London Chest Hospital

BACKGROUND: Methods of classifying chronic obstructive pulmonary disease (COPD) depend largely upon spirometric measurements but disability is only weakly related to measurements of lung function. With the increased use of pulmonary rehabilitation, a need has been identified for a simple and standardised method of categorising disability in COPD. This study examined the validity of the Medical Research Council (MRC) dyspnoea scale for this purpose. METHODS: One hundred patients with COPD were recruited from an outpatient pulmonary rehabilitation programme. Assessments included the MRC dyspnoea scale, spirometric tests, blood gas tensions, a shuttle walking test, and Borg scores for perceived breathlessness before and after exercise. Health status was assessed using the St George's Respiratory Questionnaire (SGRQ) and Chronic Respiratory Questionnaire (CRQ). The Nottingham Extended Activities of Daily Living (EADL) score and Hospital Anxiety and Depression (HAD) score were also measured. RESULTS: Of the patients studied, 32 were classified as having MRC grade 3 dyspnoea, 34 MRC grade 4 dyspnoea, and 34 MRC grade 5 dyspnoea. Patients with MRC grades 1 and 2 dyspnoea were not included in the study. There was a significant association between MRC grade and shuttle distance, SGRQ and CRQ scores, mood state and EADL. Forced expiratory volume in one second (FEV1) was not associated with MRC grade. Multiple logistic regression showed that the determinants of disability appeared to vary with the level of disability. Between MRC grades 3 and 4 the significant covariates were exercise performance, SGRQ and depression score, whilst between grades 4 and 5 exercise performance and age were the major determinants. CONCLUSIONS: The MRC dyspnoea scale is a simple and valid method of categorising patients with COPD in terms of their disability that could be used to complement FEV1 in the classification of COPD severity.

BACKGROUND: In acute ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to treat the artery responsible for the infarct (infarct, or culprit, artery) improves prognosis. The value of PCI in noninfarct coronary arteries with major stenoses (preventive PCI) is unknown. METHODS: From 2008 through 2013, at five centers in the United Kingdom, we enrolled 465 patients with acute STEMI (including 3 patients with left bundle-branch block) who were undergoing infarct-artery PCI and randomly assigned them to either preventive PCI (234 patients) or no preventive PCI (231 patients). Subsequent PCI for angina was recommended only for refractory angina with objective evidence of ischemia. The primary outcome was a composite of death from cardiac causes, nonfatal myocardial infarction, or refractory angina. An intention-to-treat analysis was used. RESULTS: By January 2013, the results were considered conclusive by the data and safety monitoring committee, which recommended that the trial be stopped early. During a mean follow-up of 23 months, the primary outcome occurred in 21 patients assigned to preventive PCI and in 53 patients assigned to no preventive PCI (infarct-artery-only PCI), which translated into rates of 9 events per 100 patients and 23 per 100, respectively (hazard ratio in the preventive-PCI group, 0.35; 95% confidence interval [CI], 0.21 to 0.58; P<0.001). Hazard ratios for the three components of the primary outcome were 0.34 (95% CI, 0.11 to 1.08) for death from cardiac causes, 0.32 (95% CI, 0.13 to 0.75) for nonfatal myocardial infarction, and 0.35 (95% CI, 0.18 to 0.69) for refractory angina. CONCLUSIONS: In patients with STEMI and multivessel coronary artery disease undergoing infarct-artery PCI, preventive PCI in noninfarct coronary arteries with major stenoses significantly reduced the risk of adverse cardiovascular events, as compared with PCI limited to the infarct artery. (Funded by Barts and the London Charity; PRAMI Current Controlled Trials number, ISRCTN73028481.).

