnormal calcium release in failing heart.
Lyon AR, 2015, Disparate worlds drawing closer together: cardiovascular biomarkers predict cancer outcomes in treatment-naive patients, Heart, Vol: 101, Pages: 1853-1854, ISSN: 1468-201X
Lyon A, Bossone E, Schneider B, et al., 2015, Current state of knowledge on Takotsubo Syndrome: a Position Statement from the Taskforceon Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology, European Journal of Heart Failure, Vol: 18, Pages: 8-27, ISSN: 1879-0844
Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognised inmodern cardiology practice. This Position Statement from the ESC Heart Failure Association providesa comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome,including nomenclature, definition and diagnosis, primary and secondary clinical subtypes,anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications,prognosis, clinical investigations and treatment approaches. Novel structured approaches to diagnosis,risk stratification, and management are presented with new algorithms to aid decision-making bypractising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayedpresentation) and the management of complex cases with ongoing symptoms after recovery, recurrentepisodes or spontaneous presentation. The unmet needs and future directions for research in thissyndrome are also discussed.
Greenberg B, Butler J, Felker GM, et al., 2015, CUPID 2: A Phase 2b Trial Investigating the Efficacy and Safety of the Intracoronary Administration of AAV1/SERCA2a in Patients with Advanced Heart Failure, 19th Annual Scientific Meeting of the Heart-Failure-Society-of-America, Publisher: Elsevier, Pages: 939-940, ISSN: 1071-9164
Ng FS, Lyon AR, Shadi IT, et al., 2015, Modulation of Gap Junctional Coupling as an Anti-Arrhythmic Strategy to Prevent Reperfusion Ventricular Fibrillation, SET for Britain 2010 (House of Commons, UK Parliament)
Ng FS, Lyon AR, Shadi IT, et al., 2015, Gap Junctional Uncoupling with Carbenoxolone Slows Conduction and Increases Vulnerability to Ventricular Arrhythmias in Structurally Normal Hearts: An Optical Mapping Study, British Cardiovascular Society Annual Conference 2010, Pages: A5-A6
Izgi C, Ray S, Nyktari E, et al., 2015, Myocardial edema in Takotsubo syndrome mimicking apical hypertrophic cardiomyopathy: An insight into diagnosis by cardiovascular magnetic resonance, Heart & Lung, Vol: 44, Pages: 481-485, ISSN: 0147-9563
Myocardial edema is one of the characteristic features in the pathogenesis of Takotsubo syndrome. We report a middle aged man who presented with typical clinical and echocardiographic features of apical variant of Takotsubo syndrome. However, a cardiovascular magnetic resonance study performed 10 days after presentation did not show any apical ‘ballooning’ but revealed features of an apical hypertrophic cardiomyopathy on cine images. Tissue characterization with T2 weighted images proved severe edema as the cause of significantly increased apical wall thickness. A follow-up cardiovascular magnetic resonance study was performed 5 months later which showed that edema, wall thickening and the appearance of apical hypertrophic cardiomyopathy all resolved, confirming Takotsubo syndrome as the cause of the initial appearance. As the affected myocardium most commonly involves the apical segments, an edema induced increase in apical wall thickness may lead to appearances of an apical hypertrophic cardiomyopathy rather than apical ballooning in the acute to subacute phase of Takotsubo syndrome.
