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ObjectiveThe study evaluated the feasibility of mindfulness-based cognitive therapy (MBCT) in patients with non-cardiac chest pain by assessing their willingness to participate and adhere to the programme, and for these data to help further refine the content of MBCT for chest pain.Patients and methodsThis prospective 2:1 randomised controlled trial compared the intervention of adapted MBCT as an addition to usual care with just usual care in controls. Among 573 patients who attended the rapid access chest pain clinic over the previous 12 months and were not diagnosed with a cardiac cause but had persistent chest pain were invited. The intervention was a 2-hour, weekly, online guided 8-week MBCT course. Compliance with attendance and the home practice was recorded. Enrolled patients completed the Seattle angina questionnaire (SAQ), Hospital Anxiety and Depression Scale, Cardiac Anxiety Questionnaire, Five-Facet Mindfulness Questionnaire, and Euro Quality of Life–5 Dimensions–5 Level at baseline assessment and after 8-week period.ResultsPersistent chest pain was reported by 114 patients. Of these, 33 (29%) patients with a mean age of 54.2 (±12.2) years and 68% women, consented to the study. Baseline questionnaires revealed mild physical limitation (mean SAQ, 76.8±25), high levels of anxiety (76%) and depression (53%), modest cardiac anxiety (CAQ,1.78±0.61) and mindfulness score (FFMQ, 45.5±7.3). Six patients subsequently withdrew due to bereavement, caring responsibilities and ill health. Of the remaining 27 participants, 18 in the intervention arm attended an average of 5 sessions with 61% attending ≥6 sessions. Although not statistically powered, the study revealed a significant reduction in general anxiety, improved mindfulness and a trend towards improvement in SAQ scores in the intervention arm.ConclusionOne-third of patients with persistent non-cardiac chest pain were willing to participate in mindfulness-based therapy. An improvement in anxiety and mindfulness was detected in this feasibility study. A larger trial is required to demonstrate improvement in chest pain symptoms.

Summary Bleeding and thrombosis are major complications in patients supported with extracorporeal membrane oxygenation (ECMO). In this multicentre observational study of 152 consecutive patients (≥18 years) with severe COVID‐19 supported by veno‐venous (VV) ECMO in four UK commissioned centres during the first wave of the COVID‐19 pandemic (1 March to 31 May 2020), we assessed the incidence of major bleeding and thrombosis and their association with 180‐day mortality. Median age (range) was 47 years (23–65) and 75% were male. Overall, the 180‐day survival was 70·4% (107/152). The rate of major bleeding was 30·9% (47/152), of which intracranial bleeding (ICH) was 34% (16/47). There were 96 thrombotic events (63·1%) consisting of venous 44·7% [68/152 of which 66·2% were pulmonary embolism (PE)], arterial 18·6% (13/152) and ECMO circuit thrombosis 9·9% (15/152). In multivariate analysis, only raised lactate dehydrogenase (LDH) at the initiation of VV ECMO was associated with an increased risk of thrombosis [hazard ratio (HR) 1·92, 95% CI 1·21‐3·03]. Major bleeding and ICH were associated with 3·87‐fold (95% CI 2·10–7·23) and 5·97‐fold [95% confidence interval (CI) 2·36–15·04] increased risk of mortality and PE with a 2·00‐fold (95% CI1·09–3·56) risk of mortality. This highlights the difficult balancing act often encountered when managing coagulopathy in COVID‐19 patients supported with ECMO.

ObjectivesTo develop and validate a tool to predict the risk of an older adult experiencing medication-related harm (MRH) requiring healthcare use following hospital discharge.Design, setting, participantsMulticentre, prospective cohort study recruiting older adults (≥65 years) discharged from five UK teaching hospitals between 2013 and 2015.Primary outcome measureParticipants were followed up for 8 weeks in the community by senior pharmacists to identify MRH (adverse drug reactions, harm from non-adherence, harm from medication error). Three data sources provided MRH and healthcare use information: hospital readmissions, primary care use, participant telephone interview. Candidate variables for prognostic modelling were selected using two systematic reviews, the views of patients with MRH and an expert panel of clinicians. Multivariable logistic regression with backward elimination, based on the Akaike Information Criterion, was used to develop the PRIME tool. The tool was internally validated.Results1116 out of 1280 recruited participants completed follow-up (87%). Uncertain MRH cases (‘possible’ and ‘probable’) were excluded, leaving a tool derivation cohort of 818. 119 (15%) participants experienced ‘definite’ MRH requiring healthcare use and 699 participants did not. Modelling resulted in a prediction tool with eight variables measured at hospital discharge: age, gender, antiplatelet drug, sodium level, antidiabetic drug, past adverse drug reaction, number of medicines, living alone. The tool’s discrimination C-statistic was 0.69 (0.66 after validation) and showed good calibration. Decision curve analysis demonstrated the potential value of the tool to guide clinical decision making compared with alternative approaches.ConclusionsThe PRIME tool could be used to identify older patients at high risk of MRH requiring healthcare use following hospital discharge. Prior to clinical use we recommend the tool’s evaluation in other settings.

BACKGROUND: Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis. OBJECTIVES: The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a). METHODS: In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays. RESULTS: Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P

Background: Non-invasive ventilation (NIV) for respiratory failure and airway clearance is an established intervention in cystic fibrosis (CF), but its therapeutic benefit on lung function and survival remains under-investigated. Methods: Using data from the UK CF Registry between 2007 and 2015, we explored the patterns of NIV use, and assessed changes in mean percent predicted FEV1 (ppFEV1) prior to and after NIV use, and the survival of patients on NIV. Results: Among 11,079 patients, 1107 had at least one record of NIV treatment. Incidence and prevalence of NIV was lower in children and followed non-linear temporal patterns. Adjusting for other risk factors, ppFEV1 rose by 0.70 (95%CI: -0.83, 2.24) after first NIV use in children. In adults with a low ppFEV1 (

Summary Background Cardiac catheterization is the gold-standard modality for investigation of cardiovascular morphology before bidirectional cavopulmonary connection, but requires general anaesthesia and is associated with procedural risk. Aims To assess the diagnostic accuracy and safety of computed tomography in diagnosing great vessel stenosis/hypoplasia compared with cardiac catheterization and surgical findings. Methods Twenty-seven patients (10 after Norwood stage I) underwent computed tomography before surgery between January 2010 and June 2016; 16 of these patients also underwent cardiac catheterization. Proximal and distal pulmonary artery, aortic isthmus and descending aorta measurements, radiation dose and complications were compared via Bland-Altman analyses and correlation coefficients. Results The accuracy of computed tomography in detecting stenosis/hypoplasia of either pulmonary artery was 96.1% compared with surgical findings. For absolute vessel measurements and Z-scores, there was high correlation between computed tomography and angiography at catheterization (r = 0.98 for both) and a low mean bias (0.71 mm and 0.48; respectively). The magnitude of intertechnique differences observed for individual patients was low (95% of the values ranged between −0.9 and 2.3 mm and between −0.7 and 1.7, respectively). Four patients (25%) experienced minor complications from cardiac catheterization, whereas there were no complications from computed tomography. Patients tended to receive a higher radiation dose with cardiac catheterization than with computed tomography, even after exclusion of interventional catheterization procedures (median 2.5 mSv [interquartile range 1.3 to 3.4 mSv] versus median 1.3 mSv [interquartile range 0.9 to 2.6 mSv], respectively; P = 0.13). All computed tomography scans were performed without sedation. Conclusions Computed tomography may replace cardiac catheterization in identification of great vessel stenosis/hypoplasia before bidirectional cavopulmonary connection when no intervention before surgery is required. Computed tomography carries lower morbidity, can be performed without sedation and may be associated with less radiation.

