Charlie Elliot

Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England, United Kingdom

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Publications (47)267.62 Total impact

  • PLoS ONE 05/2015; 10(5):e0127415. DOI:10.1371/journal.pone.0127415 · 3.53 Impact Factor
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    ABSTRACT: We evaluated the prevalence and prognostic value of CT-pulmonary angiographic (CTPA) measures in 292 treatment naive patients with pulmonary arterial hypertension (PAH). Pulmonary artery calcification (13%) and thrombus (10%) were exclusively seen in PAH-congenital heart disease. Oesophageal dilation (46%) was most frequent in PAH-systemic sclerosis. Ground glass opacification (GGO) (41%), pericardial effusion (38%), lymphadenopathy (19%) and pleural effusion (11%) were common. On multivariate analysis, inferior vena caval area, the presence of pleural effusion and septal lines predicted outcome. In PAH, CTPA provides diagnostic and prognostic information. In addition, the presence of GGO on a CT performed for unexplained breathlessness should alert the physician to the possibility of PAH. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Thorax 12/2014; 70(4). DOI:10.1136/thoraxjnl-2014-206088 · 8.56 Impact Factor
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    ABSTRACT: The goal of this study was to determine the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) features in patients with pulmonary hypertension. The prognostic significance of LGE in the clinical assessment of patients with pulmonary hypertension remains uncertain. Consecutive patients with suspected pulmonary hypertension seen at a specialist pulmonary hypertension referral center who underwent right heart catheterization and CMR with LGE imaging within 48 h were identified. Short-axis late-enhancement imaging was performed using a 3-dimensional gradient spoiled echocardiography sequence on a 1.5-T scanner. Three groups were identified: 1) no late enhancement of the myocardium; 2) late enhancement at the right ventricular insertion points (LGE-IP); and 3) late enhancement involving the right ventricular insertion points and the interventricular septum (LGE-S). Of 194 patients, 162 had pulmonary hypertension. LGE was identified in 135 of 162 (83%) patients with pulmonary hypertension, and 47 (29%) of patients demonstrated LGE-S. Patients with LGE-S had significantly higher right ventricular end-diastolic volume index (p = 0.013) and lower mixed venous oxygen saturation (p = 0.045) than patients with LGE-IP alone. The presence of LGE-S (p = 0.022), but not LGE-IP alone, right ventricular end-systolic volume (p = 0.045), right ventricular ejection fraction (p = 0.034), mixed venous oxygen saturation (p = 0.021), mean right atrial pressure (0.027), and male sex (p = 0.002) predicted mortality. At multivariate analysis, male sex was the only significant predictor of mortality independent of covariate predictors (p = 0.027). The presence of LGE at the right ventricular insertion points is suggestive of the presence of pulmonary hypertension. LGE may also be more extensive, involving the septum; however, after multivariable analysis including other factors associated with pulmonary hypertension, septal LGE was not associated with an increase in overall mortality. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    JACC Cardiovascular Imaging 12/2014; 7(12):1209-17. DOI:10.1016/j.jcmg.2014.08.014 · 6.99 Impact Factor
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    ABSTRACT: To assess the sensitivity of the hyperpolarized (129) Xe chemical shift saturation recovery (CSSR) technique for noninvasive quantification of changes to lung microstructure and function in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc).
    Magnetic Resonance in Medicine 08/2014; DOI:10.1002/mrm.25400 · 3.40 Impact Factor
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    ABSTRACT: Rationale: Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP) confers important additional morbidity and mortality. Objectives: To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist (ERA) bosentan in this patient group. Methods: In a randomized, double-blind, placebo-controlled study, 60 patients with fibrotic IIP and right heart catheter confirmed PH were randomized 2:1 to bosentan (n=40) or placebo (n=20). The primary study end point was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks. Main Results: Sixty patients (42 men; mean age 66.6±9.2 years), with a mean pulmonary artery pressure of 36.0 (±8.9) mmHg, PVRi 13.0 (±6.7) Wood Units.m2 and reduced cardiac index of 2.21 (±0.5) L/min/m2 were recruited to the study. Accounting for deaths and withdrawals, paired right heart catheter (RHC) data were available for analysis in 39 patients (bosentan=25, placebo=14). No difference in the primary outcome was detected, with seven (28.0%) patients receiving bosentan, and four (28.6%) receiving placebo achieving a reduction in PVRi of ≥20% (p=0.97) at 16 weeks. There was no change in functional capacity or symptoms between the two groups at 16 weeks, nor any difference in rates of serious adverse events or deaths (three deaths in each group). Conclusions: This study shows no difference in invasive pulmonary haemodynamics, functional capacity or symptoms between the bosentan and placebo groups over 16 weeks. Our data does not support therefore the use of the dual ERA, bosentan in patients with PH and fibrotic IIP. Clinical trial registration available at, ID NCT00637065.
