Publications by authors named "Michael Roughton"

89 Publications

Is Cardiomegaly an Indication of "Heart-Sparing Effect" in Small Fetuses?

Fetal Diagn Ther 2021 Oct 15:1-7. Epub 2021 Oct 15.

Fetal Medicine Unit, St. George's University Hospitals NHS Foundation Trust, London, United Kingdom.

Introduction: This study aimed to test the hypothesis that cardiac size is maintained in small fetuses presenting with cardiomegaly.

Materials And Methods: We identified singleton fetuses with estimated fetal weight <10th centile and with cardiomegaly without another more likely cardiac or extra-cardiac cause. We used Z-scores for cardiac and thoracic circumferences normalized for gestational age (GA), biparietal diameter (BPD), head circumference (HC), and femur length (FL), obtained from 188 normally grown fetuses.

Results: When comparing chest size, small fetuses had significantly lower thoracic circumferences median Z-scores (IQR) for GA = -4.82 (-6.15 to -3.51), BPD = -2.42 (-4.04 to -1.48), HC = -2.72 (-4.53 to -1.90), and FL = -1.60 (-2.87 to -0.71); p < 0.001 for all. When comparing heart size, small fetuses showed lower cardiac circumferences median Z-scores (IQR) for GA = -1.59 (-2.79 to -0.16); p < 0.001, similar cardiac circumferences Z-scores for BPD = 0.29 (-0.65 to 1.28); p = 0.284 and HC = 0.11 (-1.13 to 0.96); p = 0.953, and higher cardiac circumferences Z-scores for FL = 0.94 (-0.05 to 2.13); p < 0.001.

Conclusions: Our results show that in small fetuses with cardiomegaly, the heart maintains normal dimensions when normalized to cranial diameters and higher dimensions when normalized to long bones. This provides insight into cardiac adaptation to adverse intrauterine environment.
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http://dx.doi.org/10.1159/000519059DOI Listing
October 2021

Six-minute walk test: prognostic value and effects of nebivolol versus placebo in elderly patients with heart failure from the SENIORS trial.

Clin Res Cardiol 2021 Aug 2;110(8):1193-1201. Epub 2020 Nov 2.

University of East Anglia and Norfolk and Norwich University Hospital, Norwich, UK.

Background: There is limited information about the 6-min walk test (6MWT) in elderly patients with heart failure. We evaluated 6MWT and the effect of nebivolol on 6MWT from the SENIORS trial.

Methods And Results: The SENIORS trial evaluated nebivolol versus placebo on death and hospitalisation in patients aged ≥ 70 years with heart failure. A total of 1982 patients undertook a 6MWT at baseline and 1716 patients at 6 months. Patients were divided into tertiles (≤ 200 m, 201 to ≤ 300 m and > 300 m) and to change in distance walked between baseline and 6 months (< 0 m, 0 to < 30 m and ≥ 30 m). The primary outcome was all-cause mortality and cardiovascular hospital admission. Secondary endpoint was all-cause mortality. Baseline walk distance of ≤ 200 m incurred a greater risk of the primary and secondary outcomes (HR 1.41, CI 95% 1.17-1.69, p < 0.001) and (HR 1.37, CI 95% 1.05-1.78, p = 0.019). A decline in walk distance over 6 months was associated with increased risk of clinical events. Nebivolol had no influence on change in walk distance over 6 months.

Conclusions: The 6MWT has prognostic utility in elderly patients. Those who walked less than 200 m were at highest risk. Nebivolol had no effect on 6MWT.
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http://dx.doi.org/10.1007/s00392-020-01768-wDOI Listing
August 2021

Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study.

Clin Endocrinol (Oxf) 2019 12 1;91(6):776-785. Epub 2019 Oct 1.

University of Sheffield, Sheffield, UK.

Objectives: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD.

Design: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906).

Patients: Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long-acting pasireotide during the extension.

Results: Eighty-one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months' treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late-night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty-two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia-related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA ) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty-six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA  ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment.

Conclusions: Long-acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long-term therapy for CD.
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http://dx.doi.org/10.1111/cen.14081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899900PMC
December 2019

Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing's disease: interim results from a long-term real-world evidence study.

Pituitary 2019 Oct;22(5):542-551

Section of Endocrinology, Diabetology and Metabolism, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialities (PROMISE), University of Palermo, Palermo, Italy.

Purpose: Clinical trials have demonstrated the favorable efficacy/safety profile of pasireotide in patients with Cushing's disease (CD). We report interim long-term results of an ongoing real-world evidence study of subcutaneous pasireotide in patients with CD.

Methods: Adults with CD receiving pasireotide, initiated before (prior-use) or at study entry (new-use), were monitored for ≤ 3 years during a multicenter observational study ( http://clinicaltrials.gov identifier NCT02310269). Primary objective was to assess long-term safety of pasireotide alone or with other CD therapies.

Results: At the time of this interim analysis, 127 patients had received pasireotide (new-use, n = 31; prior-use, n = 96). Eight patients had completed the 3-year observation period, 53 were ongoing, and 66 had discontinued. Among 31 new-use and 92 prior-use patients with ≥ 1 safety assessment, respectively: 24 (77%) and 37 (40%) had drug-related adverse events (AEs); 7 (23%) and 10 (11%) had serious drug-related AEs. Most common drug-related AEs were nausea (14%), hyperglycemia (11%) and diarrhea (11%); these were more frequently reported in new users and mostly of mild-to-moderate severity. 14 (45%) new-use and 15 (16%) prior-use patients experienced hyperglycemia-related AEs. Mean urinary free cortisol (mUFC) was within normal range at baseline and months 1, 12 and 24, respectively, in: 1/16 (6%), 9/18 (50%), 1/3 (33%) and 0/0 new users; 28/43 (65%), 15/27 (56%), 27/33 (82%) and 12/19 (63%) prior users.

Conclusions: Pasireotide is well tolerated and provides sustained reductions in mUFC during real-world treatment of CD. The lower rate of hyperglycemia-related AEs in prior users suggests that hyperglycemia tends not to deteriorate if effectively managed soon after onset.

