Charlie Elliot

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

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Publications (64)358.89 Total impact


  • No preview · Article · Jan 2016

  • No preview · Article · Jan 2016
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    ABSTRACT: Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety.
    Preview · Article · Nov 2015 · Circulation Cardiovascular Interventions

  • No preview · Article · Oct 2015 · British journal of hospital medicine (London, England: 2005)
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    ABSTRACT: Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of <20 mmHg, cardiovascular magnetic resonance imaging was performed within 24 hours of right heart catheterization. In patients with PH, fractional longitudinal motion (fractional tricuspid annulus to apex distance [f-TAAD]) was significantly greater than fractional transverse motion (fractional septum to free wall distance [f-SFD]; P = 0.002). In patients without PH, no significant difference between f-SFD and f-TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH.
    Full-text · Article · Sep 2015

  • No preview · Article · Sep 2015 · European Respiratory Journal

  • No preview · Conference Paper · Sep 2015

  • No preview · Article · Sep 2015 · European Respiratory Journal

  • No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: Purpose: Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). Methods: A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. Results: 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Conclusion: Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.
    Full-text · Article · May 2015 · PLoS ONE
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    Preview · Article · Feb 2015 · Journal of Cardiovascular Magnetic Resonance
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    Full-text · Article · Feb 2015 · Journal of Cardiovascular Magnetic Resonance
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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 http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · Dec 2014 · Thorax
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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.
    No preview · Article · Dec 2014 · JACC Cardiovascular Imaging
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    ABSTRACT: Introduction Recent studies have suggested that the coexistence of emphysema and fibrosis alters clinical outcome. The aim of this study was to investigate the comparative clinical characteristics, pulmonary function, haemodynamics and right ventricular (RV) function and outcome in patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema (PH-CPFE), chronic obstructive pulmonary disease (PH-COPD) and interstitial lung disease (PH-ILD). Methods In 79, incident patients with pulmonary hypertension associated with respiratory disease, cardiovascular magnetic resonance imaging was performed at 1.5T. Emphysema and fibrosis were scored on high resolution computed tomography scans. Demographic data, lung function tests and right heart catheterisation were also performed. Results Patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema syndrome had lower right ventricular ejection fraction when compared to both patients with PH-COPD and PH –ILD (p < 0.05). At Kaplan-Meier analysis, patients with PH-CPFE patients had significantly worse outcome than those with PH-COPD (p = 0.015), and borderline worse outcome than patients with PH-ILD (p = 0.050), Figure. 48 of 94 patients were diagnosed with severe PH-RESP, defined at mPAP≥40 mmHg. WHO functional class (p = 0.036), TLCO (p = 0.019), RVEF (p = 0.033) were significant independent predictors of outcome in patients with severe PH-RESP. Conclusion Patients with severe PH-RESP have a dire clinical outcome. RVEF is an independent predictor of adverse outcome in these patients and may be a powerful biomarker for use in clinical trials of targeted therapy in patients with pulmonary hypertension associated with lung disease, particularly given the unreliable performance of echocardiography in patients with advanced lung disease.
    No preview · Article · Dec 2014 · Thorax
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    ABSTRACT: Introduction The management and follow-up of pulmonary embolism (PE) is delivered by various specialities resulting in both under and over investigation for suspected chronic thromboembolic pulmonary hypertension (CTEPH). To standardise our approach to long-term PE management a “one-stop” clinic was established in Sheffield in March 2010 to review all patients approximately 3 months after their presentation with acute PE. The aim of this study was to evaluate the incidence and severity of CTEPH identified from a one-stop clinic using an investigative strategy based on careful clinical assessment Methods Consecutive patients attending the one-stop PE clinic following hospital admission with acute PE were identified. During the one-stop consultation a haematologist and respiratory physician reviewed the patient jointly. The need for further investigation was based on clinical assessment. CTEPH was defined as mean pulmonary artery pressure (mPAP) at right heart catheterisation ≥25 mmHg and required multimodality imaging (isotope perfusion scanning, CT pulmonary angiography and MR imaging including MRA and MR perfusion mapping) demonstrating classical features of CTEPH. Results Over a 3-year period between March 2010 and March 2013, 616 patients (mean age 67.7 years, 50% male) attended the one-stop PE clinic approximately 3 months following their acute presentation. 