    American Journal of Respiratory and Critical Care Medicine 06/2014; DOI:10.1164/rccm.201403-0446OC · 11.99 Impact Factor
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    ABSTRACT: Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary arterial hypertension (PAH). There are few data on clinical use and long-term tolerability in a wider range of patients with pulmonary hypertension (PH). All patients treated with ambrisentan over a 4-year period were identified. Baseline characteristics, liver function test (LFT) results and World Health Organization (WHO) functional class were retrieved from hospital databases. 272 patients received ambrisentan between March 2009 and June 2013 (32% idiopathic PAH, 36% connective tissue disease PAH, 11% congenital heart disease PAH, 6% portopulmonary hypertension, 1% HIV PAH, 4% PH in association with lung disease, 8% chronic thromboembolic PH and 2% PH in association with sarcoidosis). 33.5% of patients received ambrisentan as monotherapy and 12% received ambrisentan as their initial PH therapy. 18% stopped treatment due to side effects and 12% stopped due to lack of efficacy. Oedema was the most common side effect leading to cessation of therapy, which occurred in 7% of patients. 57% of patients who discontinued ambrisentan due to side effects also discontinued other PAH therapies due to side effects previously or subsequently. Ambrisentan was discontinued in two (<1%) patients due to abnormal LFTs. The 3-year survival in congenital heart disease PAH, idiopathic PAH and systemic sclerosis-associated PAH was 80%, 62%, and 38%, respectively (p = 0.003). Survival was superior in patients in whom WHO functional class improved in response to therapy. Ambrisentan is used as an initial therapy and as monotherapy in a minority of patients in a large UK PH referral centre. Discontinuation due to side effects, and especially oedema, was higher than reported in previous studies while discontinuation due to abnormal LFTs was very uncommon. A majority of patients who discontinued therapy due to side effects also previously or subsequently discontinued other PAH therapies. Improvement in WHO functional class was associated with superior survival.
    Therapeutic Advances in Respiratory Disease 04/2014; 8(3). DOI:10.1177/1753465814532304
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    ABSTRACT: Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI.
    03/2014; 4(1):61-70. DOI:10.1086/674882
  • The Lancet 02/2014; 383:S99. DOI:10.1016/S0140-6736(14)60362-7 · 45.22 Impact Factor
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    ABSTRACT: Physicians treating acute pulmonary embolism (PE) are faced with difficult management decisions while specific guidance from recent guidelines may be absent. Fourteen clinical dilemmas were identified by physicians and haematologists with specific interests in acute and chronic PE. Current evidence was reviewed and a practical approach suggested. Management dilemmas discussed include: sub-massive PE, PE following recent stroke or surgery, thrombolysis dosing and use in cardiac arrest, surgical or catheter-based therapy, failure to respond to initial thrombolysis, PE in pregnancy, right atrial thrombus, role of caval filter insertion, incidental and sub-segmental PE, differentiating acute from chronic PE, early discharge and novel oral anticoagulants. The suggested approaches are based on a review of the available evidence and guidelines and on our clinical experience. Management in an individual patient requires clinical assessment of risks and benefits and also depends on local availability of therapeutic interventions.
    Thorax 12/2013; 69(2). DOI:10.1136/thoraxjnl-2013-204667 · 8.56 Impact Factor
  • Obstetric Medicine 12/2013; 6(4):144-154. DOI:10.1177/1753495X13495193
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    ABSTRACT: -There is limited data on the prognostic value of cardiovascular magnetic resonance (CMR) measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of CMR indices for age and gender on prognostic value. -Consecutive patients with idiopathic pulmonary arterial hypertension (IPAH) underwent CMR imaging at 1.5T. Steady state free precession (SSFP) cardiac volumes and mass measurements were corrected for age, gender and BSA according to reference data and prognostic significance assessed. 80 patients with IPAH were identified, 23 patients died during the mean follow-up of 32 +/- 14 months. Corrected for age, gender and BSA, RV end-systolic volume (p=0.004) strongly predicted mortality, independent of WHO functional class, mean right atrial pressure (mRAP), cardiac index (CI) and mixed venous oxygen saturations (mVO2). -Consideration should be given to correcting CMR measures, for age, gender and BSA, particularly given the changing demographics of patients with IPAH. Corrected right ventricular end-systolic volume is a strong prognostic marker in IPAH, independent of invasively derived measurements, mRAP, CI and mVO2.