Clinical Trial Registration Number: NCT02310269.
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http://dx.doi.org/10.1007/s11102-019-00984-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728293PMC
October 2019

Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial.

Lancet Diabetes Endocrinol 2018 01 12;6(1):17-26. Epub 2017 Oct 12.

Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK.

Background: Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease.

Methods: In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries. Exclusion criteria included previous pasireotide treatment, mitotane therapy within 6 months, and pituitary irradiation within 10 years. We randomly allocated patients 1:1 (block size of four) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mg every 4 weeks for 12 months (in the core phase). We stratified randomisation by screening mUFC concentration (1·5 to <2·0 × ULN and 2·0-5·0 × ULN). The dose could be uptitrated (from 10 mg to 30 mg or from 30 mg to 40 mg) at month 4 if the mUFC concentration was greater than 1·5 × ULN, and at month 7, month 9, or month 12 if the mUFC concentration was greater than 1·0 × ULN. Investigators, patients, site personnel, and those assessing outcomes were masked to dose group allocation. The primary endpoint was the proportion of patients in each group with an mUFC concentration of less than or equal to the ULN at month 7. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01374906.

Findings: Between Dec 28, 2011, and Dec 9, 2014, we randomly allocated 150 patients to receive pasireotide 10 mg (74 [49%] patients) or 30 mg (76 [51%] patients). The primary efficacy endpoint was met by 31 (41·9% [95% CI 30·5-53·9]) of 74 patients in the 10 mg group and 31 (40·8% [29·7-52·7]) of 76 in the 30 mg group. The most common adverse events were hyperglycaemia (36 [49%] in the 10 mg group and 36 [47%] in the 30 mg group), diarrhoea (26 [35%] and 33 [43%]), cholelithiasis (15 [20%] and 34 [45%]), diabetes mellitus (14 [19%] and 18 [24%]), and nausea (15 [20%] and 16 [21%]). Serious adverse events suspected to be study drug related were reported in eight (11%) patients in the 10 mg group and four (5%) in the 30 mg group. Two (3%) patients in the 30 mg group died during the study (pulmonary artery thrombosis and cardiorespiratory failure); neither death was judged to be related to the study drug.

Interpretation: Long-acting pasireotide normalised mUFC concentration in about 40% of patients with Cushing's disease at month 7 and had a similar safety profile to that of twice-daily subcutaneous pasireotide. Long-acting pasireotide is an efficacious treatment option for some patients with Cushing's disease who have persistent or recurrent disease after initial surgery or are not surgical candidates, and provides a convenient monthly administration schedule.

Funding: Novartis Pharma AG.
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http://dx.doi.org/10.1016/S2213-8587(17)30326-1DOI Listing
January 2018

Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation.

Circ Cardiovasc Interv 2016 07;9(7)

From the Department of Cardiology (A.C.L., R.J.J., R.K., T.M.S., P.S., M.R., A.D., C.D.M., S.W.D.), Department of Cardiovascular Magnetic Resonance (F.A., D.J.P., R.H.M.), and Department of Surgery (N.E.M.), Royal Brompton and Harefield NHS Trust, London, United Kingdom; Department of Statistics, London School of Hygiene and Tropical Medicine, University College London, United Kingdom (K.H.); and Department of Cardiovascular Medicine, Imperial College, London, United Kingdom (D.J.P., R.H.M.).

Background: Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported.

Methods And Results: A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival.

Conclusions: RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.115.003486DOI Listing
July 2016

Clinical and economic consequences of non-cardiac incidental findings detected on cardiovascular computed tomography performed prior to transcatheter aortic valve implantation (TAVI).

Int J Cardiovasc Imaging 2015 Oct 12;31(7):1435-46. Epub 2015 Jun 12.

Department of Cardiology, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK.

Transcatheter aortic valve implantation (TAVI) is an effective treatment option for patients with severe degenerative aortic valve stenosis who are high risk for conventional surgery. Computed tomography (CT) performed prior to TAVI can detect pathologies that could influence outcomes following the procedure, however the incidence, cost, and clinical impact of incidental findings has not previously been investigated. 279 patients underwent CT; 188 subsequently had TAVI and 91 were declined. Incidental findings were classified as clinically significant (requiring treatment), indeterminate (requiring further assessment), or clinically insignificant. The primary outcome measure was all-cause mortality up to 3 years. Costs incurred by additional investigations resultant to incidental findings were estimated using the UK Department of Health Payment Tariff. Incidental findings were common in both the TAVI and medical therapy cohorts (54.8 vs. 70.3%; P = 0.014). Subsequently, 45 extra investigations were recommended for the TAVI cohort, at an overall average cost of £32.69 per TAVI patient. In a univariate model, survival was significantly associated with the presence of a clinically significant or indeterminate finding (HR 1.61; P = 0.021). However, on multivariate analysis outcomes after TAVI were not influenced by any category of incidental finding. Incidental findings are common on CT scans performed prior to TAVI. However, the total cost involved in investigating these findings is low, and incidental findings do not independently identify patients with poorer outcomes after TAVI. The discovery of an incidental finding on CT should not necessarily influence or delay the decision to perform TAVI.
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http://dx.doi.org/10.1007/s10554-015-0685-zDOI Listing
October 2015

Systemic right ventricular fibrosis detected by cardiovascular magnetic resonance is associated with clinical outcome, mainly new-onset atrial arrhythmia, in patients after atrial redirection surgery for transposition of the great arteries.

Circ Cardiovasc Imaging 2015 May;8(5)

From the NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital (R.R., M.A.G., S.Y.H., S.E., L.S., W.L., T.W., M.S., K.P.M., P.J.K., D.J.P., S.V.B.-N.), National Heart and Lung Institute (M.A.G., S.Y.H., S.E., L.S., W.L., T.W., M.S., K.P.M., P.J.K., M.R., D.J.P., S.V.B.-N.), Royal Brompton Hospital, Imperial College London, London, United Kingdom; and Section of Clinical Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (R.R.).

Background: We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance predicts outcomes in patients with transposition of the great arteries post atrial redirection surgery. These patients have a systemic right ventricle (RV) and are at risk of arrhythmia, premature RV failure, and sudden death.