RATIONALE: Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin-5. A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans. OBJECTIVES: To investigate the effect of three intravenous infusions of mepolizumab, 250 or 750 mg at monthly intervals, on clinical outcome measures in 362 patients with asthma experiencing persistent symptoms despite inhaled corticosteroid therapy (400-1,000 mug of beclomethasone or equivalent). METHODS: Multicenter, randomized, double-blind, placebo-controlled study. MEASUREMENTS AND MAIN RESULTS: Morning peak expiratory flow, forced expiratory volume in 1 second, daily beta(2)-agonist use, symptom scores, exacerbation rates, and quality of life measures. Sputum eosinophil levels were also measured in a subgroup of 37 individuals. Mepolizumab was associated with a significant reduction in blood and sputum eosinophils in both treatment groups (blood, P < 0.001 for both doses; sputum, P = 0.006 for 250 mg and P = 0.004 for 750 mg). There were no statistically significant changes in any of the clinical end points measured. There was a nonsignificant trend for decrease in exacerbation rates in the mepolizumab 750-mg treatment group (P = 0.065). CONCLUSIONS: Mepolizumab treatment does not appear to add significant clinical benefit in patients with asthma with persistent symptoms despite inhaled corticosteroid therapy. Further studies are needed to investigate the effect of mepolizumab on exacerbation rates, using protocols specifically tailored to patients with asthma with persistent airway eosinophilia.

Understanding and improving the prognosis of a disease or health condition is a priority in clinical research and practice. In this article, the authors introduce a framework of four interrelated themes in prognosis research, describe the importance of the first of these themes (understanding future outcomes in relation to current diagnostic and treatment practices), and introduce recommendations for the field of prognosis research

AIMS: The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. METHODS AND RESULTS: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. CONCLUSION: Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Non-invasive ventilation has been used in chronic respiratory failure due to chronic obstructive pulmonary disease (COPD), but the effect of the addition of nasal positive-pressure ventilation to long-term oxygen therapy (LTOT) has not been determined. We report a randomized crossover study of the effect of the combination of nasal pressure support ventilation (NPSV) and domiciliary LTOT as compared with LTOT alone in stable hypercapnic COPD. Fourteen patients were studied, with values (mean +/- SD) of Pao2 of 45.3 +/- 5.7 mm Hg, PaCO2 of 55.8 +/- 3.6 mm Hg, and FEV1 of 0.86 +/- 0.32 L. A 4 wk run-in period (on usual therapy) was followed by consecutive 3-mo periods of: (1) oxygen therapy alone, and (2) oxygen plus NPSV in randomized order. Assessments were made during run-in and at the end of each study period. There were significant improvements in daytime arterial PaO2 and PaCO2, total sleep time, sleep efficiency, and overnight PaCO2 following 3 mo of oxygen plus NPSV as compared with run-in and oxygen alone. Quality of life with oxygen plus NPSV was significantly better than with oxygen alone. The degree of improvement in daytime PaCO2 was correlated with the improvement in mean overnight PaCO2. Nasal positive-pressure ventilation may be a useful addition to LTOT in stable hypercapnic COPD.

RATIONALE: Vitamin D was used to treat tuberculosis (TB) in the preantibiotic era. Prospective studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed. OBJECTIVES: To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status. METHODS: A double-blind randomized controlled trial was conducted in 192 healthy adult TB contacts in London, United Kingdom. Participants were randomized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was assessed with a functional whole blood assay (BCG-lux assay), which measures the ability of whole blood to restrict luminescence, and thus growth, of recombinant reporter mycobacteria in vitro; the readout is expressed as a luminescence ratio (luminescence postinfection/baseline luminescence). IFN-gamma responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay. Vitamin D supplementation significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro compared with placebo (mean luminescence ratio at follow-up, 0.57, vs. 0.71, respectively; 95% confidence interval for difference, 0.01-0.25; p=0.03) but did not affect antigen-stimulated IFN-gamma secretion. CONCLUSIONS: A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses. Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection. Clinical trial registered with www.clinicaltrials.gov (NCT 00157066).

We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium, tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This was a multicentre, randomised, double-blind, placebo- and active-controlled, 26-week trial. Patients (n = 2144) were randomised (2:2:2:2:1) to receive once-daily QVA149 (indacaterol 110 μg/glycopyrronium 50 μg), indacaterol 150 μg, glycopyrronium 50 μg, open-label tiotropium 18 μg or placebo. The primary end-point was trough forced expiratory volume in 1 s (FEV1) at week 26 for QVA149 versus its monocomponents. Secondary end-points included dyspnoea, health status, rescue medication use and safety. Trough FEV1 at week 26 was significantly improved (p<0.001) with QVA149 compared with indacaterol and glycopyrronium (least squares mean (LSM) differences 0.07 L and 0.09 L, respectively), tiotropium and placebo (LSM differences 0.08 L and 0.20 L, respectively); these beneficial effects were sustained throughout the 26-week study. QVA149 significantly improved dyspnoea and health status versus placebo (p<0.001 and p = 0.002, respectively) and tiotropium (p = 0.007 and p = 0.009, respectively) at week 26. All treatments were well tolerated. Dual bronchodilation with once-daily QVA149 demonstrated superior and clinically meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator, with a safety and tolerability profile similar to placebo, supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist combinations for the treatment of COPD.