Dyer BT, Elder JM, Lagarto J, et al., 2015, Application of label-free autofluorescence lifetime in vivo to measure changes in myocardial fibrosis and metabolism in a doxorubicin cardiomyopathy heart failure model, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 151-151, ISSN: 0195-668X
Akashi YJ, Nef HM, Lyon AR, 2015, Epidemiology and pathophysiology of Takotsubo syndrome, NATURE REVIEWS CARDIOLOGY, Vol: 12, Pages: 387-397, ISSN: 1759-5002
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- Citations: 214
Patel HC, Otero S, Moser JB, et al., 2015, A cross-sectional imaging study to identify organs at risk of thermal injury during renal artery sympathetic denervation, International Journal of Cardiology, Vol: 197, Pages: 235-240, ISSN: 1874-1754
BackgroundThe technology used to perform catheter-based renal artery sympathetic denervation has evolved: catheters can now access arteries as small as 3 mm in diameter and create ablation zones of up to 10 mm in depth. Recent evidence suggests that the procedure may be more effective if a more thorough ablation strategy is employed. Limited data are available regarding inadvertent soft tissue thermal injury during such procedures. We used computed tomography (CT) to identify structures lying within the expected thermal ablation field or the ‘at risk zone’ (ARZ).Methods63 consecutive CT aortograms were reviewed, yielding 100 renal arteries anatomically eligible for treatment. Structures lying within a predefined ARZ (within 10 mm of the renal artery wall) were recorded.ResultsThe 63 subjects had a mean age of 74.6 years, 48% were males and 88% had hypertension. The inferior vena cava and renal veins were in the ARZ in all cases. Psoas muscles and small bowel were within the ARZ in at least a fifth of the kidneys. Other structures found in the ARZ included the liver, pancreas, adrenal glands and diaphragm.ConclusionsThis study describes the variable anatomical relationship between renal arteries and important abdominal structures that may be exposed to thermal energy during modern denervation procedures. The consequence of delivering such thermal energy to these structures is unknown but clinicians should be alert to the presenting symptoms if these structures are damaged. CT may have a pre-procedure role in assessing this risk.Keywords Renal denervation; Safety; Anatomy; Ablation; Cross-sectional imaging
Shao Y, Redfors B, Ali A, et al., 2015, Takotsubo syndrome and McConnell's phenomenon., International Journal of Cardiology, Vol: 197, Pages: 349-350, ISSN: 1874-1754
Hayward C, Patel H, Lyon A, et al., 2015, GENE THERAPY FOR HEART FAILURE: THE CHALLENGE OF NEUTRALISING ANTIBODIES, British-Cardiac-Society (BCS) Annual Conference on Hearts and Genes, Publisher: BMJ PUBLISHING GROUP, Pages: A24-A24, ISSN: 1355-6037
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- Citations: 1
Dyer BT, Elder JM, Lagarto J, et al., 2015, LABEL-FREE AUTOFLUORESCENCE LIFETIME TO ASSESS CHANGES IN MYOCARDIAL FIBROSIS AND METABOLISM <i>IN VIVO</i> IN A DOXORUBICIN CARDIOMYOPATHY HEART FAILURE MODEL, British-Cardiac-Society (BCS) Annual Conference on Hearts and Genes, Publisher: BMJ PUBLISHING GROUP, Pages: A94-A94, ISSN: 1355-6037
Harris SJ, Maruzzo M, Martin-Liberal J, et al., 2015, Serum troponin surveillance to predict cardiotoxicity of doxorubicin in adults with metastatic sarcoma., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) / Clinical Science Symposium on Predicting and Improving Adverse Outcomes in Older Adults with Cancer, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Citro R, Lyon AR, Silverio A, et al., 2015, Bubbles in ballooning: safety and utility, Journal of The American Society of Echocardiography, Vol: 28, Pages: 845-845, ISSN: 0894-7317
Roca-Alonso L, Castellano L, Mills A, et al., 2015, Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in beta-adrenergic signaling and enhances apoptosis, Cell Death & Disease, Vol: 6, ISSN: 2041-4889
The use of anthracyclines such as doxorubicin (DOX) has improved outcome in cancer patients, yet associated risks ofcardiomyopathy have limited their clinical application. DOX-associated cardiotoxicity is frequently irreversible and typicallyprogresses to heart failure (HF) but our understanding of molecular mechanisms underlying this and essential for development ofcardioprotective strategies remains largely obscure. As microRNAs (miRNAs) have been shown to play potent regulatory roles inboth cardiovascular disease and cancer, we investigated miRNA changes in DOX-induced HF and the alteration of cellularprocesses downstream. Myocardial miRNA profiling was performed after DOX-induced injury, either via acute application toisolated cardiomyocytes or via chronic exposure in vivo, and compared with miRNA profiles from remodeled hearts followingmyocardial infarction. The miR-30 family was downregulated in all three models. We describe here that miR-30 act regulating theβ-adrenergic pathway, where preferential β1- and β2-adrenoceptor (β1AR and β2AR) direct inhibition is combined with Giα-2targeting for fine-tuning. Importantly, we show that miR-30 also target the pro-apoptotic gene BNIP3L/NIX. In aggregate, wedemonstrate that high miR-30 levels are protective against DOX toxicity and correlate this in turn with lower reactive oxygenspecies generation. In addition, we identify GATA-6 as a mediator of DOX-associated reductions in miR-30 expression. Inconclusion, we describe that DOX causes acute and sustained miR-30 downregulation in cardiomyocytes via GATA-6. miR-30overexpression protects cardiac cells from DOX-induced apoptosis, and its maintenance represents a potential cardioprotectiveand anti-tumorigenic strategy for anthracyclines.