    Circulation Cardiovascular Imaging 11/2013; 7(1). DOI:10.1161/CIRCIMAGING.113.000338 · 6.75 Impact Factor
  • Thorax 11/2013; 68(Suppl 3):A146-A147. DOI:10.1136/thoraxjnl-2013-204457.308 · 8.56 Impact Factor
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    ABSTRACT: OBJECTIVES: The aim of this study was to develop a composite numerical model based on parameters from cardiac magnetic resonance (CMR) imaging for noninvasive estimation of the key hemodynamic measurements made at right heart catheterization (RHC). BACKGROUND: Diagnosis and assessment of disease severity in patients with pulmonary hypertension is reliant on hemodynamic measurements at RHC. A robust noninvasive approach that can estimate key RHC measurements is desirable. METHODS: A derivation cohort of 64 successive, unselected, treatment naive patients with suspected pulmonary hypertension from ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) underwent RHC and CMR within 12 h. Predicted mean pulmonary arterial pressure (mPAP) was derived using multivariate regression analysis of CMR measurements. The model was tested in an independent prospective validation cohort of 64 patients with suspected pulmonary hypertension. Surrogate measures of pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were estimated by left atrial volumetry and pulmonary arterial phase contrast imaging, respectively. Noninvasive pulmonary vascular resistance (PVR) was calculated from the CMR-derived measurements, defined as: (CMR-predicted mPAP - CMR-predicted PCWP)/CMR phase contrast CO. RESULTS: The following composite statistical model of mPAP was derived: CMR-predicted mPAP = -4.6 + (interventricular septal angle × 0.23) + (ventricular mass index × 16.3). In the validation cohort a strong correlation between mPAP and MR estimated mPAP was demonstrated (R(2) = 0.67). For detection of the presence of pulmonary hypertension the area under the receiver-operating characteristic (ROC) curve was 0.96 (0.92 to 1.00; p < 0.0001). CMR-estimated PVR reliably identified invasive PVR ≥3 Wood units (WU) with a high degree of accuracy, the area under the ROC curve was 0.94 (0.88 to 0.99; p < 0.0001). CONCLUSIONS: CMR imaging can accurately estimate mean pulmonary artery pressure in patients with suspected pulmonary hypertension and calculate PVR by estimating all major pulmonary hemodynamic metrics measured at RHC.
    JACC. Cardiovascular imaging 06/2013; 6(10). DOI:10.1016/j.jcmg.2013.01.013 · 6.99 Impact Factor
  • BMJ (online) 04/2013; 346:f2028. DOI:10.1136/bmj.f2028 · 16.38 Impact Factor
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    ABSTRACT: Catheter-related blood stream infection (CR-BSI) in patients with pulmonary hypertension (PH) receiving intravenous iloprost via an indwelling central line has previously not been fully described. Recent studies have suggested a link between the pH of prostanoid infusions and the rate and nature of CR-BSI. We have investigated CR-BSI in patients receiving intravenous iloprost at our unit. Databases and hospital records were interrogated for all patients receiving intravenous iloprost between September 2007 and June 2012. Fifty-nine patients received intravenous iloprost via an indwelling central catheter with a total of 23,072 treatment days. There were 15 episodes of CR-BSI, identified using a systematic screening protocol, involving 11 patients giving an overall CR-BSI rate of 0.65/1,000 treatment days. CR-BSI rate for Gram-positive organisms was 0.26/1,000 treatment-days and for Gram-negative organisms was 0.39/1,000 treatment-days. The pH of iloprost in typical dosing regimens was comparable to the pH used in standard-diluent treprostinil and dissimilar to alkaline epoprostenol infusions. The proportion of Gram-negative CR-BSI was similar to that reported for standard-diluent treprostinil. CRP was normal on admission in 33 % of cases of confirmed CR-BSI and remained normal in 13 % of cases. CR-BSI rates with intravenous iloprost are comparable to those observed for other prostanoids. The high proportion of Gram-negative organisms observed and the neutral pH of iloprost infusions support the previously hypothesised link between pH and antimicrobial activity. Although usually elevated during a CR-BSI, CRP may be normal in early infection and a normal result cannot completely exclude infection.
