97 results on '"Elliot CA"'
Search Results
2. P38 Assessing the repeatability of NT-proBNP testing using laboratory and point of care testing in PAH (REPEAT-PAH)
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Durrington, C, primary, Battersby, C, additional, Holt, L, additional, Fairman, A, additional, Salisbury, T, additional, Turton, H, additional, Watson, L, additional, Hameed, AG, additional, Charalampopoulos, A, additional, Elliot, CA, additional, Rothman, AMK, additional, Middleton, J, additional, Zafar, H, additional, Condliffe, R, additional, Lewis, RA, additional, Kiely, DG, additional, and Thompson, AAR, additional
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- 2022
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3. Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood
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Kariotis, S, Jammeh, E, Swietlik, EM, Pickworth, JA, Rhodes, CJ, Otero, P, Wharton, J, Iremonger, J, Dunning, MJ, Pandya, D, Mascarenhas, TS, Errington, N, Thompson, AAR, Romanoski, CE, Rischard, F, Garcia, JGN, Yuan, JX-J, An, T-HS, Desai, AA, Coghlan, G, Lordan, J, Corris, PA, Howard, LS, Condliffe, R, Kiely, DG, Church, C, Pepke-Zaba, J, Toshner, M, Wort, S, Gräf, S, Morrell, NW, Wilkins, MR, Lawrie, A, Wang, D, Bleda, M, Hadinnapola, C, Haimel, M, Auckland, K, Tilly, T, Martin, JM, Yates, K, Treacy, CM, Day, M, Greenhalgh, A, Shipley, D, Peacock, AJ, Irvine, V, Kennedy, F, Moledina, S, MacDonald, L, Tamvaki, E, Barnes, A, Cookson, V, Chentouf, L, Ali, S, Othman, S, Ranganathan, L, Gibbs, JSR, DaCosta, R, Pinguel, J, Dormand, N, Parker, A, Stokes, D, Ghedia, D, Tan, Y, Ngcozana, T, Wanjiku, I, Polwarth, G, Mackenzie Ross, RV, Suntharalingam, J, Grover, M, Kirby, A, Grove, A, White, K, Seatter, A, Creaser-Myers, A, Walker, S, Roney, S, Elliot, CA, Charalampopoulos, A, Sabroe, I, Hameed, A, Armstrong, I, Hamilton, N, Rothman, AMK, Swift, AJ, Wild, JM, Soubrier, F, Eyries, M, Humbert, M, Montani, D, Girerd, B, Scelsi, L, Ghio, S, Gall, H, Ghofrani, A, Bogaard, HJ, Noordegraaf, AV, Houweling, AC, Veld, AHI, and Schotte, G
- Abstract
Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.
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- 2021
4. Global Chemical Characterization of Sargassum spp. Seaweeds from Different Locations on Caribbean Islands: A Screening of Organic Compounds and Heavy Metals Contents
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Jérôme Bauta, Elliot Calbrix, Sophie Capblancq, Christine Cecutti, Jérôme Peydecastaing, Christine Delgado Raynaud, Antoine Rouilly, Valérie Simon, Guadalupe Vaca-Medina, Virginie Vandenbossche, Emeline Vedrenne, and Pascale De Caro
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Sargassum fluitans ,Sargassum natans ,chemical composition ,elemental analysis ,caribbean ,macroalgae ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Biology (General) ,QH301-705.5 - Abstract
Large-scale strandings of Sargassum spp. seaweeds occur annually on the beaches of the Caribbean islands and cause major environmental, health, and economic problems. In order to support an approach of valorisation of algae, an exhaustive characterisation of the composition of these seaweeds has been performed by analysing the contents in alginates, structural carbohydrates (fucans and glucans), minerals, proteins, lipids, mannitol, polyphenols, and heavy metals. Nine batches were collected at different harvesting sites over the years 2021 and 2022, to estimate the spatial and temporal variation in Sargassum composition. A batch of floats was harvested and analysed to estimate the differences in composition between floats and whole algae. Samples collected during the same year (floats or entire plant, freshly collected or stored) showed no significant differences in composition. However, slight differences were observed between batches collected in the two years. Some samples showed significant amounts of heavy metals, especially arsenic. A detailed structural carbohydrates analysis was carried out and discussed with literature data. As the nitrogen content of algae is an interesting parameter for food or agronomic uses, protein analysis enabled us to calculate a new nitrogen–protein conversion factor, specific to these algae species.
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- 2024
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5. Physicochemical Characterization and Asymmetric Catalytic Properties of New Biobased Organocatalytic Surfactants
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Elliot Calbrix, Pascale de Caro, Sophie Thiebaud-Roux, Christine Cecutti, and Emeline Vedrenne
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surfactant ,biobased ,green chemistry ,organocatalyst ,Organic chemistry ,QD241-441 - Abstract
In organic synthesis, the solvent is the chemical compound that represents the largest proportion of the process. However, conventional solvents are often toxic and dangerous for the environment, and an interesting alternative is to replace them by water. In this context, catalyst surfactants allow both organic reagents in water to be solubilized and organic reactions to be catalyzed. This article describes the synthesis of new biobased organocatalytic surfactants soluble in water, composed of a hydrocarbon chain grafted onto an imidazolidinone moiety. The imidazolidinone moiety acts as catalyst, but also as the polar head of the surfactant, while the fatty chain constitutes the hydrophobic tail. The five steps of the synthesis were optimized, respecting the principles of green chemistry, and two organocatalytic surfactants were obtained with a good selectivity. Surface properties in an aqueous medium were then evaluated with the use of tensiometric analysis. Their molecular organization in vesicles was characterized by Dynamic Light Scattering. The presence of vesicles allows reactions to be carried out in an organized aqueous medium. Model catalytic reactions performed in aqueous medium validated the feasibility of replacing conventional hazardous organic solvents. The newly synthesized biobased surfactants showed satisfactory catalytic activity and allowed the expected products to be obtained with good enantioselectivity.
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- 2025
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6. Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood
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Kariotis, S, Jammeh, E, Swietlik, EM, Pickworth, JA, Rhodes, CJ, Otero, P, Wharton, J, Iremonger, J, Dunning, MJ, Pandya, D, Mascarenhas, TS, Errington, N, Thompson, AAR, Romanoski, CE, Rischard, F, Garcia, JGN, Yuan, JX-J, An, T-HS, Desai, AA, Coghlan, G, Lordan, J, Corris, PA, Howard, LS, Condliffe, R, Kiely, DG, Church, C, Pepke-Zaba, J, Toshner, M, Wort, S, Graf, S, Morrell, NW, Wilkins, MR, Lawrie, A, Wang, D, Bleda, M, Hadinnapola, C, Haimel, M, Auckland, K, Tilly, T, Martin, JM, Yates, K, Treacy, CM, Day, M, Greenhalgh, A, Shipley, D, Peacock, AJ, Irvine, V, Kennedy, F, Moledina, S, MacDonald, L, Tamvaki, E, Barnes, A, Cookson, V, Chentouf, L, Ali, S, Othman, S, Ranganathan, L, Gibbs, JSR, DaCosta, R, Pinguel, J, Dormand, N, Parker, A, Stokes, D, Ghedia, D, Tan, Y, Ngcozana, T, Wanjiku, I, Polwarth, G, Mackenzie Ross, RV, Suntharalingam, J, Grover, M, Kirby, A, Grove, A, White, K, Seatter, A, Creaser-Myers, A, Walker, S, Roney, S, Elliot, CA, Charalampopoulos, A, Sabroe, I, Hameed, A, Armstrong, I, Hamilton, N, Rothman, AMK, Swift, AJ, Wild, JM, Soubrier, F, Eyries, M, Humbert, M, Montani, D, Girerd, B, Scelsi, L, Ghio, S, Gall, H, Ghofrani, A, Bogaard, HJ, Noordegraaf, AV, Houweling, AC, Veld, AHI, Schotte, G, Kariotis, Sokratis [0000-0001-9993-6017], Pickworth, Josephine A [0000-0002-7199-364X], Rhodes, Christopher J [0000-0002-4962-3204], Wharton, John [0000-0001-8110-2575], Iremonger, James [0000-0003-3953-8812], Dunning, Mark J [0000-0002-8853-9435], Errington, Niamh [0000-0001-6768-7394], Thompson, AA Roger [0000-0002-0717-4551], Howard, Luke S [0000-0003-2822-210X], Graf, Stefan [0000-0002-1315-8873], Wilkins, Martin R [0000-0003-3926-1171], Lawrie, Allan [0000-0003-4192-9505], Wang, Dennis [0000-0003-0068-1005], Apollo - University of Cambridge Repository, Gräf, Stefan [0000-0002-1315-8873], Pickworth, Josephine A. [0000-0002-7199-364X], Rhodes, Christopher J. [0000-0002-4962-3204], Dunning, Mark J. [0000-0002-8853-9435], Thompson, A. A. Roger [0000-0002-0717-4551], Howard, Luke S. [0000-0003-2822-210X], Wilkins, Martin R. [0000-0003-3926-1171], Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, and ACS - Atherosclerosis & ischemic syndromes
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HYPOXIA-INDUCED PROLIFERATION ,OPERATED CALCIUM-ENTRY ,Classification and taxonomy ,Science ,PROGNOSTIC IMPACT ,General Physics and Astronomy ,Down-Regulation ,631/114/2404 ,General Biochemistry, Genetics and Molecular Biology ,38/91 ,Functional clustering ,Genomic analysis ,631/114/1386 ,631/1647/2217 ,Humans ,Familial Primary Pulmonary Hypertension ,HLA-DP beta-Chains ,RISK SCORE CALCULATOR ,OUTCOMES ,Pulmonary Arterial Hypertension ,Science & Technology ,Multidisciplinary ,Gene Expression Profiling ,692/4019/592/75 ,article ,49/39 ,General Chemistry ,Multidisciplinary Sciences ,IRON-DEFICIENCY ,Cardiovascular diseases ,UK National PAH Cohort Study Consortium ,REGISTRY ,ASSESSMENTS ,SURVIVAL ,Science & Technology - Other Topics ,Transcriptome ,5-Aminolevulinate Synthetase - Abstract
Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH., Idiopathic pulmonary arterial hypertension is a rare and fatal disease with a heterogeneous treatment response. Here the authors show that unsupervised machine learning of whole blood transcriptomes from 359 patients with idiopathic pulmonary arterial hypertension identifies 3 subgroups (endophenotypes) that improve risk stratification and provide new molecular insights.
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- 2020
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7. P177 Computed tomography diagnostic model for diagnosis of pulmonary hypertension
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Swift, AJ, primary, Chin, M, additional, Currie, B, additional, Elliot, CA, additional, Charalampopolous, A, additional, Rajaram, S, additional, Wild, JM, additional, Johns, C, additional, and Kiely, DG, additional
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- 2017
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8. S52 Computed tomography in the diagnosis of left heart disease in patients with suspected pulmonary hypertension
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Currie, B, primary, Johns, C, additional, Chin, M, additional, Elliot, CA, additional, Condliffe, RA, additional, Charalampopolous, A, additional, Rajaram, S, additional, Wild, JM, additional, Kiely, DG, additional, and Swift, AJ, additional
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- 2017
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9. P183 Impact of patient choice on survival in patients with chronic thromboembolic pulmonary hypertension offered pulmonary endarterectomy
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Quadery, SR, primary, Swift, AJ, additional, Billings, C, additional, Thompson, AAR, additional, Elliot, CA, additional, Hurdman, J, additional, Garrod, S, additional, Charalampopolous, A, additional, Sabroe, I, additional, Armstrong, I, additional, Hamilton, N, additional, Sephton, P, additional, Lewis, RA, additional, Prasannan, P, additional, Jenkins, DP, additional, Pepke-Zaba, J, additional, Screaton, N, additional, Lawrie, A, additional, Johns, CS, additional, Rajaram, S, additional, Hill, C, additional, Wild, JM, additional, Condliffe, R, additional, and Kiely, DG, additional
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- 2017
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10. Beyond MRV: combining remote sensing and ecosystem modeling for geospatial monitoring and attribution of forest carbon fluxes over Maryland, USA
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George C Hurtt, Lei Ma, Rachel Lamb, Elliot Campbell, Ralph O Dubayah, M Hansen, Chengquan Huang, Haley Leslie-Bole, Andrew Lister, Jiaming Lu, Frances Marie S Panday, Quan Shen, Carlos E Silva, and H Tang
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forest ,carbon ,monitoring ,climate mitigation ,remote sensing ,modeling ,Environmental technology. Sanitary engineering ,TD1-1066 ,Environmental sciences ,GE1-350 ,Science ,Physics ,QC1-999 - Abstract
Members of the U.S. Climate Alliance, a coalition of 24 states committed to achieving the emissions reductions outlined in the 2015 Paris Agreement, are considering policy options for inclusion of forest carbon in climate mitigation plans. These initiatives are generally limited by a lack of relevant data on forest carbon stocks and fluxes past-to-future. Previously, we developed a new forest carbon modeling system that combined high-resolution remote sensing, field data, and ecological modeling to estimate contemporary above-ground forest carbon stocks, and projected future forest carbon sequestration potential for the state of Maryland. Here we extended this work to provide a consistent geospatial approach for monitoring changes in forest carbon stocks over time. Utilizing the same data and modeling system developed previously for planning, we integrated historical input data on weather and disturbance to reconstruct the history of vegetation dynamics and forest above-ground carbon stocks annually over the period 1984–2016 at 30 m resolution and provided an extension to 2023. Statewide, forested land had an average annual net above ground carbon sink of 1.37 TgC yr ^−1 , comparable to prior estimates. However, unlike the prior estimates, there was considerable variation around this mean. The statewide net above ground flux ranged interannually from −0.65 to 2.77 Tg C yr ^−1 . At the county scale, the average annual net above ground flux ranged spatially from 0.01 to 0.13 Tg C yr ^−1 and spatiotemporally from −0.43 to 0.24 Tg C yr ^−1 . Attribution analyses indicate the primary importance of persistent and regrowing forests, vegetation structure, local disturbance, and rising CO _2 to the mean flux, and the primary importance of weather to the large-scale interannual variability. These results have important implications for state climate mitigation planning, reporting and assessment. With this approach, it is now possible to monitor changes in forest carbon stocks spatiotemporally over policy relevant domains with a consistent framework that is also enabled for future planning.
