422 results on '"Sanjay K Prasad"'
Search Results
2. Correction: Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.
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Ulrike Esslinger, Sophie Garnier, Agathe Korniat, Carole Proust, Georgios Kararigas, Martina Müller-Nurasyid, Jean-Philippe Empana, Michael P Morley, Claire Perret, Klaus Stark, Alexander G Bick, Sanjay K Prasad, Jennifer Kriebel, Jin Li, Laurence Tiret, Konstantin Strauch, Declan P O'Regan, Kenneth B Marguiles, Jonathan G Seidman, Pierre Boutouyrie, Patrick Lacolley, Xavier Jouven, Christian Hengstenberg, Michel Komajda, Hakon Hakonarson, Richard Isnard, Eloisa Arbustini, Harald Grallert, Stuart A Cook, Christine E Seidman, Vera Regitz-Zagrosek, Thomas P Cappola, Philippe Charron, François Cambien, and Eric Villard
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0172995.].
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- 2020
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3. Scar shape analysis and simulated electrical instabilities in a non-ischemic dilated cardiomyopathy patient cohort.
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Gabriel Balaban, Brian P Halliday, Wenjia Bai, Bradley Porter, Carlotta Malvuccio, Pablo Lamata, Christopher A Rinaldi, Gernot Plank, Daniel Rueckert, Sanjay K Prasad, and Martin J Bishop
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Biology (General) ,QH301-705.5 - Abstract
This paper presents a morphological analysis of fibrotic scarring in non-ischemic dilated cardiomyopathy, and its relationship to electrical instabilities which underlie reentrant arrhythmias. Two dimensional electrophysiological simulation models were constructed from a set of 699 late gadolinium enhanced cardiac magnetic resonance images originating from 157 patients. Areas of late gadolinium enhancement (LGE) in each image were assigned one of 10 possible microstructures, which modelled the details of fibrotic scarring an order of magnitude below the MRI scan resolution. A simulated programmed electrical stimulation protocol tested each model for the possibility of generating either a transmural block or a transmural reentry. The outcomes of the simulations were compared against morphological LGE features extracted from the images. Models which blocked or reentered, grouped by microstructure, were significantly different from one another in myocardial-LGE interface length, number of components and entropy, but not in relative area and transmurality. With an unknown microstructure, transmurality alone was the best predictor of block, whereas a combination of interface length, transmurality and number of components was the best predictor of reentry in linear discriminant analysis.
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- 2019
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4. Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular magnetic resonance.
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Vassilios S Vassiliou, Paul D Flynn, Claire E Raphael, Simon Newsome, Tina Khan, Aamir Ali, Brian Halliday, Annina Studer Bruengger, Tamir Malley, Pranev Sharma, Subothini Selvendran, Nikhil Aggarwal, Anita Sri, Helen Berry, Jackie Donovan, Willis Lam, Dominique Auger, Stuart A Cook, Dudley J Pennell, and Sanjay K Prasad
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Medicine ,Science - Abstract
BackgroundAortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis.MethodsA total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a).ResultsThirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42).ConclusionThere is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis.
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- 2017
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5. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.
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Ulrike Esslinger, Sophie Garnier, Agathe Korniat, Carole Proust, Georgios Kararigas, Martina Müller-Nurasyid, Jean-Philippe Empana, Michael P Morley, Claire Perret, Klaus Stark, Alexander G Bick, Sanjay K Prasad, Jennifer Kriebel, Jin Li, Laurence Tiret, Konstantin Strauch, Declan P O'Regan, Kenneth B Marguiles, Jonathan G Seidman, Pierre Boutouyrie, Patrick Lacolley, Xavier Jouven, Christian Hengstenberg, Michel Komajda, Hakon Hakonarson, Richard Isnard, Eloisa Arbustini, Harald Grallert, Stuart A Cook, Christine E Seidman, Vera Regitz-Zagrosek, Thomas P Cappola, Philippe Charron, François Cambien, and Eric Villard
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Medicine ,Science - Abstract
AimsDilated cardiomyopathy (DCM) is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS) to assess the contribution of missense variants to sporadic DCM.Methods and results116,855 single nucleotide variants (SNVs) were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-valueConclusionWe identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology.
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- 2017
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6. Associations of genetically predicted vitamin D status and deficiency with the risk of carotid artery plaque: a Mendelian randomization study
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Devendra Meena, Marie-Joe Dib, Jingxian Huang, Alexander Smith, Jian Huang, Amrit S. Lota, Sanjay K. Prasad, Dipender Gill, Abbas Dehghan, and Ioanna Tzoulaki
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Medicine ,Science - Abstract
Abstract Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (βCAC = − 0.14, P = 0.23; βcIMT = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.
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- 2024
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7. Heterogeneity of Fractional Anisotropy and Mean Diffusivity Measurements by In Vivo Diffusion Tensor Imaging in Normal Human Hearts.
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Laura-Ann McGill, Andrew D Scott, Pedro F Ferreira, Sonia Nielles-Vallespin, Tevfik Ismail, Philip J Kilner, Peter D Gatehouse, Ranil de Silva, Sanjay K Prasad, Archontis Giannakidis, David N Firmin, and Dudley J Pennell
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Medicine ,Science - Abstract
Cardiac diffusion tensor imaging (cDTI) by cardiovascular magnetic resonance has the potential to assess microstructural changes through measures of fractional anisotropy (FA) and mean diffusivity (MD). However, normal variation in regional and transmural FA and MD is not well described.Twenty normal subjects were scanned using an optimised cDTI sequence at 3T in systole. FA and MD were quantified in 3 transmural layers and 4 regional myocardial walls.FA was higher in the mesocardium (0.46 ±0.04) than the endocardium (0.40 ±0.04, p≤0.001) and epicardium (0.39 ±0.04, p≤0.001). On regional analysis, the FA in the septum was greater than the lateral wall (0.44 ±0.03 vs 0.40 ±0.05 p = 0.04). There was a transmural gradient in MD increasing towards the endocardium (epicardium 0.87 ±0.07 vs endocardium 0.91 ±0.08×10-3 mm2/s, p = 0.04). With the lateral wall (0.87 ± 0.08×10-3 mm2/s) as the reference, the MD was higher in the anterior wall (0.92 ±0.08×10-3 mm2/s, p = 0.016) and septum (0.92 ±0.07×10-3 mm2/s, p = 0.028). Transmurally the signal to noise ratio (SNR) was greatest in the mesocardium (14.5 ±2.5 vs endocardium 13.1 ±2.2, p
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- 2015
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8. Machine learning analysis of complex late gadolinium enhancement patterns to improve risk prediction of major arrhythmic events
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Hassan A. Zaidi, Richard E. Jones, Daniel J. Hammersley, Suzan Hatipoglu, Gabriel Balaban, Lukas Mach, Brian P. Halliday, Pablo Lamata, Sanjay K. Prasad, and Martin J. Bishop
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late gadolinium enhanced ,cardiovascular magnetic resonance ,sudden cardiac death ,coronary artery disease ,arrhythmic risk stratification ,scar heterogeneity ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundMachine learning analysis of complex myocardial scar patterns affords the potential to enhance risk prediction of life-threatening arrhythmia in stable coronary artery disease (CAD).ObjectiveTo assess the utility of computational image analysis, alongside a machine learning (ML) approach, to identify scar microstructure features on late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) that predict major arrhythmic events in patients with CAD.MethodsPatients with stable CAD were prospectively recruited into a CMR registry. Shape-based scar microstructure features characterizing heterogeneous (‘peri-infarct’) and homogeneous (‘core’) fibrosis were extracted. An ensemble of machine learning approaches were used for risk stratification, in addition to conventional analysis using Cox modeling.ResultsOf 397 patients (mean LVEF 45.4 ± 16.0) followed for a median of 6 years, 55 patients (14%) experienced a major arrhythmic event. When applied within an ML model for binary classification, peri-infarct zone (PIZ) entropy, peri-infarct components and core interface area outperformed a model representative of the current standard of care (LVEFClass I): AUROC (95%CI) 0.81 (0.81–0.82) vs. 0.64 (0.63–0.65), p = 0.002. In multivariate cox regression analysis, these features again remained significant after adjusting for LVEFClass I: PIZ entropy hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.38–2.56, p
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- 2023
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9. Explainable Anatomical Shape Analysis Through Deep Hierarchical Generative Models.
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Carlo Biffi, Juan J. Cerrolaza, Giacomo Tarroni, Wenjia Bai, Antonio de Marvao, Ozan Oktay, Christian Ledig, Loïc Le Folgoc, Konstantinos Kamnitsas, Georgia Doumou, Jinming Duan 0001, Sanjay K. Prasad, Stuart A. Cook, Declan P. O'Regan, and Daniel Rueckert
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- 2020
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10. 3D Electrophysiological Modeling of Interstitial Fibrosis Networks and Their Role in Ventricular Arrhythmias in Non-Ischemic Cardiomyopathy.
