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Patrick SK Liu-Shiu-Cheong,1,2 Brian J Lipworth,3 Jonathan R Weir-McCall,1,4 J Graeme Houston,5 Allan D Struthers1 1Division of Molecular and Clinical Medicine, University of Dundee, Dundee DD1 9SY, UK; 2Department of Respiratory Medicine, Victoria Hospital, NHS Fife, Kirkcaldy KY2 5AH, UK; 3Scottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK; 4Department of Radiology, University of Cambridge, Cambridge CB2 0QQ, UK; 5Imaging Science and Technology, University of Dundee, Dundee DD1 9SY, UKCorrespondence: Brian J LipworthScottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, United KingdomTel +44 1382 383188Email b.j.lipworth@dundee.ac.ukBackground: Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD).Methods: We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT).Results: Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterialpressure 30 mm Hg, FEV1 60% and resting SpO2 96%. After 12 months, there was no significant difference in the change in RVM from baseline (allopurinol 1.85g vs placebo 0.97g with mean difference 0.88g, CI − 4.77 to 3.01, p =0.7). There were also no significant changes in other cardiac parameters measured on MRI, in QOL, spirometry and 6MWT. Subgroup analysis showed that allopurinol significantly reduced RVM compared to placebo with -6.16g vs 0.75g and mean difference 6.92g (CI 1.14 to 12.69, p = 0.02) in COPD patients with more severe airflow limitation.Conclusion: Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation.Keywords: pulmonary hypertension, right ventricle, allopurinol, chronic lung disease

Jonathan R Weir-McCall,1 Patrick SK Liu-Shiu-Cheong,2 Allan D Struthers,1 Brian J Lipworth,2 J Graeme Houston1 1Division of Molecular and Clinical Medicine, Medical Research Institute, University of Dundee, Dundee, UK; 2Scottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Dundee, UK Background: Both pulmonary arterial stiffening and systemic arterial stiffening have been described in COPD. The aim of the current study was to assess pulse wave velocity (PWV) within these two arterial beds to determine whether they are separate or linked processes. Materials and methods: In total, 58 participants with COPD and 21 healthy volunteers (HVs) underwent cardiac magnetic resonance imaging (MRI) and were tested with a panel of relevant biomarkers. Cardiac MRI was used to quantify ventricular mass, volumes, and pulmonary (pulse wave velocity [pPWV] and systemic pulse wave velocity [sPWV]). Results: Those with COPD had higher pPWV (COPD: 2.62 vs HV: 1.78 ms-1, p=0.006), higher right ventricular mass/volume ratio (RVMVR; COPD: 0.29 vs HV: 0.25 g/mL, p=0.012), higher left ventricular mass/volume ratio (LVMVR; COPD: 0.78 vs HV: 0.70 g/mL, p=0.009), and a trend toward a higher sPWV (COPD: 8.7 vs HV: 7.4 ms-1, p=0.06). Multiple biomarkers were elevated: interleukin-6 (COPD: 1.38 vs HV: 0.58 pg/mL, p=0.02), high-sensitivity C-reactive protein (COPD: 6.42 vs HV: 2.49 mg/L, p=0.002), surfactant protein D (COPD: 16.9 vs HV: 9.13 ng/mL, p=0.001), N-terminal pro-brain natriuretic peptide (COPD: 603 vs HV: 198 pg/mL, p=0.001), and high-sensitivity troponin I (COPD: 2.27 vs HV: 0.92 pg/mL, p

The study was funded by the Souter Charitable Foundation and the Chest, Heart and Stroke Scotland Charity. J.R.W.M. is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (grant no. WT 085664) in the form of a clinical research fellowship. Aims : Unrecognized myocardial infarctions (UMIs) have been described in 19-30% of the general population using late gadolinium enhancement (LGE) on cardiac magnetic resonance. However, these studies have focused on an unselected cohort including those with known cardiovascular disease (CVD). The aim of the current study was to ascertain the prevalence of UMIs in a non-high-risk population using magnetic resonance imaging (MRI). Methods and Results : A total of 5000 volunteers aged >40 years with no history of CVD and a 10-year risk of CVD of

BACKGROUND: Pulmonary pulse wave velocity (PWV) allows the non-invasive measurement of pulmonary arterial stiffening, but has not previously been assessed in COPD. The aim of the current study was to assess PWV in COPD and its association with right ventricular (RV) remodelling. METHODS: Fifty-eight participants with COPD underwent pulmonary function tests, 6-min walk test and cardiac MRI, while 21 healthy controls (HCs) underwent cardiac MRI. Thirty-two COPD patients underwent a follow-up MRI to assess for longitudinal changes in RV metrics. Cardiac MRI was used to quantify RV mass, volumes and PWV. Differences in continuous variables between the COPD and HC groups was tested using an independent t-test, and associations between PWV and right ventricular parameters was examined using Pearson's correlation coefficient. RESULTS: Those with COPD had reduced pulsatility (COPD (mean±SD):24.88±8.84% vs. HC:30.55±11.28%, p=0.021), pulmonary acceleration time (COPD:104.0±22.9ms vs. HC: 128.1±32.2ms, p