This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation. In this randomized, controlled study, 126 patients with chronic obstructive pulmonary disease (COPD) were stratified for dyspnoea using the Medical Research Council (MRC) dyspnoea score into MRC3/4 (Moderate) (n=66) and MRC 5 (Severe) dyspnoeic (n=60) groups. The patients were randomly assigned to an eight week programme of either exercise plus education (Exercise group) or education (Control group). Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting. Severely dyspnoeic patients were all treated at home. Those in the Exercise group received an individualized training programme. There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group, who received exercise training; baseline (mean+/-SEM) 191+/-22 m, post-rehabilitation 279+/-22 m (p<0.001). There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise. Neither group of control patients improved. Health status, assessed by the Total Chronic Respiratory Disease Questionnaire score, increased in the moderately dyspnoeic patients receiving exercise from 80+/-18 to 95+/-17 (p<0.0001) after rehabilitation. Much smaller changes were seen in the other three groups. Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea.

Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 - 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432-912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9-412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (-29·1%;23·8-38·5). YLLs decreased in self-harm (-27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation.

BACKGROUND: Atrial fibrillation (AF) occurs in 20% to 40% of patients after CABG. Identification of patients vulnerable for arrhythmia will allow targeting of those most likely to benefit from prophylactic therapy. The aim of the present study was to evaluate accuracy of a prospectively defined signal-averaged P-wave duration (SAPD) cutoff and additional preoperative characteristics for the prediction of AF after CABG. METHODS AND RESULTS: Patients undergoing elective isolated CABG were recruited to the present prospective study. SAPD was recorded in all patients. Filtered signals from 3 orthogonal leads were combined in a vector analysis, and total SAPD was measured preoperatively. Postoperative in-hospital AF occurred in 92 (28.2%) of 326 patients. Patients who developed AF were older (65.9 versus 61.7 years of age; P<0.0005) and had longer SAPD (158 versus 145 ms; P<0.0005) than non-AF patients. Incidence of AF increased in patients > or =75 years of age and increased progressively throughout the range of SAPD. Stepwise logistic regression analysis of preoperative variables identified that SAPD >155 ms (odds ratio, 5.37; 95% CI, 3.10 to 9.30; P<0.0005), advanced age (odds ratio, 1. 53; 95% CI, 1.26 to 1.86 per 5-year increase in age; P<0.0005), and male sex (odds ratio, 2.88; 95% CI, 1.30 to 6.40; P<0.01) independently predicted AF. Prospectively defined SAPD >155 ms predicted AF with positive and negative predictive accuracy of 49% and 84%, respectively. CONCLUSIONS: A combination of prolonged SAPD, advanced age, and male sex identifies patients at high risk for development of AF after CABG.

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

Asthmatic children, known to be susceptible to exercise-induced bronchoconstriction, exercised by running or walking on a treadmill. Changes in airways obstruction were estimated by measurement of peak expiratory flow rate before, during, and after exercise. Post exercise bronchoconstriction reached a maximum when the duration of exercise was 6 to 8 minutes and when the gradient of the treadmill was 10 to 15%; exercise for longer periods or at steeper gradients produced no significant increase in bronchoconstriction. Bronchoconstriction was much greater after running than after walking at the same oxygen consumption in 4 out of the 5 subjects tested. The reproducibility of bronchoconstriction was good in individual patients when tests performed within one day or within one week were compared. Reproducibility diminished as the interval between tests increased to one month or one year. When tests were repeated at 2-hourly intervals throughout the day, no significant diminution in exercise-induced bronchoconstriction was noted. Variations in pre-exercise peak expiratory flow rate had no significant effect on exercise-induced bronchoconstriction in individual subjects. The range of response of normal children to treadmill exercise is defined and the value of the test in discriminating between asthmatic and other children is shown. If several tests are to be carried out by an individual patient, they should be performed on separate days at the same time of day and should be completed within one week. This will allow accurate comparisons to be made between tests in, for example, the assessment of the effect of different drugs in an individual patient.