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Gabriel Balaban, Caroline Mendonça Costa, Bradley Porter, Brian Halliday, Christopher A. Rinaldi, Sanjay K. Prasad, Gernot Plank, Tevfik F. Ismail, and Martin J. Bishop 0001
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- 2020
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11. The Effects of Non-ischemic Fibrosis Texture and Density on Mechanisms of Reentry.
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Gabriel Balaban, Caroline Mendonça Costa, Brian Halliday, Bradley Porter, Wenjia Bai, Gernot Plank, Christopher A. Rinaldi, Daniel Rueckert, Sanjay K. Prasad, and Martin J. Bishop 0001
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- 2018
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12. Learning Interpretable Anatomical Features Through Deep Generative Models: Application to Cardiac Remodeling.
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Carlo Biffi, Ozan Oktay, Giacomo Tarroni, Wenjia Bai, Antonio M. Simoes Monteiro de Marvao, Georgia Doumou, Martin Rajchl, Reem Bedair, Sanjay K. Prasad, Stuart A. Cook, Declan P. O'Regan, and Daniel Rueckert
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- 2018
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13. Comprehensive Phenotypic Characterization of Late Gadolinium Enhancement Predicts Sudden Cardiac Death in Coronary Artery Disease
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Richard E. Jones, Hassan A. Zaidi, Daniel J. Hammersley, Suzan Hatipoglu, Ruth Owen, Gabriel Balaban, Antonio de Marvao, François Simard, Amrit S. Lota, Ciara Mahon, Batool Almogheer, Lukas Mach, Francesca Musella, Xiuyu Chen, John Gregson, Laura Lazzari, Andrew Ravendren, Francisco Leyva, Shihua Zhao, Ali Vazir, Pablo Lamata, Brian P. Halliday, Dudley J. Pennell, Martin J. Bishop, and Sanjay K. Prasad
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Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine - Abstract
Background Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD). Objectives The authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD). Methods Patients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD. Results Of 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell’s C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell’s C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models. Conclusions Comprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in implantable cardioverter-defibrillator (ICD) insertion guidelines. These results signify the potential for a more personalized approach to determining ICD candidacy in CAD.
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- 2023
14. Magnetic resonance imaging mimicking pathology detects myocardial fibrosis: a door to hope for improving the whole course management
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Minjie Lu, Leyi Zhu, Sanjay K. Prasad, and Shihua Zhao
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Multidisciplinary - Published
- 2023
15. Energy-efficient resource allocation with a combinatorial auction pricing mechanism
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Sanjay K. Prasad, Puja S. Prasad, and Nupur Neti
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Computational Theory and Mathematics ,Artificial Intelligence ,Computer Networks and Communications ,Applied Mathematics ,Electrical and Electronic Engineering ,Computer Science Applications ,Information Systems - Published
- 2022
16. Explainable Shape Analysis through Deep Hierarchical Generative Models: Application to Cardiac Remodeling.
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Carlo Biffi, Juan J. Cerrolaza, Giacomo Tarroni, Wenjia Bai, Ozan Oktay, Loïc Le Folgoc, Konstantinos Kamnitsas, Antonio de Marvao, Georgia Doumou, Jinming Duan 0001, Sanjay K. Prasad, Stuart A. Cook, Declan P. O'Regan, and Daniel Rueckert
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- 2019
17. Performance of artificial intelligence for biventricular cardiovascular magnetic resonance volumetric analysis in the clinical setting
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Suzan Hatipoglu, Raad H. Mohiaddin, Peter Gatehouse, Francisco Alpendurada, A. John Baksi, Cemil Izgi, Sanjay K. Prasad, Dudley J. Pennell, and Sylvia Krupickova
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Magnetic Resonance Spectroscopy ,Artificial Intelligence ,Predictive Value of Tests ,Humans ,Stroke Volume ,Ventricular Function, Left - Abstract
Background Cardiovascular magnetic resonance (CMR) derived ventricular volumes and function guide clinical decision-making for various cardiac pathologies. We aimed to evaluate the efficiency and clinical applicability of a commercially available artificial intelligence (AI) method for performing biventricular volumetric analysis. Methods Three-hundred CMR studies (100 with normal CMR findings, 50 dilated cardiomyopathy, 50 hypertrophic cardiomyopathy, 50 ischaemic heart disease and 50 congenital or valvular heart disease) were randomly selected from database. Manual biventricular volumetric analysis (CMRtools) results were derived from clinical reports and automated volumetric analyses were performed using short axis volumetry AI function of CircleCVI42v5.12 software. For 20 studies, a combined method of manually adjusted AI contours was tested and all three methods were timed. Clinicians` confidence in AI method was assessed using an online survey. Results Although agreement was better for left ventricle than right ventricle, AI analysis results were comparable to manual method. Manual adjustment of AI contours further improved agreement: within subject coefficient of variation decreased from 5.0–4.5% for left ventricular ejection fraction (EF) and from 9.9–7.1% for right ventricular EF. Twenty manual analyses were performed in 250min12s whereas same task took 5min48s using AI method. Clinicians were open to adopt AI but concerns about accuracy and validity were raised. Conclusions The AI method provides clinically valid outcomes and saves significant time. To address concerns raised by survey participants and overcome shortcomings of the automated myocardial segmentation, visual assessment of contours and performing manual corrections where necessary appears to be a practical approach.
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- 2022
18. Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data
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Upasana Tayal, Job A.J. Verdonschot, Mark R. Hazebroek, James Howard, John Gregson, Simon Newsome, Ankur Gulati, Chee Jian Pua, Brian P. Halliday, Amrit S. Lota, Rachel J. Buchan, Nicola Whiffin, Lina Kanapeckaite, Resham Baruah, Julian W.E. Jarman, Declan P. O’Regan, Paul J.R. Barton, James S. Ware, Dudley J. Pennell, Bouke P. Adriaans, Sebastiaan C.A.M. Bekkers, Jackie Donovan, Michael Frenneaux, Leslie T. Cooper, James L. Januzzi, John G.F. Cleland, Stuart A. Cook, Rahul C. Deo, Stephane R.B. Heymans, Sanjay K. Prasad, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - B06 Imaging, RS: Carim - H01 Clinical atrial fibrillation, MUMC+: MA Cardiologie (9), MUMC+: MA Med Staf Spec Cardiologie (9), FONDATION LEDUCQ, and Imperial College Healthcare NHS Trust- BRC Funding
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Cardiomyopathy, Dilated ,Male ,Proteomics ,Cardiac & Cardiovascular Systems ,STRATEGIES ,Cardiomyopathy ,heart ,1117 Public Health and Health Services ,proteomics ,Humans ,POSITION STATEMENT ,1102 Cardiorespiratory Medicine and Haematology ,Science & Technology ,Dilated/diagnosis ,Stroke Volume ,Middle Aged ,R1 ,Fibrosis ,machine learning ,Cardiovascular System & Hematology ,Creatinine ,Cardiomyopathy, Dilated/diagnosis ,Cardiovascular System & Cardiology ,ESC WORKING GROUP ,Female ,Cardiology and Cardiovascular Medicine ,Cardiomyopathies ,Life Sciences & Biomedicine - Abstract
BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine. ispartof: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY vol:79 issue:22 pages:2219-2232 ispartof: location:United States status: published
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- 2022
19. Role of Targeted Therapy in Dilated Cardiomyopathy: The Challenging Road Toward a Personalized Approach
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Job A. J. Verdonschot, Mark R. Hazebroek, James S. Ware, Sanjay K. Prasad, and Stephane R. B. Heymans
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dilated cardiomyopathy ,personalized ,phenotyping ,therapy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2019
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20. Diastolic Ventricular Interaction in Heart Failure With Preserved Ejection Fraction
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Sathish K. Parasuraman, Brodie L. Loudon, Crystal Lowery, Donnie Cameron, Satnam Singh, Konstantin Schwarz, Nicholas D. Gollop, Amelia Rudd, Fergus McKiddie, Jim J. Phillips, Sanjay K. Prasad, Andrew M. Wilson, Srijita Sen‐Chowdhry, Allan Clark, Vassilios S. Vassiliou, Dana K. Dawson, and Michael P. Frenneaux
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diastolic ventricular interaction ,exercise pulmonary hypertension ,heart failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Exercise‐induced pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). We hypothesized that this could result in pericardial constraint and diastolic ventricular interaction in some patients during exercise. Methods and Results Contrast stress echocardiography was performed in 30 HFpEF patients, 17 hypertensive controls, and 17 normotensive controls (healthy). Cardiac volumes, and normalized radius of curvature (NRC) of the interventricular septum at end‐diastole and end‐systole, were measured at rest and peak‐exercise, and compared between the groups. The septum was circular at rest in all 3 groups at end‐diastole. At peak‐exercise, end‐systolic NRC increased to 1.47±0.05 (P
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- 2019
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21. A genotype-phenotype taxonomy of hypertrophic cardiomyopathy
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Lara Curran, Antonio de Marvao, Paolo Inglese, Kathryn A McGurk, Pierre-Raphaël Schiratti, Adam Clement, Sean L Zheng, Surui Li, Chee Jian Pua, Mit Shah, Mina Jafari, Pantazis Theotokis, Rachel J Buchan, Sean J Jurgens, Claire E Raphael, Arun John Baksi, Antonis Pantazis, Brian P Halliday, Dudley J Pennell, Wenjia Bai, Calvin W L Chin, Rafik Tadros, Connie R Bezzina, Hugh Watkins, Stuart A Cook, Sanjay K Prasad, James S Ware, and Declan P O’Regan
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BackgroundHypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes but there is no systematic framework for classifying morphology or assessing associated risks. Here we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression.MethodsWe enrolled 436 HCM patients (median age 60 years; 28.8% women) with clinical, genetic and imaging data. An independent cohort of 60 HCM patients from Singapore (median age 59 years; 11% women) and a reference population from UK Biobank (n = 16,691, mean age 55 years; 52.5% women) were also recruited. We used machine learning to analyse the three-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree.ResultsCarriers of pathogenic or likely pathogenic variants for HCM (P/LP) variants had lower left ventricular mass, but greater basal septal hypertrophy, with reduced lifespan (mean follow-up 9.9 years) compared to genotype negative individuals (hazard ratio: 2.66; 95% confidence interval [CI]: 1.42-4.96;P< 0.002). Four main phenotypic branches were identified using unsupervised learning of three-dimensional shape: 1) non-sarcomeric hypertrophy with co-existing hypertension; 2) diffuse and basal asymmetric hypertrophy associated with outflow tract obstruction; 3) isolated basal hypertrophy; 4) milder non-obstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for P/LP variants: 2.18 [95% CI: 1.93-2.28,P= 0.0001]). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalisable to an independent cohort (trustworthinessM1: 0.86-0.88).ConclusionsWe report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.