BackgroundThe 4-m gait speed (4MGS) test is a simple physical performance measure and surrogate marker of frailty that is associated with adverse outcomes in older adults. We aimed to assess the ability of 4MGS to predict prognosis in patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods213 participants hospitalised with AECOPD (52% male, mean age 72 years and mean forced expiratory volume in 1 s (FEV1) 35% predicted) were enrolled. 4MGS and baseline demographics were recorded at hospital discharge. All-cause readmission and mortality were collected for 1 year after discharge and multivariable Cox proportional hazards regressions were performed. Kaplan–Meier and competing risks analyses were conducted comparing time to all-cause readmission and mortality between 4MGS quartiles.Results111 participants (52%) were readmitted and 35 (16%) died during the follow-up period. 4MGS was associated with all-cause readmission, with an adjusted subdistribution hazard ratio of 0.868 (95% CI 0.797–0.945; p=0.001) per 0.1 m·s−1 increase in gait speed, and with all-cause mortality, with an adjusted subdistribution hazard ratio of 0.747 (95% CI 0.622–0.898; p=0.002) per 0.1 m·s−1 increase in gait speed. Readmission and mortality models incorporating 4MGS had higher discrimination than age or FEV1 % pred alone, with areas under the receiver operator characteristic curves of 0.73 and 0.80, respectively. Kaplan–Meier and competing risks curves demonstrated that those in slower gait speed quartiles had reduced time to readmission and mortality (log-rank, both pConclusions4MGS provides a simple means of identifying at-risk patients with COPD at hospital discharge. This provides valuable information to plan post-discharge care and support.

RationaleDietary nitrate supplementation has been proposed as a strategy to improve exercise performance, both in healthy individuals and in people with COPD. We aimed to assess whether it could enhance the effect of pulmonary rehabilitation (PR) in COPD.MethodsThis double-blind, placebo-controlled, parallel group, randomised controlled study performed at four UK centres, enrolled adults with Global Initiative for Chronic Obstructive Lung Disease grade II–IV COPD and Medical Research Council dyspnoea score 3–5 or functional limitation to undertake a twice weekly 8-week PR programme. They were randomly assigned (1:1) to either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate), or placebo nitrate-deplete BRJ, consumed 3 hours prior to undertaking each PR session. Allocation used computer-generated block randomisation.MeasurementsThe primary outcome was change in incremental shuttle walk test (ISWT) distance. Secondary outcomes included quality of life, physical activity level, endothelial function via flow-mediated dilatation, fat-free mass index and blood pressure parameters.Results165 participants were recruited, 78 randomised to nitrate-rich BRJ and 87 randomised to placebo. Exercise capacity increased more with active treatment (n=57) than placebo (n=65); median (IQR) change in ISWT distance +60 m (10, 85) vs +30 m (0, 70), estimated treatment effect 30 m (95% CI 10 to 40); p=0.027. Active treatment also impacted on systolic blood pressure: treatment group −5.0 mm Hg (−5.0, –3.0) versus control +6.0 mm Hg (−1.0, 15.5), estimated treatment effect −7 mm Hg (95% CI 7 to −20) (pConclusionsDietary nitrate supplementation appears to be a well-tolerated and effective strategy to augment the benefits of PR in COPD.Trial registration numberISRCTN27860457.

Background: Lung volume reduction surgery is a proven treatment for emphysematous patients with hyperinflation, but the precarious health of candidates has prompted development of less invasive approaches. Bronchoscopic implanted endobronchial coils, shape-memory nitinol filaments, shrink emphysematous lung tissue to restore elastic recoil and to tether airways to maintain patency. Studies have demonstrated an acceptable safety profile and improvements in lung function, exercise capacity, and quality of life out to 3 years. Volume reduction is key. However, data for longer-term survival are limited. Objective: The aim of this study was to establish the 5-year overall and transplant-free survivals of subjects whose procedure in the first randomized controlled trial, RESET, achieved clinically meaningful reduction in residual volume (RV). Methods: Patients and their primary care doctors were contacted to confirm vital status and history of additional interventions. Death certificates were acquired via the General Registry Office. Survival time was calculated for responders achieving a reduction of ≥10% in RV compared to non-responders. Results: 39 patients completed the planned bilateral sequential treatments. Six patients received unilateral implants. At 5 years, 22 patients had died. The overall survivals at 1, 2, 3, 4 and 5 years were 88.9, 88.9, 77.8, 64.4 and 50.6%, respectively. Two patients underwent lung transplantation at 52 and 59 months and were alive at 5 years. The transplant-free (TF) survivals at 1, 2, 3, 4 and 5 years were 88.9, 88.9, 77.8, 64.4 and 46.7%, respectively. Volume reduction responders (n = 18) at 3 months had a 5-year TF survival of 66.7% compared to 36.4% for non-responders (n = 22; p = 0.07). Higher baseline inspiratory capacity (HR 0.13, 95% CI 0.02–0.73; p = 0.02) and partial pressure of oxygen (pO2) (HR 0.57, 95% CI 0.38–0.86; p < 0.01) values were predictive of survival for the entire cohort and were not influenced by age. Conclusions: Endobronchial coil implantation appears to confer a 5-year survival advantage for those who achieved a 10% reduction in RV at 3 months. Ongoing trials are designed to clarify the mechanisms of action of coils and to refine patient selection.

BACKGROUND: Patients with acute decompensated heart failure with diuretic resistance (ADHF-DR) have a poor prognosis. The aim of this study was to assess in patients with ADHF-DR, whether haemodynamic changes during ultrafiltration (UF) are associated with changes in renal function (Δcreatinine) and whether Δcreatinine post UF is associated with mortality. METHODS: Seventeen patients with ADHF-DR underwent 20 treatments with UF. Serial bloods (4-6 hourly) from the onset of UF treatment were measured for renal function, electrolytes and central venous saturation (CVO2). Univariate and multivariate analysis were performed to assess the relationship between changes in markers of haemodynamics [heart rate (HR), systolic blood pressure (SBP), packed cell volume (PCV) and CVO2] and Δcreatinine. Patients were followed up and mortality recorded. Cox-regression survival analysis was performed to determine covariates associated with mortality. RESULTS: Renal function worsened after UF in 17 of the 20 UF treatments (baseline vs. post UF creatinine: 164±58 vs. 185±69μmol/l, P

OBJECTIVE Premature atherosclerosis has been observed among HIV-infected individuals with high cardiovascular risk using one-dimensional ultrasound carotid intima-media thickness. We evaluated the assessment of HIV-infected individuals with low traditional cardiovascular disease risk using cardiovascular magnetic resonance, which allows three-dimensional assessment of the carotid artery wall. METHODS Carotid cardiovascular magnetic resonance was performed in 33 HIV-infected individuals (cases) (19 male, 14 female), and 35 HIV-negative controls (20 male, 15 female). Exclusion criteria included smoking, hypertension, hyperlipidemia (total cholesterol/HDL ratio > 5) or family history of premature atherosclerosis. Cases were stable on combination antiretroviral therapy with plasma HIV-1 RNA