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- 2024
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11. Defining priorities for emergency medical services education research: A modified Delphi study
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Scott Lancaster, William J. Leggio, Stephanie Ashford, Elliot Carhart, Kim D. McKenna, and Remle P. Crowe
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Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Objective As out‐of‐hospital medicine evolves, emergency medical services (EMS) education practices must also be updated to ensure that EMS professionals acquire and maintain the skills needed to best serve patients. We aimed to identify and rank the top 10 research priorities related to EMS education in the United States. Methods We conducted a convenience survey of EMS educators to identify challenges facing EMS education before leveraging a purposefully selected panel of EMS educators to prioritize research gaps through a modified Delphi approach. Data were collected electronically (March 2021–June 2021) over 4 survey rounds consisting of idea generation (Rounds 1 and 2), importance scoring (Round 3), and consensus ranking (Round 4). At the end of Round 4, composite scores were used to generate a list of 10 prioritized research gaps related to EMS education. Results In the pre‐Delphi survey, 463 EMS educators identified 2055 challenges facing EMS education. We recruited 32 EMS education experts as Delphi panelists and 28 completed all 4 rounds. Panelists submitted 77 knowledge gaps. The top 10 knowledge gaps included defining competency of EMS learners and educators, association of curricula and accreditation requirements with real‐world practice, the effects of diversity and cultural humility among educators and learners on equitable patient care, evidence‐based teaching methods, and public perception of the EMS profession and education system. Conclusions Although 10 gaps were prioritized, panelists deemed all 77 gaps as having considerable importance for EMS education. This suite of knowledge gaps is intended to guide researchers and research‐funding bodies for future resource allocation.
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- 2023
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12. S111 Differences in characteristics and outcomes in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension
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Ramjug, S, primary, Hussain, N, additional, Hurdman, J, additional, Billings, C, additional, Elliot, CA, additional, Kiely, DG, additional, Sabroe, I, additional, Rajaram, S, additional, Swift, AJ, additional, and Condliffe, R, additional
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- 2016
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13. P28 Chronic thromboembolic pulmonary hypertension: long term outcomes in surgical and non-surgical patients
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Quadery, SR, primary, Condliffe, RA, additional, Billings, C, additional, Thompson, R, additional, Elliot, CA, additional, Charalampopolous, A, additional, Hurdman, J, additional, Hamilton, N, additional, Armstrong, I, additional, Sephton, P, additional, Sabroe, I, additional, Swift, A, additional, Wild, J, additional, and Kiely, DG, additional
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- 2016
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14. A SARS-CoV-2 Vaccine Designed for Manufacturability Results in Unexpected Potency and Non-Waning Humoral Response
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Elliot Campbell, Julie Dobkin, Louis J. Osorio, Afsal Kolloli, Santhamani Ramasamy, Ranjeet Kumar, Derek B. Sant’Angelo, Selvakumar Subbian, Lisa K. Denzin, and Stephen Anderson
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SARS-CoV-2 ,COVID-19 ,vaccine ,durable immunity ,emerging variants ,protection ,Medicine - Abstract
The rapid development of several highly efficacious SARS-CoV-2 vaccines was an unprecedented scientific achievement that saved millions of lives. However, now that SARS-CoV-2 is transitioning to the endemic stage, there exists an unmet need for new vaccines that provide durable immunity and protection against variants and can be more easily manufactured and distributed. Here, we describe a novel protein component vaccine candidate, MT-001, based on a fragment of the SARS-CoV-2 spike protein that encompasses the receptor binding domain (RBD). Mice and hamsters immunized with a prime-boost regimen of MT-001 demonstrated extremely high anti-spike IgG titers, and remarkably this humoral response did not appreciably wane for up to 12 months following vaccination. Further, virus neutralization titers, including titers against variants such as Delta and Omicron BA.1, remained high without the requirement for subsequent boosting. MT-001 was designed for manufacturability and ease of distribution, and we demonstrate that these attributes are not inconsistent with a highly immunogenic vaccine that confers durable and broad immunity to SARS-CoV-2 and its emerging variants. These properties suggest MT-001 could be a valuable new addition to the toolbox of SARS-CoV-2 vaccines and other interventions to prevent infection and curtail additional morbidity and mortality from the ongoing worldwide pandemic.
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- 2023
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15. P157 Hepatocyte growth factor concentration correlates with haemodynamic severity in connective tissue disease-associated pulmonary arterial hypertension
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Condliffe, R, primary, Elliot, CA, additional, Sabroe, I, additional, Zamanian, RT, additional, Morton, A, additional, Swift, AJ, additional, Kiely, DG, additional, and Lawrie, A, additional
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- 2013
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16. Emergency medical services education research priorities during COVID‐19: A modified Delphi study
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Rebecca E. Cash, William J. Leggio, Jonathan R. Powell, Kim D. McKenna, Paul Rosenberger, Elliot Carhart, Adrienne Kramer, Juan A. March, Ashish R. Panchal, and for the Pandemic Educational Effects Task Force
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COVID‐19 ,education and training ,emergency medical services ,emergency medical technician ,paramedic ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Objective Our objective was to identify research priorities to understand the impact of COVID‐19 on initial emergency medical services (EMS) education. Methods We used a modified Delphi method with an expert panel (n = 15) of EMS stakeholders to develop consensus on the research priorities that are most important and feasible to understand the impact of the COVID‐19 pandemic on initial EMS education. Data were collected from August 2020 to February 2021 over 5 rounds (3 electronic surveys and 2 live virtual meetings). In Round 1, participants submitted research priorities over 9 specific areas. Responses were thematically analyzed to develop a list of research priorities reviewed in Round 2. In Round 3, participants rated the priorities by importance and feasibility, with a weighted score (2/3*importance+1/3*feasibility) used for preliminary prioritization. In Round 4, participants ranked the priorities. In Round 5, participants provided their agreement or disagreement with the group's consensus of the top 8 research priorities. Results During Rounds 1 and 2, 135 ideas were submitted by the panel, leading to a preliminary list of 27 research priorities after thematic analysis. The top 4 research priorities identified by the expert panel were prehospital internship access, impact of lack of field and clinical experience, student health and safety, and EMS education program availability and accessibility. Consensus was reached with 10/11 (91%) participants in Round 5 agreeing. Conclusions The identified research priorities are an important first step to begin evaluating the EMS educational infrastructure, processes, and outcomes that were affected or threatened through the pandemic.
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- 2021
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17. Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach
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Kiely, DG, primary, Condliffe, R, additional, Webster, V, additional, Mills, GH, additional, Wrench, I, additional, Gandhi, SV, additional, Selby, K, additional, Armstrong, IJ, additional, Martin, L, additional, Howarth, ES, additional, Bu’Lock, FA, additional, Stewart, P, additional, and Elliot, CA, additional
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- 2010
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18. Plasma levels of TNF-α, IL-6, IFN-γ, IL-12, IL-17, IL-22, and IL-23 in achalasia, eosinophilic esophagitis (EoE), and gastroesophageal reflux disease (GERD)
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Steven Clayton, Elliot Cauble, Ambuj Kumar, Nirav Patil, Dennis Ledford, Narasaiah Kolliputi, Maria F. Lopes-Virella, Donald Castell, and Joel Richter
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Achalasia ,Eosinophilic esophagitis ,GERD ,Inflammatory cytokines ,IL-6 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract An elevation of serum inflammatory biomarkers in achalasia patients compared with controls recently was demonstrated. It has not been determined whether the elevation of inflammatory cytokines is unique to achalasia or occurs with other diseases involving the esophagus. The primary aim of our study was to compare the differences in plasma immunological profiles (TNF- α receptor, IL-6, IFN-γ, IL-12, IL-17, IL-22, and IL-23) of patients with achalasia, eosinophilic esophagitis (EoE), and gastroesophageal reflux disease (GERD). A secondary aim of this study was to classify these same plasma cytokine profiles in the three achalasia subtypes. Methods Plasma from 53 patients with achalasia, 22 with EoE, and 20 with GERD (symptoms plus esophagitis or + reflux study) were analyzed. Exclusion criteria: malignancy, autoimmune condition, immunodeficiency disorder, and treatment with steroids/immune modulating drugs. Cytokine levels were assayed via multiplex enzyme-linked immunosorbent assay (ELISA). Results Our key finding revealed significant elevations in IL- 6 (p = 0.0158) in achalasia patients compared with EoE patients. Overall, plasma inflammatory biomarker patterns were not different in the three subtypes of achalasia. Conclusion There were no differences between the cytokine levels of any of the measured biomarkers between the achalasia and GERD groups suggesting that luminal stasis does increase biomarker levels for any of the cytokines examined in our study. While these results are an early first step towards clarifying some aspects of the pathogenesis of achalasia, they bring about many more questions that require further investigation and expansion. Further investigation with a larger cohort and a broader panel of biomarkers is needed.
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- 2019
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19. Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension.
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Rhodes CJ, Wharton J, Boon RA, Roexe T, Tsang H, Wojciak-Stothard B, Chakrabarti A, Howard LS, Gibbs JS, Lawrie A, Condliffe R, Elliot CA, Kiely DG, Huson L, Ghofrani HA, Tiede H, Schermuly R, Zeiher AM, Dimmeler S, and Wilkins MR
- Abstract
Rationale: MicroRNAs (miRNAs or miRs) are implicated in the pathogenesis of various cardiovascular diseases, including pulmonary arterial hypertension (PAH).Objectives: We sought to measure changes in plasma levels of miRNAs in patients with PAH and relate them to the severity of the disease.Methods: A microarray screen was performed on total plasma RNA from eight patients with PAH and eight healthy control subjects. Quantitative polymerase chain reaction confirmed reduced miR-150 concentrations and was then used to measure miR-150 levels in (1) two separate cohorts of patients with PAH, from London (n = 145) and Sheffield (n = 30), respectively; (2) circulating microvesicles and blood cells; and (3) lungs from a monocrotaline rat model.Measurements and Main Results: Fifty-eight miRNAs showed differences in plasma concentration and miR-150 the largest down-regulation in PAH. Receiver-operator-characteristic analysis showed both raw and normalized plasma miR-150 levels correlated with 2-year survival (P < 0.01) in patients with PAH. Cox regression analysis confirmed miR-150 levels as a significant predictor of survival. Age, baseline cardiac index, World Health Organization functional class, 6-minute walk distance, disease duration, and red cell distribution width also predicted survival. Entering these covariates in a multivariable model verified plasma miR-150 levels as an independent predictor of survival in PAH (hazard ratio, 0.533; P = 0.010). miR-150 levels also predicted survival in a second, independent PAH cohort. miR-150 levels were significantly reduced in circulating microvesicles from patients with PAH and the lungs of the monocrotaline rat.Conclusions: Reduced circulating miR-150 levels are associated with poor survival in PAH. [ABSTRACT FROM AUTHOR]- Published
- 2013
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20. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland.