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- 2023
22. 13 Myocardial fibrosis entropy is associated with life-threatening arrhythmia in non-ischaemic cardiomyopathy
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Daniel J Hammersley, Hassan A Zaidi, Richard E Jones, Suzan Hatipoglu, Emmanuel Androulakis, Lukas Mach, Amrit S Lota, Upasana Tayal, Zohya Khalique, Antonio De Marvao, Resham Baruah, Kaushik Guha, Dudley J Pennell, Brian P Halliday, Martin J Bishop, and Sanjay K Prasad
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- 2023
23. 32 Myocardial fibrosis predicts ventricular arrhythmias and sudden death after cardiac electronic device implantation
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Francisco Leyva, Abbasin Zegard, Osita Okafor, Paul Foley, Fraz Umar, Robin J Taylor, Howard Marshall, Berthold Stegemann, William Moody, Richard P Steeds, Brian P Halliday, Daniel J Hammersley, Richard E Jones, Sanjay K Prasad, and Tian Qiu
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- 2023
24. Genetic Architecture of Acute Myocarditis and the Overlap with Inherited Cardiomyopathy
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Amrit S. Lota, Mark R. Hazebroek, Pantazis Theotokis, Rebecca Wassall, Sara Salmi, Brian P. Halliday, Upasana Tayal, Job Verdonschot, Devendra Meena, Ruth Owen, Antonio de Marvao, Alma Iacob, Momina Yazdani, Daniel J. Hammersley, Richard E. Jones, Riccardo Wage, Rachel Buchan, Fredrik Vivian, Yakeen Hafouda, Michela Noseda, John Gregson, Tarun Mittal, Joyce Wong, Jan Lukas Robertus, A. John Baksi, Vassilios Vassiliou, Ioanna Tzoulaki, Antonis Pantazis, John G.F. Cleland, Paul J.R. Barton, Stuart A. Cook, Dudley J. Pennell, Pablo Garcia-Pavia, Leslie T. Cooper, Stephane Heymans, James S. Ware, Sanjay K. Prasad, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), British Heart Foundation, Medical Research Council (Reino Unido), Wellcome Trust, Fondation Leducq, Instituto de Salud Carlos III, Fundación ProCNIC, Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España), and Ministerio de Ciencia (España)
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Cardiomyopathy, Dilated ,Adult ,Male ,Cardiomyopathy ,Arrhythmogenic right ventricular dysplasia ,Heart failure ,Heart ,Stroke Volume ,Middle Aged ,Ventricular Function, Left ,Myocarditis ,Desmoplakins ,Physiology (medical) ,Dilated ,Humans ,Female ,Cardiology and Cardiovascular Medicine - Abstract
Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterized cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared with
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- 2022
25. Lowering the Recommended Maximal Wall Thickness Threshold Improves Diagnostic Sensitivity in Asians With Hypertrophic Cardiomyopathy
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Jennifer Bryant, Annette Schumacher-Maurer, Sanjay K Prasad, Benjamin Huang, Hak-Chiaw Tang, Ben Corden, Thu-Thao Le, Vineet Tornekar, Briana Ang, Chee Jian Pua, Stuart A. Cook, Calvin W. L. Chin, and Desiree-Faye Toh
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medicine.medical_specialty ,asymmetrical hypertrophy ,business.industry ,Hypertrophic cardiomyopathy ,Body size ,medicine.disease ,hypertrophic cardiomyopathy ,cardiovascular magnetic resonance ,sex-specific diagnostic thresholds ,Internal medicine ,RC666-701 ,cardiovascular system ,Cardiology ,Medicine ,Diseases of the circulatory (Cardiovascular) system ,cardiovascular diseases ,business ,Wall thickness ,Sensitivity (electronics) - Abstract
Background: Hypertrophic cardiomyopathy (HCM) is defined as left ventricular end-diastolic maximal wall thickness (WTMax) ≥15.0 mm, without accounting for ethnicity, sex, and body size. It is well-established that Asians have smaller hearts than do Caucasians. Objectives: This study aims to examine the implications of this single absolute WTMax threshold on the diagnosis of HCM in Asians. Methods: The study consisted of 360 healthy volunteers (male: n = 174; age: 50 ± 12 years) and 114 genetically characterized patients with HCM (male: n = 83; age: 52 ± 13 years; genotype-positive, n = 39). All participants underwent cardiovascular magnetic resonance. WTMax was measured semiautomatically at end-diastole according to the standard 16 myocardial segments. Results: Healthy male volunteers had increased WTMax compared with that of female volunteers (8.4 ± 1.2 mm vs 6.6 ± 1.1 mm, respectively; P < 0.001). Conversely, WTMax was similar between male and female patients with HCM (15.2 ± 3.4 mm vs 14.7 ± 3.0 mm, respectively; P = 0.484) and between those with and without a pathogenic gene variant (P = 0.828). Using the recommended diagnostic threshold of 15.0 mm, 56 patients with HCM had WTMax 15.0 mm (specificity of 100% and sensitivity of 51%). Lowering WTMax thresholds to 10.0 mm in female patients and 12.0 mm in male patients did not affect specificity (100%) but significantly improved sensitivity (84%). Despite lower left ventricular mass, female patients with HCM demonstrated more features of adverse cardiac remodeling than did male patients: increased myocardial fibrosis, higher asymmetric ratio, and disproportionately worse myocardial strain. Conclusions: The study highlights cautious application of guideline-recommended WTMax to diagnose HCM in Asians. Lowering WTMax to account for ethnicity and sex improves diagnostic sensitivity without compromising specificity.
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- 2021
26. Moderate excess alcohol consumption and adverse cardiac remodelling in dilated cardiomyopathy
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Inga Voges, Amrit Lota, Resham Baruah, Paul J.R. Barton, James S. Ware, John Gregson, Sanjay K Prasad, Nicola Whiffin, Brian P Halliday, Julian W.E. Jarman, Dudley J. Pennell, Angharad M. Roberts, Michael P. Frenneaux, A. John Baksi, Rachel Buchan, Upasana Tayal, Stuart A. Cook, and John G.F. Cleland
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Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Alcohol Drinking ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Alcoholic cardiomyopathy ,Left ventricular hypertrophy ,Ventricular Function, Left ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Ventricular Remodeling ,business.industry ,Cardiomyopathy, Alcoholic ,Dilated cardiomyopathy ,Prognosis ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,Ventricle ,Heart failure ,Cohort ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Cohort study - Abstract
ObjectiveThe effect of moderate excess alcohol consumption is widely debated and has not been well defined in dilated cardiomyopathy (DCM). There is need for a greater evidence base to help advise patients. We sought to evaluate the effect of moderate excess alcohol consumption on cardiovascular structure, function and outcomes in DCM.MethodsProspective longitudinal observational cohort study. Patients with DCM (n=604) were evaluated for a history of moderate excess alcohol consumption (UK government guidelines; >14 units/week for women, >21 units/week for men) at cohort enrolment, had cardiovascular magnetic resonance and were followed up for the composite endpoint of cardiovascular death, heart failure and arrhythmic events. Patients meeting criteria for alcoholic cardiomyopathy were not recruited.ResultsDCM patients with a history of moderate excess alcohol consumption (n=98, 16%) had lower biventricular function and increased chamber dilatation of the left ventricle, right ventricle and left atrium, as well as increased left ventricular hypertrophy compared with patients without moderate alcohol consumption. They were more likely to be male (alcohol excess group: n=92, 94% vs n=306, 61%, p=ConclusionDCM patients with moderate excess alcohol consumption have adverse cardiac structure and function at presentation, but this is largely due to biological sex. Alcohol may contribute to sex-specific phenotypic differences in DCM. These findings help to inform lifestyle discussions for patients with DCM.