The 4-m gait speed (4MGS), a simple physical performance measure and surrogate marker of frailty, consistently predicts adverse prognosis in older adults. We hypothesised that 4MGS could predict all-cause mortality and nonelective hospitalisation in patients with idiopathic pulmonary fibrosis (IPF).4MGS and lung function were measured at baseline in 130 outpatients newly diagnosed with IPF. Survival status and nonelective hospital admissions were recorded over 1 year. We assessed the predictive value of 4MGS (as a continuous variable and as a binary variable: slow versus preserved 4MGS) by calculating hazard ratios using Cox proportional regression, adjusting for potential confounding variables. Receiver operating characteristic curves assessed discrimination between the multivariable regression models and established prognostic indices.Continuous 4MGS and slow 4MGS were independent predictors of all-cause mortality (4MGS: HR 0.03, 95% CI 0.01–0.31; p=0.004; slow 4MGS: 2.63, 95% CI 1.01–6.87; p=0.049) and hospitalisation (4MGS: HR 0.02, 95% CI 0.01–0.14; pIn patients with IPF, 4MGS is an independent predictor of all-cause mortality and nonelective hospitalisation.

BACKGROUND: In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS: AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS: Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p

Aims and Objectives: To explore the effect contact with a heart failure nurse can have on patients' illness beliefs, mood and quality of life. \ud \ud Background: There is growing interest in patients' illness beliefs and the part they play in a patients understanding of chronic disease. \ud \ud Design: Secondary analysis on two independent datasets. Patients were recruited from five UK hospitals, four in London and one in Sussex. Patients were recruited from an inpatient and outpatient setting. The first dataset recruited 174 patients with newly diagnosed heart failure, whilst the second dataset recruited 88 patients with an existing diagnosis of heart failure. \ud \ud Methods: Patients completed the Minnesota Living with Heart Failure Questionnaire, Hospital Anxiety and Depression Scale, Illness Perception Questionnaire and the Treatment Representations Inventory at baseline and six months. We used a linear regression model to assess the association that contact with a heart failure nurse had on mood, illness beliefs and quality of life over a six-month period. \ud \ud Results: Patients who had contact with a heart failure nurse were more satisfied with their treatment and more likely to believe that their heart failure was treatable. Contact with a heart failure nurse did not make a statistically significant difference to mood or quality of life. \ud \ud Conclusions: This study has shown that contact with a heart failure nurse can improve patient satisfaction with treatment decisions but has less influence on a patient's beliefs about their personal control, treatment control and treatment concerns. With appropriate support, skills and training, heart failure nurses could play an important role in addressing individual patient's beliefs. There is a need to further investigate this. \ud \ud Relevance to clinical practice: Exploring patients' illness beliefs and mood could help to enhance person-centred care. Heart failure nurses would need additional training in the techniques used. © 2014 John Wiley & Sons Ltd.

SummaryBackgroundThe presence of lipids in alveolar macrophages (AMs) may impair their phagocytic response, and determine airway inflammation and obstruction.ObjectiveTo determine the factors such as severity of asthma, chronic cough, airway inflammation and obesity that may influence the presence of lipids in lung macrophages.MethodsBronchoalveolar lavage fluid (BALF) was obtained from 38 asthmatics (21 severe and 17 mild/moderate), 16 subjects with chronic cough and 11 healthy control subjects. The presence of lipids in macrophages was detected using an Oil-red-O stain and an index of lipid-laden macrophages (LLMI) was obtained.ResultsLLMI scores were higher in healthy subjects (median 48 [IQR 10–61]) and the severe asthma group (37 [11.5–61]) compared to mild/moderate asthmatics (7 [0.5–37]; p

IntroductionNon-invasive ventilation (NIV) is used in cystic fibrosis (CF) to support airway clearance techniques (ACTs) by augmenting tidal volumes and reducing patient effort. However, the evidence base for this is limited. We hypothesised that NIV, in addition to usual ACT, would increase sputum clearance. In addition, we investigated ease of sputum clearance (EoC), work of breathing (WoB) and NIV tolerability.MethodsAdults with CF (16+ years) at the end of hospitalisation for a pulmonary exacerbation were randomised to a cross-over trial of NIV-supported ACT or ACT alone in two consecutive days. No other changes to standard care were made. The primary outcome was the total 24-hour expectorated sputum wet weight after the intervention. Spirometry was completed pre-treatment and post-treatment. Oxygen saturations were measured pre-treatment, during treatment and post-treatment. EoC and WoB were assessed using Visual Analogue Scale.Results14 subjects completed the study (7 male, mean age 35 [SD 17] years, mean forced expiratory volume in 1 s [FEV1] 49 [20] % predicted). The difference between treatment regimens was −0.98 g sputum (95% CI −11.5 to 9.6, p=0.84) over 24 hours. During treatment oxygen saturations were significantly higher with NIV-supported ACT (mean difference 2.0, 95% CI 0.9 to 2.6, p=0.0004). No other significant differences were found in post-treatment FEV1, EoC, WoB, oxygen saturations or subject preference.ConclusionsThere was no difference in treatment effect between NIV-supported ACT and ACT alone, although the study was underpowered. Oxygen saturations were significantly higher during NIV-supported ACT, but with no effect on post-treatment saturations. NIV was well tolerated.Trial registration numberNCT01885650.

Aims Post-mortem examination of the heart in young sudden cardiac death (SCD) is vital as the underlying aetiology is often an inherited cardiac disease with implications for surviving relatives. Our aim is to demonstrate the improvement in diagnostic quality offered by a specialist cardiac pathology service established to investigate SCD with fast-track reporting on hearts sent by pathologists in cases of SCD. Methods and results A tertiary centre prospective observational study was conducted. Detailed histopathological examination was performed in a tertiary centre specialized in the investigation of cardiac pathology in SCD. Hearts from 720 consecutive cases of SCD referred by coroners and pathologists from 2007 to 2009 were included. A comparison was drawn with diagnoses from referring pathologists. Most SCDs occurred in males (66%), with the median age being 32 years. The majority (57%) of deaths occurred at home. The main diagnoses were a morphologically normal heart ( n = 321; 45%), cardiomyopathy ( n = 207, 29%), and coronary artery pathology ( n = 71; 10%). In 158 out of a sample of 200 consecutive cases, a cardiac examination was also performed by the referring pathologist with a disparity in diagnosis in 41% of the cases ( κ = 0.48). Referring pathologists were more inclined to diagnose cardiomyopathy than normality with only 50 out of 80 (63%) normal hearts being described correctly. Conclusion Expert cardiac pathology improves the accuracy of coronial post-mortem diagnoses in young SCD. This is important as the majority of cases may be due to inherited cardiac diseases and the autopsy guides the appropriate cardiological evaluation of blood relatives for their risk of sudden death.