An index of severity of coronary artery disease is described which takes into account the site, severity and number of all lesions in the coronary arteries. A percentage figure is computed with low percentages indicating severe disease. Ten year follow-up for 1050 medically treated patients are given. During the period of observation the overall mortality rate was 6.3%. 68% of deaths occurring in the first year and 97% in the first five years. Survival curves are drawn for five years and cindicate significant differences in survival between the four quartikes of the coronary index. In particular, a high risk group is described with a coronary index of 25% or less. Left ventricular abnormalities further decrease the survival rates.

OBJECTIVE: To characterise clinical, investigative, and prognostic features of women referred with chest pain who subsequently underwent coronary angiography. DESIGN: Analysis of all women with angina referred to one consultant during 1987-91 who subsequently underwent coronary angiography, with follow up to present day. SETTING: Cardiothoracic centre. SUBJECTS: Women with normal coronary arteries; women with coronary artery disease shown on angiography; men with coronary artery disease matched for age; men referred with chest pain during the same period subsequently found to have normal coronary arteries. MAIN OUTCOME MEASURES: Risk factor analysis; results of exercise testing and coronary angiography; intervention; morbidity and mortality. RESULTS: Women comprised 23% (202/886) of patients referred with chest pain who subsequently underwent angiography. 83/202 women had normal coronary angiograms compared with 55/684 men (41% v 8%, P < 0.01). Diabetes mellitus was the only risk factor more frequently encountered in women with coronary artery disease (P = 0.001). The specificity and positive predictive value of exercise testing before angiography were significantly lower in women than men (71% v 93%, P < 0.001 and 76% v 95%, P < 0.001, respectively). Revascularisation procedures were as common in women with coronary artery disease as in men (81 (68%) v 70 (59%)), and there was no difference in event rate during follow up. Many patients with normal coronary arteries, irrespective of sex, had symptoms during follow up (61 (73%) women, 36 (65%) men) and continued to take antianginal drugs (27 (33%) women, 14 (28%) men); 14 (17%) women and six (11%) men required hospital readmission for severe symptoms. CONCLUSIONS: In this series, although women comprised the minority of patients referred with chest pain, a diagnosis of normal coronary arteries was five times more common in women than men. Risk factor analysis and exercise testing were of limited value in predicting coronary artery disease in women. There was no sex bias regarding revascularisation procedures, and outcome was similar. A diagnosis of non-cardiac chest pain in patients with normal coronary arteries was of little benefit to the patient with regard to morbidity.

UK Biobank is a prospective cohort study with 500,000 participants aged 40 to 69. Recently an enhanced imaging study received funding. Cardiovascular magnetic resonance (CMR) will be part of a multi-organ, multi-modality imaging visit in 3-4 dedicated UK Biobank imaging centres that will acquire and store imaging data from 100,000 participants (subject to successful piloting). In each of UK Biobank's dedicated bespoke imaging centres, it is proposed that 15-20 participants will undergo a 2 to 3 hour visit per day, seven days a week over a period of 5-6 years. The imaging modalities will include brain MRI at 3 Tesla, CMR and abdominal MRI at 1.5 Tesla, carotid ultrasound and DEXA scans using carefully selected protocols. We reviewed the rationale, challenges and proposed approaches for concise phenotyping using CMR on such a large scale. Here, we discuss the benefits of this imaging study and review existing and planned population based cardiovascular imaging in prospective cohort studies. We will evaluate the CMR protocol, feasibility, process optimisation and costs. Procedures for incidental findings, quality control and data processing and analysis are also presented. As is the case for all other data in the UK Biobank resource, this database of images and related information will be made available through UK Biobank's Access Procedures to researchers (irrespective of their country of origin and whether they are academic or commercial) for health-related research that is in the public interest.