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- 2021
27. The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of aetiology in dilated cardiomyopathy
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Ravi J. Amin, Deborah Morris-Rosendahl, Mat Edwards, Upasana Tayal, Rachel Buchan, Daniel J. Hammersley, Richard E. Jones, Sabiha Gati, Zohya Khalique, Batool Almogheer, Dudley J. Pennell, Arun John Baksi, Antonis Pantazis, James S. Ware, Sanjay K. Prasad, Brian P. Halliday, British Heart Foundation, National Heart & Lung Institute Foundation, and Sir Jules Thorn Charitable Trust
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Cardiology and Cardiovascular Medicine - Abstract
BackgroundGuidelines recommend genetic testing and cardiovascular magnetic resonance (CMR) for the investigation of dilated cardiomyopathy (DCM). However, the incremental value is unclear. We assessed the impact of these investigations in determining etiology.MethodsSixty consecutive patients referred with DCM and recruited to our hospital biobank were selected. Six independent experts determined the etiology of each phenotype in a step-wise manner based on (1) routine clinical data, (2) clinical and genetic data and (3) clinical, genetic and CMR data. They indicated their confidence (1-3) in the classification and any changes to management at each step.ResultsSix physicians adjudicated 60 cases. The addition of genetics and CMR resulted in 57 (15.8%) and 26 (7.2%) changes in the classification of etiology, including an increased number of genetic diagnoses and a reduction in idiopathic diagnoses. Diagnostic confidence improved at each step (p < 0.0005). The number of diagnoses made with low confidence reduced from 105 (29.2%) with routine clinical data to 71 (19.7%) following the addition of genetics and 37 (10.3%) with the addition of CMR. The addition of genetics and CMR led to 101 (28.1%) and 112 (31.1%) proposed changes to management, respectively. Interobserver variability showed moderate agreement with clinical data (κ = 0.44) which improved following the addition of genetics (κ = 0.65) and CMR (κ = 0.68).ConclusionWe demonstrate that genetics and CMR, frequently changed the classification of etiology in DCM, improved confidence and interobserver variability in determining the diagnosis and had an impact on proposed management.
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- 2022
28. Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy
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John Farrant, Susanna Dodd, Carly Vaughan, Anna Reid, Matthias Schmitt, Clifford Garratt, Mohammed Akhtar, Masliza Mahmod, Stefan Neubauer, Robert M Cooper, Sanjay K Prasad, Anvesha Singh, Ladislav Valkovič, Betty Raman, Zakariye Ashkir, Dannii Clayton, Olatz Baroja, Beatriz Duran, Catherine Spowart, Emma Bedson, Josephine H Naish, Chris Harrington, and Christopher A Miller
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Cardiology and Cardiovascular Medicine - Abstract
AimsHypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.MethodsThe Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I–III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.ConclusionTEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.Trial registration numbersNCT04706429andISRCTN57145331.
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- 2023
29. Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies
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Antonio de Marvao, Francesca Girolami, Antonis Pantazis, Francesco Mazzarotto, A. John Baksi, James S. Ware, Kathryn A. McGurk, Iacopo Olivotto, Megan H. Hawley, Angharad M. Roberts, Sanjay K Prasad, Roddy Walsh, Elisabetta Cerbai, Paul J.R. Barton, Beatrice Boschi, Ben Statton, Soha Romeih, Leander Beekman, Elisabeth M. Lodder, Declan P. O'Regan, Matteo Beltrami, Connie R. Bezzina, Magdi H. Yacoub, Birgit Funke, Mona Allouba, Yasmine Aguib, Stuart A. Cook, Fondation Leducq, British Heart Foundation, Wellcome Trust, Guys & St Thomas NHS Foundation Trust, Department of Health, Imperial College Healthcare NHS Trust- BRC Funding, Mason Medical Research Foundation, The Academy of Medical Sciences, Cardiology, ACS - Amsterdam Cardiovascular Sciences, Human Genetics, and ACS - Heart failure & arrhythmias
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Cardiomyopathy, Dilated ,Heart Defects, Congenital ,0301 basic medicine ,Population ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Biology ,DIAGNOSIS ,Article ,CLASSIFICATION ,DISEASE ,Congenital ,03 medical and health sciences ,0302 clinical medicine ,Dilated ,medicine ,Humans ,Genetic Testing ,cardiovascular diseases ,education ,Genetics (clinical) ,Heart Defects ,CARDIOLOGY ,Genetic testing ,Genetics & Heredity ,Genetics ,0604 Genetics ,education.field_of_study ,Science & Technology ,CARDIOMYOPATHY ,medicine.diagnostic_test ,MUTATIONS ,STATEMENT ,Hypertrophic cardiomyopathy ,1103 Clinical Sciences ,Dilated cardiomyopathy ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Genetic architecture ,030104 developmental biology ,Hypertrophic ,cardiovascular system ,Left ventricular noncompaction ,MYH7 ,Cardiomyopathies ,Life Sciences & Biomedicine - Abstract
Purpose: To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases. Methods: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes. Conclusion: LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.
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- 2021
30. Myocardial fibrosis predicts ventricular arrhythmias and sudden death after cardiac electronic device implantation
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Francisco Leyva, Abbasin Zegard, Osita Okafor, Paul Foley, Fraz Umar, Robin J. Taylor, Howard Marshall, Berthold Stegemann, William Moody, Richard P. Steeds, Brian P. Halliday, Daniel J. Hammersley, Richard E. Jones, Sanjay K. Prasad, and Tian Qiu
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted educational grants Background Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias. We sought to determine whether presence of MF on visual assessment (MFVA) and gray zone fibrosis (GZF) mass predicts SCD and ventricular fibrillation / sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation. Methods In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of sudden cardiac death (SCD) and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation. Results Among 700 patients (age 68.0 ± 12.0yrs [mean ± SD]), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over 6.93 yrs (median; interquartile range 5.82-9.32). MFVA predicted SCD (hazard ratio [HR]: HR:26.3 [95% confidence interval [CI] 3.70-3337]; negative predictive value: 100%). In competing risks analyses, MFVA also predicted the arrhythmic endpoint (subdistribution [sHR]: 19.9 [95% CI 6.40-61.9]; negative predictive value:98.6%). Compared with no MFVA, a GZF mass measured with the 5SD method (GZF5SD) > 17 g was associated with highest risk of SCD (HR: 44.6;95% CI 6.12-5685) and the arrhythmic endpoint (sHR: 30.3 [95% CI 9.60-95.8]). Adding GZF5SD mass to MFVA led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint. Conclusions In CIED recipients, MFVA excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF5SD mass added predictive value in relation to SCD and the arrhythmic endpoint.
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- 2022
31. Cardiovascular magnetic resonance in heart failure
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Brian P. Halliday and Sanjay K. Prasad
- Abstract
Cardiovascular magnetic resonance (CMR) has an increasingly important role in the assessment of patients with heart failure. One major advantage of this modality is the ability to perform tissue characterization without exposure to ionizing radiation, enabling accurate diagnosis and improved prognostication. Given the high spatial resolution and the ability to image in any plane, it also provides reference-standard quantification of chamber size and function. Accurate assessment of left ventricular ejection fraction is fundamental to current decision-making in the contemporary management of heart failure. This chapter covers the basics of magnetic resonance imaging, including the components of a typical scan performed to evaluate a patient with heart failure, and discusses the major benefits CMR offers in the assessment of patients with heart failure and reduced ejection fraction and those with preserved ejection fraction.
