Publications
395 results found
Bunclark K, Newnham M, Chiu Y-D, et al., 2020, A multicenter study of anticoagulation in operable chronic thromboembolic pulmonary hypertension, International Conference of the American-Thoracic-Society, Publisher: WILEY, Pages: 114-122, ISSN: 1538-7933
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- Citations: 55
Babu A, Ruggiero A, Cannon JE, et al., 2019, EVOLVING SURGICAL EXPERTISE AND PATIENT CHOICE IN PULMONARY ENDARTERECTOMY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A155-A156, ISSN: 0040-6376
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- Citations: 1
Sathianandan S, McCabe C, Dimopoulos K, et al., 2019, SILDENAFIL IN THE TREATMENT OF GROUP 3 PULMONARY HYPERTENSION, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A152-A152, ISSN: 0040-6376
Bunclark K, Liley J, Newnham M, et al., 2019, MACHINE LEARNING TOOL PROVIDES NEW INSIGHTS INTO RISK ASSESSMENT IN PULMONARY ENDARTERECTOMY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A154-A155, ISSN: 0040-6376
Mahomed AS, Burke-Gaffney A, Moledina S, et al., 2019, THE EFFECTS OF BMPRII LOSS ON ENDOTHELIAL SHEAR ADAPTATION IN THE PULMONARY VASCULAR ENDOTHELIUM, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A61-A61, ISSN: 0040-6376
Toe QK, Ying H, Issitt T, et al., 2019, HEPCIDIN DOWN REGULATES BMPRII IN PULMONARY ARTERY ENDOTHELIAL CELLS MIMICKING PULMONARY ARTERY HYPERTENSION PHENOTYPES, THORAX, Vol: 74, Pages: A61-A62, ISSN: 0040-6376
Bukhari MS, Mohd-Ghazaly M, Toe QK, et al., 2019, S97 Haemoglobin challenge induces dysfunction in human pulmonary artery endothelial cells: potential relevance to pulmonary artery hypertension, Thorax, Vol: 74, Pages: A60-A61, ISSN: 0040-6376
McCabe C, Vranesic II, Verdes MC, et al., 2019, Reply to Echocardiographic predictors of outcome in PAH, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 294, Pages: 58-58, ISSN: 0167-5273
McCabe C, Vranesic II, Verdes MC, et al., 2019, Right ventricular systolic to diastolic duration ratio: A novel predictor of outcome in adult idiopathic pulmonary arterial hypertension, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 293, Pages: 218-222, ISSN: 0167-5273
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- Citations: 9
Kempny A, Dimopoulos K, Fraisse AE, et al., 2019, Blood viscosity and its relevance to the diagnosis and management of pulmonary hypertension: a new elephant in the cathlab, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 3036-3036, ISSN: 0195-668X
Sathianandan S, Rawal B, Nashat H, et al., 2019, A retrospective review of computed tomography (CT) findings in Eisenmenger Syndrome and their prognostic implications, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Issitt T, Toe Q, Ghazaly MM, et al., 2019, Pulmonary vascular cell mitochondrial dysfunction in response to hepcidin, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936
Hastings R, Mahboobani S, Kempny A, et al., 2019, Impact of ILD severity and subtype on outcomes in CTD-associated PAH, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Mahomed A, Burke-Gaffney A, Moledina S, et al., 2019, Late Breaking Abstract - The effects of BMPRII loss on endothelial shear adaptation in the pulmonary vascular endothelium, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Cogliano M, Lawrie A, Kiely DG, et al., 2019, Thoracic CT features of patients with BMPR2 mutation: preliminary analysis from the UK National Cohort Study of Idiopathic and Heritable PAH, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Connolly M, Wort S, Garfield B, et al., 2019, MiR-1-5p targets TGF-βR1 and is suppressed in the hypertrophying hearts of rats with pulmonary arterial hypertension, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Toe Q, Ghazaly MM, Issit TJ, et al., 2019, Cell freehaemoglobin and pulmonary artery endothelial cell dysfunction, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Kiely D, Levin D, Hassoun P, et al., 2019, Statement on imaging and pulmonary hypertension from the Pulmonary Vascular Research Institute (PVRI), Pulmonary Circulation, Vol: 9, Pages: 1-32, ISSN: 2045-8940
Pulmonary hypertension is highly heterogeneous and despite treatment advances it remains a life shortening condition. There have been significant advances in imaging technologies, but despite evidence of their potential clinical utility practice remains variable, dependent in part on imaging availability and expertise. This statement summarises current and emerging imaging modalities and their potential role in the diagnosis and assessment of suspected pulmonary hypertension. It also includes a review of commonly encountered clinical and radiological scenarios, and imaging and modeling-based biomarkers. An expert panel was formed including clinicians, radiologists, imaging scientists and computational modelers. Section editors generated a series of summary statements 1based on a review of the literature and professional experience and following consensus review, a diagnostic algorithm and fifty five statements were agreed. The diagnostic algorithm and summary statements, emphasise the key role and added value of imaging in the diagnosis and assessment of pulmonary hypertension and highlight areas requiring further research.
