Harefield NHS Foundation Trust Research Articles

Comparison of outcomes between aortic root replacement and supra-coronary interposition graft for type A aortic dissection: A retrospective case series.

The decision to conserve or replace the native aortic valve following acute type-A aortic dissection (ATAAD) is an area of cardiac surgery without standardized practice. This single-center retrospective study analysed the long-term performance of the native aortic valve and root following surgery for ATAAD. Between 2009 and 2018 all cases ATAAD treated at Royal Brompton and Harefield NHS Foundation Trust were analysed. Patients were divided into two groups: (a) ascending aorta (interposition) graft (AAG) without valve replacement and (b) nonvalve-sparing aortic root replacement (ARR). Preoperative covariates were compared, as well as operative characteristics and postoperative complications. Long-term survival and echocardiographic outcomes were analysed using regression analysis. In total, 116 patients were included: 63 patients in the AAG group and 53 patients in the ARR group. In patients where the native aortic valve was conserved, nine developed severe aortic regurgitation and two patients developed dilation of the aortic root requiring subsequent replacement during the follow-up period. Aortic regurgitation at presentation was not found to be associated with subsequent risk of developing severe aortic regurgitation or reintervention on the aortic valve. Overall mortality was observed to be significantly lower in patients undergoing AAG (17.5% vs. 41.5%, p = .004). With careful patient selection, the native aortic root shows good long-term durability both in terms of valve competence and stable root dimensions after surgery for ATAAD. This study supports the consideration of conservation of the aortic valve during emergency surgery for type-A dissection, in the absence of a definitive indication for root replacement, including in cases where aortic regurgitation complicates the presentation.

Mapping the global research landscape and hotspot of exercise therapy and chronic obstructive pulmonary disease: A bibliometric study based on the web of science database from 2011 to 2020.

Background: The application of exercise therapy (ET) in chronic obstructive pulmonary disease (COPD) is generating increasing clinical efficacy and social-economic value. In this study, research trends, evolutionary processes and hot topics in this field are detailed, as well as predictions of future development directions. Methods: Search for literature in the field of COPD and ET and analyze data to generate knowledge graphs using VOSiewer and CiteSpace software. The time frame for the search was from 2011 to January 2021. Then we extracted full-text key information (such as title, journal category, publication date, author, country and institution, abstract, and keyword) and obtained the co-citation analysis. Use hierarchal clustering analysis software developed by VOSviewer to map common citations, and use Citespace software to plot trend networks. Results: The United States topped the list with 27.91% of the number of articles posted, followed by the UK at 25.44%. Imperial College London was the highest number of article publications in institutions, followed by Maastricht University and the University of Toronto. The Royal Brompton Harefield NHS Foundation Trust was one of many research institutions and currently holds the highest average citations per item (ACI) value, followed by Imperial College London and the University of Leuven. Judging from the number of publications related to ET and COPD, it is mainly published in cell biology, respiratory pulmonary diseases, and rehabilitation experiments study medicine. The European Respiration Journal is the most widely published in this field, followed by the International Journal of Chronic Obstructive Pulmonary Disease and Respiratory Medicine. Conclusion: COPD combined with ET is widely used in clinical practice and is on the rise. A distinctive feature of the field is multidisciplinary integration. Rehabilitation research for COPD involves multidisciplinary collaboration, tissue engineering, and molecular biology mechanism studies to help patients remodel healthy breathing. Multidisciplinary rehabilitation measures provide a solid foundation for advancing clinical efficacy in the field of COPD.

"Primary Pulmonary Angiosarcoma in 25-Year Old Patient"

Hind Elhassan1*, Abdelrahman Abdelbar1, Danielle Bury2, Stuart Mellor3, Andrew Nicholson4 and Joseph Zacharias1 Author Affiliations 1Cardiothoracic Department, Blackpool Teaching Hospital NHS Foundation Trust, UK 2Histopathology Department, Blackpool Teaching Hospital NHS Foundation Trust, UK 3Radiology Department, East Lancashire Hospital NHS Foundation Trust, UK 4Histopathology Department, Royal Brompton & Harefield NHS Foundation Trust, UK Received: February 14, 2022 | Published: February 23, 2022 Corresponding author: Hind Elhassan, Cardiothoracic Department, Blackpool Teaching Hospital NHS Foundation Trust, UK DOI: 10.26717/BJSTR.2022.42.006703

Improving transthoracic echocardiography (TTE) training for junior doctors in Harefield Hospital during COVID-19