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- 2022
32. Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study
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George D. Thornton, Tarique A. Musa, Marzia Rigolli, Margaret Loudon, Calvin Chin, Silvia Pica, Tamir Malley, James R. J. Foley, Vassilios S. Vassiliou, Rhodri H. Davies, Gabriella Captur, Laura E. Dobson, James C. Moon, Marc R. Dweck, Saul G. Myerson, Sanjay K. Prasad, John P. Greenwood, Gerry P. McCann, Anvesha Singh, and Thomas A. Treibel
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Aged, 80 and over ,Male ,Magnetic Resonance Spectroscopy ,Contrast Media ,Gadolinium ,Stroke Volume ,Aortic Valve Stenosis ,Fibrosis ,Ventricular Function, Left ,Cohort Studies ,Cicatrix ,Humans ,Female ,Longitudinal Studies ,Cardiology and Cardiovascular Medicine ,Original Investigation ,Aged - Abstract
IMPORTANCE: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m(2). Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. OBJECTIVE: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. DESIGN, SETTING, AND PARTICIPANTS: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. EXPOSURES: SAVR or TAVR. MAIN OUTCOMES AND MEASURES: All-cause and cardiovascular (CV) mortality after aortic valve intervention. RESULTS: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm(2)/m(2). Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P
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- 2022
33. Cardiovascular Magnetic Resonance in Heritable Cardiomyopathies
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Daniel Hammersley, Lukas Mach, Brian P Halliday, Sanjay K Prasad, and Richard E. Jones
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Heart Ventricles ,Cardiomyopathy ,Magnetic Resonance Imaging, Cine ,Magnetic resonance imaging ,General Medicine ,Tissue characterization ,030204 cardiovascular system & hematology ,equipment and supplies ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Cardiology ,Humans ,030212 general & internal medicine ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business ,human activities - Abstract
Cardiovascular magnetic resonance represents the imaging modality of choice for the investigation of patients with heritable cardiomyopathies. The combination of gold-standard volumetric analysis with tissue characterization can deliver precise phenotypic evaluation of both cardiac morphology and the underlying myocardial substrate. Cardiovascular magnetic resonance additionally has an established role in risk-stratifying patients with heritable cardiomyopathy and an emerging role in guiding therapies. This article explores the application and utility of cardiovascular magnetic resonance techniques with specific focus on the major heritable cardiomyopathies.
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- 2021
34. Quality assurance of quantitative cardiac T1-mapping in multicenter clinical trials – A T1 phantom program from the hypertrophic cardiomyopathy registry (HCMR) study
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Dipan J. Shah, Han W. Kim, Michael Salerno, Bette Kim, Aleksandra Radjenovic, Milind Y. Desai, Iulia A. Popescu, Sven Plein, David M. Higgins, Tarik Hafyane, Michelle Michels, Stefan K. Piechnik, Kyle Autry, Kelvin Chow, Christopher M. Kramer, Stefan L. Zimmerman, James A. White, Ntobeko A B Ntusi, Taigang He, Dana Dawson, Craig S. Broberg, Ornella Rimoldi, Linda Calistri, Amedeo Chiribiri, Chiara Bucciarelli-Ducci, Steffen Huber, Lisa M Anderson, Mark B.M. Hofman, Sanjay K Prasad, Joanne Wormleighton, Qiang Zhang, Stefano Colagrande, Flett Andrew, Michael Jerosch-Herold, Luca Biasiolli, Elizabeth R. Jenista, Konrad Werys, Iacopo Carbone, Heiko Mahrholdt, Javier Sanz, Raymond Y. Kwong, Jeanette Schulz-Menger, Redha Boubertakh, Saidi A Mohiddin, David A. Broadbent, Gerry P McCann, Scott Semple, David E. Newby, Vanessa M Ferreira, Stefan Neubauer, Cardiology, Radiology and nuclear medicine, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias
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Magnetic Resonance Spectroscopy ,Coefficient of variation ,Phantom study ,030204 cardiovascular system & hematology ,Imaging phantom ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Quantitative T1-mapping ,Registries ,Cardiac MRI ,Protocol (science) ,medicine.diagnostic_test ,business.industry ,Phantoms, Imaging ,Hypertrophic cardiomyopathy ,Reproducibility of Results ,Magnetic resonance imaging ,Cardiomyopathy, Hypertrophic ,Reference Standards ,medicine.disease ,Magnetic Resonance Imaging ,Confidence interval ,Multicenter study ,Quality assurance ,Standardization ,Clinical trial ,Cardiovascular and Metabolic Diseases ,Cardiology and Cardiovascular Medicine ,Nuclear medicine ,business - Abstract
Background Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials. Purpose To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use. Methods MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites. Results T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R2 > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions. Conclusions The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials., Highlights • CMR T1 correlated with reference T1 and T2; this derives the QA model for T1-map. • The proposed QA model is robust to temperature variations and phantom aging. • This QA method requires no frequent phantom replacements. • The T1-map QA program can be readily deployed in multicenter trials.
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- 2021
35. Myocardial Fibrosis in Dilated Cardiomyopathy
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Brian P Halliday and Sanjay K Prasad
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medicine.medical_specialty ,business.industry ,Internal medicine ,Cardiology ,Medicine ,Radiology, Nuclear Medicine and imaging ,Dilated cardiomyopathy ,Myocardial fibrosis ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease - Published
- 2021
36. Predictors and Mechanisms of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy
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Elisa Di Pietro, Gajen Kanaganayagam, Rory O'Hanlon, Fouad R. Amin, Simon Newsome, Michael P. Frenneaux, Sabine Ernst, Peter D. Gatehouse, John Gregson, Ruth Owen, Alphonsus C. Liew, Sanjay K Prasad, Vassilios S. Vassiliou, Dudley J. Pennell, Frances M. Mitchell, Claire E. Raphael, and Robert Cooper
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Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Ventricular tachycardia ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Fibrosis ,Median follow-up ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Prospective Studies ,cardiovascular diseases ,030212 general & internal medicine ,Aged ,business.industry ,Myocardium ,Hazard ratio ,Hypertrophic cardiomyopathy ,Atrial fibrillation ,Cardiomyopathy, Hypertrophic ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Ventricle ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Atrial fibrillation (AF) in hypertrophic cardiomyopathy (HC) is associated with significant symptomatic deterioration, heart failure, and thromboembolic disease. There is a need for better mechanistic insight and improved identification of at risk patients. We used cardiovascular magnetic resonance (CMR) to assess predictors of AF in HC, in particular the role of myocardial fibrosis. Consecutive patients with HC referred for CMR 2003 to 2013 were prospectively enrolled. CMR parameters including left ventricular volumes, presence and percentage of late gadolinium enhancement in the left ventricle (%LGE) and left atrial volume index (LAVi) were measured. Overall, 377 patients were recruited (age 62 ± 14 years, 73% men). Sixty-two patients (16%) developed new-onset AF during a median follow up of 4.5 (interquartile range 2.9 to 6.0) years. Multivariable analysis revealed %LGE (hazard ratio [HR] 1.3 per 10% (confidence interval: 1.0 to 1.5; p = 0.02), LAVi (HR 1.4 per 10 mL/m 2[1.2 to 1.5; p < 0.001]), age at HC diagnosis, nonsustained ventricular tachycardia and diabetes to be independent predictors of AF. We constructed a simple risk prediction score for future AF based on the multivariable model with a Harrell's C-statistic of 0.73. In conclusion, the extent of ventricular fibrosis and LA volume independently predicted AF in patients with HC. This finding suggests a mechanistic relation between fibrosis and future AF in HC. CMR with quantification of fibrosis has incremental value over LV and LA measurements in risk stratification for AF. A risk prediction score may be used to identify patients at high risk of future AF who may benefit from more intensive rhythm monitoring and a lower threshold for oral anticoagulation.
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- 2020
37. Myocardial fibrosis and ventricular ectopy in patients with non-ischemic systolic heart failure: results from the DANISH trial
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Marie Bayer Elming, Rune Boas, Sophia Hammer-Hansen, Inga Voges, Eva Nyktari, Jesper Hastrup Svendsen, Steen Pehrson, Ulrik Dixen, Berit T. Philbert, Sanjay K. Prasad, Lars Køber, and Jens Jakob Thune
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Death, Sudden, Cardiac ,Predictive Value of Tests ,Risk Factors ,Denmark ,Humans ,Contrast Media ,Gadolinium ,Cardiomyopathies ,Fibrosis ,Ventricular Premature Complexes ,Heart Failure, Systolic - Abstract
Patients with non-ischemic systolic heart failure (HF) have increased risk of sudden cardiovascular death (SCD). The initiation and substrate for ventricular arrhythmias remains poorly understood. Our purpose was to describe the relationship between cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and Holter recorded ventricular arrhythmic activity. Patients from the DANISH trial underwent a Holter-recording and a CMR-scan. The presence of non-sustained ventricular tachycardia (NSVT) and premature ventricular contractions (PVC) were examined in relation to presence and amount of LGE. Outcome measures were all-cause mortality and SCD. Overall, 180 patients were included. LGE was present in 86 (47%). NSVT occurred in 72 (40%), not different according to LGE status (p = 0.65). The amount of LGE was not correlated to the occurrence of NSVT (p = 0.40). The occurrence of couplet PVCs (p = 0.997), frequent PVCs (p = 0.12), PVCs in bigemini (p = 0.29), in trigemini (p = 0.26), or in quadrimini (p = 0.35) did not differ according to LGE status. LGE was significantly associated with risk of all-cause mortality (HR 2.14; 95% CI 1.05-4.37, p = 0.04). NSVT did not increase risk of all-cause mortality in either patients with LGE (HR 1.00; 95% CI 0.46-2.16, p = 0.996) or without LGE (HR 1.37; 95% CI 0.46-4.08, p = 0.57). There was no interaction between LGE and NSVT for the risk of all-cause mortality (p = 0.62). In patients with non-ischemic systolic HF there was no relationship between the presence of LGE and NSVT or any other Holter recorded ventricular tachyarrhythmia. LGE was associated with increased risk of mortality, independent of the presence of NSVT.