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Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JS, Howard LS, Pepke-Zaba J, Sheares KK, Corris PA, Fisher AJ, Lordan JL, Gaine S, Coghlan JG, Wort SJ, Gatzoulis MA, Peacock AJ, Ling, Yi, Johnson, Martin K, and Kiely, David G
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Rationale: Incident pulmonary arterial hypertension was underrepresented in most pulmonary hypertension registries and may have a different disease profile to prevalent disease.Objectives: To determine the characteristics and outcome of a purely incident, treatment-naive cohort of idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension and to determine the changes in presentations and survival over the past decade in the United Kingdom and Ireland.Methods: All consecutive newly diagnosed patients from 2001 to 2009 were identified prospectively.Measurements and Main Results: A total of 482 patients (93% idiopathic, 5% heritable, and 2% anorexigen-associated pulmonary arterial hypertension) were diagnosed, giving rise to an estimated incidence of 1.1 cases per million per year and prevalence of 6.6 cases per million in 2009. Younger patients (age ≤ 50 yrs) had shorter duration of symptoms, fewer comorbidities, better functional and exercise capacity, higher percent diffusing capacity of carbon monoxide, more severe hemodynamic impairment, but better survival compared with older patients. In comparison with the earlier cohorts, patients diagnosed in 2007-2009 were older, more obese, had lower percent diffusing capacity of carbon monoxide,(,) and more comorbidities, but better survival. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) equation, REVEAL risk score, and Pulmonary Hypertension Connection Registry survival equation accurately predicted survival of our incident cohort at 1 year.Conclusions: This study highlights the influence of age on phenotypes of incident pulmonary arterial hypertension and has shown the changes in demographics and epidemiology over the past decade in a national setting. The results suggest that there may be two subtypes of patients: the younger subtype with more severe hemodynamic impairment but better survival, compared with the older subtype who has more comorbidities. [ABSTRACT FROM AUTHOR]- Published
- 2012
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21. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era.
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Condliffe R, Kiely DG, Peacock AJ, Corris PA, Gibbs JS, Vrapi F, Das C, Elliot CA, Johnson M, DeSoyza J, Torpy C, Goldsmith K, Hodgkins D, Hughes RJ, Pepke-Zaba J, Coghlan JG, Condliffe, Robin, Kiely, David G, Peacock, Andrew J, and Corris, Paul A
- Abstract
Rationale: Pulmonary arterial hypertension in association with connective tissue disease (CTD-PAH) has historically had a poor prognosis, with a 1-year survival rate among patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) of 45%. However, more therapies have become available.Objectives: To investigate the survival and characteristics of all patients diagnosed with CTD-PAH in the U.K. pulmonary hypertension service.Methods: National registry of all incident cases of CTD-PAH diagnosed consecutively between January 2001 and June 2006.Measurements and Main Results: Patients with CTD-PAH (429; 73% SSc-PAH) were diagnosed by a catheter-based approach. One- and 3-year survival rates were 78 and 47% for patients with isolated SSc-PAH. Survival was worse for those with respiratory disease-associated SSc-PAH (3-yr survival, 28%; P = 0.005) whereas survival among patients with exercise-induced SSc-PAH was superior (3-yr survival, 86%; P = < 0.001). Age, sex, mixed venous oxygen saturation, and World Health Organization functional class were independent predictors of survival in isolated SSc-PAH. Nineteen percent of patients with exercise-induced SSc-PAH and 39% of patients with isolated SSc-PAH who were in functional classes I and II had evidence of disease progression. The prevalence of diagnosed SSc-PAH is 2.93 per 1 million. The 3-year survival rate of 75% for those with pulmonary arterial hypertension associated with systemic lupus erythematosus (SLE-PAH) was significantly better than that for patients with SSc-PAH (P = 0.01).Conclusions: Survival of patients with SSc-PAH in the modern treatment era is better than in historical series. A significant proportion of patients with mild functional impairment or exercise-induced SSc-PAH have evidence of disease progression. Survival of patients with respiratory disease-associated pulmonary hypertension is inferior. SLE-PAH has a better prognosis than SSc-PAH. [ABSTRACT FROM AUTHOR]- Published
- 2009
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22. Advancing breeding phenology does not affect incubation schedules in chestnut‐crowned babblers: Opposing effects of temperature and wind
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Elliot Capp, Andrea L. Liebl, Alexandra G. Cones, and Andrew F. Russell
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allometry ,climate change ,incubation bouts ,incubation constancy ,nest attentiveness ,recess bouts ,Ecology ,QH540-549.5 - Abstract
Abstract Projecting population responses to climate change requires an understanding of climatic impacts on key components of reproduction. Here, we investigate the associations among breeding phenology, climate and incubation schedules in the chestnut‐crowned babbler (Pomatostomus ruficeps), a 50 g passerine with female‐only, intermittent incubation that typically breeds from late winter (July) to early summer (November). During daylight hours, breeding females spent an average of 33 min on the nest incubating (hereafter on‐bouts) followed by 24‐min foraging (hereafter off‐bouts), leading to an average daytime nest attentiveness of 60%. Nest attentiveness was 25% shorter than expected from allometric calculations, largely because off‐bout durations were double the expected value for a species with 16 g clutches (4 eggs × 4 g/egg). On‐bout durations and daily attentiveness were both negatively related to ambient temperature, presumably because increasing temperatures allowed more time to be allocated to foraging with reduced detriment to egg cooling. By contrast, on‐bout durations were positively associated with wind speed, in this case because increasing wind speed exacerbated egg cooling during off‐bouts. Despite an average temperature change of 12°C across the breeding season, breeding phenology had no effect on incubation schedules. This surprising result arose because of a positive relationship between temperature and wind speed across the breeding season: Any benefit of increasing temperatures was canceled by apparently detrimental consequences of increasing wind speed on egg cooling. Our results indicate that a greater appreciation for the associations among climatic variables and their independent effects on reproductive investment are necessary to understand the effects of changing climates on breeding phenology.
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- 2018
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23. On the calculation of normal modes of a coupled ice-shelf/sub-ice-shelf cavity system
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MICHAEL H. MEYLAN, LUKE G. BENNETTS, ROGER J. HOSKING, and ELLIOT CATT
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Environmental sciences ,GE1-350 ,Meteorology. Climatology ,QC851-999 - Published
- 2017
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24. Malignant Peritoneal Mesothelioma in the setting of a Ventriculo-Peritoneal Shunt: A novel clinical presentation
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Monira Haque, Nadia Hameed, Christopher T Perry, Elliot Carter, and Wadad S Mneimneh
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
We report a case of malignant peritoneal mesothelioma (MPM) in a 31-year-old male with history of cerebral palsy, hydrocephalus, and ventriculoperitoneal shunt (VPS) placed since infancy. He presented with fever, abdominal pain and distension. Computed tomography scan revealed a thick-walled rim-enhancing fluid collection, interpreted as pseudocyst. Intraoperatively, diffuse nodular peritoneal thickening with adhesions was demonstrated. The resection specimen consisted of multiple membranous fragments displaying firm nodules. Microscopic examination revealed a tumefactive malignant-appearing epithelioid proliferation involving the peritoneum, focally invading the underlying fat. Immunohistochemically, the tumor cells expressed keratin AE1/AE3, CK7, CK5/6, Calretinin, WT1 and D2-40, and were negative for CEA and MOC31. The findings were consistent with MPM, epithelioid type. The patient’s condition continued to decline with increasing abdominal distension during the month following the original diagnosis. While atypical mesothelial hyperplasia has been described in association with long standing VPS, well-documented cases of MPM have not been previously reported in such context.
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- 2018
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25. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer study)
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Mark B Gabbay, Adele Ring, Richard Byng, Pippa Anderson, Rod S Taylor, Caryn Matthews, Tirril Harris, Vashti Berry, Paula Byrne, Elliot Carter, Pam Clarke, Laura Cocking, Suzanne Edwards, Richard Emsley, Mauro Fornasiero, Lucy Frith, Shaun Harris, Peter Huxley, Siw Jones, Peter Kinderman, Michael King, Liv Kosnes, Daniel Marshall, Dave Mercer, Carl May, Debbie Nolan, Ceri Phillips, Tim Rawcliffe, Alexandra V Sardani, Elizabeth Shaw, Sam Thompson, Jane Vickery, Brian Wainman, and Mark Warner
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pilot randomised controlled trial ,debt ,depression ,counselling ,citizens advice ,Medical technology ,R855-855.5 - Abstract
Background: Depression and debt are common in the UK. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer) aimed to assess the clinical effectiveness and cost-effectiveness of the addition of a primary care debt counselling advice service to usual care for patients with depression and debt. However, the study was terminated early during the internal pilot trial phase because of recruitment delays. This report describes the rationale, methods and findings of the pilot study, and implications for future research. Objectives: The overarching aim of the internal pilot was to identify and resolve problems, thereby assessing the feasibility of the main trial. The specific objectives were to confirm methods for practice recruitment and the ability to recruit patients via the proposed approaches; to determine the acceptability of the study interventions and outcome measures; to assess contamination; to confirm the randomisation method for main trial and the level of participant attrition; and to check the robustness of data collection systems. Design: An adaptive, parallel, two-group multicentre randomised controlled pilot trial with a nested mixed-methods process and economic evaluation. Both individual- and cluster (general practice)-level were was used in the pilot phase to assign participants to intervention or control groups. Setting: General practices in England and Wales. Participants: Individuals were included who were aged ≥ 18 years, scored ≥ 14 on the Beck Depression Inventory II and self-identified as having debt worries. The main exclusion criteria were being actively suicidal or psychotic and/or severely depressed and unresponsive to treatment; having a severe addiction to alcohol/illicit drugs; being unable/unwilling to give written informed consent; currently participating in other research including follow-up phases; having received Citizens Advice Bureau (CAB) debt advice in the past year; and not wanting debt advice via a general practice. Interventions: The participants in the intervention group were given debt advice provided by the CAB and shared biopsychosocial assessment, in addition to treatment as usual (TAU) and two debt advice leaflets. The participants in the control group were given advice leaflets provided by the general practitioner and TAU only. Main outcome measures: (1) Outcomes of the pilot trial – the proportion of eligible patients who consented, the number of participants recruited compared with target, assessment of contamination, and assessment of patient satisfaction with intervention and outcome measures. (2) Participant outcomes – primary – Beck Depression Inventory II; secondary – psychological well-being, health and social care utilisation, service satisfaction, substance misuse, record of priority/non-priority debts, life events and difficulties, and explanatory measures. Outcomes were assessed at baseline (pre-randomisation) and at 4 months post randomisation. Other data sources – qualitative interviews were conducted with participants, clinicians and CAB advisors. Results: Of the 238 expressions of interest screened, 61 participants (26%) were recruited and randomised (32 in the intervention group and 29 in the control group). All participants provided baseline outcomes and 52 provided the primary outcome at 4 months’ follow-up (14.7% dropout). Seventeen participants allocated to the intervention saw a CAB advisor. Descriptive statistics are reported for participants with complete outcomes at baseline and 4 months’ follow-up. Our qualitative findings suggest that the relationship between debt and depression is complex, and the impact of each on the other is compounded by other psychological, social and contextual influences. Conclusions: As a result of low recruitment, this trial was terminated at the internal pilot phase and was too small for inferential statistical analysis. We recommend ways to reduce this risk when conducting complex trials among vulnerable populations recruited in community settings. These cover trial design, the design and delivery of interventions, recruitment strategies and support for sites. Trial registration: Current Controlled Trials ISRCTN79705874. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 35. See the NIHR Journals Library website for further project information. Mark Gabbay and Adele Ring are part-funded by NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) North West Coast and Richard Byng and Rod S Taylor, Vashti Berry and Elizabeth Shaw part-funded by NIHR CLAHRC South West Peninsula.