Methods And Results: Fifty-five patients (aged 27±7 years) underwent LGE cardiovascular magnetic resonance and were followed for a median 7.8 (interquartile range, 3.8-9.6) years in a prospective single-center cohort study. RV LGE was present in 31 (56%) patients. The prespecified composite clinical end point comprised new-onset sustained tachyarrhythmia (atrial/ventricular) or decompensated heart failure admission/transplantation/death. Univariate predictors of the composite end point (n=22 patients; 19 atrial/2 ventricular tachyarrhythmia, 1 death) included RV LGE presence and extent, RV volumes/mass/ejection fraction, right atrial area, peak Vo(2), and age at repair. In bivariate analysis, RV LGE presence was independently associated with the composite end point (hazard ratio, 4.95 [95% confidence interval, 1.60-15.28]; P=0.005), and only percent predicted peak Vo(2) remained significantly associated with cardiac events after controlling for RV LGE (hazard ratio, 0.80 [95% confidence interval, 0.68-0.95]; P=0.009/5%). In 8 of 9 patients with >1 event, atrial tachyarrhythmia, itself a known risk factor for mortality, occurred first. There was agreement between location and extent of RV LGE at in vivo cardiovascular magnetic resonance and histologically documented focal RV fibrosis in an explanted heart. There was RV LGE progression in a different case restudied for clinical indications.

Conclusions: Systemic RV LGE is strongly associated with adverse clinical outcome especially arrhythmia in transposition of the great arteries, thus LGE cardiovascular magnetic resonance should be incorporated in risk stratification of these patients.
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http://dx.doi.org/10.1161/CIRCIMAGING.114.002628DOI Listing
May 2015

Utility of the SENIORS elderly heart failure risk model applied to the RICA registry of acute heart failure.

Int J Cardiol 2015 Mar 4;182:449-53. Epub 2015 Jan 4.

Norwich Medical School, University of East Anglia, Norfolk and Norwich University Hospital, Norwich, UK.

Background: Heart failure (HF) is predominantly a disease of the elderly. Reliable risk stratification would help in the management of this population, but no model has been well evaluated in elderly HF patients in both acute and chronic settings and not being restricted by ejection fraction. To evaluate the utility of the SENIORS risk model, developed from a clinical trial of elderly patients with chronic HF, in an independent cohort (National Spanish Registry: RICA) of elderly acute HF patients.

Methods: We applied the SENIORS risk model to 926 patients in RICA to estimate risk at one year of a) composite outcome of all-cause mortality or cardiovascular hospital admission and b) all-cause mortality.

Results: In the RICA registry mean age was 78years, mean ejection fraction 51% and 87% were in NYHA II and III. At one year death/CV hospitalization occurred in 31.9% and all-cause mortality in 19.5%. The risk model provided good separation of Kaplan Meier curves stratified by tertile for death/CV hospitalization and all-cause mortality. The observed versus expected rates of death/CV hospitalization in the lowest, middle and highest risk tertiles were (%) 34/24, 45/41 and 57/67, and for death 13/16, 32/38 and 44/70 respectively. C-statistic for all-cause mortality or CV hospitalization was 0.60 and for all-cause mortality 0.66.

Conclusion: The SENIORS risk model was a reliable tool for relative risk stratification among acute heart failure patients in a "real world" registry, but predicted versus observed risk showed some variability. The model provides a useful basis for clinical risk prediction.
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http://dx.doi.org/10.1016/j.ijcard.2014.12.173DOI Listing
March 2015

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

J Cardiovasc Magn Reson 2014 Aug 12;16:49. Epub 2014 Aug 12.

Background: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness.

Methods: CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments.

Results: Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P<0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P<0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P=0.021). There was a significant negative association between hyperemic MBF and wall thickness (β=-0.047 ml/g/min per mm, 95% CI: -0.057 to -0.038, P<0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P=0.003).

Conclusions: Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia.
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http://dx.doi.org/10.1186/s12968-014-0049-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145339PMC
August 2014

Calibration of myocardial T2 and T1 against iron concentration.

J Cardiovasc Magn Reson 2014 Aug 12;16:62. Epub 2014 Aug 12.

Background: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.

Methods: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.

Results: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001).

Conclusion: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies.
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http://dx.doi.org/10.1186/s12968-014-0062-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145261PMC
August 2014

Influence of systolic blood pressure on clinical outcomes in elderly heart failure patients treated with nebivolol: data from the SENIORS trial.

Eur J Heart Fail 2014 Sep 17;16(9):1009-15. Epub 2014 Jul 17.

Department of Internal Medicine, IMIBIC/Hospital Reina Sofia de Córdoba, University of Córdoba, Spain.

Aims: There is limited information about the effects of beta-blockers in heart failure (HF) stratified by blood pressure, especially in the elderly and those with preserved EF. We evaluate the effects of nebivolol on outcomes in elderly patients with HF stratified by baseline systolic blood pressure (SBP) and EF.

Methods And Results: The SENIORS trial evaluated the effects of nebivolol and enrolled 2128 patients ≥ 70 years of age with HF. Patients were divided into three baseline pre-treatment SBP categories (<110, 110-130, and >130 mmHg). In addition, we evaluated the influence of SBP (≤ 130 and > 130 mmHg) on patients with LVEF <40% vs. ≥ 40%. Low baseline SBP was associated with worse clinical outcomes irrespective of treatment group, both in patients with reduced EF and in those with preserved EF. Nebivolol had similar benefits irrespective of baseline SBP: the hazard ratio (HR) for primary outcome of all-cause mortality or cardiovascular hospitalization in the three SBP categories for nebivolol vs. placebo was 0.85 [95% confidence interval (CI) 0.50-1.45], 0.79 (95% CI 0.61-1.01), and 0.88 (95% CI 0.72-1.07), respectively (P for interaction = 0.61). Similar results were obtained for the secondary endpoint of all-cause mortality. There was no significant interaction for the effects of nebivolol by baseline SBP stratified by LVEF.