Inhaled corticosteroids (ICS) are effective in the treatment of asthma and markedly reduce the numbers of inflammatory cells in bronchial biopsies. However, the effect of ICS on the inflammatory profile of biopsies in smokers with chronic obstructive pulmonary disease (COPD) is unknown. We have performed a double-blind, placebo-controlled, randomized study to compare fluticasone propionate (FP) 500 microg twice daily via a dry powder inhaler and placebo (P) over a 3-month period in subjects with COPD. Fiberoptic bronchoscopy and bronchial biopsy was carried out at baseline and after the 3 months of treatment. Thirty-one subjects completed the trial and 30 paired biopsies were available for analysis. Compared with P (n = 14), subjects on inhaled FP (n = 16) had no significant reductions in the primary endpoints: CD8+, CD68+ cells, or neutrophils, considered to be of importance in COPD. However, there was a reduction in the CD8:CD4 ratio in the epithelium and of the numbers of subepithelial mast cells in the FP group. CD4+ cells were significantly raised in the P group in both subepithelium and epithelium. Symptoms significantly improved, and there were significantly fewer exacerbations in subjects on FP, compared to subjects on P. The data indicate that inhaled fluticasone does affect selected aspects of airway inflammation in COPD, and this may explain, in part, the decrease in exacerbations seen in long-term studies with fluticasone propionate.

The EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting. Furthermore, interim analysis of the specific protocols should underscore the prognostic potential of CMR. Multi-center registry with consecutive enrolment of patients in 57 centers in 15 countries. More than 27000 consecutive patients were enrolled. The most important indications were risk stratification in suspected CAD/Ischemia (34.2%), workup of myocarditis/cardiomyopathies (32.2%), as well as assessment of viability (14.6%). Image quality was diagnostic in more than 98% of cases. Severe complications occurred in 0.026%, always associated with stress testing. No patient died during or due to CMR. In 61.8% CMR findings impacted on patient management. Importantly, in nearly 8.7% the final diagnosis based on CMR was different to the diagnosis before CMR, leading to a complete change in management. Interim analysis of suspected CAD and risk stratification in HCM specific protocols revealed a low rate of adverse events for suspected CAD patients with normal stress CMR (1.0% per year), and for HCM patients without LGE (2.7% per year). The most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM. The EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting in a large number of cases (n > 27000). Based on our data CMR is frequently performed in European daily clinical routine. The most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.

1. The results of studies during simple progressive exercise to exhaustion and steady-state submaximal exercise in 117 boys and girls aged 6–16 years are presented. 2. In the simple progressive exercise test, the highest work load achieved and the submaximal heart rate were related to size and sex. The maximum heart rate and submaximal ventilation were largely independent of size and sex. 3. Steady-state exercise was performed at one-third and two-thirds of the maximum work load achieved in the simple progressive test. The Indirect (CO2) Fick method was used to measure cardiac output. 4. At any given level of steady-state work, tidal volume, dead space, heart rate and stroke volume were closely related to size, with girls having higher heart rates and smaller stroke volumes than boys. Minute ventilation and cardiac output were virtually independent of size and sex. The cardiac output in children was the same as that in the adult for any given oxygen consumption. Blood lactate was related to size at any given work load, but was independent of size at any given fraction of the maximum working capacity.

Magnetic Resonance (MR), which has no known biological hazard, is capable of producing high resolution thin tomographic images in any plane and blocks of 3-dimensional information. It can be used to study blood flow and to gain information about the composition of important materials seen and quantified on dimensionally accurate images. The MR image is a thin tomographic slice or a true three dimensional block of data which can be reconstructed in any desired way rather than a shadowgram of all the structures in the beam. It is the only imaging technique which can acquire data in a 3-dimensional format. CT images can be reconstructed to form a pseudo 3-D image or a hologram but the flexibility conferred by acquiring the data as a true 3-D block gives many advantages. The spatial resolution of MR images are theoretically those of low powered microscopy, the practical limits with the present generation of equipment are voxel sizes of one third by one third by two millimetres. The term Magnetic Resonance Imaging (MRI) is used commonly, particularly in the USA, avoiding association with the term, nuclear, and emphasizing the imaging potential of the technique. The terms Nuclear Magnetic Resonance (NMR) or Magnetic Resonance (MR) more correctly describe the most powerful diagnostic instrument yet devised. The simplified description of the phenomena involved in MR which follows is intended to be comprehensive and does not require foreknowledge of classical physics, quantum mechanics, fluency with mathematical formulae or an understanding of image reconstruction. There are many explanations of MR, some omitting the more difficult concepts. An accurate, comprehensive description is found on the textbook on MR by Gadian, Nuclear Magnetic Resonance and its Applications for Living Systems (Oxford University Press, 1982).