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- 2017
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26. S52 Computed tomography in the diagnosis of left heart disease in patients with suspected pulmonary hypertension
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Currie, B, Johns, C, Chin, M, Elliot, CA, Condliffe, RA, Charalampopolous, A, Rajaram, S, Wild, JM, Kiely, DG, and Swift, AJ
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BackgroundIdentification of patients with left heart disease (LHD) as the cause of pulmonary hypertension is challenging, developing a tool that can identify these patients would reduce unnecessary referral for investigation at specialist centres and may reduce the burden of invasive investigations. The aim was to investigate the capability of computed tomography (CT)-derived metrics for the diagnosis LHD in a cohort of patients with suspected pulmonary hypertension.MethodsPatients with suspected pulmonary hypertension who underwent CT and RHC were identified. Derivation and validation cohorts were randomly constructed to derive and test a binary logistic regression model. All image analysis took place on PACS system blinded to patient’s cardiac catheter data and diagnosis. CT measurements of the cardiac chambers and vessels were taken. LHD was defined by increased pulmonary arterial wedge pressure (PAWP) ≥15 mmHg. A second threshold of 18 mmHg defined more advanced LHD. Backward binary logistic regression in a derivation cohort identified a model for predicting Group 2 PH. This model was tested in the validation cohort and compared to individual CT derived variables using receiver operating characteristic curve analysis and chi-square.ResultsThe CT scans were from 66 different centres and 446 patients were identified, derivation cohort (n=235) and validation cohort (n=211). Left atrial area was found to be most significant individual predictor of elevated PAWP, area under curve (AUC) 0.86, p<0.001, the accuracy was higher for identification of PAWP ≥18, AUC 0.87, p=0.87, p<0.001. Derived regression models did not add diagnostic value AUC in validation cohort 0.87, p<0.001. A limit for enlarged left atrial area was set at 27.5 cm2. This had sensitivity 65% and specificity 90% in predicting Group 2 PH using PAWP ≥18 mmHg as a threshold.ConclusionsCT derived left atrial area is a specific predictor of LHD in suspected pulmonary hypertension. Composite models did not increase diagnostic value. Left atrial area on CT may be a useful tool for diagnosing PH-LHD and may reduce unnecessary referrals to specialist PH centres and reduce the number of invasive investigations.[Figure]
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- 2017
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27. P183 Impact of patient choice on survival in patients with chronic thromboembolic pulmonary hypertension offered pulmonary endarterectomy
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Quadery, SR, Swift, AJ, Billings, C, Thompson, AAR, Elliot, CA, Hurdman, J, Garrod, S, Charalampopolous, A, Sabroe, I, Armstrong, I, Hamilton, N, Sephton, P, Lewis, RA, Prasannan, P, Jenkins, DP, Pepke-Zaba, J, Screaton, N, Lawrie, A, Johns, CS, Rajaram, S, Hill, C, Wild, JM, Condliffe, R, and Kiely, DG
- Abstract
IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is potentially curable by pulmonary endarterectomy (PEA). Despite this a significant proportion of patients offered PEA decline surgery.ObjectiveTo compare long term survival and prognostic indicators in patients with technically operable CTEPH who underwent PEA and those who declined surgery.MethodsData were collected for consecutive, treatment-naive patients diagnosed with CTEPH between 2001 and 2014 identified from the ASPIRE-pulmonary-hypertension-registry.ResultsOf 588 patients with CTEPH, 368 patients were offered surgery. Seventy six percent (n=281) underwent PEA, 20% (n=72) declined surgery and 4% (n=15) were planned to undergo surgery. Five year survival was superior in patients undergoing PEA at 83% compared to patients who declined surgery at 56% (p=0.001, log-rank test). In patients who were offered surgery, mixed venous oxygen saturation (SvO2) (p=0.003), gas transfer (DLco) (p=0.042), history of coronary artery disease (p=0.031) and patient choice (declining surgery) (p<0.001) were independent predictors of mortality. For patients who declined surgery a median threshold of DLco 62%, right atrial pressure 11 mmHg, and SvO262% the positive and negative predictive values for 3 year survival were 31% and 100%, 32% and 95% and 30% and 97%, respectively.[Figure]ConclusionIn a cohort of consecutive patients with CTEPH the long-term survival of patients undergoing PEA is excellent and superior to patients declining surgery and strongly favours surgical intervention in eligible patients. More work is required to understand factors influencing decision making in CTEPH and to ensure that patients are counselled and supported to make informed decisions.
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- 2017
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28. P177 Computed tomography diagnostic model for diagnosis of pulmonary hypertension
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Swift, AJ, Chin, M, Currie, B, Elliot, CA, Charalampopolous, A, Rajaram, S, Wild, JM, Johns, C, and Kiely, DG
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IntroductionPulmonary hypertension (PH) is severe cardiorespiratory condition associated with poor prognosis with diagnosis reliant on invasive right heart catheterization (RHC). Several measurements on computed tomography (CT) have been shown to have diagnostic value in PH, however few studies have attempted to identify the added value of combining CT metrics for the diagnosis of PH.The aim of this study is to develop a composite diagnostic CT model for patients with suspected PH.MethodsPatients with suspected PH who underwent CT and RHC were identified. Standard axial and reconstructed images were used to derive CT metrics of cardiac and pulmonary vasculature anatomy. A derivation and validation cohort were randomly constructed to derive and test a binary logistic regression model of PH. Receiver operating characteristic (ROC) analysis assessed the diagnostic value of the model and individual metrics.Results491 patients were identified (derivation cohort n=247 and validation n=244). Main pulmonary arterial (MPA) diameter, right ventricular outflow tract (RVOT) thickness, right ventricular muscle area and interventricular septal (IVS) angle variables correlated strongest to mean pulmonary arterial pressure, r=0.458 (p<0.001), r=0.441 (p<0.001), r=0.481 (p<0.001) and r=0.622 (p<0.001), respectively. The diagnostic regression model included RVOT, IVS angle, MPA diameter, LV size and the interlobar artery to bronchus ratio. The area under the curve from ROC analysis was 0.931 (p=<0.001) in the derivation cohort and a 0.938 (p=<0.001) value in the validation cohort, more accurate the individual CT metrics (p<0.05). A highly sensitive threshold of 0 units had a sensitivity of 95% and specificity of 50% and a highly specific threshold of 3.3 units had sensitivity of 69% and specificity of 100%.[Figure]ConclusionA multivariate diagnostic model derived from axial CT images is accurate in suspected PH. The identified highly sensitive and specific thresholds may help in both patient screening and in selection for referral to specialist centres.
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- 2017
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29. Do Hemodynamic Definitions of Chronic Thromboembolic Pulmonary Hypertension Distinguish Between Distinct Phenotypes of Chronic Thromboembolic Pulmonary Disease?
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Cerrone E, Hameed AG, Kiely DG, Condliffe R, Swift AJ, Rajaram S, Smith I, Hurdman JA, Elliot CA, Thompson AAR, Rothman AM, and Charalampopoulos A
- Abstract
Background: Chronic thromboembolic pulmonary disease (CTEPD) is defined by chronic organized thrombi in the pulmonary circulation without or with pulmonary hypertension (CTEPH). The current definition of CTEPH has adopted lower mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) thresholds. Our aim was to identify its impact on the characterization of patients with CTEPD., Methods: All consecutive CTEPD patients referred for cardiopulmonary exercise testing (CPET) in a PH center were divided into four groups based on pulmonary haemodynamics. Group A: mPAP≤20 mmHg, Group B: mPAP>20 mmHg with PVR>2 and ≤3 WU, Group C: mPAP>20 mmHg with PVR>3 WU, Group D: mPAP>20 mmHg with PVR<2 WU (''unclassified''). We compared CPET, CT pulmonary angiography, and MRI data across the groups., Results: There was mild aerobic capacity impairment, mild/moderate ventilatory inefficiency, and no significant cardiac limitation on CPET in all groups. However, patients in Groups A and D had better ventilatory efficiency and less oxygen desaturation on exercise due to lower dead-space ventilation. There was no difference in chronic pulmonary emboli burden and distribution, or resting RV function between the groups. Seventeen patients were reclassified as having ''CTEPH'' based on the current definition. No functional deterioration was noted within a median period of 13 months on repeat CPET., Conclusions: CTEPD patients with similar clot burden and RV function without or with mild/moderate PH displayed a similar pattern of cardiopulmonary limitation, except for ventilatory efficiency. The current definition for CTEPH may lead to reclassification of CTEPH in a considerable number of patients.
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- 2024
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30. The spectrum of systemic sclerosis-associated pulmonary hypertension: Insights from the ASPIRE registry.
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Smith H, Thompson AAR, Akil M, Alabed S, Charalampopoulos A, Dwivedi K, Elliot CA, Hameed A, Haque A, Hamilton N, Hill C, Hurdman J, Kilding R, Kuet KP, Rajaram S, Rothman AMK, Swift AJ, Wild JM, Kiely DG, and Condliffe R
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- Humans, Male, Female, Middle Aged, Survival Rate trends, Retrospective Studies, Vascular Resistance physiology, Pulmonary Wedge Pressure physiology, Adult, Follow-Up Studies, Registries, Scleroderma, Systemic complications, Scleroderma, Systemic physiopathology, Hypertension, Pulmonary etiology, Hypertension, Pulmonary physiopathology, Hypertension, Pulmonary diagnosis
- Abstract
Background: There are limited data assessing the spectrum of systemic sclerosis-associated pulmonary hypertension (PH)., Methods: Data for 912 systemic sclerosis patients assessed between 2000 and 2020 were retrieved from the Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry and classified based on 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines and multimodality investigations., Results: Reduction in pulmonary vascular resistance (PVR) diagnostic threshold to >2WU resulted in a 19% increase in precapillary PH diagnoses. Patients with PVR ≤2WU had superior survival to PVR >2-3WU which was similar to PVR >3-4WU. Survival in pulmonary arterial hypertension (PAH) was superior to PH associated with lung disease. However, patients with mild parenchymal disease on CT had similar characteristics and outcomes to patients without lung disease. Combined pre- and postcapillary PH had significantly poorer survival than isolated postcapillary PH. Patients with mean pulmonary arterial wedge pressure (PAWP) 13-15 mm Hg had similar haemodynamics and left atrial volumes to those with PAWP >15 mm Hg. Unclassified-PH had more frequently dilated left atria and higher PAWP than PAH. Although Unclassified-PH had a similar survival to No-PH, 36% were subsequently diagnosed with PAH or PH associated with left heart disease. The presence of 2-3 radiological signs of pulmonary veno-occlusive disease was noted in 7% of PAH patients and was associated with worse survival. Improvement in incremental shuttle walking distance of ≥30 m following initiation of PAH therapy was associated with superior survival. PAH patients diagnosed after 2011 had greater use of combination therapy and superior survival., Conclusion: A number of systemic sclerosis PH phenotypes can be recognized and characterized using haemodynamics, lung function and multimodality imaging., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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31. Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry.
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Durrington C, Hurdman JA, Elliot CA, Maclean R, Van Veen J, Saccullo G, De-Foneska D, Swift AJ, Smitha R, Hill C, Thomas S, Dwivedi K, Alabed S, Wild JM, Charalampopoulos A, Hameed A, Rothman AMK, Watson L, Hamilton N, Thompson AAR, Condliffe R, and Kiely DG
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- Humans, Follow-Up Studies, Risk Factors, Registries, Chronic Disease, Hypertension, Pulmonary complications, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary epidemiology, Pulmonary Embolism complications, Pulmonary Embolism diagnosis, Pulmonary Embolism epidemiology, Thromboembolism complications, Thromboembolism diagnosis
- Abstract
Background: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined., Methods: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included., Results: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents., Conclusions: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH., Competing Interests: Conflict of interest: C. Durrington reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports lecture honoraria from Janssen Pharmaceuticals, outside the submitted work. C.A. Elliot reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D. De-Fonseka reports a leadership role on the Pleural Specialist Advisory Group and Pleural Disease Guideline Committee for the British Thoracic Society, outside the submitted work. A.J. Swift reports support for the present manuscript from a Wellcome Trust fellowship, and also reports grants from Janssen Pharmaceuticals, NIHR and Wellcome Trust, and consulting fees from Janssen Pharmaceuticals, outside the submitted work. K. Dwivedi reports support for the present manuscript from Wellcome 4Ward North fellowship, and also reports grants from Janssen, and lecture honoraria from Royal College of Radiologists, and is a committee member for the Royal College of Radiologists Artificial Intelligence Working Group and Royal College of Radiologists RADIANT group, outside the submitted work. A. Charalampopoulos reports lecture honoraria from Janssen and Boehringer, outside the submitted work. A. Hameed reports lecture honoraria and travel support from Janssen, outside the submitted work. A.M.K. Rothman reports grants from a Wellcome Trust Clinical Research Career Development Fellowship (206632/Z/17/Z), MRC (experimental medicine grant MR/W026279/1), Abbott Laboratories, Medtronic Inc., Endotronix, SoniVie, NXT Biomedical, Gradient and Neptune Medical, outside the submitted work. N. Hamilton reports consulting fees and travel support from Janssen, lecture honoraria from MSD and Janssen, advisory board participation with Bayer, MSD, Janssen and Vifor, and a leadership role as pharmacist for the NHS Specialist Respiratory Clinical Reference Group, outside the submitted work. A.A.R. Thompson reports grants from the British Heart Foundation and NIHR, and lecture honoraria and travel support from Janssen-Cilag Ltd, outside the submitted work. R. Condliffe reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D.G. Kiely reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports grants from Janssen Pharmaceuticals, NIHR Sheffield Biomedical Research Centre and Ferrer, consulting fees and lecture honoraria from Janssen Pharmaceuticals, Ferrer, Altavant, MSD and United Therapeutics, travel support from Janssen, Ferrer, MSD and United Therapeutics, advisory board membership for Janssen and MSD, and leadership roles as a member of the Clinical Reference Group for Specialised Respiratory Medicine (NHS England) and lead of the UK National Audit of Pulmonary Hypertension, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)
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- 2024
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32. Physical activity has a stronger correlation with arterial stiffness than strength, balance, or BMI in an older population.