Masding A, Preston SD, Toshner M, et al., 2019, Chronic thromboembolic pulmonary hypertension following long-term peripherally inserted central venous catheter use, Pulmonary Circulation, Vol: 9, ISSN: 2045-8940
A 36-year-old woman presented with recurrent pulmonary emboli (PE) despite oral anticoagulation. She was a type I diabetic with severe gastroparesis requiring insertion of multiple long-term peripherally inserted central catheters (PICC) over a 10-year period. Imaging at presentation demonstrated a PICC-associated mobile mass in the right atrium and signs of pulmonary hypertension (PH). She was thrombolyzed and fully anticoagulated, and diabetic management without PICC strongly recommended. PH persisted, however, and she developed chronic thromboembolic pulmonary hypertension (CTEPH), for which successful pulmonary endarterectomy (PEA) surgery led to symptomatic and hemodynamic improvement. This was the first case of CTEPH reported related to long-term PICC use outside the setting of malignant disease, and a novel observation that the PEA specimen contained multiple plastic fragments. Long-term PICC placement increases the risk of CTEPH, a life-threatening, albeit treatable, complication.
Favoccia C, Constantine AH, Wort SJ, et al., 2019, Eisenmenger syndrome and other types of pulmonary arterial hypertension related to adult congenital heart disease, Expert Review of Cardiovascular Therapy, Vol: 17, Pages: 449-459, ISSN: 1477-9072
Introduction: Eisenmenger syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD). It is characterised by a severe rise in pulmonary vascular resistance resulting in shunt reversal and cyanosis. Areas covered: In this paper, an overview of ES and other types of PAH related to CHD (PAH-CHD) in adults is provided. The modern management of PAH-CHD in tertiary centers, with emphasis on co-morbidities and complications is described. Expert opinion: PAH-CHD is a wide spectrum of conditions, of which ES is the archetype. The size and location of the shunt, the degree of adaptation of the right ventricle to the increased afterload and other compensatory mechanisms, such as secondary erythrocytosis, define the clinical presentation and natural history of these patients. PAH therapies have improved the quality of life and outcome of many patients with PAH-CHD, but expert multidisciplinary management remains essential in optimising the care of this rare and complex group of patients.