Conclusions: Elderly HF patients with lower SBP have a worse outcome than those with higher SBP, but nebivolol appears to be safe and well tolerated, with similar benefits on the composite outcome of death or cardiovascular hospital admission irrespective of baseline SBP and LVEF.
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http://dx.doi.org/10.1002/ejhf.136DOI Listing
September 2014

Does manual therapy provide additional benefit to breathing retraining in the management of dysfunctional breathing? A randomised controlled trial.

Disabil Rehabil 2015 15;37(9):763-70. Epub 2014 Jul 15.

School of Health Science and Social Care, Brunel University , London , UK .

Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB.

Methods: Sixty subjects with primary DB were randomised into either breathing retraining (standard treatment; n = 30) or breathing retraining plus MT (intervention; n = 30) group. Both the groups received standardised respiratory physiotherapy, which included: DB education, breathing retraining, home regimen, and audio disc. Intervention group subjects additionally received MT following further assessment. Data from 57 subjects were analysed.

Results: At baseline, standard treatment group subjects were statistically younger (41.7 + 13.5 versus 50.8 + 13.0 years; p = 0.001) with higher Nijmegen scores (38.6 + 9.5 versus 31.5 + 6.9; p = 0.001). However, no significant difference was found between the groups for primary outcome Nijmegen score (95% CI (-1.1, 6.6) p = 0.162), or any secondary outcomes (Hospital Anxiety & Depression Score, spirometry or exercise tolerance).

Conclusion: Breathing retraining is currently the mainstay of treatment for patients with DB. The results of this study suggest MT provides no additional benefit in this patient group.

Implications For Rehabilitation: Dysfunctional breathing (DB) is associated with significant patient morbidity but often goes unrecognised, leading to prolonged investigation and significant use of health care resources. Breathing retraining remains the primary management of this condition. However, physiotherapists are also using manual therapy (MT) as an adjunctive treatment for patients with DB. However, the results of this study suggest that MT provides no further benefit and cannot be recommended in the clinical management of this condition.
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http://dx.doi.org/10.3109/09638288.2014.941020DOI Listing
December 2015

Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy.

Heart 2014 Dec 24;100(23):1851-8. Epub 2014 Jun 24.

Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK Imperial College London, London, UK.

Objective: Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM.

Methods: We conducted a prospective cohort study in a tertiary referral centre. Consecutive patients with HCM (n=711, median age 56.3 years, IQR 46.7-66.6; 70.0% male) underwent LGE-CMR and were followed for a median 3.5 years. The primary end point was SCD or aborted SCD.

Results: Overall, 471 patients (66.2%) had myocardial fibrosis (median 5.9% of left ventricular mass, IQR: 2.2-13.3). Twenty-two (3.1%) reached the primary end point. The extent but not the presence of fibrosis was a significant univariable predictor of the primary end point (HR per 5% LGE: 1.24, 95% CI 1.06 to 1.45; p=0.007 and HR for LGE: 2.69, 95% CI 0.91 to 7.97; p=0.073, respectively). However, on multivariable analysis, only LV-EF remained statistically significant (HR: 0.92, 95% CI 0.89 to 0.95; p<0.001). For the secondary outcome of cardiovascular mortality/aborted SCD, the presence and the amount of fibrosis were significant predictors on univariable but not multivariable analysis after adjusting for LV-EF and non-sustained ventricular tachycardia.

Conclusions: The amount of myocardial fibrosis was a strong univariable predictor of SCD risk. However, this effect was not maintained after adjusting for LV-EF. Further work is required to elucidate the interrelationship between fibrosis and traditional predictors of outcome in HCM.
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http://dx.doi.org/10.1136/heartjnl-2013-305471DOI Listing
December 2014

Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan.

J Cardiovasc Magn Reson 2014 Jun 10;16:40. Epub 2014 Jun 10.

Haematology Department, University College London Hospitals, London, UK.

Background: There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC.

Methods: Here, we used an optimised liver T2* sequence calibrated against 50 liver biopsy samples on 25 patients with transfusional haemosiderosis using ordinary least squares linear regression, and assessed the method reproducibility in 96 scans over an LIC range up to 42 mg/g dry weight (dw) using Bland-Altman plots. Using mixed model linear regression we compared the new T2*-LIC with R2-LIC (Ferriscan) on 92 scans in 54 patients with transfusional haemosiderosis and examined method agreement using Bland-Altman approach.

Results: Strong linear correlation between ln(T2*) and ln(LIC) led to the calibration equation LIC = 31.94(T2*)-1.014. This yielded LIC values approximately 2.2 times higher than the proof-of-concept T2* method. Comparing this new T2*-LIC with the R2-LIC (Ferriscan) technique in 92 scans, we observed a close relationship between the two methods for values up to 10 mg/g dw, however the method agreement was poor.

Conclusions: New calibration of T2* against liver biopsy estimates LIC in a reproducible way, correcting the proof-of-concept calibration by 2.2 times. Due to poor agreement, both methods should be used separately to diagnose or rule out liver iron overload in patients with increased ferritin.
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http://dx.doi.org/10.1186/1532-429X-16-40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064805PMC
June 2014

Effects of nebivolol on biomarkers in elderly patients with heart failure.

Int J Cardiol 2014 Aug 17;175(2):253-60. Epub 2014 May 17.

Norwich Medical School, University of East Anglia, UK; Previously Royal Brompton and Harefield NHS Foundation Trust/Imperial College, London, UK.

Background: Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure.

Methods: In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT-BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour necrosis factor-alpha (TNF-α), serum uric acid (SUA), symmetrical dimethyl arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA) at baseline (before study drug), at 6 months and 12 months in a prespecified substudy.

Results: One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample. There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo (P=0.08) and sFas showed a numerical increase in patients on placebo (P=0.08). Mean baseline LVEF was 35% in both groups and at 12 months was 43% on nebivolol group and 34% on placebo group (P=0.01).

Conclusion: There were trends but no clear changes associated with nebivolol in neurohormones, cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure. Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure.
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http://dx.doi.org/10.1016/j.ijcard.2014.05.018DOI Listing
August 2014

Organizational index mapping to identify focal sources during persistent atrial fibrillation.

