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.

The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

Human congestive heart failure is characterized by complex neurohumoral activation associated with the up-regulation of vasoconstricting and salt-retaining mediators and the compensatory rise of counter-regulatory hormones. In the present study, we provide the first evidence that relaxin (RLX), known as a pregnancy hormone, represents a potential compensatory mediator in human heart failure: plasma concentrations of RLX and myocardial expression of the two RLX genes (H1 and H2) correlate with the severity of disease and RLX responds to therapy. The failing human heart is a relevant source of circulating RLX peptides, and myocytes as well as interstitial cells produce RLX. Elevation of ventricular filling pressure up-regulates RLX expression and the hormone acts as a potent inhibitor of endothelin 1, the most powerful vasoconstrictor in heart failure. Furthermore, RLX modulates effects of angiotensin II, another crucial mediator. Our data identify RLX as a new player in human heart failure with potential diagnostic and therapeutic relevance.

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations.Design Retrospective pooled analysis of individual patient data.Setting 18 hospitals in Europe and the United States.Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measuresObstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. ResultsWe included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory.Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates. IntroductionIn the United States, about 10.2 million people have chest pain complaints each year, 1 and more than 1.1 million diagnostic procedures of catheter based coronary angiography are performed on inpatients each year. 2 In a recent report based on the national cardiovascular data registry of the American College of Cardiology, 3 only 41% of patients undergoing elective procedures of catheter based coronary angiographies are diagnosed with obstructive coronary artery disease. The report's authors concluded that better risk stratification was needed, underlined by decision analyses showing that the choice of further diagnostic investigation in patients with chest pain depends primarily on the pretest probability of coronary artery disease. [4][5][6] The American College of Cardiology/American Heart Associatio...

Background-Noninvasive coronary angiography with the use of multislice computed tomography (CT) scanners is feasible with high sensitivity and negative predictive value; however, the radiation exposure associated with this technique is rather high. We evaluated coronary angiography using whole-heart 320-row CT, which avoids exposure-intensive overscanning and overranging. Methods and Results-A total of 30 consecutive patients with suspected coronary artery disease referred for clinically indicated conventional coronary angiography (CCA) were included in this prospective intention-to-diagnose study. CT was performed with the use of up to 320 simultaneous detector rows before same-day CCA, which, together with quantitative analysis, served as the reference standard.

Multisegment reconstruction has superior diagnostic accuracy and image quality compared with halfscan reconstruction in patients with normal heart rates.

Background-The ubiquitin-proteasome system is the major intracellular protein degradation pathway in eucaryotic cells.It regulates central mediators of proliferation, inflammation, and apoptosis that are fundamental pathomechanisms in the development of vascular restenosis. Methods and Results-Effects of proteasome inhibition on neointima formation were studied in a balloon injury model in the rat carotid artery. Local application of the proteasome inhibitor MG132 (1 mmol/L) resulted in significant inhibition of intimal hyperplasia, that is, by 74% (Pϭ0.008). This effect was accompanied by decreased proliferation, reduced infiltration of macrophages, and prolonged apoptosis, as determined by immunohistochemical and TUNEL analyses. Functional effects of proteasome inhibition on proliferation, activation of nuclear factor kappa B, and apoptosis were further characterized in rat primary vascular smooth muscle cells. MG132 dose-dependently inhibited vascular smooth muscle cell proliferation with 50% inhibition at 10 mol/L. TNF␣-induced degradation of IB␣ and ␤ was blocked, and activation of nuclear factor kappa B was suppressed in a concentration-dependent manner in bandshift assays. Moreover, proteasome inhibition (1 to 50 mol/L MG132) induced apoptotic cell death up to 80%, as confirmed by DNA/Histone-ELISA and TUNEL-FACS analysis. Specificity of proteasome inhibition was shown by accumulation of multiubiquitinylated proteins and accumulation of specific proteasomal substrates. Conclusions-These proof-of-principle experiments demonstrate that inhibition of the ubiquitin-proteasome system effectively reduces neointima formation in vivo, which corresponds to strong antiproliferative, anti-inflammatory, and proapoptotic effects in vitro and in vivo. Our data suggest the ubiquitin-proteasome system as a new target in the prevention of vascular restenosis.

In patients referred for conventional coronary angiography, multislice CT compares favorably with MRI for noninvasive detection of coronary stenoses.