The TASCFORCE study (Tayside Screening for Cardiovascular Events) was funded by the Souter Charitable Foundation and the Chest, Heart and Stroke Scotland Charity. The SUMMIT study (Surrogate Markers of Micro- and Macrovascular Hard End-Points for Innovative Diabetes Tools) was supported by the Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006). The initial stages of the CaPS (Caerphilly Prospective Study) was funded by the MRC with a grant from the British Heart Foundation funding the measurement of the pulse wave velocity. The statistician was funded by TENOVUS, Tayside. J.R. Weir-McCall is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (Grant no. WT 085664) in the form of a Clinical Research Fellowship. C.M. McEniery is supported by the NIHR (National Institute of Health Research) Cambridge Biomedical Research Centre. Current distance measurement techniques for pulse wave velocity (PWV) calculation are susceptible to intercenter variability. The aim of this study was to derive and validate a formula for this distance measurement. Based on carotid femoral distance in 1183 whole-body magnetic resonance angiograms, a formula was derived for calculating distance. This was compared with distance measurements in 128 whole-body magnetic resonance angiograms from a second study. The effects of recalculation of PWV using the new formula on association with risk factors, disease discrimination, and prediction of major adverse cardiovascular events were examined within 1242 participants from the multicenter SUMMIT study (Surrogate Markers of Micro- and Macrovascular Hard End-Points for Innovative Diabetes Tools) and 825 participants from the Caerphilly Prospective Study. The distance formula yielded a mean error of 7.8 mm (limits of agreement =−41.1 to 56.7 mm; P

Current distance measurement techniques for pulse wave velocity (PWV) calculation are susceptible to intercenter variability. The aim of this study was to derive and validate a formula for this distance measurement. Based on carotid femoral distance in 1183 whole-body magnetic resonance angiograms, a formula was derived for calculating distance. This was compared with distance measurements in 128 whole-body magnetic resonance angiograms from a second study. The effects of recalculation of PWV using the new formula on association with risk factors, disease discrimination, and prediction of major adverse cardiovascular events were examined within 1242 participants from the multicenter SUMMIT study (Surrogate Markers of Micro- and Macrovascular Hard End-Points for Innovative Diabetes Tools) and 825 participants from the Caerphilly Prospective Study. The distance formula yielded a mean error of 7.8 mm (limits of agreement =-41.1 to 56.7 mm;P

Contract grant sponsor: Souter Charitable Trust, and Chest, Heart and Stroke Scotland; Contract grant sponsor: Wellcome Trust; contract grant number: WT 085664 (Clinical Research Fellowship to J.W-McC.) Purpose: To scan a volunteer population using 3.0T magnetic resonance imaging (MRI). MRI of the left ventricular (LV) structure and function in healthy volunteers has been reported extensively at 1.5T. Materials and Methods: A population of 1528 volunteers was scanned. A standardized approach was taken to acquire steady-state free precession (SSFP) LV data in the short-axis plane, and images were quantified using commercial software. Six observers undertook the segmentation analysis. Results: Mean values (±standard deviation, SD) were: ejection fraction (EF) = 69 ± 6%, end diastolic volume index (EDVI) = 71 ± 13 ml/m2 , end systolic volume index (ESVI) = 22 ± 7 ml/m2 , stroke volume index (SVI) = 49 ± 8 ml/m2 , and LV mass index (LVMI) = 55 ± 12 g/m2 . The mean EF was slightly larger for females (69%) than for males (68%), but all other variables were smaller for females (EDVI 68v77 ml/m2 , ESVI 21v25 ml/m2 , SVI 46v52 ml/m2 , LVMI 49v64 g/m2, all P < 0.05). The mean LV volume data mostly decreased with each age decade (EDVI males: -2.9 ± 1.3 ml/m2 , females: -3.1 ± 0.8 ml/m2 ; ESVI males: -1.3 ± 0.7 ml/m2 , females: -1.7 ± 0.5 ml/m2 ; SVI males: -1.7 ± 0.9 ml/m2 , females: -1.4 ± 0.6 ml/m2 ; LVMI males: -1.6 ± 1.1 g/m2 , females: -0.2 ± 0.6 g/m2 but the mean EF was virtually stable in males (0.6 ± 0.6%) and rose slightly in females (1.2 ± 0.5%) with age. Conclusion: LV reference ranges are provided in this population-based MR study at 3.0T. The variables are similar to those described at 1.5T, including variations with age and gender. These data may help to support future population-based MR research studies that involve the use of 3.0T MRI scanners. Publisher PDF