Kempny A, Dimopoulos K, Fraisse A, et al., 2019, Blood viscosity and its relevance to the diagnosis and management of pulmonary hypertension, Journal of the American College of Cardiology, Vol: 73, Pages: 2640-2642, ISSN: 0735-1097
Wei W, Tuna S, Keogh MJ, et al., 2019, Germline selection shapes human mitochondrial DNA diversity, Science, Vol: 364, ISSN: 0036-8075
INTRODUCTIONOnly 2.4% of the 16.5-kb mitochondrial DNA (mtDNA) genome shows homoplasmic variation at >1% frequency in humans. Migration patterns have contributed to geographic differences in the frequency of common genetic variants, but population genetic evidence indicates that selection shapes the evolving mtDNA phylogeny. The mechanism and timing of this process are not clear.Unlike the nuclear genome, mtDNA is maternally transmitted and there are many copies in each cell. Initially, a new genetic variant affects only a proportion of the mtDNA (heteroplasmy). During female germ cell development, a reduction in the amount of mtDNA per cell causes a “genetic bottleneck,” which leads to rapid segregation of mtDNA molecules and different levels of heteroplasmy between siblings. Although heteroplasmy is primarily governed by random genetic drift, there is evidence of selection occurring during this process in animals. Yet it has been difficult to demonstrate this convincingly in humans.RATIONALETo determine whether there is selection for or against heteroplasmic mtDNA variants during transmission, we studied 12,975 whole-genome sequences, including 1526 mother–offspring pairs of which 45.1% had heteroplasmy affecting >1% of mtDNA molecules. Harnessing both the mtDNA and nuclear genome sequences, we then determined whether the nuclear genetic background influenced mtDNA heteroplasmy, validating our findings in another 40,325 individuals.RESULTSPreviously unknown mtDNA variants were less likely to be inherited than known variants, in which the level of heteroplasmy tended to increase on transmission. Variants in the ribosomal RNA genes were less likely to be transmitted, whereas variants in the noncoding displacement (D)–loop were more likely to be transmitted. MtDNA variants predicted to affect the protein sequence tended to have lower heteroplasmy levels than synonymous variants. In 12,975 individuals, we identified a correlation between
Diller G-P, Kempny A, Babu-Narayan SV, et al., 2019, Machine learning algorithms estimating prognosis and guiding therapy in adult congenital heart disease: data from a single tertiary centre including 10 019 patients, European Heart Journal, Vol: 40, Pages: 1069-1077, ISSN: 1522-9645
Aims: To assess the utility of machine learning algorithms on estimating prognosis and guiding therapy in a large cohort of patients with adult congenital heart disease (ACHD) or pulmonary hypertension at a single, tertiary centre. Methods and results: We included 10 019 adult patients (age 36.3 ± 17.3 years) under follow-up at our institution between 2000 and 2018. Clinical and demographic data, ECG parameters, cardiopulmonary exercise testing, and selected laboratory markers where collected and included in deep learning (DL) algorithms. Specific DL-models were built based on raw data to categorize diagnostic group, disease complexity, and New York Heart Association (NYHA) class. In addition, models were developed to estimate need for discussion at multidisciplinary team (MDT) meetings and to gauge prognosis of individual patients. Overall, the DL-algorithms-based on over 44 000 medical records-categorized diagnosis, disease complexity, and NYHA class with an accuracy of 91.1%, 97.0%, and 90.6%, respectively in the test sample. Similarly, patient presentation at MDT-meetings was predicted with a test sample accuracy of 90.2%. During a median follow-up time of 8 years, 785 patients died. The automatically derived disease severity-score derived from clinical information was related to survival on Cox analysis independently of demographic, exercise, laboratory, and ECG parameters. Conclusion: We present herewith the utility of machine learning algorithms trained on large datasets to estimate prognosis and potentially to guide therapy in ACHD. Due to the largely automated process involved, these DL-algorithms can easily be scaled to multi-institutional datasets to further improve accuracy and ultimately serve as online based decision-making tools.
Bhatti Y, Rice AJ, Kempny A, et al., 2019, Early histological changes of pulmonary arterial hypertension disclosed by invasive cardiopulmonary exercise testing, Pulmonary Circulation, Vol: 9, Pages: 1-4, ISSN: 2045-8940
Early diagnosis of pulmonary artery hypertension (PAH) is diagnostically challenging given the extent of pulmonary vascular remodeling required to bring about clinical signs and symptoms. Exercise testing can be invaluable in this setting, as stressing the cardiopulmonary system may unmask early disease. This report describes a young patient with a positive family history of PAH in whom contemporaneous invasive cardiopulmonary exercise testing and surgical lung biopsy reveal the novel association between exercise pulmonary hypertension (ePH) and early histological changes of PAH. Exercise PH currently carries no pathological correlates which means the hemodynamic effects of early pulmonary vascular remodeling remain unknown. Following the recent proceedings from the World Symposium in Pulmonary Hypertension 2018, which broaden the hemodynamic definition of PAH, this report suggests an important association between ePH and early pulmonary vascular remodeling supporting a role for exercise hemodynamic evaluation in patients at increased familial risk of PAH.
