The oxygen uptake efficiency slope in adults with CHD: group validity.

The maximal oxygen uptake (V02 max) is a well-validated measure of cardiorespiratory function that is calculated during a maximal cardiopulmonary exercise test. V02 max enables physicians to objectively assess cardiopulmonary function to aid in decision-making for patients with CHD. A significant proportion of these patients however are unable to achieve a maximal exercise test, and as such, there is a need for reliable submaximal predictors of cardiorespiratory reserve.The oxygen uptake efficiency slope represents a measure of how effectively oxygen is extracted from the lungs and taken into the body and can be calculated from a submaximal exercise test. Its reliability as a predictor of cardiorespiratory reserve has been validated in various patient populations, but there is limited evidence for its validity in adult patients with CHD.Retrospective analysis of cardiopulmonary exercise test data in 238 consecutive patients with CHD who completed a maximal cardiopulmonary exercise test at our tertiary cardiology centre demonstrated a strong correlation between peak V02 and the oxygen uptake efficiency slope (0.936). A strong correlation with peak V02 was also demonstrated when oxygen uptake efficiency slope was calculated at ventilatory anaerobic threshold (OUESVAT), 75% (OUES75), and 90% (OUES90) of the test (0.833, 0.905, 0.927 respectively).In adult patients with CHD who are unable to complete a maximal cardiopulmonary exercise test, the oxygen uptake efficiency slope is a reliable indicator of cardiopulmonary fitness which correlates strongly with peak V02 at or beyond the ventilatory anaerobic threshold. Further research is required to validate the findings in patients with less common anatomies and to assess the relationship between the oxygen uptake efficiency slope and mortality.

Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction.

NEW FINDINGS: What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes. Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal-averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT-PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara-Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal-averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2, KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after-depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+ -Ca2+ exchange current. These data suggest that diabetes leads to pro-arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population.

Forecasting expenditure on capital projects.

S-curves are widely used for planning, forecasting and control of cost, time and resources of a project. In this paper, a comparison of two S-curve models developed at the Department of Health and Social Security (DHSS) and Bradford University is carried out both from the viewpoint of predictive accuracy and ease of use. The models are validated using expenditure data for 21 recent U.K. health building projects. Methods of least squares is used to estimate the parameters of the two models. These parameters are categorized according to the total cost of the projects. Both the models are shown to be of comparable accuracy for fitting actual expenditure data. The DHSS model has a major advantage of simplicity of form and use, although the slightly greater mathematical complexity of the Keller-Singh model is off-set by the readily interpretable nature of its form and basic parameters. It is concluded that both or either of the models could be used by clients/contractors for effective planning and control of project costs.