Background Primary percutaneous coronary intervention (PPCI) programmes vary in admission criteria from open referral to acceptance of electrocardiogram (ECG) protocol positive patients only. Rigid criteria may result in some patients with acutely occluded coronary arteries not receiving timely reperfusion therapy. Objective To compare the prevalence of acute coronary occlusion and, in these cases, single time point biomarker estimates of myocardial infarct size between patients presenting with protocol positive ECG changes and those presenting with less diagnostic changes in the primary angioplasty cohort of an open access PPCI programme. Methods We retrospectively performed a single centre cross sectional analysis of consecutive patients receiving PPCI between January and August 2008. Cases were categorised according to presenting ECG—group A: protocol positive (ST segment elevation/left bundle branch block/posterior ST elevation myocardial infarction), group B: ST segment depression or T-wave inversion, or group C: minor ECG changes. Clinical characteristics, coronary flow grades and 12 h postprocedure troponin-I levels were reviewed. Results During the study period there were 513 activations of the PPCI service, of which 390 underwent immediate angiography and 308 underwent PPCI. Of those undergoing PPCI, 221 (72%) were in group A, 41 (13%) in group B and 46 (15%) in group C. Prevalence of coronary occlusion was 75% in group A compared with 73% in group B and 63% in group C. Median 12 h postintervention troponin-I (25th–75th percentile) for those with coronary occlusion was significantly higher in group A patients; 28.9 μg/l (13.2–58.5) versus 18.1 μg/l (6.7–32.4) for group B (p=0.03); and 15.5 μg/l (3.8–22.0) for group C (p Conclusions A number of patients referred to an open access PPCI programme have protocol negative ECGs but myocardial infarction and acute coronary artery occlusion amenable to angioplasty.

Aims Cyclophilin A (CyPA) represents a ubiquitous intracellular protein, which is secreted by inflammatory and by dying/necrotic cells. The aim of this study was to evaluate the prognostic relevance of CyPA expression in endomyocardial biopsies of consecutive patients with congestive heart failure. Methods and results A total of 227 unselected patients (age 53.9 ± 15 years) with congestive heart failure undergoing endomyocardial biopsy for diagnostic reasons were enrolled. Biopsies were analysed using established histopathological and immunohistological criteria together with CyPA staining. Virus genome was studied by polymerase chain reaction. CyPA was significantly enhanced in patients with inflammatory cardiomyopathy (n = 127) as compared with patients with non-inflammatory cardiomyopathy (n = 100, P < 0.0001). During a mean follow-up of 16.3 months, 60 patients (26.4%) reached the primary endpoint, a composite of all-cause death, heart transplantation, malignant arrhythmia, and heart failure-related rehospitalization. Of all clinical (ejection fraction, New York Heart Association functional class), laboratory (brain natriuretic peptide), and immunohistological parameters (CyPA, extracellular matrix metalloproteinase inducer, CD68, CD3, major hisocompatibility complex II, and virus genome) tested, only CyPA was identified as an independent predictor for the composite endpoint [hazard ratio (HR) 2.4; 95% confidence interval (CI) 1.2–5.2; P = 0.019] as well as for all-cause death and heart transplantation alone (HR 4.7; 95% CI 1.1–19.8; P = 0.036). Subgroup analysis revealed CyPA as a predictor in patients with non-inflammatory cardiomyopathy for the composite endpoint (HR 3.0; 95% CI 1.3–6.6; P = 0.007) as well as all-cause death or heart transplantation alone (HR 6.4; 95% CI 1.4–28.1; P = 0.014). Conclusions CyPA is an independent predictor of clinical outcome in patients with congestive heart failure undergoing endomyocardial biopsy.

Background A polymorphism (rs35705950) 3 kb upstream of MUC5B , the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We set out to verify whether this variant is also a risk factor for fibrotic lung disease in other settings and to confirm the published findings in a UK Caucasian IPF population. Methods Caucasian UK healthy controls (n=416) and patients with IPF (n=110), sarcoidosis (n=180) and systemic sclerosis (SSc) (n=440) were genotyped to test for association. The SSc and sarcoidosis cohorts were subdivided according to the presence or absence of fibrotic lung disease. To assess correlation with disease progression, time to decline in forced vital capacity and/or lung carbon monoxide transfer factor was used in the IPF and SSc groups, while a persistent decline at 4 years since baseline was evaluated in patients with sarcoidosis. Results A significant association of the MUC5B promoter single nucleotide polymorphism with IPF (p=2.04×10 –17 ; OR 4.90, 95% CI 3.42 to 7.03) was confirmed in this UK population. The MUC5B variant was not a risk factor for lung fibrosis in patients with SSc or sarcoidosis and did not predict more rapidly progressive lung disease in any of the groups. Rather, a trend for a longer time to decline in forced vital capacity was observed in patients with IPF. Conclusions We confirm the MUC5B variant association with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association.

Background Azithromycin is widely used as an immunomodulatory agent in the treatment of cystic fibrosis with previous literature documenting improvements in lung function and a reduction in infective exacerbations. The maximal study period in adults has been six months. Methods 81 adult patients taking continuous azithromycin were retrospectively identified. Percentage predicted FEV 1 and courses of intravenous antibiotics were examined at yearly intervals two years prior to and two years after azithromycin initiation. Results FEV 1 deteriorated in the two years before starting azithromycin by a mean of 2.02% per year. In the year following initiation, FEV 1 increased by 1.15% ( P =0.01). However, a mean 2.58% reduction was observed in year two. There was no statistically significant effect on courses of intravenous antibiotics. Conclusions Azithromycin resulted in an improved FEV 1 at year one. This effect was not sustained beyond the first year of treatment.

Aims To determine the clinical impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point of quantitative myocardial perfusion, as well as secondary end points including atheroma burden, exercise capacity, symptoms, and quality of life. Methods We conducted a single-blinded randomized controlled trial in 20 patients with refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint was change in quantitative myocardial perfusion reserve (MPR) assessed by cardiovascular magnetic resonance. Secondary endpoints included measures of atheroma burden, exercise capacity, symptoms and quality of life. Results The primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31–0.63) compared with sham (−0.16; 95% CI − 0.33–0.02) yielding a net treatment increase of 0.63 (95% CI 0.37–0.89; P Conclusion Lipoprotein apheresis may represent an effective novel treatment for patients with refractory angina and raised lipoprotein(a) improving myocardial perfusion, atheroma burden, exercise capacity and symptoms.

The impact of depressive symptoms on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been thoroughly evaluated in prospective studies. We prospectively enrolled 230 consecutive patients hospitalised for AECOPD, without previous diagnosis of depression. Depressive symptoms were evaluated with Beck's depression inventory. Pulmonary function tests, arterial blood gases, COPD assessment test (CAT) and Borg dyspnoea scale were recorded on admission and on days 3, 10 and 40. Patients were evaluated monthly for 1 year. Patients with depressive symptoms required longer hospitalisation (mean ± sd 11.6 ± 3.7 versus 5.6 ± 4.1 days, p

Background The aim of this study was to examine the relationship between pulmonary exacerbations and physical activity (PA) in adults with cystic fibrosis (CF). Methods We grouped adults with CF according to their exacerbation status in the year before study enrolment: (1) 2 exacerbations/year. PA was assessed objectively by means of an accelerometer at the time of study enrolment. Results Patients with >2 exacerbations/year spent less time in PA; specifically, fewer activities of mild intensity [>3 metabolic equivalents (METs)], and lower active energy expenditure (P = 0.01 and P = 0.03, respectively). After correcting for relevant confounders, PA levels were not related to the exacerbation frequency in the preceding year. PA at moderate intensity (4.8–7.2 METs) or greater (>7.2 METs) was independently associated with gender and FEV1 % predicted (P = 0.007 and P = 0.04, respectively). Compared with men, women had reduced vigorous activities (P = 0.01) and active energy expenditure (P = 0.01). Conclusions Adult CF patients with more pulmonary exacerbations in the preceding year have more advanced disease and are less active than their peers. PA was independently associated with gender and airflow obstruction. Gender differences in PA are evident in CF adults.