Price LC, Seckl MJ, Dorfmüller P, et al., 2019, Tumoral pulmonary hypertension, European Respiratory Review, Vol: 28, ISSN: 0905-9180
Tumoral pulmonary hypertension (PH) comprises a variety of subtypes in patients with a current or previous malignancy. Tumoral PH principally includes the tumour-related pulmonary microvascular conditions pulmonary tumour microembolism and pulmonary tumour thrombotic microangiopathy. These inter-related conditions are frequently found in post mortem specimens but are notoriously difficult to diagnose ante mortem The outlook for patients remains extremely poor although there is some emerging evidence that pulmonary vasodilators and anti-inflammatory approaches may improve survival. Tumoral PH also includes pulmonary macroembolism and tumours that involve the proximal pulmonary vasculature, such as angiosarcoma; both may mimic pulmonary embolism and chronic thromboembolic PH. Finally, tumoral PH may develop in response to treatments of an underlying malignancy. There is increasing interest in pulmonary arterial hypertension induced by tyrosine kinase inhibitors, such as dasatanib. In addition, radiotherapy and chemotherapeutic agents such as mitomycin-C can cause pulmonary veno-occlusive disease. Tumoral PH should be considered in any patient presenting with unexplained PH, especially if it is poorly responsive to standard approaches or there is a history of malignancy. This article will describe subtypes of tumoral PH, their pathophysiology, investigation and management options in turn.
Sofianopoulou E, Kaptoge S, Gräf S, et al., 2019, Traffic exposures, air pollution and outcomes in pulmonary arterial hypertension: A United Kingdom cohort study analysis., European Respiratory Journal, Vol: 53, Pages: 1-12, ISSN: 0903-1936
While traffic and air pollution exposure is associated with increased mortality in numerous diseases, its association with disease severity and outcomes in pulmonary arterial hypertension (PAH) remains unknown.Exposure to particulate matter ≤2.5 μm3 (PM2.5), nitrogen dioxide (NO2) and indirect measures of traffic-related air pollution (distance to main road and length of roads within buffer zones surrounding residential addresses) were estimated for 301 patients with idiopathic/heritable PAH recruited in the UK PAH national Cohort study. Associations with transplant-free survival and pulmonary hemodynamic severity at baseline were assessed, adjusting for confounding variables defined a priori.Higher estimated exposure to PM2.5 was associated with higher risk of death or lung transplant (Unadjusted hazard ratio (HR) 2.68; 95% CI 1.11-6.47 per 3 μg·m-3, p=0.028). This association remained similar when adjusted for potential confounding variables (HR 4.38; 95% CI 1.44-13.36 per 3 μg·m-3, p=0.009). No associations were found between NO2 exposure or other traffic pollution indicators and transplant-free survival Conversely, indirect measures of exposure to traffic-related air pollution within the 500-1000 m buffer zones correlated with the ERS/ESC risk categories as well as pulmonary hemodynamics at baseline. This association was strongest for pulmonary vascular resistance.In idiopathic/heritable PAH, indirect measures of exposure to traffic-related air pollution were associated with disease severity at baseline, whereas higher PM2.5 exposure may independently predict shorter transplant-free survival.