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Hill H, Elliot CA, Lizamore CA, and Hamlin MJ
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Background: Arterial stiffness is associated with an array of debilitating health conditions. While exercise typically has beneficial effects on both arterial stiffness and overall health, more research is needed to understand the associations of different types of fitness indices with arterial stiffness. Aim: To investigate the relationship between balance, strength, cardiovascular fitness and physical activity with arterial stiffness (as measured by pulse wave velocity (PWV)) in older adults. Method: Eighty retirement-village residents (24 males, 56 females, age: 78.2 ± 6.4 years, weight: 69.4 ± 12.5 kg, height: 162.9 ± 8.5 cm) completed the Yale Physical Activity Survey, PWV measurement, 30-s sit-to-stand leg strength test, hand grip strength assessment, 4-stage balance test, and a 6-min walk fitness test. The number of exiting risk factors (smoking, previous heart incidents, previous stroke(s), having hypertension, or taking anti-hypertension medication) were tallied. Pearson's correlations were used to assess the relationship between PWV and health and fitness parameters. Results were interpreted using qualitative inference. Results: The number of risk factors (r = 0.57, p < 0.001), age (r = 0.51, p < 0.001) and systolic blood pressure (r = 0.50, p = 0.001) had strong, harmful associations with PWV. Total physical activity minutes/week (r = -0.31 p = 0.01), total energy expenditure Kcal/week (r = -0.30, p = 0.01), and the 6-min walk test (r = -0.29, p = 0.01) had a moderate, beneficial association with PWV, while sit-to-stand (r = -0.27, p = 0.02) and balance (r = -0.27, p = 0.01) had a weak, beneficial association with PWV. Hand grip strength (r = 0.02, p = 0.94) and body mass index (r = -0.04, p = 0.75) had no significant associations with PWV. Discussion: All measured fitness indices had beneficial associations with PWV. However, having more risk factors, increased age, and higher systolic blood pressure had significant (harmful) associations with PWV in our older population. Conclusion: Controlling cardiovascular risk factors, especially high systolic blood pressure, is likely to have the largest beneficial effect on PWV. Improving general physical activity, including walking capacity, may prove beneficial in improving PWV in an older population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hill, Elliot, Lizamore and Hamlin.)
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- 2023
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33. Establishing minimally important differences for cardiac MRI end-points in pulmonary arterial hypertension.
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Alabed S, Garg P, Alandejani F, Dwivedi K, Maiter A, Karunasaagarar K, Rajaram S, Hill C, Thomas S, Gossling R, Sharkey MJ, Salehi M, Wild JM, Watson L, Hameed A, Charalampopoulos A, Lu H, Rothman AMK, Thompson AAR, Elliot CA, Hamilton N, Johns CS, Armstrong I, Condliffe R, van der Geest RJ, Swift AJ, and Kiely DG
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- Humans, Female, Adult, Middle Aged, Aged, Male, Quality of Life, Magnetic Resonance Imaging methods, Stroke Volume physiology, Familial Primary Pulmonary Hypertension, Ventricular Function, Right, Predictive Value of Tests, Pulmonary Arterial Hypertension diagnostic imaging, Ventricular Dysfunction, Right
- Abstract
Background: Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives"., Methods: Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements., Results: 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening., Conclusions: This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR., Competing Interests: Conflict of interest: A.J. Swift has received research grant funding from Janssen Pharmaceuticals, and consultancy fees from Janssen Pharmaceuticals and General Electric. D.G. Kiely has received grant funding from Ferrer and Janssen Pharmaceuticals, and speaker and consultancy fees and funding for travel from Acceleron, Altavant, Ferrer, Janssen, MSD and United Therapeutics. The other authors have no relationships relevant to the contents of this paper to disclose., (Copyright ©The authors 2023.)
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- 2023
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34. Association between Yoga Participation and Arterial Stiffness: A Cross-Sectional Study.
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Raj T, Elliot CA, Stoner L, Higgins S, Paterson C, and Hamlin MJ
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- Adult, Humans, Female, Male, Cross-Sectional Studies, Pulse Wave Analysis, Arterial Pressure, Risk Factors, Blood Pressure physiology, Cardiovascular Diseases epidemiology, Vascular Stiffness physiology
- Abstract
Background: Yoga may help adults of all fitness levels increase their physical activity and decrease their cardiovascular disease risk., Aim: To determine if arterial stiffness is lower (beneficial) in yoga versus non-yoga participants., Method: This cross-sectional study included 202 yoga (48.4 + 14.1 years, 81% female) and 181 (42.8 + 14.1 years, 44% female) non-yoga participants. The primary outcome was carotid-femoral pulse wave velocity (cfPWV). The two groups were compared using analysis of covariance with adjustments for demographic (age and sex), hemodynamic (mean arterial pressure and heart rate), lifestyle (physical activity levels, sedentary behaviour, smoking status and perceived stress score) and cardiometabolic (waist-to-hip ratio, total cholesterol and fasting glucose) factors., Results: Following adjustments, cfPWV was significantly lower in yoga compared to non-yoga participants with a mean difference: -0.28 m.s
-1 , (95% CI = -0.55 to 0.08)., Conclusion: At a population level, yoga participation may assist with decreasing the risk of cardiovascular disease in adults.- Published
- 2023
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35. Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis.
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Hoeper MM, Dwivedi K, Pausch C, Lewis RA, Olsson KM, Huscher D, Pittrow D, Grünig E, Staehler G, Vizza CD, Gall H, Distler O, Opitz C, Gibbs JSR, Delcroix M, Park DH, Ghofrani HA, Ewert R, Kaemmerer H, Kabitz HJ, Skowasch D, Behr J, Milger K, Lange TJ, Wilkens H, Seyfarth HJ, Held M, Dumitrescu D, Tsangaris I, Vonk-Noordegraaf A, Ulrich S, Klose H, Claussen M, Eisenmann S, Schmidt KH, Swift AJ, Thompson AAR, Elliot CA, Rosenkranz S, Condliffe R, Kiely DG, and Halank M
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- Carbon Monoxide therapeutic use, Familial Primary Pulmonary Hypertension, Female, Humans, Male, Peptides therapeutic use, Prognosis, Registries, Hypertension, Pulmonary drug therapy
- Abstract
Background: Among patients meeting diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH), there is an emerging lung phenotype characterised by a low diffusion capacity for carbon monoxide (DLCO) and a smoking history. The present study aimed at a detailed characterisation of these patients., Methods: We analysed data from two European pulmonary hypertension registries, COMPERA (launched in 2007) and ASPIRE (from 2001 onwards), to identify patients diagnosed with IPAH and a lung phenotype defined by a DLCO of less than 45% predicted and a smoking history. We compared patient characteristics, response to therapy, and survival of these patients to patients with classical IPAH (defined by the absence of cardiopulmonary comorbidities and a DLCO of 45% or more predicted) and patients with pulmonary hypertension due to lung disease (group 3 pulmonary hypertension)., Findings: The analysis included 128 (COMPERA) and 185 (ASPIRE) patients with classical IPAH, 268 (COMPERA) and 139 (ASPIRE) patients with IPAH and a lung phenotype, and 910 (COMPERA) and 375 (ASPIRE) patients with pulmonary hypertension due to lung disease. Most patients with IPAH and a lung phenotype had normal or near normal spirometry, a severe reduction in DLCO, with the majority having no or a mild degree of parenchymal lung involvement on chest computed tomography. Patients with IPAH and a lung phenotype (median age, 72 years [IQR 65-78] in COMPERA and 71 years [65-76] in ASPIRE) and patients with group 3 pulmonary hypertension (median age 71 years [65-77] in COMPERA and 69 years [63-74] in ASPIRE) were older than those with classical IPAH (median age, 45 years [32-60] in COMPERA and 52 years [38-64] in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries). While 99 (77%) patients in COMPERA and 133 (72%) patients in ASPIRE with classical IPAH were female, there was a lower proportion of female patients in the IPAH and a lung phenotype cohort (95 [35%] COMPERA; 75 [54%] ASPIRE), which was similar to group 3 pulmonary hypertension (336 [37%] COMPERA; 148 [39%] ASPIRE]). Response to pulmonary arterial hypertension therapies at first follow-up was available from COMPERA. Improvements in WHO functional class were observed in 54% of patients with classical IPAH, 26% of patients with IPAH with a lung phenotype, and 22% of patients with group 3 pulmonary hypertension (p<0·0001 for classical IPAH vs IPAH and a lung phenotype, and p=0·194 for IPAH and a lung phenotype vs group 3 pulmonary hypertension); median improvements in 6 min walking distance were 63 m, 25 m, and 23 m for these cohorts respectively (p=0·0015 for classical IPAH vs IPAH and a lung phenotype, and p=0·64 for IPAH and a lung phenotype vs group 3 pulmonary hypertension), and median reductions in N-terminal-pro-brain-natriuretic-peptide were 58%, 27%, and 16% respectively (p=0·0043 for classical IPAH vs IPAH and a lung phenotype, and p=0·14 for IPAH and a lung phenotype vs group 3 pulmonary hypertension). In both registries, survival of patients with IPAH and a lung phenotype (1 year, 89% in COMPERA and 79% in ASPIRE; 5 years, 31% in COMPERA and 21% in ASPIRE) and group 3 pulmonary hypertension (1 year, 78% in COMPERA and 64% in ASPIRE; 5 years, 26% in COMPERA and 18% in ASPIRE) was worse than survival of patients with classical IPAH (1 year, 95% in COMPERA and 98% in ASPIRE; 5 years, 84% in COMPERA and 80% in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries)., Interpretation: A cohort of patients meeting diagnostic criteria for IPAH with a distinct, presumably smoking-related form of pulmonary hypertension accompanied by a low DLCO, resemble patients with pulmonary hypertension due to lung disease rather than classical IPAH. These observations have pathogenetic, diagnostic, and therapeutic implications, which require further exploration., Funding: COMPERA is funded by unrestricted grants from Acceleron, Bayer, GlaxoSmithKline, Janssen, and OMT. The ASPIRE Registry is supported by Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK., Competing Interests: Declaration of interests MMH received fees for lectures or consultations from Acceleron, Actelion, Bayer, GlaxoSmithKline, Janssen, MSD, and Pfizer. KD has received research funding from Janssen Pharmaceuticals, National Institute of Health Research (NIHR), UK and The Wellcome Trust, UK. RAL has received honoraria and research grants from Janssen Pharmaceuticals. KMO has received fees for lectures or consultations from Acceleron, Actelion, Bayer, GlaxoSmithKline, Janssen, MSD, Pfizer, and United Therapeutics. DH has received travel compensation from Shire. DP has received fees for consultations from Actelion, Amgen, Aspen, Bayer, Biogen, Boehringer Ingelheim, Daiichi Sankyo, MSD, Novartis, Sanofi-Genzyme, Takeda and Viatris. EG has received fees for lectures or consultations from Actelion, Bayer, GlaxoSmithKline, Janssen, MSD, Pfizer, and United Therapeutics. GS has received honoraria for lectures or consultancy for Actelion, Bayer, GlaxoSmithKline, Novartis, and Pfizer. CDV has received fees for lectures or consultations from Acceleron, Actelion, Bayer, GlaxoSmithKline, Janssen, MSD, Pfizer, and United Therapeutics. HG reports personal fees from Actelion, AstraZeneca, Bayer, Bristol Myers Squib, GlaxoSmithKline, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. OD has or has had a consultancy relationship or has received research funding from 4 D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, Bristol Myers Squib, ChemoAb, EpiPharm, Ergonex, espeRare foundation, GlaxoSmithKline, Genentech/Roche, Inventiva, Janssen, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Serodapharm, and Sinoxa in the area of potential treatments of scleroderma and its complications including PAH; and reports a patent mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143). JSRG has received fees for lectures or consultations from Acceleron, Actelion, Aerovate, Bayer, Complexia, Janssen, MSD, Pfizer, and United Therapeutics. MD reports research grants from Actelion/J&J; speaker and consultant fees from Bayer, MSD, Acceleron, AOP, Daiichi Sankyo, outside of the submitted work; and being a holder of the Janssen Chair for Pulmonary Hypertension at the Katholieke Universiteit Leuven, Leuven, Belgium. D-HP has received lecture fees from Janssen Pharmaceuticals. HAG has received honorariums for consultations or speaking at conferences from Bayer HealthCare, Actelion, Pfizer, Janssen, Merck/MSD, and Gossamer; is member of advisory boards for Acceleron, Bayer HealthCare AG, Pfizer, GlaxoSmithKline, Actelion, Merck/MSD, Janssen, and Gossamer; and has received public grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Institute, State Government of Hessen, and the German Ministry for Education and Research. RE has received speaker fees and honoraria for consultations from Actelion, Bayer, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer, and United Therapeutics. HKa has received honoraria for lectures or consultancy from Actelion, Bristol Myers Squibb, and Janssen. H-JK has received fees from Actelion, Anamed, AstraZeneca, Berlin Chemie/Menarini, Boehringer Ingelheim, Chiesi, Daiichi-Sankyo, Dräger, Fisher & Paykel Healthcare, GlaxoSmithKline, Heinen + Löwenstein, Lilly, MSD, Novartis, Pfizer, Weinmann, Philips Healthcare, Pulmonx, ResMed, Roche, Sanofi-Genzyme, Sapio Life, Weinmann. DS received fees for lectures, consulting, or research support to institution from Actelion, Bayer, GlaxoSmithKline, Janssen, MSD and Pfizer. JB received grants from Actelion, Boehringer Ingelheim and Roche; and honoraria from Bayer, Biogen, Boehringer-Ingelheim, Galapagos, Novartis, Roche, and Sanofi/Genzyme. KM has received fees from Actelion, AstraZeneca, GlaxoSmithKline, Janssen, MSD, Novartis and Sanofi-Aventis. TJL has received speaker fees and honoraria for consultation from Acceleron, Actelion, Bayer, GlaxoSmithKline, Janssen-Cilag, MSD, Pfizer, and United Therapeutics. HW received fees for lectures or consultations from Actelion, Bayer, Biotest, Boehringer, GlaxoSmithKline, Janssen, Pfizer and Roche. H-JS has received speaker fees and honoraria for consultations from Actelion, Bayer, GlaxoSmithKline, Janssen, and MSD. MHe has received speaker fees and honoraria for consultations from Actelion, Bayer, Boehringer Ingelheim Pharma, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Nycomed, Roche and Servier. DD declares honoraria for lectures or consultancy from Actelion, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Servier and Vifor. IT has received fees from Actelion, Bayer, ELPEN, GlaxoSmithKline, Janssen, MSD, Pfizer, and United Therapeutics. AV-N reports receiving fees for lectures or consultations from Actelion, Bayer, GlaxoSmithKline, Janssen, MSD and Pfizer. SU reports personal fees from Actelion, Janssen, MSD, and Orpha-Swiss outside of the submitted work. HKl has received speaker fees and honoraria for consultations from Actelion, Bayer, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, and United Therapeutics. MC reports honoraria for lectures from Boehringer Ingelheim Pharma and Roche Pharma, and for serving on advisory boards from Boehringer Ingelheim. SE has received honoraria for lectures or consultations from Actelion, MSD, Bayer, Acceleron, Gilead, AstraZeneca, Pulmox, Boston Scientific, and Boehringer Ingelheim. K-HS has received fees for lectures and educational events from Abbott, Janssen, and MSD. AJS has received research grants from GlaxoSmithKline, Janssen Pharmaceuticals, Wellcome Trust, and NIHR; has undertaken consultancy work and received honoraria for lectures from Janssen Pharmaceuticals; and has undertaken consultancy work for General Electric. AART is supported by a British Heart Foundation Intermediate Clinical Fellowship (FS/18/13/33281) and has received research grants to their institution from Janssen Pharmaceuticals and GlaxoSmithKline. CAE has received honoraria for lectures or consultations from Actelion, GlaxoSmithKline, Janssen and MSD. SR has received fees for lectures or consultations from Abbott, Acceleron, Actelion, Bayer, Bristol Myers Squib, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor; and research grants to institution from AstraZeneca, Actelion, Bayer Janssen and Novartis. RC has received honoraria for lectures or consultations from Actelion, GlaxoSmithKline, Janssen, and MSD. DGK has received honoraria for lectures or consultations from Acceleron, Actelion, Ferrer, GlaxoSmithKline, Janssen Pharmaceuticals, and MSD; and research grants to institution from Actelion, GlaxoSmithKline and Janssen Pharmaceuticals. MHa has received speaker fees and honoraria for consultations from Acceleron, Actelion, AstraZeneca, Bayer, BerlinChemie, GlaxoSmithKline, Janssen, and Novartis. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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36. Imaging and Risk Stratification in Pulmonary Arterial Hypertension: Time to Include Right Ventricular Assessment.