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- 2022
38. Exposure to Elevated Nitrogen Dioxide Concentrations and Cardiac Remodeling in Patients With Dilated Cardiomyopathy
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DANIELA Fecht, MARC CHADEAU-HYAM, RUTH OWEN, JOHN GREGSON, BRIAN P. HALLIDAY, Amrit S. Lota, JOHN GULLIVER, JAMES S. WARE, DUDLEY J. PENNELL, FRANK J. KELLY, ANOOP S.V. SHAH, MARK R. MILLER, DAVID E. NEWBY, SANJAY K. PRASAD, UPASANA TAYAL, Medical Research Council, Imperial College Healthcare NHS Trust- BRC Funding, Wellcome Trust, British Heart Foundation, and National Heart & Lung Institute Foundation
- Subjects
particulate matter ,Cardiomyopathy, Dilated ,Heart Failure ,Male ,Air Pollutants ,Ventricular Remodeling ,Nitrogen Dioxide ,heart failure ,1103 Clinical Sciences ,1110 Nursing ,heart ,Cross-Sectional Studies ,Cardiovascular System & Hematology ,Air Pollution ,Humans ,Female ,Prospective Studies ,Cardiology and Cardiovascular Medicine ,cardiomyopathy ,1102 Cardiorespiratory Medicine and Haematology ,Nitrogen dioxide - Abstract
BACKGROUND: Empirical evidence suggests a strong link between exposure to air pollution and heart failure incidence, hospitalizations, and mortality, but the biological basis of this remains unclear. We sought to determine the relationship between differential air pollution levels and changes in cardiac structure and function in patients with dilated cardiomyopathy.METHODS AND RESULTS: We undertook a prospective longitudinal observational cohort study of patients in England with dilated cardiomyopathy (enrollment 2009-2015, n = 716, 66% male, 85% Caucasian) and conducted cross sectional analysis at the time of study enrollment. Annual average air pollution exposure estimates for nitrogen dioxide (NO 2) and particulate matter with diameter of 2.5 µm or less (PM 2.5) at enrolment were assigned to each residential postcode (on average 12 households). The relationship between air pollution and cardiac morphology was assessed using linear regression modelling. Greater ambient exposure to NO 2 was associated with higher indexed left ventricular (LV) mass (4.3 g/m 2 increase per interquartile range increase in NO 2, 95% confidence interval 1.9-7.0 g/m 2) and lower LV ejection fraction (-1.5% decrease per interquartile range increase in NO 2, 95% confidence interval -2.7% to -0.2%), independent of age, sex, socioeconomic status, and clinical covariates. The associations were robust to adjustment for smoking status and geographical clustering by postcode area. The effect of air pollution on LV mass was greatest in women. These effects were specific to NO 2 exposure. CONCLUSIONS: Exposure to air pollution is associated with raised LV mass and lower LV ejection fraction, with the strongest effect in women. Although epidemiological associations between air pollution and heart failure have been established and supported by preclinical studies, our findings provide novel empirical evidence of cardiac remodeling and exposure to air pollution with important clinical and public health implications.
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- 2022
39. Direct and indirect effect of the COVID-19 pandemic on patients with cardiomyopathy
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Daniel J Hammersley, Rachel J Buchan, Amrit S Lota, Lukas Mach, Richard E Jones, Brian P Halliday, Upasana Tayal, Devendra Meena, Abbas Dehghan, Ioanna Tzoulaki, A John Baksi, Antonis Pantazis, Angharad M Roberts, Sanjay K Prasad, James S Ware, Wellcome Trust, British Heart Foundation, National Heart & Lung Institute Foundation, and Sir Jules Thorn Charitable Trust
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cardiomyopathies ,Cardiomyopathy, Dilated ,Male ,Cardiac & Cardiovascular Systems ,ESC ,Comorbidity ,Emotional Adjustment ,Health Services Accessibility ,State Medicine ,Prevalence ,Diseases of the circulatory (Cardiovascular) system ,Humans ,Heart Failure and Cardiomyopathies ,CARDIOLOGY ,Health Services Needs and Demand ,Science & Technology ,STATEMENT ,SARS-CoV-2 ,delivery of health care ,COVID-19 ,Cardiomyopathy, Hypertrophic ,Middle Aged ,Survival Analysis ,United Kingdom ,Hospitalization ,Mental Health ,RC666-701 ,Cardiovascular System & Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine - Abstract
Objectives(1) To evaluate the prevalence and hospitalisation rate of COVID-19 infections among patients with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) in the Royal Brompton and Harefield Hospital Cardiovascular Research Centre (RBHH CRC) Biobank. (2) To evaluate the indirect impact of the pandemic on patients with cardiomyopathy through the Heart Hive COVID-19 study. (3) To assess the impact of the pandemic on national cardiomyopathy-related hospital admissions.Methods(1) 1236 patients (703 DCM, 533 HCM) in the RBHH CRC Biobank were assessed for COVID-19 infections and hospitalisations; (2) 207 subjects (131 cardiomyopathy, 76 without heart disease) in the Heart Hive COVID-19 study completed online surveys evaluating physical health, psychological well-being, and behavioural adaptations during the pandemic and (3) 11 447 cardiomyopathy-related hospital admissions across National Health Service (NHS) England were studied from NHS Digital Hospital Episode Statistics over 2019–2020.ResultsA comparable proportion of patients with cardiomyopathy in the RBHH CRC Biobank had tested positive for COVID-19 compared with the UK population (1.1% vs 1.6%, p=0.14), but a higher proportion of those infected were hospitalised (53.8% vs 16.5%, p=0.002). In the Heart Hive COVID-19 study, more patients with cardiomyopathy felt their physical health had deteriorated due to the pandemic than subjects without heart disease (32.3% vs 13.2%, p=0.004) despite only 4.6% of the cardiomyopathy cohort reporting COVID-19 symptoms. A 17.9% year-on-year reduction in national cardiomyopathy-related hospital admissions was observed in 2020.ConclusionPatients with cardiomyopathy had similar reported rates of testing positive for COVID-19 to the background population, but those with test-proven infection were hospitalised more frequently. Deterioration in physical health amongst patients could not be explained by COVID-19 symptoms, inferring a significant contribution of the indirect consequences of the pandemic.Trial registration numberNCT04468256
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- 2022
40. Left ventricular shape predicts arrhythmic risk in fibrotic dilated cardiomyopathy
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Gabriel Balaban, Brian P Halliday, Daniel Hammersley, Christopher A Rinaldi, Sanjay K Prasad, Martin J Bishop, and Pablo Lamata
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Cardiomyopathy, Dilated ,Ventricular Remodeling ,Contrast Media ,Arrhythmias, Cardiac ,Gadolinium ,Stroke Volume ,Prognosis ,Fibrosis ,Ventricular Function, Left ,Death, Sudden, Cardiac ,Predictive Value of Tests ,Physiology (medical) ,cardiovascular system ,Humans ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine - Abstract
Aims Remodelling of the left ventricular (LV) shape is one of the hallmarks of non-ischaemic dilated cardiomyopathy (DCM) and may contribute to ventricular arrhythmias and sudden cardiac death. We sought to investigate a novel three dimensional (3D) shape analysis approach to quantify LV remodelling for arrhythmia prediction in DCM. Methods and results We created 3D LV shape models from end-diastolic cardiac magnetic resonance images of 156 patients with DCM and late gadolinium enhancement (LGE). Using the shape models, principle component analysis, and Cox-Lasso regression, we derived a prognostic LV arrhythmic shape (LVAS) score which identified patients who reached a composite arrhythmic endpoint of sudden cardiac death, aborted sudden cardiac death, and sustained ventricular tachycardia. We also extracted geometrical metrics to look for potential prognostic markers. During a follow-up period of up to 16 years (median 7.7, interquartile range: 3.9), 25 patients met the arrhythmic endpoint. The optimally prognostic LV shape for predicting the time-to arrhythmic event was a paraboloidal longitudinal profile, with a relatively wide base. The corresponding LVAS was associated with arrhythmic events in univariate Cox regression (hazard ratio = 2.0 per quartile; 95% confidence interval: 1.3–2.9), in univariate Cox regression with propensity score adjustment, and in three multivariate models; with LV ejection fraction, New York Heart Association Class III/IV (Model 1), implantable cardioverter-defibrillator receipt (Model 2), and cardiac resynchronization therapy (Model 3). Conclusion Biomarkers of LV shape remodelling in DCM can help to identify the patients at greatest risk of lethal ventricular arrhythmias.
- Published
- 2022
41. Thrombosis Risk with Transcatheter Aortic Valve Replacement
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Ying X Gue, Diana A. Gorog, Saeed Mirsadraee, Sanjay K Prasad, Rahim Kanji, and Vasileios F. Panoulas
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medicine.medical_specialty ,Transcatheter aortic ,business.industry ,medicine.medical_treatment ,medicine.disease ,Thrombosis ,Stenosis ,Valve replacement ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Stroke ,Thrombotic complication - Abstract
The introduction of transcatheter aortic valve implantation (TAVI) has revolutionised the management of aortic stenosis (AS), with procedure numbers rapidly increasing. Although there has been enth...