16 patients were diagnosed with CTEPH. An overall diagnostic rate of CTEPH of 2.6% for patients seen at the clinic and an annual incidence of 8.9/million/year was observed based on a referral population of 600,000. This compares to an annual incidence of CTEPH of 4.8/million/year in patients referred to the SPVDU over the same time period, based on a referral population of 15 million. The 16 patients with CTEPH had mPAP 37 ± 11 mmHg, pulmonary vascular resistance (PVR) 362 ± 240 dynes, significantly lower than patients with CTEPH diagnosed at the SPVDU until 2010 (n = 242) mPAP 48 ± 11 mmHg and PVR 735 ± 389 dynes (Hurdman et al Eur Respir J 2012:39(4):945–955). Conclusion Introduction of a one-stop PE clinic for routine follow-up of patients with acute pulmonary embolism identifies patients with higher rates of CTEPH with less severe pulmonary haemodynamic changes.
    No preview · Article · Dec 2014 · Thorax
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    ABSTRACT: Rationale There is limited data on predictors of survival in patients with Pulmonary Hypertension (PH) in the context of Heart Failure and Preserved Ejection Fraction (HF-pEF). Simple non-invasive tests to aid the physician in prognostication would be valuable. The aim of this study was to examine demographic and non-invasive predictors of outcome in PH-HF-pEF in a large well phenotyped PH registry. Method In the ASPIRE Registry (Hurdman J et al Eur Resp J, 2012), 1737 consecutive, incident, treatment-naıve patients with suspected PH underwent diagnostic evaluation between February 2001 and 2010. Patients were diagnosed as PH-HF-pEF if no other causes of PH could be identified and they fulfilled the following criteria: signs and symptoms of heart failure; mean pulmonary artery pressure ≥25 mmHg at rest and pulmonary arterial wedge pressure >15 mmHg by RHC; preserved left ventricular systolic function (ejection fraction ≥50%) by echocardiography or CMR. Predictors of survival were assessed using forward stepwise Cox regression analysis. Variables with a p-value Results 98 patients who fulfilled the diagnostic criteria for PH-HF-pEF were identified. Maximum duration of follow-up was 10 years with a mean follow up 4.9 ± 2.3 years, during which 33 (34%) patients died. After multivariate analysis, only ISWT distance HR 0.99 CI (0.99–1.00) and TLCO HR 0.96 CI(0.94–0.98) at baseline, were predictors of outcome (p < 0.01). Median predicted TLCO in the PH-HF-pEF population was 65%. The 5-year survival in those with a TLCO <65% predicted was 60%, compared with 85% in those whose TLCO was ≥65% (p < 0.01). Conclusions Simple non-invasive testing such as TLCO and exercise capacity measured by the ISWT predict outcome in patients with PH-HF-pEF.
    No preview · Article · Dec 2014 · Thorax
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    ABSTRACT: Background Heart-rate recovery during the first minute of rest (HRR1) after a six minute walk test (6MWT) has been shown to be a strong predictor of clinical worsening in patients with pulmonary arterial hypertension.1 No data as yet has been published regarding the utility of HRR1 as a predictor of mortality. Aim To assess the prognostic value of HRR1 after an Incremental Shuttle Walk Test (ISWT) in patients with pulmonary hypertension (PH). Methods Data was retrieved for consecutive cases of PH diagnosed in our unit from 2001–2010. ISWT was performed routinely as part of baseline assessment according to a modified protocol of Singh et al.2 Only treatment-naive patients with ISWT and HRR data from -90 to +30 days from date of diagnosis were included. HRR1 was defined as the difference between maximum heart rate during the ISWT and heart rate after 1 min of rest following the termination of ISWT. Results Data was available for 491 patients (including patients from each of the 5 main PH diagnostic groups). HRR1 correlated significantly with ISWT distance, highest heart-rate, maximal change in heart-rate,% predicted carbon monoxide diffusion (DLco%pred), pulmonary vascular resistance, cardiac output and mixed venous oxygen saturation (p all ≤0.01). Using a cut-off point of 18bpm the Kaplan Meier graph for survival for patients with HRR1 >18 bpm (n = 179) was significantly better than HRR1 ≤18 bpm (n = 312), p = 0.007 (Figure 1) for all patients and for diagnostic Groups 1 and 2 separately (p = 0.045, p = 0.006). Using univariate Cox proportional hazard analysis for all patients HRR1 (continuous data) had a Hazard Ratio for mortality (HR) of 0.990 with a confidence interval (CI) of 0.962–0.997, p = 0.008. Compared to patients with HRR1 >18, those with HRR1≤18 had a HR of 1.559 (CI 1.127–2.156) p = 0.007. Grouping patients by median distance walked and HRR1–18 demonstrated that the HRR1 proved a useful predictor only in patients who walked less than 180 m. Conclusion HRR1 following ISWT predicts outcome in patients with pulmonary hypertension with more severe disease. References