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Alandejani F, Hameed A, Tubman E, Alabed S, Shahin Y, Lewis RA, Dwivedi K, Mahmood A, Middleton J, Watson L, Alkhanfar D, Johns CS, Rajaram S, Garg P, Condliffe R, Elliot CA, Thompson AAR, Rothman AMK, Charalampopoulos A, Lawrie A, Wild JM, Swift AJ, and Kiely DG
- Abstract
Background: Current European Society of Cardiology and European Respiratory Society guidelines recommend regular risk stratification with an aim of treating patients with pulmonary arterial hypertension (PAH) to improve or maintain low-risk status (<5% 1-year mortality)., Methods: Consecutive patients with PAH who underwent cardiac magnetic resonance imaging (cMRI) were identified from the Assessing the Spectrum of Pulmonary hypertension Identified at a Referral centre (ASPIRE) registry. Kaplan-Meier survival curves, locally weighted scatterplot smoothing regression and multi-variable logistic regression analysis were performed., Results: In 311 consecutive, treatment-naïve patients with PAH undergoing cMRI including 121 undergoing follow-up cMRI, measures of right ventricular (RV) function including right ventricular ejection fraction (RVEF) and RV end systolic volume and right atrial (RA) area had prognostic value. However, only RV metrics were able to identify a low-risk status. Age ( p < 0.01) and RVEF ( p < 0.01) but not RA area were independent predictors of 1-year mortality., Conclusion: This study highlights the need for guidelines to include measures of RV function rather than RA area alone to aid the risk stratification of patients with PAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alandejani, Hameed, Tubman, Alabed, Shahin, Lewis, Dwivedi, Mahmood, Middleton, Watson, Alkhanfar, Johns, Rajaram, Garg, Condliffe, Elliot, Thompson, Rothman, Charalampopoulos, Lawrie, Wild, Swift and Kiely.)
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- 2022
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37. CMR Measures of Left Atrial Volume Index and Right Ventricular Function Have Prognostic Value in Chronic Thromboembolic Pulmonary Hypertension.
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Shahin Y, Alabed S, Rehan Quadery S, Lewis RA, Johns C, Alkhanfar D, Sukhanenko M, Alandejani F, Garg P, Elliot CA, Hameed A, Charalampopoulos A, Wild JM, Condliffe R, Swift AJ, and Kiely DG
- Abstract
Providing prognostic information is important when counseling patients and planning treatment strategies in chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to assess the prognostic value of gold standard imaging of cardiac structure and function using cardiac magnetic resonance imaging (CMR) in CTEPH. Consecutive treatment-naive patients with CTEPH who underwent right heart catheterization and CMR between 2011 and 2017 were identified from the ASPIRE (Assessing-the-Specturm-of-Pulmonary-hypertensIon-at-a-REferral-center) registry. CMR metrics were corrected for age and sex where appropriate. Univariate and multivariate regression models were generated to assess the prognostic ability of CMR metrics in CTEPH. Three hundred and seventy-five patients (mean+/-standard deviation: age 64+/-14 years, 49% female) were identified and 181 (48%) had pulmonary endarterectomy (PEA). For all patients with CTEPH, left-ventricular-stroke-volume-index-%predicted (LVSVI%predicted) ( p = 0.040), left-atrial-volume-index (LAVI) ( p = 0.030), the presence of comorbidities, incremental shuttle walking test distance (ISWD), mixed venous oxygen saturation and undergoing PEA were independent predictors of mortality at multivariate analysis. In patients undergoing PEA, LAVI ( p < 0.010), ISWD and comorbidities and in patients not undergoing surgery, right-ventricular-ejection-fraction-%predicted (RVEF%pred) ( p = 0.040), age and ISWD were independent predictors of mortality. CMR metrics reflecting cardiac function and left heart disease have prognostic value in CTEPH. In those undergoing PEA, LAVI predicts outcome whereas in patients not undergoing PEA RVEF%pred predicts outcome. This study highlights the prognostic value of imaging cardiac structure and function in CTEPH and the importance of considering left heart disease in patients considered for PEA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shahin, Alabed, Rehan Quadery, Lewis, Johns, Alkhanfar, Sukhanenko, Alandejani, Garg, Elliot, Hameed, Charalampopoulos, Wild, Condliffe, Swift and Kiely.)
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- 2022
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38. Physical Activity, Mental Health and Wellbeing during the First COVID-19 Containment in New Zealand: A Cross-Sectional Study.
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O'Brien WJ, Badenhorst CE, Draper N, Basu A, Elliot CA, Hamlin MJ, Batten J, Lambrick D, and Faulkner J
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- Adult, Communicable Disease Control, Cross-Sectional Studies, Exercise, Female, Humans, Male, Middle Aged, New Zealand, SARS-CoV-2, COVID-19, Mental Health
- Abstract
Strategies implemented worldwide to contain COVID-19 outbreaks varied in severity across different countries, and established a new normal for work and school life (i.e., from home) for many people, reducing opportunities for physical activity. Positive relationships of physical activity with both mental and physical health are well recognised, and therefore the aim was to ascertain how New Zealand's lockdown restrictions impacted physical activity, mental health and wellbeing. Participants ( n = 4007; mean ± SD: age 46.5 ± 14.7 years, 72% female, 80.7% New Zealand European) completed (10-26 April 2020) an online amalgamated survey (Qualtrics): International Physical Activity Questionnaire: Short Form; Depression, Anxiety and Stress Scale-9; World Health Organisation-Five Well-Being Index; Stages of Change Scale. Positive dose-response relationships between physical activity levels and wellbeing scores were demonstrated for estimates that were unadjusted (moderate activity OR 3.79, CI 2.88-4.92; high activity OR 8.04, CI 6.07-10.7) and adjusted (confounding variables: age, gender, socioeconomic status, time sitting and co-morbidities) (moderate activity 1.57, CI 1.11-2.52; high activity 2.85, CI 1.97-4.14). The study results support previous research demonstrating beneficial effects of regular physical activity on mental health and wellbeing. Governments may use these results to promote meeting physical activity guidelines in order to protect mental health and wellbeing during the ongoing COVID-19 restrictions and future pandemics.
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- 2021
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39. Cardiovascular magnetic resonance predicts all-cause mortality in pulmonary hypertension associated with heart failure with preserved ejection fraction.
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Garg P, Lewis RA, Johns CS, Swift AJ, Capener D, Rajaram S, Thompson AAR, Condliffe R, Elliot CA, Charalampopoulos A, Hameed AG, Rothman A, Wild JM, and Kiely DG
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- Humans, Magnetic Resonance Imaging, Cine, Magnetic Resonance Spectroscopy, Predictive Value of Tests, Prognosis, Stroke Volume, Ventricular Function, Left, Ventricular Function, Right, Heart Failure diagnostic imaging, Hypertension, Pulmonary diagnostic imaging, Ventricular Dysfunction, Right diagnostic imaging
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This study aimed to determine the prognostic value of cardiovascular magnetic resonance (CMR) in patients with heart failure with preserved ejection fraction and associated pulmonary hypertension (pulmonary hypertension-HFpEF). Patients with pulmonary hypertension-HFpEF were recruited from the ASPIRE registry and underwent right heart catheterisation (RHC) and CMR. On RHC, the inclusion criteria was a mean pulmonary artery pressure (MPAP) ≥ 25 mmHg and pulmonary arterial wedge pressure > 15 mmHg and, on CMR, a left atrial volume > 41 ml/m
2 with left ventricular ejection fraction > 50%. Cox regression was performed to evaluate CMR against all-cause mortality. In this study, 116 patients with pulmonary hypertension-HFpEF were identified. Over a mean follow-up period of 3 ± 2 years, 61 patients with pulmonary hypertension-HFpEF died (53%). In univariate regression, 11 variables demonstrated association to mortality: indexed right ventricular (RV) volumes and stroke volume, right ventricular ejection fraction (RVEF), indexed RV mass, septal angle, pulmonary artery systolic/diastolic area and its relative area change. In multivariate regression, only three variables were independently associated with mortality: RVEF (HR 0.64, P < 0.001), indexed RV mass (HR 1.46, P < 0.001) and IV septal angle (HR 1.48, P < 0.001). Our CMR model had 0.76 area under the curve (P < 0.001) to predict mortality. This study confirms that pulmonary hypertension in patients with HFpEF is associated with a poor prognosis and we observe that CMR can risk stratify these patients and predict all-cause mortality. When patients with HFpEF develop pulmonary hypertension, CMR measures that reflect right ventricular afterload and function predict all-cause mortality., (© 2021. The Author(s).)- Published
- 2021
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40. The Effect of Sleep Quality and Quantity on Athlete's Health and Perceived Training Quality.