Little is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy-resistant asthma (STRA).Relationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA.Serum 25-hydroxyvitamin D [25(OH)D(3)] was measured in 86 children (mean age, 11.7 yr): 36 with STRA, 26 with moderate asthma (MA), and 24 without asthma (control subjects). Relationships between 25(OH)D(3), the asthma control test (ACT), spirometry, corticosteroid use, and exacerbations were assessed. Twenty-two of 36 children with STRA underwent fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy with assessment of airway inflammation and remodeling.25(OH)D(3) levels (median [IQR]) were significantly lower in STRA (28 [22-38] nmol/L) than in MA (42.5 [29-63] nmol/L) and control subjects (56.5 [45-67] nmol/L) (P0.001). There was a positive relationship between 25(OH)D(3) levels and percent predicted FEV(1) (r = 0.4, P0.001) and FVC (r = 0.3, P = 0.002) in all subjects. 25(OH)D(3) levels were positively associated with ACT (r = 0.6, P0.001), and inversely associated with exacerbations (r = -0.6, P0.001) and inhaled steroid dose (r = -0.39, P = 0.001) in MA and STRA. Airway smooth muscle (ASM) mass, but not epithelial shedding or reticular basement membrane thickness, was inversely related to 25(OH)D(3) levels (r = -0.6, P = 0.008). There was a positive correlation between ASM mass and bronchodilator reversibility (r = 0.6, P = 0.009) and an inverse correlation between ASM mass and ACT (r = -0.7, P0.001).Lower vitamin D levels in children with STRA were associated with increased ASM mass and worse asthma control and lung function. The link between vitamin D, airway structure, and function suggests vitamin D supplementation may be useful in pediatric STRA.

To report blood pressure control in the Hypertension in the Very Elderly Trial, a placebo-controlled trial of hypertensive (systolic blood pressure (SBP) 160-199 mm Hg, diastolic blood pressure (DBP)

Background Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity

Background Hospitalisation for acute exacerbations of COPD is associated with high risk of readmission. However, no tool has been validated to stratify patients at discharge for risk of readmission. Aim To evaluate the ability of the 4 m gait speed (4MGS), a surrogate marker of frailty, to predict risk of future readmission in hospitalised patients with an acute exacerbation of COPD (AECOPD). Methods 213 patients hospitalised with an AECOPD were recruited prospectively. 4MGS was measured on day of discharge. Logistic regression models were used to assess the association between 4MGS and readmission at 90 days after discharge. Results Baseline characteristics of the cohort: 52% men; mean age 72 years; median FEV 1 35%predicted. Mean (SD) 4MGS at hospital discharge was 0.61 (0.26) ms −1 . Significant increased rates of all-cause readmission at 90 days were seen across quartiles of decreasing 4MGS (Q4 fastest: 11.5%; Q3: 20.4%; Q2: 30.2%; Q1 slowest: 48.2%; p trend 1 %predicted and number of exacerbations in past year in those aged 65 or over predicted 90-day readmission with a C-statistic of 0.86. Conclusions The 4MGS, a surrogate marker of physical frailty, independently predicts the risk of readmission in older patients hospitalised for acute exacerbation of COPD. Trial registration number NCT01507415.

SummaryBackgroundLung volume reduction surgery improves survival in selected patients with emphysema, and has generated interest in bronchoscopic approaches that might achieve the same effect with less morbidity and mortality. Previous trials with endobronchial valves have yielded modest group benefits because when collateral ventilation is present it prevents lobar atelectasis.MethodsWe did a single-centre, double-blind sham-controlled trial in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax. We enrolled stable outpatients with chronic obstructive pulmonary disease who had a forced expiratory volume in 1 s (FEV1) of less than 50% predicted, significant hyperinflation (total lung capacity >100% and residual volume >150%), a restricted exercise capacity (6 min walking distance

The management and impact of concomitant coronary artery disease in patients referred for TAVI remains contentious. We describe the prevalence, clinical impact and management of coronary artery disease (CAD) in patients in the United Kingdom TAVI Registry.All-inclusive study of patients undergoing TAVI in the United Kingdom (excluding Northern Ireland) from January 2007 to December 2011. Coronary artery disease at the time of TAVI was demonstrated on invasive angiography.2588 consecutive patients were entered in the U.K. TAVI Registry. CAD was reported in 1171 pts with left main stem involvement in 12.4% of this cohort (n=145). Most patients were free of chest pain, but limited by dyspnoea (NYHA Class IIIIV 81.9%). Angina was however more prevalent in those patients with CAD (p0.0001). Hybrid PCI was uncommon, performed in only 14.7% of the CAD cohort (n=172). Survival at 30days, 1year, and 4years was 93.7%, 81.4% and 72.0% respectively. Adjusting for confounders in a multivariate model the presence and extent of CAD was not associated with early (30-days, p=0.36) or late (4years, p=0.10) survival.This contemporary study of coronary artery disease management in an "all-comers" patient population undergoing TAVI demonstrates that whilst often an indicator of significant underlying comorbidity coronary artery disease is not associated with decreased short or long-term survival. The majority of patients with aortic stenosis and concomitant CAD can be managed effectively by TAVI alone. However, the importance of the Heart Team in making decisions on individual patients must not be underestimated.

Background— We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality. Methods and Results— Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 μmol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P Conclusions— We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors.

The U.K. Transcatheter Aortic Valve Implantation Registry reported 30-day and 1-year mortality rates of 7.1% and 21.4%, respectively, for patients who underwent transcatheter aortic valve replacement (TAVR) in the United Kingdom between 2007 and 2009. The study aim was to report long-term outcomes in this same cohort of patients.There are few data on outcomes beyond 3 years after TAVR in any notable number of patients.Data from all TAVR procedures performed in the United Kingdom between January 2007 and December 2009 were prospectively collected. All-cause mortality status was reported in March 2014. Mortality tracking was achieved in 97.7% patients.The minimal time from replacement to census was 4.1 years, and the maximal time was 7.0 years. The 3- and 5-year survival rates were 61.2% and 45.5%, respectively. Independent predictors of 3-year mortality were renal dysfunction (hazard ratio [HR]: 1.65), atrial fibrillation (HR: 1.36), logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) ≥18.5 (HR: 1.33), respiratory dysfunction (HR: 1.28), and ventricular dysfunction (left ventricular ejection fraction 30%) (HR: 1.53). Coronary artery disease (HR: 1.28) and age (HR: 1.03) were additional independent predictors of mortality at 5 years. Stroke within 30 days of TAVR was the only independent procedural predictor of mortality at 3 and 5 years (HR: 2.17 at 3 years). Device type, access route, and paravalvular leak did not independently predict long-term outcome.In the large U.K. Transcatheter Aortic Valve Implantation Registry, long-term outcomes after TAVR are favorable with 3- and 5-year survival rates of 61.2% and 45.5%, respectively. Long-term survival after TAVR is largely determined by intrinsic patient factors. Other than stroke, procedural variables, including paravalvular aortic leak, did not appear to be independent predictors of long-term survival.

Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the treatment for pulmonary arterial hypertension (PAH).This study compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the current practice of adding bosentan, an endothelin receptor antagonist.Twenty-six patients with PAH, idiopathic or associated with connective tissue disease, World Health Organization (WHO) functional class III, were randomized in a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) over 16 weeks.Changes in right ventricular (RV) mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac function, brain natriuretic peptide, and Borg dyspnea index.When analyzed by intention to treat, there were no significant differences between the two treatment groups. One patient on sildenafil died suddenly. Patients on sildenafil who completed the protocol showed significant changes from baseline, namely, reductions in RV mass (-8.8 g; 95% confidence interval [CI], -2, -16; n = 13, p = 0.015) and plasma brain natriuretic peptide levels (-19.4 fmol x ml(-1); 95% CI, -5, -34; p = 0.014) and improvements in 6-minute walk distance (114 m; 95% CI, 67, 160; p = 0.0002), cardiac index (0.3 L x min(-1) x m(-2); 95% CI, 0.1, 0.4; p = 0.008), and systolic left ventricular eccentricity index (-0.2; 95% CI, -0.02, -0.37; p = 0.031). Bosentan improved 6-minute walk distance (59 m; 95% CI, 29, 89; n = 12, p = 0.001) and cardiac index (0.3; 95% CI, 0.1, 0.4; p = 0.008).Sildenafil added to conventional treatment reduces RV mass and improves cardiac function and exercise capacity in patients with PAH, WHO functional class III. Safety monitoring is important until more experience is obtained.

BACKGROUND The results of the Hypertension in the Very Elderly Trial showed positive benefits from blood pressure-lowering treatment in those aged 80 and over. METHOD An analysis by the pre-specified subgroups [age, sex, history of cardiovascular disease (CVD) and initial SBP] was performed. The Hypertension in the Very Elderly Trial was a randomized, double-blind, placebo-controlled trial of 3845 participants aged 80 and over with SBPs of 160-199 mmHg and diastolic pressures below 110 mmHg recruited from Europe, China, Australasia and Tunisia. Active treatment was indapamide sustained-release 1.5 mg with the addition of perindopril 2-4 mg as required to reach a target blood pressure of less than 150/80 mmHg. RESULTS For total mortality, benefits were consistent: men [hazard ratio 0.82, 95% confidence interval (CI) 0.62-1.11], women (hazard ratio 0.77, 95% CI 0.66-0.99), those aged 80-84.9 (hazard ratio 0.76, 95% CI 0.60-0.96), those aged 85 and over (hazard ratio 0.87, 95% CI 0.64-1.20), those with a history of CVD (hazard ratio 0.76, 95% CI 0.48-1.20) and those without (hazard ratio 0.81, 95% CI 0.65-0.99), and similarly across a range of baseline SBPs. The point estimates for cardiovascular mortality, strokes, heart failure and cardiovascular events were all in favour of benefit. In the per-protocol analysis, strokes were reduced by 34% (P = 0.026), total mortality by 28% (P = 0.001), cardiovascular event by 37% (P < 0.001) and heart failure by 72% (P < 0.001). CONCLUSION In hypertensive patients aged 80 or more, treatment based on indapamide (sustained-release) 1.5 mg showed consistent benefits across pre-specified subgroups including those without established CVD (the majority), supporting the need for treatment even at this advanced age. There were too few aged 90 or over to determine benefit from treatment at extreme age.

Background Long term nationally representative mortality rates following acute coronary syndrome (ACS) admissions are lacking beyond 5years. We report rates and causes of mortality at approximately 10years from PRAIS-UK. Methods PRAIS-UK was a prospective registry of 1046 non-ST-elevation ACS admissions to 56 UK hospitals between 1998 and 1999. 493 patients surviving to 6months were consented to long term follow-up. We identified deaths and causes (ICD codes) via the UK central death register and examined the influence of baseline characteristics and early revascularisation procedures. A modified GRACE risk score was constructed to determine the association of baseline score with long term risk of death. Results The mean age was 66years and 40% were women. After a median follow-up of 11.6years (IQR 6.3–11.9), 46% (225) of patients had died with 55% being classified as cardiovascular. In a multivariate analysis, the following variables were associated with higher mortality (hazard ratio [HR] and 95% confidence intervals [CI]): age (10years increase) 2.14 (1.87 to 2.45), ST depression or bundle branch block (compared to normal ECG) 1.68 (1.06 to 2.67), and history of heart failure (compared to no HF) 1.81 (1.28 to 2.56). The HR for risk of death in patients who received a revascularisation procedure (versus those who did not) in the first 6months was 0.41 (0.24 to 0.69). The mean adapted GRACE score was 99.3±26.4, associated with approximately 50% mortality at 10years. Conclusions Non-ST elevation ACS is associated with about 50% mortality over 10years that may be improved by early revascularisation. Well designed long-term registries can provide key data to determine prognosis and burden of disease.

Objectives To examine the associations between illness perception, self-care behaviour, and quality of life in patients admitted to hospital with a primary diagnosis of heart failure (HF), and the changes in these at 2 and 6 months after discharge. Design Longitudinal questionnaire-based study. Setting Three London hospitals with specialist heart failure services. Participants A convenience sample of 88 patients (70% male, mean age 70) admitted to hospital with a primary diagnosis of heart failure were recruited prior to discharge. Participants were over the age of 18, able to understand English, and with the cognitive ability to complete the questionnaires. Thirty-eight patients did not provide follow-up data: 21 (24%) died during the 6-month follow-up period, and 17 (19%) did not return their post-discharge questionnaires. Methods The Revised Illness Perception Questionnaire, the Self-Care Heart Failure Index, Hospital Anxiety and Depression scale, and the Minnesota Living with Heart Failure (MLHF) Questionnaires were completed prior to discharge from hospital, and 2 and 6 months after discharge. Results HF symptoms improved over time (MLHF score co-efficient [95%CI] −0.915 [−1.581, −0.250], P < 0.001). Patients appeared to believe that many of the causes of their illness were outside their control. Although self-care maintenance (e.g. weighing daily) improved over time, this did not translate into increased involvement in self-care management (e.g. adjusting diuretic dose) or the ability to act on changes in symptoms. Self-care confidence was lower in those who reported a more negative emotional impact of their illness, but was higher in those who had high scores on illness coherence. Conclusions Six months following hospital discharge, patients’ symptom control had improved. Many continued to believe that their illness was outside their control, and although self-care maintenance improved this was not associated with greater self-care management, particularly if the patient's emotional state was negative, and their understanding of their condition was poor. Our data suggest that a more participative person-centred approach, tailoring the disease management programme to address the patient's illness beliefs and emotional state, assisting the individual to identify barriers and solutions, may help increase self-care confidence and management.