Hayward C, Banner NR, Morley-Smith A, et al., 2015, The Current and Future Landscape of SERCA Gene Therapy for Heart Failure: A Clinical Perspective, HUMAN GENE THERAPY, Vol: 26, Pages: 293-304, ISSN: 1043-0342
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- Citations: 28
Moliner-Borja P, Pareek N, Mc Alindon E, et al., 2015, Three years of clinical experience of a cardio-oncology service in the United Kingdom, Publisher: WILEY, Pages: 25-26, ISSN: 1388-9842
Dyer BTB, de Jesus Reis Lagarto J, Sikkel M, et al., 2015, Application of label-free autofluorescence lifetime in vivo to measure changes in myocardial fibrosis and metabolism associated with myocardial infarction and heart failure, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 17, Pages: 367-367, ISSN: 1388-9842
Hayward C, Patel HC, Manohar SG, et al., 2015, Gene therapy for G<sub>M1</sub> gangliosidosis: challenges of translational medicine, ANNALS OF TRANSLATIONAL MEDICINE, Vol: 3, ISSN: 2305-5839
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- Citations: 6
Wright PT, Tranter MH, Morley-Smith A, et al., 2015, Is High-Dose Catecholamine Administration in Small Animals an Appropriate Model for Takotsubo Syndrome? - Reply -, CIRCULATION JOURNAL, Vol: 79, Pages: 898-899, ISSN: 1346-9843
Hayward C, Patel H, Manohar S, et al., 2015, HEART RATE VARIABILITY, ASSESSED IN ONE MINUTE WINDOWS, PROVIDES INSIGHT INTO THE TIME COURSE OF CHANGES IN AUTONOMIC NERVOUS SYSTEM ACTIVITY, Scientific Session of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: A403-A403, ISSN: 0735-1097
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- Citations: 2
Wage R, Patel H, Smith GC, et al., 2015, The utility of magnetic resonance imaging in a trial to assess the effect of renal denervation in heart failure with preserved ejection fraction, Journal of Cardiovascular Magnetic Resonance, Pages: 1-2, ISSN: 1097-6647
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- Citations: 1
Cross MJ, Berridge BR, Clements PJM, et al., 2015, Physiological, pharmacological and toxicological considerations of drug-induced structural cardiac injury, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 172, Pages: 957-974, ISSN: 0007-1188
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- Citations: 50
Shao Y, Redfors B, Ali A, et al., 2015, McConnell's sign - An insight into the pathogenesis of Takotsubo syndrome?, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 178, Pages: 40-43, ISSN: 0167-5273
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- Citations: 8
Lagarto J, Dyer BT, Talbot C, et al., 2015, Application of time-resolved autofluorescence to label-free in vivo optical mapping of changes in tissue matrix and metabolism associated with myocardial infarction and heart failure, Biomedical Optics Express, Vol: 6, Pages: 324-346, ISSN: 2156-7085
We investigate the potential of an instrument combining timeresolvedspectrofluorometry and diffuse reflectance spectroscopy tomeasure structural and metabolic changes in cardiac tissue in vivo in a 16week post-myocardial infarction heart failure model in rats. In the scarregion, we observed changes in the fluorescence signal that can beexplained by increased collagen content, which is in good agreement withhistology. In areas remote from the scar tissue, we measured changes in thefluorescence signal (p < 0.001) that cannot be explained by differences incollagen content and we attribute this to altered metabolism within themyocardium. A linear discriminant analysis algorithm was applied to themeasurements to predict the tissue disease state. When we combine allmeasurements, our results reveal high diagnostic accuracy in the infarctedarea (100%) and border zone (94.44%) as well as in remote regions fromthe scar (> 77%). Overall, our results demonstrate the potential of ourinstrument to characterize structural and metabolic changes in a failing heartin vivo without using exogenous labels.
Citro R, Lyon AR, Meimoun P, et al., 2015, Standard and Advanced Echocardiography in Takotsubo (Stress) Cardiomyopathy: Clinical and Prognostic Implications, JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, Vol: 28, Pages: 57-74, ISSN: 0894-7317
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- Citations: 78
Park JES, Lyon AR, Shao D, et al., 2014, Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models, THORAX, Vol: 69, Pages: 1120-1127, ISSN: 0040-6376
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- Citations: 12
Patel HC, Hayward C, Ozdemir BA, et al., 2014, Magnitude of Blood Pressure Reduction in the Placebo Arms of Modern Hypertension Trials Implications for Trials of Renal Denervation, Hypertension, Vol: 65, Pages: 401-406, ISSN: 1524-4563
Land S, Niederer SA, Louch WE, et al., 2014, Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 307, Pages: H1487-H1496, ISSN: 0363-6135
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- Citations: 20
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