Dimopoulos K, Muthiah K, Alonso-Gonzalez R, et al., 2019, Heart or heart-lung transplantation for patients with congenital heart disease in England, Heart, Vol: 105, Pages: 596-602, ISSN: 1355-6037
BACKGROUND: Increased longevity in patients with congenital heart disease (CHD) is associated with late complications, mainly heart failure, which may not be amenable to redo surgery and become refractory to medical therapy and so, trigger referral for transplantation. We assessed the current role and future prospects of heart and heart-lung transplantation for patients with CHD in England. METHODS: We performed a retrospective analysis of hospital episodes for England for 1997-2015, identifying patients with a CHD code (ICD-10 'Q2xx.x'), who underwent heart or heart-lung transplantation. RESULTS: In total, 469 transplants (82.2% heart and 17.8% heart-lung) were performed in 444 patients. Half of patients transplanted had mild or moderate CHD complexity, this percentage increased with time (p=0.001). While overall, more transplantations were performed over the years, the proportion of heart-lung transplants declined (p<0.0001), whereas the proportion of transplants performed in adults remained static. Mortality was high during the first year, especially after heart-lung transplantation, but remained relatively low thereafter. Older age and heart-lung transplantation were strong predictors of death. While an increase in CHD transplants is anticipated, actual numbers in England seem to lag behind the increase in CHD patients with advanced heart failure. CONCLUSIONS: The current and future predicted increase in the numbers of CHD transplants does not appear to parallel the expansion of the CHD population, especially in adults. Further investment and changes in policy should be made to enhance the number of donors and increase CHD transplant capacity to address the increasing numbers of potential CHD recipients and optimise transplantation outcomes in this growing population.
Rhodes CJ, Batai K, Bleda M, et al., 2019, Genetic determinants of risk in pulmonary arterial hypertension: international case-control studies and meta-analysis, Lancet Respiratory Medicine, Vol: 7, Pages: 227-238, ISSN: 2213-2600
BackgroundRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.MethodsWe did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.FindingsA locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13 × 10–15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65 × 10–20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69 × 10–12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-media
Kempny A, McCabe C, Dimopoulos K, et al., 2019, Incidence, mortality and bleeding rates associated with pulmonary embolism in England between 1997 and 2015, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 277, Pages: 229-234, ISSN: 0167-5273
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- Citations: 14
Garfield B, Crosby A, Shao D, et al., 2019, Growth/differentiation factor 15 causes TGFβ activated kinase 1 dependent muscle atrophy in pulmonary arterial hypertension, Thorax, Vol: 74, Pages: 164-176, ISSN: 1468-3296
Introduction Skeletal muscle dysfunction is a clinically important complication of pulmonary arterial hypertension (PAH). Growth/differentiation factor 15 (GDF-15), a prognostic marker in PAH, has been associated with muscle loss in other conditions. We aimed to define the associations of GDF-15 and muscle wasting in PAH, to assess its utility as a biomarker of muscle loss and to investigate its downstream signalling pathway as a therapeutic target.Methods GDF-15 levels and measures of muscle size and strength were analysed in the monocrotaline (MCT) rat, Sugen/hypoxia mouse and in 30 patients with PAH. In C2C12 myotubes the downstream targets of GDF-15 were identified. The pathway elucidated was then antagonised in vivo.Results Circulating GDF-15 levels correlated with tibialis anterior (TA) muscle fibre diameter in the MCT rat (Pearson r=−0.61, p=0.003). In patients with PAH, plasma GDF-15 levels of <564 pg/L predicted those with preserved muscle strength with a sensitivity and specificity of ≥80%. In vitro GDF-15 stimulated an increase in phosphorylation of TGFβ-activated kinase 1 (TAK1). Antagonising TAK1, with 5(Z)-7-oxozeaenol, in vitro and in vivo led to an increase in fibre diameter and a reduction in mRNA expression of atrogin-1 in both C2C12 cells and in the TA of animals who continued to grow. Circulating GDF-15 levels were also reduced in those animals which responded to treatment.Conclusions Circulating GDF-15 is a biomarker of muscle loss in PAH that is responsive to treatment. TAK1 inhibition shows promise as a method by which muscle atrophy may be directly prevented in PAH.
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