- Published
- 2020
42. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the <scp>H</scp> eart <scp>F</scp> ailure <scp>A</scp> ssociation ( <scp>HFA</scp> ), the <scp>E</scp> uropean <scp>A</scp> ssociation of <scp>C</scp> ardiovascular <scp>I</scp> maging ( <scp>EACVI</scp> ) and the <scp>Cardio‐Oncology C</scp> ouncil of the <scp>E</scp> uropean <scp>S</scp> ociety of <scp>C</scp> ardiology ( <scp>ESC</scp> )
- Author
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Thor Edvardsen, Stephan von Haehling, Tiny Jaarsma, Bernard Cosyns, Jelena Čelutkienė, Thomas Thum, Giuseppe M.C. Rosano, Jutta Bergler-Klein, José Luis Zamorano, Zaza Iakobishvili, Petros Nihoyannopoulos, Sanjay K Prasad, Dimitrios Farmakis, Eva Haegler-Laube, Frank A. Flachskampf, Chiara Bucciarelli-Ducci, Jeanette Schulz-Menger, Thomas M. Suter, Julia Grapsa, Andrew J.S. Coats, Rudolf A. de Boer, Brenda Moura, Christian Mueller, Petar M. Seferovic, Kshama Wechalekar, Vassilis I. Barberis, Massimo F Piepoli, Y N Belenkov, Thomas H. Marwick, Maurizio Galderisi, Stephane Heymans, Riccardo Asteggiano, Jeroen J. Bax, Carlo G. Tocchetti, Alain Cohen-Solal, Alexander R. Lyon, Oliver Gaemperli, Radek Pudil, Frank Ruschitzka, Markus S. Anker, Patrizio Lancellotti, Wilfried Mullens, Jean-Sébastien Hulot, Teresa López-Fernández, Indrė Čeponienė, Ovidiu Chioncel, and Tomas Lapinskas
- Subjects
medicine.medical_specialty ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Cancer ,Magnetic resonance imaging ,Speckle tracking echocardiography ,030204 cardiovascular system & hematology ,medicine.disease ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,Heart failure ,Internal medicine ,Cardiology ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Cardiac imaging ,medicine.drug - Abstract
Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.
- Published
- 2020
43. 3D Electrophysiological Modeling of Interstitial Fibrosis Networks and Their Role in Ventricular Arrhythmias in Non-Ischemic Cardiomyopathy
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Bradley Porter, Gernot Plank, Christopher A. Rinaldi, Gabriel Balaban, Martin J. Bishop, Caroline Mendonca Costa, Brian P Halliday, Tevfik F Ismail, and Sanjay K Prasad
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medicine.medical_specialty ,0206 medical engineering ,Biomedical Engineering ,02 engineering and technology ,Interstitial fibrosis ,Article ,Fibrosis ,Internal medicine ,medicine ,Humans ,business.industry ,Cardiac electrophysiology ,fibrosis ,Non ischemic cardiomyopathy ,Transient conduction ,Arrhythmias, Cardiac ,Heart ,medicine.disease ,electrophysiology ,020601 biomedical engineering ,nonischemic ,Electrophysiology ,computational model ,Nonischemic cardiomyopathy ,Cardiology ,Cardiac Electrophysiology ,business ,Cardiomyopathies ,Image based ,Arrhythmia - Abstract
Objective: Interstitial fibrosis is a pathological expansion of the heart's inter-cellular collagen matrix. It is a potential complication of nonischemic cardiomyopathy (NICM), a class of diseases involving electrical and or mechanical dysfunction of cardiac tissue not caused by atherosclerosis. Patients with NICM and interstitial fibrosis often suffer from life threatening arrhythmias, which we aim to simulate in this study. Methods: Our methodology builds on an efficient discrete finite element (DFE) method which allows for the representation of fibrosis as infinitesimal splits in a mesh. We update the DFE method with a local connectivity analysis which creates a consistent topology in the fibrosis network. This is particularly important in nonischemic disease due to the potential presence of large and contiguous fibrotic regions and therefore potentially complex fibrosis networks. Results: In experiments with an image-based model, we demonstrate that our methodology is able to simulate reentrant electrical events associated with cardiac arrhythmias. These reentries depended crucially upon sufficient fibrosis density, which was marked by conduction slowing at high pacing rates. We also created a 2D test-case which demonstrated that fibrosis topologies can modulate transient conduction block, and thereby reentrant activations. Conclusion: Ventricular arrhythmias due to interstitial fibrosis in NICM can be efficiently simulated using our methods in medical image based geometries. Furthermore, fibrosis topology modulates transient conduction block, and should be accounted for in electrophysiological simulations with interstitial fibrosis. Significance: Our study provides methodology which has the potential to predict arrhythmias and to optimize treatments non-invasively for nonischemic cardiomyopathies.
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- 2020
44. Emerging Techniques for Risk Stratification in Nonischemic Dilated Cardiomyopathy
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Stuart A. Cook, Sanjay K Prasad, Benjamin A Marrow, and Gerry P McCann
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medicine.medical_specialty ,Population ,030204 cardiovascular system & hematology ,Sudden cardiac death ,03 medical and health sciences ,0302 clinical medicine ,Cardiac magnetic resonance imaging ,Internal medicine ,medicine ,cardiovascular diseases ,030212 general & internal medicine ,education ,education.field_of_study ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Cardiopulmonary exercise testing ,Dilated cardiomyopathy ,musculoskeletal system ,medicine.disease ,Heart failure ,cardiovascular system ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment - Abstract
Dilated cardiomyopathy (DCM) is a common condition, which carries significant mortality from sudden cardiac death and pump failure. Left ventricular ejection fraction has conventionally been used as a risk marker for sudden cardiac death, but has performed poorly in trials. There have been significant advances in the areas of cardiac magnetic resonance imaging and genetics, which are able to provide useful rick prediction in DCM. Biomarkers and cardiopulmonary exercise testing are well validated in the prediction of risk in heart failure; however, they have been tested less specifically in the DCM setting. This review will discuss these methods with a view toward multiparametric risk assessment in DCM with the hope of creating parametric risk models to predict sudden cardiac death and pump failure in the DCM population.
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- 2020
45. Predictors of left ventricular remodelling in patients with dilated cardiomyopathy – a cardiovascular magnetic resonance study
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Upasana Tayal, Amrit Lota, John G.F. Cleland, Amal Muthumala, Michael P. Frenneaux, John Gregson, Sanjay K Prasad, Suzan Hatipoglu, Ramasamy Manivarmane, Ravi Assomull, Stuart A. Cook, Ricardo Wage, James S. Ware, Cemil Izgi, Andrew D Scott, Dudley J. Pennell, Jason Dungu, Brian P Halliday, Simon Newsome, Wellcome Trust, British Heart Foundation, and Medical Research Council (MRC)
- Subjects
Male ,Cardiac & Cardiovascular Systems ,Magnetic Resonance Spectroscopy ,Dilated cardiomyopathy ,Contrast Media ,Gadolinium ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Recovery ,PROGNOSTIC-SIGNIFICANCE ,Extracellular fluid ,Prospective Studies ,Prospective cohort study ,DOBUTAMINE STRESS ECHOCARDIOGRAPHY ,1102 Cardiorespiratory Medicine and Haematology ,Dobutamine stress ,BETA-BLOCKADE ,Ejection fraction ,Ventricular Remodeling ,medicine.diagnostic_test ,ASSOCIATION ,Myocardial remodelling ,PREVALENCE ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,Cardiomyopathy, Dilated ,Cardiac function curve ,medicine.medical_specialty ,IMPROVEMENT ,EJECTION FRACTION ,03 medical and health sciences ,CARDIAC-FUNCTION ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Heart Failure ,Science & Technology ,MYOCARDIAL CONTRACTILE RESERVE ,business.industry ,Stroke Volume ,Magnetic resonance imaging ,medicine.disease ,Myocardial Contraction ,Cardiovascular System & Hematology ,Heart failure ,Cardiovascular System & Cardiology ,Myocardial fibrosis ,business ,SYSTOLIC HEART-FAILURE - Abstract
Aims:\ud There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling.\ud \ud Methods and results:\ud Prospective study of patients with recent‐onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P = 0.02). Baseline myocardial strain (P = 0.39 global longitudinal strain), interstitial myocardial fibrosis (P = 0.41), replacement myocardial fibrosis (P = 0.25), and right ventricular contractile reserve (P = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = −0.22, P = 0.23) or baseline LVEF (r = 0.07, P = 0.62). Men were more likely to experience adverse LV remodelling (P = 0.01) but age (P = 0.88) and disease‐modifying heart failure medication (beta‐blocker, P = 0.28; angiotensin‐converting enzyme inhibitor, P = 0.92) did not predict follow‐up LVEF.\ud \ud Conclusions:\ud Substantial recovery of LV function occurs within 12 months in most patients with recent‐onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.