We devised a medical education quality improvement (QI) project aimed at enhancing training in transthoracic echocardiography (TTE) for junior doctors at Harefield Hospital, Royal Brompton and Harefield NHS Foundation Trust. During the COVID-19 pandemic, junior doctors expressed a desire for further

Into the red zone: behind the mask of a cardiology nurse fighting COVID-19

Into the red zone: behind the mask of a cardiology nurse fighting COVID-19

Accuracy of Pulse Oximetry in COVID-19 Patients Stepping Down from Intensive Care

Background: UK Guidelines suggest pulse oximetry, rather than blood gas sampling, is adequate for monitoring of patients with COVID-19 if CO2 retention is not suspected. However, pulse oximetry has impaired accuracy in certain patient groups, and data are lacking on its accuracy in patients with COVID-19 stepping down from Intensive Care Units (ICU) to non-ICU settings or being transferred to another ICU. Methods: We assessed agreement between pulse oximetry (SpO2) and arterial blood gas analysis (SaO2) in patients with COVID-19, deemed clinical stable to step down from an ICU to a non-ICU ward, or be transferred to another ICU. We used 90 paired SpO2 and SaO2 from 30 patients (3 paired samples per patient). Findings: Mean difference between SaO2 and SpO2 (bias) was -0.42%, with a standard deviation of 2.4 (precision). The limits of agreement between SpO2 and SaO2 were, lower limit of -5.16% (95% CI -6.51 to -4.20), upper limit of 4.32% (CI 3.36 to 5.67). Interpretation: In our setting, pulse oximetry showed a poor level of agreement with SaO2 measurement in people with COVID-19 judged clinically ready to step down from ICU to a non-ICU ward, or who were being transferred to another hospital’s ICU. In such patients, SpO2 should be interpreted with caution. Arterial blood gas assessment of SaO2 may still be clinically indicated. Funding: Imperial College London. Declaration of Interests: No authors declare any conflict of interest. Ethics Approval Statement: This evaluation was authorized by the Royal Brompton and Harefield NHS Foundation Trust Quality and Safety team. No external ethical approvals were required.

The Fungal Airway Microbiome in Cystic Fibrosis and Bronchiectasis

Background: The prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and bronchiectasis. Methods: Next generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls. Findings: ITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20·4%), whereas in bronchiectasis sputum Candida albicans (21·8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp. This study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases. Funding Statement: The project was supported by the Asmarley Trust, the Wellcome Trust and the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, Imperial College London. IF was supported by an NIHR PhD studentship. Declaration of Interests: The authors have no conflicts of interests to disclose. Ethics Approval Statement: The study was approved by the Royal Brompton and Harefield Hospital Biomedical Research Unit Ethics Committee (Advanced Lung Disease Biobank Study Number: 10/H0504/9).

Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial

SummaryBackgroundPatients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown.MethodsWe did an open-label, pilot, randomised trial to examine the effect of phased withdrawal of heart failure medications in patients with previous dilated cardiomyopathy who were now asymptomatic, whose left ventricular ejection fraction (LVEF) had improved from less than 40% to 50% or greater, whose left ventricular end-diastolic volume (LVEDV) had normalised, and who had an N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentration less than 250 ng/L. Patients were recruited from a network of hospitals in the UK, assessed at one centre (Royal Brompton and Harefield NHS Foundation Trust, London, UK), and randomly assigned (1:1) to phased withdrawal or continuation of treatment. After 6 months, patients in the continued treatment group had treatment withdrawn by the same method. The primary endpoint was a relapse of dilated cardiomyopathy within 6 months, defined by a reduction in LVEF of more than 10% and to less than 50%, an increase in LVEDV by more than 10% and to higher than the normal range, a two-fold rise in NT-pro-BNP concentration and to more than 400 ng/L, or clinical evidence of heart failure, at which point treatments were re-established. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02859311.FindingsBetween April 21, 2016, and Aug 22, 2017, 51 patients were enrolled. 25 were randomly assigned to the treatment withdrawal group and 26 to continue treatment. Over the first 6 months, 11 (44%) patients randomly assigned to treatment withdrawal met the primary endpoint of relapse compared with none of those assigned to continue treatment (Kaplan-Meier estimate of event rate 45·7% [95% CI 28·5–67·2]; p=0·0001). After 6 months, 25 (96%) of 26 patients assigned initially to continue treatment attempted its withdrawal. During the following 6 months, nine patients met the primary endpoint of relapse (Kaplan-Meier estimate of event rate 36·0% [95% CI 20·6–57·8]). No deaths were reported in either group and three serious adverse events were reported in the treatment withdrawal group: hospital admissions for non-cardiac chest pain, sepsis, and an elective procedure.InterpretationMany patients deemed to have recovered from dilated cardiomyopathy will relapse following treatment withdrawal. Until robust predictors of relapse are defined, treatment should continue indefinitely.FundingBritish Heart Foundation, Alexander Jansons Foundation, Royal Brompton Hospital and Imperial College London, Imperial College Biomedical Research Centre, Wellcome Trust, and Rosetrees Trust.

Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study

SummaryBackgroundLong-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults.MethodsIn this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured.FindingsBetween October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96–3·95; p<0·1), sputum (3·15, 1·39–7·13; p<0·05), shortness of breath (1·86, 0·97–3·57; p<0·1), and wheeze (4·00, 1·52–10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5–20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles.InterpretationShort-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects.FundingBritish Heart Foundation.

The nurse director role is more challenging than ever.

I was a nurse director for more than 20 years, initially at Royal Brompton Hospital, then at Royal Brompton and Harefield NHS Foundation Trust. It was a complex role and an overwhelmingly positive experience. Over the years, however, much has changed, and today the average tenure is about three years.

The use of electronic alerts in primary care computer systems to identify the over-prescription of short-acting beta2-agonists in people with asthma: a protocol for a systematic review

The authors wish to thank the Asthma UK Centre for Applied Research for funding this work. AB is an National Institute for Health Research (NIHR) Senior Investigator and additionally was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. MT was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Wessex, NIHR School of Primary Care Research and NIHR Southampton Biomedical Research Centre. CG was supported by the NIHR CLAHRC North Thames at Bart’s Health NHS Trust.

005 Multimodality assessment of risk in dilated cardiomyopathy- the importance of CMR

Background Dilated cardiomyopathy (DCM) has a 20% 5 year mortality. Cardiac MR (CMR) is an established outcome predictor. We evaluate the additive role of novel genetic and circulating biomarkers.Purpose Perform an integrated assessment to evaluate the prognostic importance of CMR parameters in DCM in the context of clinical, genetic and biomarker data.Methods Prospectively recruited DCM patients underwent comprehensive clinical evaluation, CMR with late-gadolinium enhancement (LGE), sequencing for rare variants in major DCM genes (titin-TTNtv, myosin heavy chain-MYH7, troponin T2-TNNT2, lamin-LMNA), biomarker assessment of BNP, troponin I (hsTnI), Galectin 3 and ST2, and follow up for clinical events. Cox proportional hazard modelling evaluated the primary composite endpoint of cardiovascular death, major arrhythmic events (aborted sudden cardiac death, appropriate ICD activation, sustained ventricular tachycardia, ventricular fibrillation) and major heart failure events (heart transplant, left ventricular assist device, unplanned heart failure hospitalisation).Results In total, 423 patients with DCM (mean age 53.6±14.1 years, 67% male) were followed up for a median of 4.0 years (IQR 2.1–5.8). Mean left ventricular ejection fraction (LVEF) was 40%±12.5%. One third of patients had mid-wall fibrosis (MWF-LGE) (n=137, 32%). Mean indexed left atrial volume (LAVi) was 61±27.6 mls.On genetic analysis, 53 patients (12.5%) had TTNtv, 14 patients (3.3%) had non-truncating variants in MYH7, 5 patients (1.2%) had non-truncating variants in TNNT2 and 5 patients (1.2%) had LMNA variants.In total, 44 patients (10.4%) met the primary endpoint. On multivariable analysis, an optimal model predicting the primary endpoint was built without genetic or biomarker data (Table 1). This consisted of LVEF, LAVi, and MWF-LGE (Table 2).On univariable analysis, BNP, Galectin 3 and hsTnI were associated with the primary endpoint (Table 2). When the novel variables were added to the optimised model, Galectin 3 and LMNA variants were predictive of the primary endpoint (Table 3). In the final adjusted model, CMR parameters remained predictive of the primary endpoint. Of these, MWF-LGE was the strongest predictor (adjusted HR 2.12 (1.06–4.02), p=0.02).View this table:Abstract 005 Table 1 Variables evaluated in building baseline Cox proportional hazard model predicting primary endpointView this table:Abstract 005 Table 2 Results of baseline Cox proportional hazard modelling predicting primary endpointView this table:Abstract 005 Table 3 Results of evaluation of biomarkers and genetic variants using Cox proportional hazard modelling predicting primary endpointView this table:Abstract 005 Table 4 Results of final adjusted Cox proportional hazard model predicting primary endpointConclusion On integrated multi-modality risk stratification in DCM, while circulating and genetic biomarkers improve risk stratification, CMR parameters remain strong independent predictors of outcome.Acknowledgements UT is supported by a Medical Research Council (UK) Clinical Research Training Fellowship. The study has also been supported by the Rosetrees Foundation, the Alexander Jansons Foundation, the Wellcome Trust and the NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.%U http://heart.bmj.com/content/heartjnl/103/Suppl_1/A4.2.full.pdf

How to survive as a woman in a man's world.