J Cardiovasc Electrophysiol 2014 Apr 24;25(4):355-363. Epub 2014 Jan 24.

Imperial College London, UK.

Introduction: Localized rotors have been implicated in the mechanism of persistent atrial fibrillation (AF). Although regions of highest dominant frequency (DF) on spectral analysis of the left atrium (LA) have been said to identify rotors, other mechanisms such as wavefront collisions will sporadically also generate an inconsistent distribution of high DF. We hypothesized that if drivers of AF were present, their distinctive spectral characteristics would result more from their temporal stability than their high frequency.

Methods And Results: Ten patients with persistent AF underwent LA noncontact mapping. Following subtraction of far-field ventricular components, noncontact electrograms at 256 sites underwent fast Fourier transform. Mean absolute difference in DF between 5 sequential 7-second segments of AF was defined as the DF variability (DFV) at each site. Mean ratio of the DF and its harmonics to the total power of the spectrum was defined as the organizational index (OI). Mean DFV was significantly lower in organized areas (OI > 1 SD above mean) than at all sites (0.34 ± 0.04 vs 0.46 ± 0.04 Hz; P < 0.001). When organized areas were ablated during wide-area circumferential ablation, AF organized in remote regions (LA appendage ΔOI ablated vs unablated: +0.21 [0.06-0.41] vs -0.04 [-0.14-0.05]; P = 0.005).

Conclusions: At sites of organized activation, the activation frequency was also significantly more stable over time. This observation is consistent with the existence of focal sources, and inconsistent with a purely random activation pattern. Ablation of such regions is technically feasible, and was associated with organization of AF in remote atrial regions.
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http://dx.doi.org/10.1111/jce.12352DOI Listing
April 2014

Inflammatory bowel disease in the UK: is quality of care improving?

Frontline Gastroenterol 2013 Oct 28;4(4):296-301. Epub 2013 Jun 28.

College of Medicine, Swansea University, Swansea, UK.

Objective: A national audit conducted in 2005/6 showed unacceptable quality of care for inpatients with inflammatory bowel disease (IBD) in the UK. This was re-audited in 2007/8 and 2010/11. The aim of this study is to examine the quality of care provided for inpatients with IBD in the UK.

Design: A programme of engagement and re-audit in 128 hospitals in the UK providing care for adult patients with IBD admitted to hospital between 1 June 2005 and 31 May 2006, 1 September 2007 and 31 August 2008 and 1 September 2010 and 31August 2011.

Interventions: Wide dissemination of the results, selected site visits, development of national service standards, and the development of an online document repository.

Main Outcome Measures: Mortality, medical and surgical treatment, specialist nursing and dietetic care were audited.

Results: Data from 1953, 2016 and 1948 patients with ulcerative colitis (UC) and 2074, 2109 and 1900 patients with Crohn's disease (CD) were audited in 2005/6, 2007/8 and 2010/11, respectively. The mortality rate fell from 1.7% to 0.8% (p=0.034) in UC and from 1.3% to 0.8% (p=0.226) in CD. The proportion of inpatients reviewed by an IBD specialist nurse has risen from 23.7% to 44.9% in UC and from 18.1% to 39.9% (p<0.001) in CD. Anti-tumour necrosis factor therapy has increased in UC and CD (p<0.001) while ciclosporin prescription has slightly fallen in UC. Laparoscopic surgeries have significantly increased in UC and CD (p<0.001).

Conclusions: The results show clear evidence of improvement in most aspects of the quality of care for IBD inpatients.
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http://dx.doi.org/10.1136/flgastro-2013-100333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369826PMC
October 2013

The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy.

Circulation 2013 Oct 21;128(15):1623-33. Epub 2013 Aug 21.

Royal Brompton Hospital, London, United Kingdom (A.G., T.F.I., A.J., F.A., K.G., N.A.I., S.R., J.K., T.D.H.B., K.M., E.L., M.R., R.W., T.C.P., R.S., J.-P.C., S.A.C., M.R.C., R.G.A., D.J.P., S.K.P.); Ealing Hospital, London, United Kingdom (R.G.A.); National Heart & Lung Institute, Imperial College, London, United Kingdom (T.F.I., K.G., R.S., J.-.P.C., S.A.C., M.R.C., D.J.P., S.K.P.); and National Heart Centre Singapore, Singapore (S.A.C.).

Background: Cardiovascular magnetic resonance is the gold-standard technique for the assessment of ventricular function. Although left ventricular volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether cardiovascular magnetic resonance assessment of RV function has prognostic value in DCM.

Methods And Results: We prospectively studied 250 consecutive DCM patients with the use of cardiovascular magnetic resonance. RVSD, defined by RV ejection fraction≤45%, was present in 86 (34%) patients. During a median follow-up period of 6.8 years, there were 52 deaths, and 7 patients underwent cardiac transplantation. The primary end point of all-cause mortality or cardiac transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients without RVSD (49% versus 10%; hazard ratio, 5.90; 95% confidence interval [CI], 3.35-10.37; P<0.001). On multivariable analysis, RVSD remained a significant independent predictor of the primary end point (hazard ratio, 3.90; 95% CI, 2.16-7.04; P<0.001), as well as secondary outcomes of cardiovascular mortality or cardiac transplantation (hazard ratio, 3.35; 95% CI, 1.76-6.39; P<0.001), and heart failure death, heart failure hospitalization, or cardiac transplantation (hazard ratio, 2.70; 95% CI, 1.32-5.51; P=0.006). Assessment of RVSD improved risk stratification for all-cause mortality or cardiac transplantation (net reclassification improvement, 0.31; 95% CI 0.10-0.53; P=0.001).

Conclusions: RVSD is a powerful, independent predictor of transplant-free survival and adverse heart failure outcomes in DCM. Cardiovascular magnetic resonance assessment of RV function is important in the evaluation and risk stratification of DCM patients.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.002518DOI Listing
October 2013

International survey of T2* cardiovascular magnetic resonance in β-thalassemia major.

Haematologica 2013 Sep 28;98(9):1368-74. Epub 2013 Jun 28.

Royal Brompton and Harefield NHS Foundation Trust, London, UK.