    No preview · Article · Dec 2014 · Thorax
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    ABSTRACT: Introduction The Incremental Shuttle Walk Test (ISWT) has been evaluated in a number of diseases and found to be a safe, reproducible test which correlates better with VO2 max than the Six-Minute Walk Test (6MWT). We aimed to evaluate the utility of the ISWT as a prognostic indicator in pulmonary hypertension (PH). Methods Data was retrieved for consecutive cases of PH diagnosed in our unit from 2001–2010, a cohort previously described.1 ISWT was performed routinely as part of baseline assessment according to a modified protocol of Singh et al.2 Data was analysed in 5 Groups according to the distance achieved based on ISWT level. A p-value of was deemed statistically significant. Results 1002 of 1,344 patients diagnosed with PH underwent baseline ISWT within 3 months of cardiac catheterization and prior to pulmonary vascular therapy. Complete baseline data was available for 998 patients. Kaplan-Meier analysis showed that increasing level of ISWT was associated with increased survival (Figure 1), including the PAH sub-group, with no ceiling effect. ISWT distance correlated with WHO Functional Class, right atrial pressure, pulmonary vascular resistance, cardiac index, mixed venous oxygen saturation and percent predicted carbon monoxide diffusion (DLco) (p all ≤0.01). Multivariate Cox regression survival analysis including sex, body mass index, age, haemodynamic parameters and percent predicted DLco, demonstrated that ISWT distance was an independent predictor of survival. One year follow-up data was available for 397 patients. Kaplan-Meier analysis showed that ISWT level on treatment at 1 year was predictive of survival (p < 0.001). Survival was also superior in patients whose ISWT distance improved from baseline ≥30 m compared to those whose distance remained stable (-20 to +20 m) or declined by ≥30 m (p = 0.20). Conclusion Baseline ISWT distance correlates with WHO functional class and pulmonary haemodynamics with no ceiling effect. It is an independent predictor of survival and change in ISWT predicts outcome. These features make it a viable alternative to the 6MWT in the assessment of patients with pulmonary hypertension, with a number of potential advantages. References
    No preview · Article · Dec 2014 · Thorax
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    ABSTRACT: Introduction and objectives Magnetic resonance (MR) imaging of the hyperpolarised noble gases 3He and 129Xe provides exquisite depiction of pulmonary ventilation. In addition, MR measurement of the apparent diffusion coefficient (ADC) of 3He gas has proven clinical utility in assessment of emphysema. Furthermore, xenon is soluble and is a promising marker of pulmonary gas-exchange. The motivation of this work was to demonstrate non-invasive quantification of whole-lung septal thickness (ST) and helium ADC in subjects with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) using 129Xe and 3He MR. Methods Hyperpolarised 129Xe spectroscopy was performed on ten healthy volunteers (23–74 yrs), four subjects with SSc and four with IPF at 1.5 T. A chemical shift saturation recovery (CSSR) method was used to assess the dynamics of xenon uptake into parenchymal tissues and blood and to derive quantitative information about lung microstructure. From the subject cohort, six volunteers and seven patients were also scanned at 1.5 T with a diffusion-weighted sequence to determine 3He ADC values. For comparison with MR experiments, standard pulmonary function tests including the diffusing capacity of carbon monoxide (DLCO) were performed. Results Pulmonary function was significantly worse in both SSc and IPF subjects than healthy volunteers (DLCO < 45% in IPF patients). Both 129Xe CSSR ST and 3He ADC values were elevated in subjects with SSc, and to a larger degree in those with IPF, compared with healthy volunteers (Figure 1, top). These two MR metrics correlated significantly, suggesting that fibrotic remodelling of tissue both degrades gas-exchange efficiency and induces alveolar widening causing less-restricted gas diffusion (although emphysema was reported for only one subject on CT). The 129Xe CSSR-derived ST values correlated well with whole-lung DLCO (Figure 1, bottom) and in healthy volunteers, ST increased with age (p < 0.05). Conclusions Hyperpolarised 129Xe and 3He MR techniques are sensitive to small changes in gas-exchange efficiency and alveolar surface geometry, respectively. These two factors appear to have an intrinsic link, identified in the presence of fibrotic lung disease without obvious emphysema. Further application of these MR techniques may prove useful in the diagnosis/assessment of different forms of ILD.
    No preview · Conference Paper · Dec 2014