Women in cardiology have to fight hard but can do it in style says Sabine Ernst ![Graphic][1] Gender never featured in the decisions of Dr Sabine Ernst, a cardiac electrophysiologist with expertise in complex arrhythmias. Today she is a consultant cardiologist and lead for electrophysiology (EP) research at the Royal Brompton and Harefield NHS Foundation Trust in London, UK, and a Reader at Imperial College London. But having found herself in what is still largely a man’s world, she has had to fight harder for promotion and still finds herself progressing more slowly than male colleagues. ‘In my academic career, if I had waited for someone to invite me to do something, I would still be waiting,’ says Ernst. During her training in EP Ernst initially received good support and mentoring from her chief in Hamburg, Professor Karl-Heinz Kuck. ‘We worked well together and I truly enjoyed the experience’, recalls Ernst. ‘This continued up to a point where I had achieved a certain level and then I had to fight for further promotion.’ Ernst was already doing the work of a consultant. She had performed first in man procedures, published extensively, ran an entire lab, had PhD students, and led the department’s educational courses. She had even pioneered remote magnetic navigation and used advanced 3D-mapping for patients with congenital heart disease, complex anatomy and arrhythmias. But she had not been promoted to any kind of leadership position and was not a consultant. ‘That was really tough because I had fought my way to the second highest academic title you can get in Germany at that stage but I still was … [1]: /embed/inline-graphic-1.gif

'Have confidence in yourself'.

Former director of nursing at Royal Brompton & Harefield NHS Foundation Trust Caroline Shuldham OBE left the NHS last year to work independently. She celebrates 45 years in nursing this year and is involved in research, teaching, mentoring, inspection and advising on care.

Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study

Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease. We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis. 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (κ=0·50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (κw=0·71 [IQR 0·64-0·77]) and connective tissue disease-related interstitial lung disease (κw=0·73 [0·68-0·78]); moderate for non-specific interstitial pneumonia (NSIP; κw=0·42 [0·37-0·49]); and fair for hypersensitivity pneumonitis (κw=0·29 [0·24-0·40]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinician's diagnosis of this disease in five of seven MDTMs, and radiologist's diagnosis of IPF in four of seven MDTMs. Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease. National Institute of Health Research, Imperial College London.

Feedback on heart attack.

The Royal Brompton & Harefield NHS Foundation Trust in London is the largest heart and lung centre in the UK. This article explores a project carried out by nurses at the trust looking at the experiences of having an acute myocardial infarction, and how patients felt about taking part in a research study.

Quantifying right ventricular diffuse fibrosis in tetralogy of Fallot - a novel customised approach for the challenges of the right ventricle

NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, London, UK Full list of author information is available at the end of the article Figure 1 Representative short-axis images from subjects scanned for RV T1 mapping by fat-water separated, MSPrep dark blood imaging. Images for five subjects with repaired tetralogy of Fallot and five healthy volunteers shown (one subject per column): Top row MoCo averaged water-only image at Ts 600 ms, Second row MoCo averaged water-only anchor image at same window/level, Third row MoCo averaged fat only image, Bottom row T1 map generated from registration and 2-parameter fit of the six images per sampling scheme. Heng et al. Journal of Cardiovascular Magnetic Resonance 2016, 18(Suppl 1):O26 http://www.jcmr-online.com/content/18/S1/O26

171 The genetic signature in ischaemic heart disease with myocardial infarction (MI) and significant left ventricular (LV) dysfunction