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Hamlin MJ, Deuchrass RW, Olsen PD, Choukri MA, Marshall HC, Lizamore CA, Leong C, and Elliot CA
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University athletes are unique because they not only have to cope with the normal psycho-physiological stress of training and playing sport, but they also need to accommodate the stress associated with their academic studies along with considerable stress from their social environment. The ability to manage and adapt to stress ultimately helps improve athletic performance, but when stress becomes too much for the athlete, it can result in maladaptation's including sleep disruption which is associated with performance loss, negative mood changes, and even injury or illness. This research aimed to determine if sleep quantity and quality were associated with maladaptation in university athletes. We examined subjective measures of sleep duration and sleep quality along with measures of mood state, energy levels, academic stress, training quality and quantity, and frequency of illness and injury in 82 young (18-23 years) elite athletes over a 1 year period in 2020. Results indicate sleep duration and quality decreased in the first few weeks of the academic year which coincided with increased training, academic and social stress. Regression analysis indicated increased levels of perceived mood (1.3, 1.1-1.5, Odds Ratio and 95% confidence limits), sleep quality (2.9, 2.5-3.3), energy levels (1.2, 1.0-1.4), training quality (1.3, 1.1-1.5), and improved academic stress (1.1, 1.0-1.3) were associated with ≥8 h sleep. Athletes that slept ≥8 h or had higher sleep quality levels were less likely to suffer injury/illness (0.8, 0.7-0.9, and 0.6, 0.5-0.7 for sleep duration and quality, respectively). In conclusion, university athletes who maintain good sleep habits (sleep duration ≥8 h/night and high sleep quality scores) are less likely to suffer problems associated with elevated stress levels. Educating athletes, coaches, and trainers of the signs and symptoms of excessive stress (including sleep deprivation) may help reduce maladaptation and improve athlete's outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hamlin, Deuchrass, Olsen, Choukri, Marshall, Lizamore, Leong and Elliot.)
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- 2021
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41. A diagnostic miRNA signature for pulmonary arterial hypertension using a consensus machine learning approach.
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Errington N, Iremonger J, Pickworth JA, Kariotis S, Rhodes CJ, Rothman AM, Condliffe R, Elliot CA, Kiely DG, Howard LS, Wharton J, Thompson AAR, Morrell NW, Wilkins MR, Wang D, and Lawrie A
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- Adult, Aged, Biomarkers blood, Cells, Cultured, Circulating MicroRNA genetics, Circulating MicroRNA metabolism, Female, Humans, Hypertension, Pulmonary genetics, Hypertension, Pulmonary metabolism, Machine Learning, Male, MicroRNAs blood, MicroRNAs genetics, MicroRNAs metabolism, Middle Aged, Myocytes, Smooth Muscle metabolism, Pulmonary Artery cytology, Circulating MicroRNA blood, Gene Expression Profiling methods, Hypertension, Pulmonary blood
- Abstract
Background: Pulmonary arterial hypertension (PAH) is a rare but life shortening disease, the diagnosis of which is often delayed, and requires an invasive right heart catheterisation. Identifying diagnostic biomarkers may improve screening to identify patients at risk of PAH earlier and provide new insights into disease pathogenesis. MicroRNAs are small, non-coding molecules of RNA, previously shown to be dysregulated in PAH, and contribute to the disease process in animal models., Methods: Plasma from 64 treatment naïve patients with PAH and 43 disease and healthy controls were profiled for microRNA expression by Agilent Microarray. Following quality control and normalisation, the cohort was split into training and validation sets. Four separate machine learning feature selection methods were applied to the training set, along with a univariate analysis., Findings: 20 microRNAs were identified as putative biomarkers by consensus feature selection from all four methods. Two microRNAs (miR-636 and miR-187-5p) were selected by all methods and used to predict PAH diagnosis with high accuracy. Integrating microRNA expression profiles with their associated target mRNA revealed 61 differentially expressed genes verified in two independent, publicly available PAH lung tissue data sets. Two of seven potentially novel gene targets were validated as differentially expressed in vitro in human pulmonary artery smooth muscle cells., Interpretation: This consensus of multiple machine learning approaches identified two miRNAs that were able to distinguish PAH from both disease and healthy controls. These circulating miRNA, and their target genes may provide insight into PAH pathogenesis and reveal novel regulators of disease and putative drug targets., Funding: This work was supported by a National Institute for Health Research Rare Disease Translational Research Collaboration (R29065/CN500) and British Heart Foundation Project Grant (PG/11/116/29288)., Competing Interests: Declaration of Competing Interest CJR declares personal consultancy fees from Actelion and United Therapeutics. JW declares personal consultancy fees from Actelion. DK reports grants, personal fees and non-financial support from Acceleron, Janssen, GSK and MSD, outside the submitted work. AART declares non-financial support from Actelion to attend educational events. RC reports personal fees from Janssen Pharmaceuticals, personal fees from MSD, outside the submitted work. LH reports consultancy fees from Bayer, GSK, MSD, and Janssen, outside the submitted work. MRW reports consultancy fees from Novartis, Acceleron, Actelion and MorphogenIX. CAE declares consultancy fees from Janssen-Cilag and Bayer. AL declares outside of scope and grant funding from Novartis, Janssen, GSK; Conference support from Actelion; Consultancy from Actelion, GSK. All other authors report no conflicts of interest., (Copyright © 2021 The University of Sheffield. Published by Elsevier B.V. All rights reserved.)
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- 2021
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42. Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry.
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Bauchmuller K, Condliffe R, Southern J, Billings C, Charalampopoulos A, Elliot CA, Hameed A, Kiely DG, Sabroe I, Thompson AAR, Raithatha A, and Mills GH
- Abstract
Pulmonary hypertension (PH) is a life-shortening condition characterised by episodes of decompensation precipitated by factors such as disease progression, arrhythmias and sepsis. Surgery and pregnancy also place additional strain on the right ventricle. Data on critical care management in patients with pre-existing PH are scarce. We conducted a retrospective observational study of a large cohort of patients admitted to the critical care unit of a national referral centre between 2000-2017 to establish acute mortality, evaluate predictors of in-hospital mortality and establish longer term outcomes in survivors to hospital discharge. 242 critical care admissions involving 206 patients were identified. Hospital survival was 59.3%, 94% and 92% for patients admitted for medical, surgical or obstetric reasons, respectively. Medical patients had more severe physiological and laboratory perturbations than patients admitted following surgical or obstetric interventions. Higher APACHE II (Acute Physiology and Chronic Health Evaluation) score, age and lactate, and lower oxygen saturation measure by pulse oximetry/inspiratory oxygen fraction ( S
pO / F2 iO ) ratio, platelet count and sodium level were identified as independent predictors of hospital mortality. An exploratory risk score, OPALS (oxygen ( S2 pO / F2 iO ) ≤185; platelets ≤196×102 9 ·L-1 ; age ≥37.5 years; lactate ≥2.45 mmol·L-1 ; sodium ≤130.5 mmol·L-1 ), identified medical patients at increasing risk of hospital mortality. One (11%) out of nine patients who were invasively ventilated for medical decompensation and 50% of patients receiving renal replacement therapy left hospital alive. There was no significant difference in exercise capacity or functional class between follow-up and pre-admission in patients who survived to discharge. These data have clinical utility in guiding critical care management of patients with known PH. The exploratory OPALS score requires validation., Competing Interests: Conflict of interest: K. Bauchmuller has nothing to disclose. Conflict of interest: R. Condliffe reports honoraria for lecturing and advisory boards from Actelion and MSD outside the submitted work. Conflict of interest: J. Southern has nothing to disclose. Conflict of interest: C. Billings has nothing to disclose. Conflict of interest: A. Charalampopoulos has nothing to disclose. Conflict of interest: C.A. Elliot received lecture and consultancy fees from Actelion, Bayer and GSK pharmaceuticals. Conflict of interest: A. Hameed has nothing to disclose. Conflict of interest: D.G. Kiely reports grants, personal fees and other support from Actelion, Bayer and GSK, and personal fees and other support from MSD, outside the submitted work. Conflict of interest: I. Sabroe has nothing to disclose. Conflict of interest: A.A.R. Thompson reports an Intermediate Clinical Fellowship (FS/18/13/3328) from the British Heart Foundation during the conduct of the study and support for travel to attend educational meetings from Actelion Pharmaceuticals Ltd outside the submitted work. Conflict of interest: A. Raithatha has nothing to disclose. Conflict of interest: G.H. Mills has nothing to disclose., (Copyright ©The authors 2021.)- Published
- 2021
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43. Association between Hamstring Flexibility and Sprint Speed after 8 Weeks of Yoga in Male Rugby Players.
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Raj T, Hamlin MJ, and Elliot CA
- Abstract
Background: A Yoga-asana-based intervention has demonstrated its ability to improve flexibility of individuals, but has not been explored in rugby players. We hypothesized that a structured yoga intervention may have an effect on flexibility and sprint performance in male rugby union players., Methods: It was a controlled trial research design and players were assigned using random sampling to one of the two groups; a yoga group ( n = 16) that practised yoga for 1 h 2 times a week for 8 weeks in addition to their normal rugby training and a control group ( n = 15) with regular rugby training but no yoga intervention. Yoga intervention included 32 yoga postures to address both the upper and lower extremities of the body. Data were collected during preseason and mid-season on hamstring flexibility (sit and reach test), and sprint performance (measured at 5, 10, and 30 m)., Results: One hundred and twenty participants were screened and thirty-one players volunteered for the study. Interactions between groups and differences between pre- and post-intervention scores were analyzed using analysis of variance using SPSS (version 24.0). Significance was set at an alpha level of P = 0.05. The yoga group showed a small nonsignificant decrease (-1.2% ± 21.4%, P = 0.05) in hamstring flexibility compared to the control group which demonstrated a large significant decrease (-14.8% ± 23.7%) (mean % change ± 95% confidence interval [CI], P < 0.05). The yoga group also showed minor nonsignificant improvements in sprint times -3.2% ± 10.4%, -0.7% ± 9.0% for the 5 and 10 m sprints, respectively, (mean % change ± 95% CI) compared to controls -0.4% ± 10.2%, 0.4% ± 7.9%., Conclusions: Findings suggest that completing a structured yoga intervention alongside normal rugby training during the rugby season, yoga helped rugby players maintain their hamstring flexibility but did little to improve sprint performance during the season., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 International Journal of Yoga.)
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- 2021
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44. Maximal Exercise Testing Using the Incremental Shuttle Walking Test Can Be Used to Risk-Stratify Patients with Pulmonary Arterial Hypertension.
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Lewis RA, Billings CG, Hurdman JA, Smith IA, Austin M, Armstrong IJ, Middleton J, Rothman AMK, Harrington J, Hamilton N, Hameed AG, Thompson AAR, Charalampopoulos A, Elliot CA, Lawrie A, Sabroe I, Wild JM, Swift AJ, Condliffe R, and Kiely DG
- Subjects
- Humans, Exercise Test, Pulmonary Arterial Hypertension, Walk Test
- Abstract
Rationale: Exercise capacity predicts mortality in pulmonary arterial hypertension (PAH), but limited data exist on the routine use of maximal exercise testing. Objectives: This study evaluates a simple-to-perform maximal test (the incremental shuttle walking test) and its use in risk stratification in PAH. Methods: Consecutive patients with pulmonary hypertension were identified from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) registry (2001-2018). Thresholds for levels of risk were identified at baseline and tested at follow-up, and their incorporation into current risk stratification approaches was assessed. Results: Of 4,524 treatment-naive patients with pulmonary hypertension who underwent maximal exercise testing, 1,847 patients had PAH. A stepwise reduction in 1-year mortality was seen between levels 1 (≤30 m; 32% mortality) and 7 (340-420 m; 1% mortality) with no mortality for levels 8-12 (≥430 m) in idiopathic and connective tissue disease-related PAH. Thresholds derived at baseline of ≤180 m (>10%; high risk), 190-330 m (5-10%; intermediate risk), and ≥340 m (<5%; low risk of 1-yr mortality) were applied at follow-up and also accurately identified levels of risk. Thresholds were incorporated into the REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management) 2.0 risk score calculator and French low-risk approach to risk stratification, and distinct categories of risk remained. Conclusions : We have demonstrated that maximal exercise testing in PAH stratifies mortality risk at baseline and follow-up. This study highlights the potential value of the incremental shuttle walking test as an alternative to the 6-minute walking test, combining some of the advantages of maximal exercise testing and maintaining the simplicity of a simple-to-perform field test.
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- 2021
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45. Partial anomalous pulmonary venous drainage in patients presenting with suspected pulmonary hypertension: A series of 90 patients from the ASPIRE registry.