- Published
- 2020
46. The Interstitium in the Hypertrophied Heart
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Sanjay K Prasad and Brian P Halliday
- Subjects
Noninvasive imaging ,Pathology ,medicine.medical_specialty ,Biopsy ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,030218 nuclear medicine & medical imaging ,Muscle hypertrophy ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Pathological ,Ventricular Remodeling ,business.industry ,Myocardium ,Fibrosis ,Magnetic Resonance Imaging ,Feature (computer vision) ,Hypertrophy, Left Ventricular ,Myocardial fibrosis ,Extracellular Space ,Cardiology and Cardiovascular Medicine ,business ,Interstitial Disease ,Tomography, Emission-Computed - Abstract
Pathological left ventricular hypertrophy is a common feature of many cardiac diseases. It results from both myocyte hypertrophy and interstitial expansion. Interstitial expansion is most commonly secondary to the accumulation of mature cross-linked collagen fibers due to dysregulated metabolism, known as interstitial fibrosis. This occurs secondary to a variety of stimuli including ischemic, toxic, metabolic, infective, genetic, and hemodynamic factors. Less commonly, interstitial expansion may occur because of the accumulation of misfolded amyloid protein or interstitial edema. It is now well recognized that the presence and extent of interstitial disease are associated with adverse outcomes. There is therefore interest in the development of novel therapies that target the pathways that drive these disease processes. With the emergence of such therapies, it is becoming increasingly important to be able to characterize the type and extent of interstitial disease to enable the use of such targeted therapies in a personalized manner.
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- 2019
47. Abstract 10211: Longitudinal Changes in Clinical and Imaging Variables During Withdrawal of Heart Failure Therapy in Patients with Recovered Dilated Cardiomyopathy: An Analysis from TRED-HF
- Author
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Brian P Halliday, Ruth Owen, John Gregson, Ali Vazir, Amrit S Lota, Zohya Khalique, Martin R Cowie, Dudley Pennell, John Cleland, and Sanjay K Prasad
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed during withdrawal of therapy. Non-invasive markers of relapse may be used to monitor patients who wish a trial of therapy withdrawal. Purpose: To profile the changes in clinical and imaging variables amongst patients with recovered DCM undergoing therapy withdrawal in TRED-HF. Methods: Patients with recovered DCM were randomised to phased withdrawal of therapy or to continue therapy for 6 months. After 6 months of continued therapy, those in the control arm underwent withdrawal of therapy in a crossover phase. Clinical variables were measured at each study visit and imaging variables were measured at baseline, 16 weeks and 6 months. Mean values and 95% CIs were calculated at each time point. Clinical variables were modelled using fractional polynomials. Results: Of 51 patients, 26 were assigned to continue therapy and 25 to withdraw therapy over the first 6 months. Of the former, 24 of 26 patients, withdrew therapy in the cross-over phase between 6-12 months. An increase in mean heart rate was noted within 4 weeks of beginning therapy withdrawal and was the earliest change observed. Heart rate and change in heart rate from baseline were closely associated with the occurrence of relapse in multivariable analysis. A rise in systolic and diastolic blood pressure was apparent by 8 weeks. A rise in mean log NT-pro-BNP was the latest change to occur and not observed until 6 months after starting therapy withdrawal. ( Figure 1 & Table 1) . A rise in mean LV mass and LVEDV and a reduction in mean LVEF was seen by 16 weeks ( Figure 2 & Table 1) . Conclusion(s): A rise in heart rate may be the earliest sign of relapse during withdrawal of medication. This is accompanied or closely followed by changes in LV structure and function, with changes in natriuretic peptide concentrations occurring later. This informs monitoring strategies in cases where it may be necessary to reduce heart failure therapy.
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- 2021
48. Abstract 10960: Genetic Overlap of Acute Myocarditis and Inherited Cardiomyopathy
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Amrit S Lota, Mark Hazebroek, Pantazis Theotokis, Rebecca Wassall, Sara Salmi, Brian Halliday, Upasana Tayal, Job Verdonschot, Devendra Meena, Antonio de Marvao, Alma Iacob, Daniel Hammersley, Richard Jones, Rick Wage, Rachel Buchan, Momina Yazdani, Michela Noseda, Tarun Mittal, Joyce Wong, Jan Lukas Robertus, John Baksi, Vassilios Vassiliou, Ioanna Tzoulaki, Antonios Pantazis, John Cleland, Paul J Barton, stuart cook, Dudley J Pennell, Pablo Garcia-Pavia, Leslie T Cooper, Stephane Heymans, James S Ware, and Sanjay K Prasad
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Myocarditis may predispose to dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Familial data indicate a potential genetic susceptibility shared with arrhythmogenic cardiomyopathy (ACM). We present the first large-scale genotype-phenotype study of adults with acute myocarditis. Methods: A cohort comprising 336 consecutive patients with acute myocarditis was enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterised cardiomyopathy-associated genes. The burden of rare protein altering variants (PAV) in ACM genes, DCM genes, and TTN specifically, were compared with local healthy controls sequenced on the same platform (n=1053). Case ascertainment was assessed against national hospital admission data. Results: We identified rare protein-altering variants in 23% of cases compared to 16% in controls (Δ+6.8%; p=0.021), with rare truncating variants (tv) in 6% of cases compared to Conclusion: We identified enrichment of cardiomyopathy gene variants in acute myocarditis patients, dominated by DSP-tv in those with normal LVEF and TTN-tv in those with reduced LVEF. Incorporation of genetic testing may be beneficial to identify such high-risk individuals and guide family screening in acute myocarditis patients.
- Published
- 2021
49. Abstract 11185: Impact of Covid-19 on Acute Myocarditis Hospital Admissions in the National Health Service of England, Uk (2019-2020)
- Author
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Amrit S Lota, Devendra Meena, Brian Halliday, Upasana Tayal, Alma Iacob, Daniel Hammersley, Richard Jones, Abbas Dehghan, Ioanna Tzoulaki, James S Ware, John Cleland, Dudley J Pennell, and Sanjay K Prasad
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Acute myocarditis has been reported in patients infected with COVID-19 in case series and imaging-based studies. We sought to assess this link by evaluating trends in hospital admissions due to acute myocarditis and COVID-19 on a national level during the pandemic. Methods: Data on all NHS England hospital admissions with a primary or secondary diagnosis of acute myocarditis were acquired and curated from the NHS Digital hospital episode statistics dataset from 2019-2020. COVID-19 data was obtained from the UK government daily statistics. Rolling averages over 28-day periods are presented. Results: Across all ages, there were 1,894 hospital admissions due to myocarditis in 2019 compared with 1,610 in 2020 (15% reduction). During the first national lockdown (23 rd Mar-19 th Jun 2020), myocarditis admissions were 32% lower than the same period in 2019. During the second lockdown (5 th Nov-2 nd Dec), myocarditis admissions were 9% greater than in 2019, although this increase was not sustained throughout December despite the subsequent surge in COVID-19 admissions. In general, patients admitted in 2020, compared to 2019, were older (median age 46 years, interquartile range 28-61 vs 41 years, IQR 26-58; p Discussion: As COVID-19 admissions peaked in early 2020, there was a sharp decline in myocarditis admissions, probably attributed to profound disruptions in healthcare provision, but possibly due to reduced transmission of other viruses during lockdown. Whilst myocarditis admissions increased during the second lockdown, there was no clear association between COVID-19 and myocarditis admission numbers. Further research may identify delayed presentations or sequelae of myocarditis, particularly following the larger COVID-19 peak in January 2021, as well as the impact of the vaccination programme.
- Published
- 2021
50. A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement
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Vasiliki Tsampasian, Francisco Alpendurada, Marc R. Dweck, David E. Newby, Dominique Auger, Claire E. Raphael, Gary Tse, Dudley J. Pennell, Sanjay K Prasad, Miguel Silva Vieira, Menelaos Pavlou, Calvin W. L. Chin, John Pepper, Vassilios S. Vassiliou, Tamir Malley, Brian P Halliday, Russell J. Everett, Andrew Jabbour, and British Heart Foundation
- Subjects
Male ,medicine.medical_specialty ,Science ,Patient demographics ,Cardiology ,Magnetic Resonance Imaging, Cine ,Infarction ,Gadolinium ,Article ,Aortic valve replacement ,Internal medicine ,Humans ,Medicine ,Aged ,Aged, 80 and over ,Heart Valve Prosthesis Implantation ,Multidisciplinary ,Framingham Risk Score ,Ejection fraction ,Interventional cardiology ,medicine.diagnostic_test ,business.industry ,Stroke Volume ,Magnetic resonance imaging ,Aortic Valve Stenosis ,Middle Aged ,medicine.disease ,Survival Analysis ,United Kingdom ,Stenosis ,Treatment Outcome ,Risk factors ,Multivariate Analysis ,cardiovascular system ,Female ,business ,Platelet Aggregation Inhibitors - Abstract
The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care.Trial Registration ClinicalTrials.gov Identifier: NCT00930735 and ClinicalTrials.gov Identifier: NCT01755936.
- Published
- 2021
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