Accumulation of myocardial iron is the cause of heart failure and early death in most transfused thalassemia major patients. T2* cardiovascular magnetic resonance provides calibrated, reproducible measurements of myocardial iron. However, there are few data regarding myocardial iron loading and its relation to outcome across the world. A survey is reported of 3,095 patients in 27 worldwide centers using T2* cardiovascular magnetic resonance. Data on baseline T2* and numbers of patients with symptoms of heart failure at first scan (defined as symptoms and signs of heart failure with objective evidence of left ventricular dysfunction) were requested together with more detailed information about patients who subsequently developed heart failure or died. At first scan, 20.6% had severe myocardial iron (T2*≤ 10 ms), 22.8% had moderate myocardial iron (T2* 10-20 ms) and 56.6% of patients had no iron loading (T2*>20 ms). There was significant geographical variation in myocardial iron loading (24.8-52.6%; P<0.001). At first scan, 85 (2.9%) of 2,915 patients were reported to have heart failure (81.2% had T2* <10 ms; 98.8% had T2* <20 ms). During follow up, 108 (3.8%) of 2,830 patients developed new heart failure. Of these, T2* at first scan had been less than 10 ms in 96.3% and less than 20 ms in 100%. There were 35 (1.1%) cardiac deaths. Of these patients, myocardial T2* at first scan had been less than 10 ms in 85.7% and less than 20 ms in 97.1%. Therefore, in this worldwide cohort of thalassemia major patients, over 43% had moderate/severe myocardial iron loading with significant geographical differences, and myocardial T2* values less than 10 ms were strongly associated with heart failure and death.
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http://dx.doi.org/10.3324/haematol.2013.083634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762092PMC
September 2013

Prognostic value of cardiovascular magnetic resonance in patients with suspected arrhythmogenic right ventricular cardiomyopathy.

Int J Cardiol 2013 Oct 20;168(4):3514-21. Epub 2013 May 20.

Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom; Centre d'Imagerie de Morges, Morges, Switzerland.

Background: Early recognition and accurate risk stratification are important in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Identification of predictors of outcome by cardiovascular magnetic resonance (CMR) in patients undergoing evaluation for ARVC is limited. We investigated the predictive value of morphological abnormalities detected by CMR for major clinical events in patients with suspected ARVC.

Methods: We performed a longitudinal study on 369 consecutive patients with at least one criterion for ARVC. Abnormal CMR was defined by the presence of one of the following: increased right ventricular (RV) volumes, reduced RV ejection fraction, RV regional wall motion abnormalities, myocardial fatty infiltration, and myocardial fibrosis. The end-point was a composite of cardiac death, sustained ventricular tachycardia, ventricular fibrillation, and appropriate ICD discharge.

Results: Twenty patients met the composite end-point over a mean follow-up of 4.3±1.5 years. An abnormal CMR was an independent predictor of outcomes (p<0.001). The presence of multiple abnormalities heralded a particular high risk of events (HR 23.0, 95% CI 5.7-93.2, p<0.001 for 2 abnormalities; HR 35.8, 95% CI 9.7-132.6, p<0.001 for 3 or more abnormalities). The positive predictive value of an abnormal CMR study was 21.0% for an adverse event, whilst the negative predictive value of a normal CMR study was 98.8% over the follow-up period.

Conclusions: CMR provides important prognostic information in patients under evaluation for ARVC. A normal study portends a good prognosis. Conversely, the presence of multiple abnormalities identifies a high risk group of patients who may benefit from ICD implantation.
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http://dx.doi.org/10.1016/j.ijcard.2013.04.208DOI Listing
October 2013

Associations between the organisation of stroke services, process of care, and mortality in England: prospective cohort study.

BMJ 2013 May 10;346:f2827. Epub 2013 May 10.

King's College London, Division of Health and Social Care Research, London SE13QD, UK.

Objective: To estimate the relations between the organisation of stroke services, process measures of care quality, and 30 day mortality in patients admitted with acute ischaemic stroke.

Design: Prospective cohort study.

Setting: Hospitals (n=106) admitting patients with acute stroke in England and participating in the Stroke Improvement National Audit Programme and 2010 Sentinel Stroke Audit.

Participants: 36,197 adults admitted with acute ischaemic stroke to a participating hospital from 1 April 2010 to 30 November 2011.

Main Outcome Measure: Associations between process of care (the assessments, interventions, and treatments that patients receive) and 30 day all cause mortality, adjusting for patient level characteristics. Process of care was measured using six individual measures of stroke care and summarised into an overall quality score.

Results: Of 36,197 patients admitted with acute ischaemic stroke, 25,904 (71.6%) were eligible to receive all six care processes. Patients admitted to stroke services with high organisational scores were more likely to receive most (5 or 6) of the six care processes. Three of the individual processes were associated with reduced mortality, including two care bundles: review by a stroke consultant within 24 hours of admission (adjusted odds ratio 0.86, 95%confidence interval 0.78 to 0.96), nutrition screening and formal swallow assessment within 72 hours (0.83, 0.72 to 0.96), and antiplatelet therapy and adequate fluid and nutrition for first the 72 hours (0.55, 0.49 to 0.61). Receipt of five or six care processes was associated with lower mortality compared with receipt of 0-4 in both multilevel (0.74, 0.66 to 0.83) and instrumental variable analyses (0.62, 0.46 to 0.83).

Conclusions: Patients admitted to stroke services with higher levels of organisation are more likely to receive high quality care as measured by audited process measures of acute stroke care. Those patients receiving high quality care have a reduced risk of death in the 30 days after stroke, adjusting for patient characteristics and controlling for selection bias.
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http://dx.doi.org/10.1136/bmj.f2827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650920PMC
May 2013

Contemporary outcomes for ulcerative colitis inpatients admitted to pediatric hospitals in the United Kingdom.

Inflamm Bowel Dis 2013 Jun;19(7):1434-40

Department of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, United Kingdom.

Background: Pediatric ulcerative colitis (UC) care is variable with a lack of appropriate guidelines to guide practice until recently.