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Lewis RA, Billings CG, Bolger A, Bowater S, Charalampopoulos A, Clift P, Elliot CA, English K, Hamilton N, Hill C, Hurdman J, Jenkins PJ, Johns C, MacDonald S, Oliver J, Papaioannou V, Rajaram S, Sabroe I, Swift AJ, Thompson AAR, Kiely DG, and Condliffe R
- Subjects
- Comorbidity, Female, Follow-Up Studies, Hemodynamics, Humans, Hypertension, Pulmonary physiopathology, Lung pathology, Male, Middle Aged, Myocardium pathology, Pulmonary Veins physiopathology, Treatment Outcome, Hypertension, Pulmonary complications, Pulmonary Veins abnormalities, Registries
- Abstract
Background and Objective: There are limited data regarding patients with PAPVD with suspected and diagnosed PH., Methods: Patients with PAPVD presenting to a large PH referral centre during 2007-2017 were identified from the ASPIRE registry., Results: Ninety patients with PAPVD were identified; this was newly diagnosed at our unit in 71 patients (78%), despite 69% of these having previously undergone CT. Sixty-seven percent had a single right superior and 23% a single left superior anomalous vein. Patients with an SV-ASD had a significantly larger RV area, pulmonary artery and L-R shunt and a higher % predicted DL
CO (all P < 0.05). Sixty-five patients were diagnosed with PH (defined as mPAP ≥ 25 mm Hg), which was post-capillary in 24 (37%). No additional causes of PH were identified in 28 patients; 17 of these (26% of those patients with PH) had a PVR > 3 WU. Seven of these patients had isolated PAPVD, five of whom (8% of those patients with PH) had anomalous drainage of a single pulmonary vein., Conclusion: Undiagnosed PAPVD with or without ASD may be present in patients with suspected PH; cross-sectional imaging should therefore be specifically assessed whenever this diagnosis is considered. Radiological and physiological markers of L-R shunt are higher in patients with an associated SV-ASD. Although many patients with PAPVD and PH may have other potential causes of PH, a proportion of patients diagnosed with PAH have isolated PAPVD in the absence of other causative conditions., (© 2020 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)- Published
- 2020
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46. Diagnostic accuracy of CT pulmonary angiography in suspected pulmonary hypertension.
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Swift AJ, Dwivedi K, Johns C, Garg P, Chin M, Currie BJ, Rothman AM, Capener D, Shahin Y, Elliot CA, Charalampopolous T, Sabroe I, Rajaram S, Hill C, Wild JM, Condliffe R, and Kiely DG
- Subjects
- Aged, Cardiac Catheterization methods, Female, Humans, Hypertension, Pulmonary physiopathology, Lung physiopathology, Male, Middle Aged, Pulmonary Artery physiopathology, ROC Curve, Computed Tomography Angiography methods, Hypertension, Pulmonary diagnosis, Pulmonary Artery diagnostic imaging, Pulmonary Wedge Pressure physiology
- Abstract
Objectives: Computed tomography (CT) pulmonary angiography is widely used in patients with suspected pulmonary hypertension (PH). However, the diagnostic and prognostic significance remains unclear. The aim of this study was to (a) build a diagnostic CT model and (b) test its prognostic significance., Methods: Consecutive patients with suspected PH undergoing routine CT pulmonary angiography and right heart catheterisation (RHC) were identified. Axial and reconstructed images were used to derive CT metrics. Multivariate regression analysis was performed in the derivation cohort to identify a diagnostic CT model to predict mPAP ≥ 25 mmHg (the existing ESC guideline definition of PH) and > 20 mmHg (the new threshold proposed at the 6th World Symposium on PH). In the validation cohort, sensitivity, specificity and compromise CT thresholds were identified with receiver operating characteristic (ROC) analysis. The prognostic value of the CT model was assessed using Kaplan-Meier analysis., Results: Between 2012 and 2016, 491 patients were identified. In the derivation cohort (n = 247), a CT model was identified including pulmonary artery diameter, right ventricular outflow tract thickness, septal angle and left ventricular area. In the validation cohort (n = 244), the model was diagnostic, with an area under the ROC curve of 0.94/0.91 for mPAP ≥ 25/> 20 mmHg respectively. In the validation cohort, 93 patients died; mean follow-up was 42 months. The diagnostic thresholds for the CT model were prognostic, log rank, all p < 0.01., Discussion: In suspected PH, a diagnostic CT model had diagnostic and prognostic utility., Key Points: • Diagnostic CT models have high diagnostic accuracy in a tertiary referral population of with suspected PH. • Diagnostic CT models stratify patients by mortality in suspected PH.
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- 2020
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47. Mild parenchymal lung disease and/or low diffusion capacity impacts survival and treatment response in patients diagnosed with idiopathic pulmonary arterial hypertension.
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Lewis RA, Thompson AAR, Billings CG, Charalampopoulos A, Elliot CA, Hamilton N, Hill C, Hurdman J, Rajaram S, Sabroe I, Swift AJ, Kiely DG, and Condliffe R
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- Familial Primary Pulmonary Hypertension, Humans, Lung diagnostic imaging, Quality of Life, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary therapy, Lung Diseases
- Abstract
There are limited published data defining survival and treatment response in patients with mild lung disease and/or reduced gas transfer who fulfil diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH).Patients diagnosed with IPAH between 2001 and 2019 were identified in the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) registry. Using prespecified criteria based on computed tomography (CT) imaging and spirometry, patients with a diagnosis of IPAH and no lung disease were termed IPAH
no-LD (n=303), and those with minor/mild emphysema or fibrosis were described as IPAHmild-LD (n=190).Survival was significantly better in IPAHno-LD than in IPAHmild-LD (1- and 5-year survival 95% and 70% versus 78% and 22%, respectively; p<0.0001). In the combined group of IPAHno-LD and IPAHmild-LD , independent predictors of higher mortality were increasing age, lower diffusing capacity of the lung for carbon monoxide ( DLCO ), lower exercise capacity and a diagnosis of IPAHmild-LD (all p<0.05). Exercise capacity and quality of life improved (both p<0.0001) following treatment in patients with IPAHno-LD , but not IPAHmild-LD A proportion of patients with IPAHno-LD had a DLCO <45%; these patients had poorer survival than patients with DLCO ≥45%, although they demonstrated improved exercise capacity following treatment.The presence of even mild parenchymal lung disease in patients who would be classified as IPAH according to current recommendations has a significant adverse effect on outcomes. This phenotype can be identified using lung function testing and clinical CT reports. Patients with IPAH, no lung disease and severely reduced DLCO may represent a further distinct phenotype. These data suggest that randomised controlled trials of targeted therapies in patients with these phenotypes are required., Competing Interests: Conflict of interest: R.A. Lewis reports non-financial support from Actelion Pharmaceuticals, outside the submitted work. Conflict of interest: A.A.R. Thompson reports grants from British Heart Foundation, during the conduct of the study; support for meeting attendance from Actelion Pharmaceuticals Ltd, outside the submitted work. Conflict of interest: C.G. Billings has nothing to disclose. Conflict of interest: A. Charalampopoulos reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, personal fees and non-financial support from Novartis, grants from Bayer and GSK, outside the submitted work. Conflict of interest: C.A. Elliot reports personal fees for advisory board work and lectures from Actelion Pharmaceuticals, GlaxoSmithKline and Bayer, grants from Pfizer, Actelion Pharmaceuticals and Bayer, support for meeting attendance from Bayer and Actelion Pharmaceuticals, outside the submitted work. Conflict of interest: N. Hamilton reports personal fees from MSD and Actelion, grants and personal fees from Bayer, outside the submitted work. Conflict of interest: C. Hill has nothing to disclose. Conflict of interest: J. Hurdman has nothing to disclose. Conflict of interest: S. Rajaram has nothing to disclose. Conflict of interest: I. Sabroe reports grants and personal fees for advisory board from AstraZeneca, grants from GSK, outside the submitted work. Conflict of interest: A.J. Swift has nothing to disclose. Conflict of interest: D.G. Kiely reports grants, personal fees and non-financial support from Actelion, Bayer and GSK, personal fees and non-financial support from MSD, outside the submitted work. Conflict of interest: R. Condliffe reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and Bayer, grants from GSK, outside the submitted work., (Copyright ©ERS 2020.)- Published
- 2020
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48. Inter-operator Reliability for Measuring Pulse Wave Velocity and Augmentation Index.
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Elliot CA, Hamlin MJ, and Lizamore CA
- Abstract
Background: Arterial stiffness is a reversible precursor to hypertension. However, research is needed to determine the minimum amount of training required before acceptable arterial stiffness measurements are collected by novice operators. Objective: To compare novice vs. experienced operator measurements over a 2-week training period to assess when expert-like measures are achieved by the novice operator. Method: Forty-one participants (18 males, 23 females, age: 46.6 ± 14.9 years; BMI: 25.2 ± 3.8; systolic blood pressure: 122.8 ± 14.7 mmHg) received alternating novice and experienced operator arterial stiffness assessments. Measurements included: pulse wave velocity (PWV; using the automatic-capture time-periods of 5-, 10-, and 20-s) and augmentation index (AIx75) measurements using the SphygmoCor XCEL System v1 (AtCor Medical Pty Ltd., Sydney, Australia). Data were chronologically arranged into quintiles. Results: The intraclass correlation coefficient for PWV substantially improved from quintile 1 ( r < 0.8) to quintile 2 and beyond (typically r > 0.8) while AIx75 improved consistently ( r = 0.7 in quintile 1 and r = 0.97 in quintile 5). The coefficient of variation was lowest in quintile 4 (PWV: 4.7-6% across the three measurement time-periods; and 15% for AIx75) but increased in quintile 5 (PWV: 6.2-10.5%; and 25% for AIx75). All measurements demonstrated acceptable to excellent reliability after quintile 2. Conclusion: To achieve expert-like PWV measurements in this study, the novice operator underwent a familiarization session including guided practice measurements on 5 different people, for 10-15 min per person on two occasions (~2.5 h). The novice operator then required ≥14 practice measurements, with accuracy continuing to improve up to 30 participants. At least 30 training measurements are recommended for novices to take acceptable AIx75 measurements after a familiarization training., (Copyright © 2020 Elliot, Hamlin and Lizamore.)
- Published
- 2020
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49. Idiopathic pulmonary arterial hypertension and co-existing lung disease: is this a new phenotype?
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Peacock AJ, Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JSR, Howard LS, Pepke-Zaba J, Sheares KKK, Corris PA, Fisher AJ, Lordan JL, Gaine S, Coghlan JG, Wort SJ, and Gatzoulis MA
- Abstract
Patients classified as idiopathic pulmonary arterial hypertension (defined as Group 1 on European Respiratory Society (ERS)/European Cardiac Society (ESC) criteria) may have evidence of minor co-existing lung disease on thoracic computed tomography. We hypothesised that these idiopathic pulmonary arterial hypertension patients ( IPAH
lung disease ) are a separate subgroup of idiopathic pulmonary arterial hypertension with different phenotype and outcome compared with idiopathic pulmonary arterial hypertension patients without co-existing lung disease ( IPAHno lung disease ). Patients with ' IPAHlung disease ' have been eligible for all clinical trials of Group 1 patients because they have normal clinical examination and normal spirometry but we wondered whether they responded to treatment and had similar survival to patients with ' IPAHno lung disease '. We described the outcome of the cohort of patients with ' IPAHno lung disease ' in a previous paper. Here, we have compared incident ' IPAHlung disease ' patients with ' IPAHno lung disease ' patients diagnosed concurrently in all eight Pulmonary Hypertension centres in the UK and Ireland between 2001-2009. Compared with ' IPAHno lung disease ' ( n = 355), ' IPAHlung disease ' patients ( n = 137) were older, less obese, predominantly male, more likely to be current/ex-smokers and had lower six-minute walk distance, lower % predicted diffusion capacity for carbon monoxide, lower mean pulmonary arterial pressure and lower pulmonary vascular resistance index. After three months of pulmonary hypertension-targeted treatment, six-minute walk distance improved equally in ' IPAHlung disease ' and ' IPAHno lung disease '. However, survival of ' IPAHlung disease ' was lower than ' IPAHno lung disease ' (one year survival: 72% compared with 93%). This survival was significantly worse in ' IPAHlung disease ' even after adjusting for age, gender, smoking history, comorbidities and haemodynamics. ' IPAHlung disease ' patients had similar short-term improvement in six-minute walk distance with anti-pulmonary arterial hypertension therapy but worse survival compared with ' IPAHno lung disease ' patients. This suggests that ' IPAHlung disease ' are a separate phenotype and should not be lumped with ' IPAHno lung disease ' in clinical trials of Group 1 pulmonary arterial hypertension., (© The Author(s) 2020.)- Published
- 2020
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50. Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension.
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Lewis RA, Johns CS, Cogliano M, Capener D, Tubman E, Elliot CA, Charalampopoulos A, Sabroe I, Thompson AAR, Billings CG, Hamilton N, Baster K, Laud PJ, Hickey PM, Middleton J, Armstrong IJ, Hurdman JA, Lawrie A, Rothman AMK, Wild JM, Condliffe R, Swift AJ, and Kiely DG
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Magnetic Resonance Imaging methods, Pulmonary Arterial Hypertension diagnosis, Pulmonary Arterial Hypertension physiopathology, Pulmonary Artery diagnostic imaging, Risk Assessment methods
- Abstract
Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality. Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making. Methods: Consecutive patients with PAH ( n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort. Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m
2 identified patients at low (<5%) and high (>10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37-54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality. Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH.- Published
- 2020
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