<h3></h3> The titingene (<i>TTN</i>) is a major determinant of myocardial function, its importance in both familial and ‘idiopathic’ Dilated Cardiomyopathy (DCM) has recently been ascertained. In some instances a second genetic mutation or a physiological perturbation (e.g. pregnancy) may reveal otherwise latent TTN mutation effects. We hypothesise that patients with pronounced LV dysfunction following MI, when controlling for infarct parameters and coronary anatomy, may have a high burden of <i>TTN </i>truncating variants (TTNtvs). We studied a large cohort of post-MI patients prospectively recruited at the Royal Brompton and Harefield NHS Foundation Trust. Gadolinium-enhanced Cardiac Magnetic Resonance was used to characterise cardiac dimensions, function and tissue properties. The size and thickness of MI, wall motion and number of hibernating segments were quantified by two experts blinded to genotype using a standard 17-segment model. Targeted re-sequencing of <i>TTN</i> and other key DCM genes was performed. Genetic variation in DCM genes in 530ethnically matchedhealthy volunteers along with public repositories was used for variant annotation and comparison. Our initial analyses show that out of the 336 post-MI patients, nine (2.7%) had a TTNtv. As hypothesised, TTNtv were significantly enriched in patients with LV ejection fraction (LVEF) &lt;35% (4.6% vs 1.4%, p = 0.01). Patients with a TTNtv had a significantly lower LVEF than those without (31.2 ± 13.9% vs 41.2 ± 14.7%; p = 0.026) Regression models taking into account cardiac, non-cardiac and genetic covariates are in process. These data identify a novel role of large effect size for <i>TTNtv</i>, in post-MI systolic dysfunction. Based on these findings it will be important to explore if genetic stratification of the post-MI patient can inform medical or revascularisation strategies.

Detecting familial hypercholesterolaemia (FH) in general practice: An audit within the Medway Clinical Commissioning Group

Detecting familial hypercholesterolaemia (FH) in general practice: An audit within the Medway Clinical Commissioning Group

Continuous positive airway pressure in older people with obstructive sleep apnoea syndrome (PREDICT): a 12-month, multicentre, randomised trial

The therapeutic and economic benefits of continuous positive airway pressure (CPAP) for moderate to severe obstructive sleep apnoea (OSA) syndrome have been established in middle-aged people; however, the benefits in older people are unknown. This trial was designed to address this evidence gap. This 12-month, multicentre, randomised trial enrolled patients across 14 National Health Service sleep centres in the UK. Consecutive patients aged 65 years or older with newly diagnosed OSA syndrome were eligible to join the trial. Patients were randomly assigned (1:1) into parallel groups to receive either CPAP with best supportive care (BSC) or BSC alone for 12 months. Randomisation was done by the Medical Research Council Clinical Trials Unit with computer-generated randomisation. The main investigator at each centre was masked to the trial randomisation. Coprimary endpoints were Epworth sleepiness score (ESS) at 3 months and cost-effectiveness over the 12-month trial period. Secondary outcomes were subjective sleepiness at 12 months, plus objective sleepiness, quality of life, mood, functionality, nocturia, mobility, accidents, cognitive function, and cardiovascular risk factors and events at 3 months and 12 months. The analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN90464927. Between Feb 24, 2010, and May 30, 2012, 278 patients were randomly assigned to the trial, of whom 231 (83%) completed the trial. 140 patients were allocated to and received CPAP plus BSC and 138 were allocated to and received BSC only. CPAP reduced ESS by 2·1 points (95% CI -3·0 to -1·3; p<0·0001) at 3 months for 124 (89%) of 140 patients compared with 124 (90%) of 138 patients given BSC, and by 2·0 points (-2·8 to -1·2; p<0·0001) at 12 months for 116 patients compared with 122 patients given BSC. The effect was greater in patients with higher CPAP usage or higher baseline ESS. Quality-adjusted life-years were similar between the groups (treatment effect 0·01 (95% CI -0·03 to 0·04; p=0·787) and health-care costs were marginally reduced with CPAP (-£35, -390 to 321; p=0·847). CPAP improved objective sleepiness (p=0·024), mobility (p=0·029), total cholesterol (p=0·048), and LDL cholesterol (p=0·042) at 3 months, but these were not sustained at 12 months. Measures of mood, functionality, nocturia, accidents, cognitive function, and cardiovascular events remained unchanged. Systolic blood pressure fell in the BSC group. 37 serious adverse events occurred in the CPAP group, and 22 in BSC group; all were independently classified as being unrelated to the trial and no significant harm was attributed to CPAP use. In older people with OSA syndrome, CPAP reduces sleepiness and is marginally more cost effective over 12 months than is BSC alone. On the basis of these results, we recommend that CPAP treatment should be offered routinely to older patients with OSA syndrome. National Institute of Health Research (NIHR) Health Technology Assessment, NIHR Respiratory Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.