Background Cardiac resynchronization therapy (CRT) is an established treatment in advanced heart failure (HF). However, an important subset does not derive a significant benefit. Despite an established predictive role in HF, the significance of right ventricular (RV) dysfunction in predicting clinical benefit from CRT remains unclear. We investigated the role of RV function, assessed by cardiovascular magnetic resonance (CMR), in predicting response to and major adverse clinical events in HF patients undergoing CRT. Methods Sixty consecutive patients were evaluated with CMR prior to CRT implantation in a tertiary cardiac centre. The primary end-point was a composite of death from any cause or unplanned hospitalization for a major cardiovascular event. The secondary end-point was response to therapy, defined as improvement in left ventricular ejection fraction ≥ 5% on echocardiography at one year. Results Eighteen patients (30%) met the primary end-point over a median follow-up period of 26 months, and 27 out of 56 patients (48%) were considered responders to CRT. On time-to-event analysis, only atrial fibrillation (HR 2.6, 95% CI 1.02-6.84, p = 0.047) and RV dysfunction, either by a reduced right ventricular ejection fraction-RVEF (HR 0.96, 95% CI 0.94-0.99, p = 0.006) or tricuspid annular plane systolic excursion-TAPSE (HR 0.88, 95% CI, 0.80-0.96, p = 0.006), were significant predictors of adverse events. On logistic regression analysis, preserved RVEF (OR 1.05, 95% CI 1.01-1.09, p = 0.01) and myocardial scar burden (OR 0.90, 95% CI 0.83-0.96, p = 0.004) were the sole independent predictors of response to CRT. Patients with marked RV dysfunction (RVEF < 30%) had a particularly low response rate (18.2%) to CRT. Conclusions Right ventricular function is an important predictor of both response to CRT and long-term clinical outcome. Routine assessment of the right ventricle should be considered in the evaluation of patients for CRT.

Objectives The goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis. Background Myocardial fibrosis occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions. Methods Between January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service. Results A total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis. Conclusions Midwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification. (The Prognostic Significance of Fibrosis Detection in Cardiomyopathy; NCT00930735)

This article is a report of a study exploring health-related quality of life in adults with congenital heart disease and the extent to which it is associated with patients' illness beliefs and emotional health. A reduction in mortality in patients with congenital heart disease has led to an increasingly older population that faces new challenges. Studies in a younger adult population have reported inconsistent findings regarding health-related quality of life. Factors such as, the complexity of the congenital heart defect, have not been found to be associated with quality of life. The association between illness beliefs and health-related quality of life has not previously been reported. A cross-sectional questionnaire study of adults with congenital heart disease attending an outpatient clinic in a specialist centre in the United Kingdom between October 2007 and May 2008. The mean age of the study population was 37·2 years. Participants reported poorer physical functioning, role functioning and general health than a general population. High levels of anxiety were reported in 38% and high levels of depression in 17%. In multivariate analysis, higher levels of anxiety and depression were associated with poorer mental functioning and higher levels of depression with poorer physical quality of life. We have reported that high levels of anxiety and depression in an older population of patients with congenital heart disease are associated with poorer quality of life. This highlights the need to routinely assess anxiety and depression in this patient group and to provide psychological support appropriately.

Background Retrospective studies have shown that the use of statins is associated with reduced mortality and decreased hospitalizations from COPD, but data from prospective studies are lacking. Methods We followed-up prospectively 245 patients admitted to hospital for exacerbations of COPD (ECOPD) with monthly evaluations for one year. The role of statins on outcomes was evaluated by Cox regression analysis after proper adjustments for age, gender, BMI, current smoking status, Charlson comorbidity index and COPD stage. Health-related quality of life (HRQoL) was evaluated by Saint George’s Respiratory Questionnaire. Results There was no effect of statins on either 30-day or 1-year mortality. Patients receiving statins presented a lower total number of ECOPD during the 1-year follow up (2.1 ± 2.7 vs. 2.8 ± 3.2 ECOPD/patient respectively, p = 0.037). After proper adjustments, the use of statins was associated with a lower risk for ECOPD [HR: 0.656 (95% CI: 0.454–0.946)] and severe ECOPD [HR: 0.608 (95%CI: 0.381–0.972)]. The group of statins presented better improvement in HRQoL at 2, 6 and 12 months (p Conclusions The use of statins in patients hospitalized for ECOPD was associated with a lower risk for subsequent ECOPD and severe ECOPD and improved HRQoL. These data support a possible beneficial role for these agents in COPD.

Patients with CKD are at higher risk for major events after percutaneous coronary intervention (PCI) compared with subjects with normal renal function. The aims of this study were to evaluate responsiveness to clopidogrel in patients with CKD and to examine the effect of antiplatelet drug response on post-PCI outcome. We retrospectively evaluated a consecutive cohort of 1567 patients with symptomatic coronary artery disease undergoing PCI, 648 (41%) of whom had stage 3 to 5 CKD. We assessed responsiveness to clopidogrel by ADP-induced platelet aggregation after oral administration of a 600-mg clopidogrel loading dose and 100 mg of aspirin. In a multivariate survival analysis that included 1335 (85%) of the cohort, stage 3 to 5 CKD and low response to clopidogrel were independent predictors of the primary end point (composite of myocardial infarction, ischemic stroke, and death within 1 year). In summary, a low response to clopidogrel might be an additional risk factor for the poorer outcomes in patients with stage 3 to 5 CKD compared with patients with better renal function.

Aim Marfan syndrome (MFS) is an inherited connective tissue disease which frequently involves the cardiovascular system. The heart can be affected since valvular regurgitation is a common complication. However, there is still debate whether a primary cardiomyopathy exists. Our aim was to evaluate the existence of a Marfan-related cardiomyopathy using cardiovascular magnetic resonance. Methods and results We retrospectively evaluated 68 consecutive adult patients with no cardiovascular surgery or significant valvular regurgitation. Left ventricular and right ventricular volumes, ejection fraction, and mass were estimated and compared with published data on a healthy control population. Patients were also assessed for heart failure, aortic dimensions, and valve disease. One quarter (25.0%) of Marfan patients had reduced left ventricular ejection fraction (LVEF), with 25.0% having increased left ventricular end-diastolic and 30.8% having increased end-systolic volumes. The right ventricular ejection fraction was reduced in 10.3%, with increased right ventricular end-diastolic volumes in 11.8% and increased end-systolic volumes in 13.2%. On univariate analysis, no association was found between reduced LVEF and age, gender, indexed aortic dimensions, presence of mitral valve prolapse, or valve regurgitation. Conclusion This study supports the existence of a primary cardiomyopathy in a subgroup of Marfan patients. The biventricular enlargement and dysfunction is usually mild, asymptomatic, and independent from other cardiovascular manifestations. Further studies are needed to assess underlying causes and natural history of this condition. Routine monitoring and treatment in MFS may need to be tailored not only to prevent aortic root expansion but also to support myocardial function.