Methods: UC inpatients <17 years old admitted to 23 U.K. pediatric hospitals had clinical details collected between September 2010 and 2011. Comparative data for 248 patients were available from a previous audit in 2008.

Results: One hundred and seventy-six patients (98 males) of median age 13 years (interquartile range, 10-13) were analyzed; 23 were elective surgical admissions, 47 new diagnoses, and 106 needed acute medical care for established UC. Median length of stay was 6 days (interquartile range, 3-10) with no deaths. Eighty-eight of 126 patients (70%) with active disease had standard stool cultures performed (3 [2%] were positive), and 57 (45%) had Clostridium difficile toxin tested (none positive). Twenty-five of 66 (38%) emergency admissions had an abdominal x-ray on admission, and 13 of 66 patients (20%) had a Pediatric Ulcerative Colitis Activity Index score. There were 3 cases of toxic megacolon and 2 thromboses. Eighty-one of 116 patients (71%) responded to steroids. Nineteen patients who did not respond adequately to steroids received rescue therapy (7 infliximab, 11 ciclosporin, and 1 both) with overall response rate of 90%; 7 patients needed surgery acutely, 5 without previous rescue therapy. Compared with the 2008 data, stool culture rates improved significantly (86 of 121 [71%] versus 76 of 147 [52%], P = 0.001) as did heparinization rates (15 of 150 [10%] versus 5 of 215 [2%], P = 0.002) and rescue therapy usage (17 of 33 [52%] versus 10 of 38 [26%], P = 0.03).

Conclusions: There were signs of improving UC care with significantly increased rates of stool culture and rescue therapy. The majority of sites, however, did not use Pediatric Ulcerative Colitis Activity Index scores.
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http://dx.doi.org/10.1097/MIB.0b013e31828133d6DOI Listing
June 2013

Reference right atrial dimensions and volume estimation by steady state free precession cardiovascular magnetic resonance.

J Cardiovasc Magn Reson 2013 Apr 8;15:29. Epub 2013 Apr 8.

Cardiac Imaging Unit, ERESA, Valencia, Spain.

Background: Cardiovascular magnetic resonance (CMR) steady state free precession (SSFP) cine sequences with high temporal resolution and improved post-processing can accurately measure RA dimensions. We used this technique to define ranges for normal RA volumes and dimensions normalized, when necessary, to the influence of gender, body surface area (BSA) and age, and also to define the best 2D images-derived predictors of RA enlargement.

Methods: For definition of normal ranges of RA volume we studied 120 healthy subjects (60 men, 60 women; 20 subjects per age decile from 20 to 80 years), after careful exclusion of cardiovascular abnormality. We also studied 120 patients (60 men, 60 women; age range 20 to 80 years) with a clinical indication for CMR in order to define the best 1D and 2D predictors of RA enlargement. Data were generated from SSFP cine CMR, with 3-dimensional modeling, including tracking of the atrioventricular ring motion and time-volume curves analysis.

Results: In the group of healthy individuals, age influenced RA 2-chamber area and transverse diameter. Gender influenced most absolute RA dimensions and volume. Interestingly, right atrial volumes did not change with age and gender when indexed to body surface area. New CMR normal ranges for RA dimensions were modeled and displayed for clinical use with normalization for BSA and gender and display of parameter variation with age. Finally, the best 2D images-derived independent predictors of RA enlargement were indexed area and indexed longitudinal diameter in the 2-chamber view.

Conclusion: Reference RA dimensions and predictors of RA enlargement are provided using state-of-the-art CMR techniques.
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http://dx.doi.org/10.1186/1532-429X-15-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627628PMC
April 2013

Clinical utility and prognostic value of left atrial volume assessment by cardiovascular magnetic resonance in non-ischaemic dilated cardiomyopathy.

Eur J Heart Fail 2013 Jun 8;15(6):660-70. Epub 2013 Mar 8.

Royal Brompton Hospital, London SW3 6NP, UK.

Aims: Echocardiographic studies have shown that left atrial volume (LAV) predicts adverse outcome in small heart failure (HF) cohorts of mixed aetiology. However, the prognostic value of LAV in non-ischaemic dilated cardiomyopathy (DCM) is unknown. Cardiovascular magnetic resonance (CMR) allows accurate and reproducible measurement of LAV. We sought to determine the long-term prognostic significance of LAV assessed by CMR in DCM.

Methods And Results: We measured LAV indexed to body surface area (LAVi) in 483 consecutive DCM patients referred for CMR. Patients were prospectively followed up for a primary endpoint of all-cause mortality or cardiac transplantation. During a median follow-up of 5.3 years, 75 patients died and 9 underwent cardiac transplantation. After adjustment for established risk factors, LAVi was an independent predictor of the primary endpoint [hazard ratio (HR) per 10 mL/m(2) 1.08; 95% confidence interval (CI) 1.01-1.15; P = 0.022]. LAVi was also independently associated with the secondary composite endpoints of cardiovascular mortality or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.19; P = 0.003), and HF death, HF hospitalization, or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.18; P = 0.001). The optimal LAVi cut-off value for predicting the primary endpoint was 72 mL/m(2). Patients with LAVi >72 mL/m(2) had a three-fold elevated risk of death or transplantation (HR 3.00; 95% CI 1.92-4.70; P < 0.001). LAVi provided incremental prognostic value for the prediction of transplant-free survival (net reclassification improvement 0.17; 95% CI 0.05-0.29; P = 0.002).

Conclusions: LAVi is a powerful independent predictor of transplant-free survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.
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http://dx.doi.org/10.1093/eurjhf/hft019DOI Listing
June 2013

Ventricular strain changes in monochorionic twins with and without twin-to-twin transfusion syndrome.

Am J Obstet Gynecol 2013 Jun 6;208(6):462.e1-6. Epub 2013 Mar 6.

Division of Cancer, Faculty of Medicine, Imperial College, London, UK.

Objective: The objective of the study was to investigate whether vector velocity imaging (VVI), a non-Doppler speckle tracking ultrasound technology, is feasible in twin pregnancies and can aid management of twin-twin transfusion syndrome (TTTS).