    European Journal of Clinical Microbiology 02/2013; 32(7). DOI:10.1007/s10096-013-1822-z · 2.54 Impact Factor
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    ABSTRACT: BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism potentially curable by surgery. Perfusion scintigraphy is currently advocated as the imaging modality of choice to exclude CTEPH due to its high sensitivity. We have evaluated the diagnostic utility of lung perfusion MRI. METHODS: Consecutive patients attending a pulmonary hypertension referral centre undergoing lung perfusion MRI, perfusion scintigraphy, CT pulmonary angiography (CTPA) and right heart catheterisation within 14 days were identified. RESULTS: Of 132 patients, 78 were diagnosed as having CTEPH. Lung perfusion MRI correctly identified 76 patients as having CTEPH with an overall sensitivity of 97%, specificity 92%, positive predictive value 95% and negative predictive value 96% compared with perfusion scintigraphy (sensitivity 96%, specificity 90%) and CTPA (sensitivity 94%, specificity 98%). No cases of surgically accessible CTEPH were missed with either modality. CONCLUSIONS: Lung perfusion MRI has high sensitivity equivalent to perfusion scintigraphy in diagnosing CTEPH but does not require ionising radiation, making it an attractive initial imaging modality to assess patients with suspected CTEPH.
    Thorax 01/2013; 68(7). DOI:10.1136/thoraxjnl-2012-203020 · 8.56 Impact Factor
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    ABSTRACT: BACKGROUND: Liver transplantation is potentially a life-saving therapeutic intervention for patients with portopulmonary hypertension and hepatopulmonary syndrome. However, due to limited data, listing criteria for patients with these conditions have not been clearly established. Indeed, this has led some to speculate that transplantation may not be appropriate in cases of moderate-to-severe portopulmonary hypertension and severe hepatopulmonary syndrome. AIM: To critically discuss the utility of LT for the treatment of hepatopulmonary syndrome and portopulmonary hypertension. METHODS: A literature search was conducted in 2012 on PubMed, Ovid Embase, Ovid Medline and Scopus using the following search terms: hepatopulmonary syndrome, portopulmonary hypertension, pulmonary arterial hypertension, liver transplantation. Relevant manuscripts were included in the review. RESULTS: Liver transplantation has established itself as an effective treatment for selected patients with hepatopulmonary syndrome and portopulmonary hypertension. A multidisciplinary team approach incorporating focused strategies (both pre- and post-operatively) aimed at improving oxygenation in patients with hepatopulmonary syndrome has led to a dramatic improvement in patient outcomes. Additionally, careful patient selection and the use of targeted pulmonary vascular therapies are successfully being used to treat portopulmonary hypertension and 'bridge' patients to successful liver transplantation. CONCLUSIONS: Liver transplantation is an effective therapy for patients with hepatopulmonary syndrome and portopulmonary hypertension. However, rigorous screening and early identification of these conditions allied with aggressive pre-operative optimisation of physiology and diligent post-operative care are imperative to ensuring a good outcome.
    Alimentary Pharmacology & Therapeutics 11/2012; 37(2). DOI:10.1111/apt.12140 · 4.55 Impact Factor
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    ABSTRACT: The phenotype and outcome of severe pulmonary hypertension in COPD is described in small numbers and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naïve cases of pulmonary hypertension in COPD.Mean follow-up was 2.3(±1.9) years. Fifty-nine patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema CT scores compared to 42 patients with mild-moderate pulmonary hypertension. One and three-year survival for severe pulmonary hypertension at 70% and 33% was inferior to 83% and 55% for mild-moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, WHO functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit although improvement in functional class and/or fall in pulmonary vascular resistance>20% following treatment identified patients with improved survival.Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggests that further evaluation of targeted therapies is warranted.
    European Respiratory Journal 09/2012; 41(6). DOI:10.1183/09031936.00079512 · 7.13 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH). A total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed. The relationship between pulmonary vascular resistance and pulmonary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (<4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P < 0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC predicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox proportional hazards regression analysis (P = 0.046 and P = 0.03, respectively). Noninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.
    Investigative radiology 08/2012; 47(10):571-7. DOI:10.1097/RLI.0b013e31826c4341 · 4.45 Impact Factor
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    ABSTRACT: 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.
    American Journal of Respiratory and Critical Care Medicine 07/2012; 186(8):790-6. DOI:10.1164/rccm.201203-0383OC · 11.99 Impact Factor

Publication Stats

525 Citations
267.62 Total Impact Points


  • 2005–2014
    • Sheffield Teaching Hospitals NHS Foundation Trust
      Sheffield, England, United Kingdom
  • 2012
    • National Institute for Health Research
      Londinium, England, United Kingdom
  • 2011
    • The University of Sheffield
      Sheffield, England, United Kingdom
  • 2009
    • The University of Edinburgh
      • Clinical Research Imaging Centre
      Edinburgh, Scotland, United Kingdom