Aims Myocardial T2* cardiovascular magnetic resonance (CMR) provides a rapid and reproducible measure of cardiac iron loading and is being increasingly used worldwide for monitoring of transfusion-dependent thalassaemia patients. Although myocardial siderosis (T2* 20 ms), the RV ejection fraction (EF) was within the normal range in 98% of patients. When myocardial T2* was

The Hypertension in the Very Elderly Trial (HYVET) is a randomized double-blind trial of active antihypertensive treatment (indapamide 1.5 mg sustained release +/-2-4 mg perindopril) vs placebo in participants over the age of 80 years with a systolic blood pressure (SBP) of 160-199 mmHg during a placebo run-in period plus a diastolic blood pressure (DBP) of

Background The baseline characteristics of patients in a multinational trial are possibly related to cardiovascular outcome. This study compared the baseline characteristics of patients recruited in China with those recruited in other countries. Methods A total of 508 Chinese hypertensive men and 728 women over the age of 80 years who entered the Hypertension in the Very Elderly Trial (HYVET) were compared with those in 860 men and 1348 women who entered the trial in other countries. Results The Chinese subjects were slightly younger, had less previous hypertension but more previous strokes than the subjects from other countries. The Chinese subjects smoked more than those from other countries, but drank less alcohol. They had less previous episodes of myocardial infarction and were, on average, lighter and shorter. The Chinese had lower mean concentrations of blood urea, uric acid and creatinine as well as higher concentrations of high density lipoprotein (HDL) cholesterol. The concentration of total cholesterol was, on average, lower in the Chinese subjects as was blood glucose. The levels of serum sodium and potassium, blood hematocrit and hemoglobin were all, on average, lower in the Chinese subjects. Conclusions Calorie restriction, compared with the rest of the world, may have resulted in lower stature and weight, and recent increases in calorie intake have not changed the metabolic profile of the very elderly hypertensive patients in China. Some of these biochemical differences may reflect different dietary lifestyle in the Chinese. Chin Med J 2008;121(16):1509-1512

Objectives we investigated the exact relationship between age and gender on augmentation pressure (AG) and augmentation index (AI) measured over the radial (muscular) and carotid (elastic) arteries. Design and methods AG is the contribution that wave reflection makes to systolic arterial pressure. AI is an indirect measure of arterial stiffness and is calculated as AG divided by pulse pressure (PP) x100. AG and AI both increase with age. AG and AI were measured in 458 subjects using SphygmoCor. A total of 755 readings were obtained (302 carotid, 453 radial). The mean age was 57.5 +/- 13.7 years. Diabetic subjects were excluded. Among the subjects, 13.5% were hypertensive. Results statistically, women had mean values of AI significantly higher than men in both radial and carotid arteries. These differences were less marked with AG. Quadratic equations better described the relationship between AI and age but not AG and age. Thus, AI increased with age up to our median age of 55 years but plateaued thereafter, whereas the AG continued to increase steadily with age. A multiple regression analysis demonstrated that both AI and AG were negatively related to height and positively related to diastolic blood pressure (DBP). Conclusions AG continues to increase in the elderly over the age of 55, but not AI. AI is higher in women and higher when measured over the carotid than the radial. AI is positively related to DBP and negatively to height. AG is proposed as a more suitable measure of arterial stiffness than AI.

In the present study, the repeatability of three techniques for measuring peripheral PWV (pulse wave velocity) has been studied. A transcranial Doppler provided a wave reading from the middle cerebral artery. Using the transit time between the R-wave of an ECG and the ‘foot’ of this wave we were able to calculate a PWV (PWV-brain). An ear clip transducer provided a pressure wave reading (PWV-ear). A third pressure reading came from a Finapres transducer on the left middle finger (PWV-finger). The PWV was calculated as distance between two points/transit time of the pulse wave. Eleven volunteers had three sets of readings averaged for each technique taken in two separate sessions. There was good agreement between observers for the mean PWV values, and good agreement for mean results in different sessions. The RC%s (repeatability coefficient percentages) for between-observer repeatability in each session were good and approximately equivalent for PWV-finger (5–7%) and PWV-brain (5–7%). The repeatability of the PWV-ear measurement was less satisfactory (8–18%). The RC% for the same observer between sessions was less good, being 11% for the PWV-finger, 16–17% for PWV-brain and 11–19% for PWV-ear. The RC%s for the inter-session inter-observer measurements were between 10.7–12.1% for the PWV-finger, 14.7–19.5% for PWV-brain and 8.3–15% for PWV-ear. The transit time RC%s were lower in most measurements. The between-observer repeatability of all measures was satisfactory. Owing to the less good repeatability on different occasions, the use of PWV-brain and PWV-ear will depend on the magnitude of differences to be expected.

Background Increased airway smooth muscle (ASM) is a feature of established asthma in schoolchildren, but nothing is known about ASM in preschool wheezers. Objective We sought to determine endobronchial biopsy specimen ASM area fraction in preschool wheezers and its association with asthma at school age. Methods ASM area, reticular basement membrane thickness, and mucosal eosinophil and ASM mast cell values were quantified in endobronchial biopsy specimens previously obtained from preschool children undergoing clinically indicated bronchoscopy: severe recurrent wheezers (n = 47; median age, 26 months) and nonwheezing control subjects (n = 21; median age, 15 months). Children were followed up, and asthma status was established at age 6 to 11 years. Preschool airway pathology was examined in relation to asthma at school age. Results Forty-two (62%) of 68 children had 1 or more evaluable biopsy specimens for ASM. At school age, 51 of 68 children were followed up, and 15 (40%) of 37 preschool wheezers had asthma. Children who had asthma and an evaluable biopsy specimen had increased preschool ASM area fraction (n = 8; median age, 8.2 years [range, 6-10.4 years]; median ASM, 0.12 [range, 0.08-0.16]) compared with that seen in children without asthma (n = 24; median age, 7.3 years [range, 5.9-11 years]; median ASM, 0.07 [range, 0.02-0.23]; P = .007). However, preschool reticular basement membrane thickness and mucosal eosinophil or ASM mast cell values were not different between those who did or did not have asthma at school age. Conclusion Increased preschool ASM is associated with those children who have asthma at school age. Thus a focus on early changes in ASM might be important in understanding the subsequent development of childhood asthma.

Background Antibiotic surveillance is mandatory to optimise antibiotic therapy. Our objectives were to evaluate antibiotic use in our pediatric intensive care unit (PICU) and to implement a simple achievable intervention aimed at improving antibiotic therapy. Method Prospective, 3 months surveillance of antibiotic use on PICU (phase I) and evaluation according to the CDC 12-step campaign with development of an attainable intervention. 3 months surveillance (phase II) after implementation of intervention with comparison of antibiotic use. Results Appropriate antibiotic use for culture-negative infection-like symptoms and targeted therapy for proven infections were the main areas for potential improvement. The intervention was a mandatory checklist requiring indication and recording likelihood of infection at start of antibiotic therapy and a review of the continuing need for therapy at 48 h and 5 days, reasons for continuation and possible target pathogen. The percentage of appropriate empiric antibiotic therapy courses for culture-negative infection-like symptoms increased from 18% (10/53) to 74% (42/57; p Conclusions Antibiotic surveillance using the CDC 12-step campaign can help to evaluate institutional antibiotic therapy. Development of an attainable intervention using a checklist can show improved antibiotic use with minimal expense.