Study Design: Twenty-seven women pregnant with monochorionic diamniotic twins affected by TTTS and 28 monochorionic pregnancies that did not develop TTTS were included in a prospective case-control study at a fetal medicine center. Fetal echocardiograms were recorded with dummy electrocardiography to retain original frame rates when exported for offline speckle tracking analysis using Syngo-VVI software (Siemens Corp, Munich, Germany). Right and left ventricular (LV) free wall Lagrangian strain was measured from the original coordinates. Within-twin pair ventricular strain differences including relationship to Quintero staging and response to laser therapy for TTTS were analyzed by Wilcoxon signed-rank test.

Results: The VVI strain measurements could be analyzed in 182 of 200 TTTS and 96 of 112 non-TTTS control ventricles. Within-pair strain was concordant in non-TTTS controls. Recipient LV strain was reduced at all Quintero stages compared with donors (P < .01). Recipient right ventricular strain was reduced only in stages 3 and 4 (P < .01). Strain improved at a median of 2 weeks following successful laser therapy. Intertwin differences in strain were independent of weight discordance.

Conclusion: Recipient LV strain is reduced in stages 1 and 2 TTTS. Within-pair strain discordance may distinguish early TTTS from growth discordance and guide timing of and management following treatment.
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http://dx.doi.org/10.1016/j.ajog.2013.02.051DOI Listing
June 2013

Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy.

JAMA 2013 Mar;309(9):896-908

Royal Brompton Hospital, London, England.

Importance: Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions.

Objective: To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy.

Design, Setting, And Patients: Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011.

Main Outcome Measures: Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation.

Results: Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P = .001 and 0.29 [95% CI, 0.11-0.48]; P = .002, respectively).

Conclusions And Relevance: Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.
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http://dx.doi.org/10.1001/jama.2013.1363DOI Listing
March 2013

Variation in gastroscopy rate in English general practice and outcome for oesophagogastric cancer: retrospective analysis of Hospital Episode Statistics.

Gut 2014 Feb 20;63(2):250-61. Epub 2013 Feb 20.

Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, UK.

Objective: To determine whether variation in gastroscopy rates in English general practice populations is associated with inequality in oesophagogastric (OG) cancer outcome.

Design: Retrospective observational study of the Hospital Episode Statistics (HES) dataset for England (2006-2008) linked to death registration.

Methods: were validated using independent local and national data. General practices with new cases of OG cancer were included. Practices were grouped into tertiles according to standardised elective gastroscopy rate per capita (low, medium or high). Outcome measures for cancer cases were: emergency admission during diagnostic pathway, major surgical resection and mortality at 1 year. Covariates were: age group, gender, comorbidity, general practice average deprivation and patient deprivation.

Results: 22 488 incident cases of OG cancer from 6513 general practices were identified. Patients registered with the low tertile group of practices had the lowest rate of major surgery, highest rate of emergency admission and highest mortality. The inequality was widest for the most socioeconomically deprived cases. After adjustment for covariates in logistic regression, the gastroscopy rate (low, medium or high) at the patient's general practice was an independent predictor of emergency admission, major surgery and mortality.

Conclusions: There is wide variation in the rate of gastroscopy among general practice populations in England. On average, OG cancer patients belonging to practices with the lowest rates of gastroscopy are at greater risk of poor outcome. These findings suggest that initiatives or current guidelines aimed at limiting the use of gastroscopy may adversely affect cancer outcomes.
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http://dx.doi.org/10.1136/gutjnl-2012-304202DOI Listing
February 2014

The organisation and structure of inflammatory bowel disease services for children and young people in the UK in 2010: significant progress but still room for improvement.

Frontline Gastroenterol 2013 Jan 18;4(1):25-31. Epub 2012 Aug 18.

Department of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, UK.

Background: Inflammatory bowel disease (IBD) is becoming more common in children. While treatment options remain limited the appropriate organisation and delivery of services are an integral part of good care.

Methods: All eligible UK paediatric sites were invited to submit data for organisation of paediatric IBD services as of 1 September 2010. Comparison, when relevant, was made with the previous paediatric audit (2008) and the concurrently running adult audit.

Results: 24/25 (96%) of sites submitted data. The median number of patients managed and the median number of new IBD (ulcerative colitis and Crohn's disease only) cases per annum was 178 (IQR 136-281) and 32 (IQR 23-50), respectively. There was an increase in the IBD workforce including whole-time equivalent (WTE) IBD nurses (1.0 vs 1.5 WTE nurses, p=0.02). 1023 patients 16 years and younger were looked after in the 202 adult sites who submitted data; only 78/202 sites indicated they cared for 16-year-old and younger children; approximately half of these 78 sites had age-appropriate support facilities. Most paediatric sites have access to urgent endoscopy (83%), telephone advice (100%) and urgent clinic appointments (91%). Most sites did not have: shared care pathways with primary care (74%), annual reviews (71%), real time patient management systems (83%) and research network trial participation (78%).

Conclusions: Many aspects of paediatric IBD care in the UK are good and have shown significant improvement over recent years. There are areas in need of further change and specific regional and national action plans should address identified deficiencies before any future audit of paediatric and adult IBD services.
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http://dx.doi.org/10.1136/flgastro-2012-100159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369787PMC
January 2013

Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

J Cardiovasc Magn Reson 2012 Dec 24;14:86. Epub 2012 Dec 24.

Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom.

Background: Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM.

Methods And Results: A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10-3 mm2/s and HA was epicardium -34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = ± 0.045, Coefficient of Variation (CoV) = 7.2%), MD (SD = ± 0.135 × 10-3 mm2/s, CoV = 18.6%) and HA (epicardium SD = ± 4.8°; mesocardium SD = ± 3.4°; endocardium SD = ± 2.9°). Reproducibility of FA was superior to MD (p = 0.003). MD was significantly higher in the septum than the reference lateral wall (0.784 ±0.188 vs 0.714 ±0.155 ×10-3 mm2/s, p <0.001) [corrected]. Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers (from -8.3° to -10.4°, all p < 0.001).

Conclusions: To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The interpretation of regional differences in the septum requires further investigation.
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http://dx.doi.org/10.1186/1532-429X-14-86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551746PMC
December 2012
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