Matthijs F.L. Meijs

Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study.

OBJECTIVES This study sought to determine the diagnostic accuracy of 64-slice computed tomographic coronary angiography (CTCA) to detect or rule out significant coronary artery disease (CAD). BACKGROUND CTCA is emerging as a noninvasive technique to detect coronary atherosclerosis. METHODS We conducted a prospective, multicenter, multivendor study involving 360 symptomatic patients with acute and stable anginal syndromes who were between 50 and 70 years of age and were referred for diagnostic conventional coronary angiography (CCA) from September 2004 through June 2006. All patients underwent a nonenhanced calcium scan and a CTCA, which was compared with CCA. No patients or segments were excluded because of impaired image quality attributable to either coronary motion or calcifications. Patient-, vessel-, and segment-based sensitivities and specificities were calculated to detect or rule out significant CAD, defined as >or=50% lumen diameter reduction. RESULTS The prevalence among patients of having at least 1 significant stenosis was 68%. In a patient-based analysis, the sensitivity for detecting patients with significant CAD was 99% (95% confidence interval [CI]: 98% to 100%), specificity was 64% (95% CI: 55% to 73%), positive predictive value was 86% (95% CI: 82% to 90%), and negative predictive value was 97% (95% CI: 94% to 100%). In a segment-based analysis, the sensitivity was 88% (95% CI: 85% to 91%), specificity was 90% (95% CI: 89% to 92%), positive predictive value was 47% (95% CI: 44% to 51%), and negative predictive value was 99% (95% CI: 98% to 99%). CONCLUSIONS Among patients in whom a decision had already been made to obtain CCA, 64-slice CTCA was reliable for ruling out significant CAD in patients with stable and unstable anginal syndromes. A positive 64-slice CTCA scan often overestimates the severity of atherosclerotic obstructions and requires further testing to guide patient management.

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension

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.

Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography.

Fat surrounding coronary arteries might aggravate coronary artery disease (CAD). We investigated the relation between epicardial adipose tissue (EAT) and pericoronary fat and coronary atherosclerosis and coronary artery calcium (CAC) in patients with suspected CAD and whether this relation is modified by total body weight. This was a cross-sectional study of 128 patients with angina pectoris (61 +/- 6 years of age) undergoing coronary angiography. EAT volume and pericoronary fat thickness were measured with cardiac computed tomography. Severity of coronary atherosclerosis was assessed by the number of stenotic (> or =50%) coronary vessels; extent of CAC was determined by the Agatston score. Patients were stratified for median total body weight (body mass index [BMI] 27 kg/m(2)). Overall, EAT and pericoronary fat were not associated with severity of coronary atherosclerosis and extent of CAC. In patients with low BMI, those with multivessel disease had increased EAT volume (100 vs 67 cm(3), p = 0.04) and pericoronary fat thickness (9.8 vs 8.4 mm, p = 0.06) compared with those without CAD. Also, patients with severe CAC had increased EAT volume (108.0 vs 69 cm(3), p = 0.02) and pericoronary fat thickness (10.0 vs 8.2 mm, p value = 0.01) compared with those with minimal/absent CAC. In conclusion, EAT and pericoronary fat were not associated with severity of coronary atherosclerosis and CAC in patients with suspected CAD. However, in those with low BMI, increased EAT and pericoronary fat were related to more severe coronary atherosclerosis and CAC. Fat surrounding coronary arteries may be involved in the process of coronary atherosclerosis, although this is different for patients with low and high BMIs.

Prediction model to estimate presence of coronary artery disease: Retrospective pooled analysis of existing cohorts

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 measures Obstructive 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. Results We 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.

CT coronary angiography in patients suspected of having coronary artery disease: decision making from various perspectives in the face of uncertainty.

PURPOSE To determine the cost-effectiveness of computed tomographic (CT) coronary angiography as a triage test, performed prior to conventional coronary angiography, by using a Markov model. MATERIALS AND METHODS A Markov model was used to analyze the cost-effectiveness of CT coronary angiography performed as a triage test prior to conventional coronary angiography from the perspective of the patient, physician, hospital, health care system, and society by using recommendations from the United Kingdom, the United States, and the Netherlands for cost-effectiveness analyses. For CT coronary angiography, a range of sensitivities (79%-100%) and specificities (63%-94%) were used to help diagnose significant coronary artery disease (CAD). Optimization criteria (ie, outcomes considered) were: revised posttest probability of CAD, life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analysis was performed. RESULTS For a prior probability of CAD of less than 40%, the probability of CAD after CT coronary angiography with negative results was less than 1%. The Markov model calculations from the patient/physician perspective suggest that CT coronary angiography maximizes life-years respectively in 60-year-old men and women at a prior probability of less than 38% and 24% and maximizes QALYs at a prior probability of less than 17% and 11%. From the hospital/health care perspective, CT coronary angiography helps reduce health care and direct nonhealth care-related costs (according to UK/U.S. recommendations), regardless of prior probability, and lowers all costs, including production losses (Netherlands recommendations) at a prior probability of less than 87%-92%. Analysis performed from a societal perspective by using a willingness-to-pay threshold level of euro 80,000/QALY suggests that CT coronary angiography is cost-effective when the prior probability is lower than 44% and 37% in men and women, respectively. Sensitivity analyses showed that results changed across the reported range of sensitivity of CT coronary angiography. CONCLUSION The optimal diagnostic work-up depends on the optimization criterion, prior probability of CAD, and the diagnostic performance of CT coronary angiography.

Variability of coronary calcium scores throughout the cardiac cycle: implications for the appropriate use of electrocardiogram-dose modulation with retrospectively gated computed tomography.

Objective:To study how much the calcium scores at various phases throughout the cardiac cycle deviate from the score in the most motionless phase during retrospectively electrocardiogram (ECG)-gated multidetector row computed tomography (MDCT) of the heart and to evaluate how to optimize ECG-based tube current modulation so that errors in calcium scoring can be minimized while dose savings can be maximized. Materials and Methods:In 73 subjects with known or suspected coronary artery disease we performed retrospectively ECG-gated 64-detector row computed tomography for calcium scoring. Four subjects were excluded after scanning because of breathing artifacts or lack of coronary calcification. The scans of 69 subjects (46 men, mean age 62 ± 6 years) were used for further analysis. Heart rate during the scan was recorded. In each patient, calcium scoring [Agatston score (AS), mass score (MS), and volume score, (VS)] was performed on 10 data sets reconstructed at 10%-intervals throughout the cardiac cycle. The most motionless phase was subjectively determined and used as the reference phase. For the score in each phase, deviation from the score in the reference phase was determined. An ECG-simulator was used to determine the amount of dose saving while scanning with dose modulation and applying diagnostic dose during 1 or several phases. Results:Mean heart rate was 63 (±13) beats per minute (bpm). In 51% of patients the reference phase was the 70% phase. Using the calcium score in the 70% phase (mid-diastole) instead of the reference at heart rates below 70 bpm would have induced a median score deviation of 0% [interquartile range: 0%–6% (AS, MS, and VS)] and using the calcium score in the 40% phase (end-systole) at heart rates ≥70 bpm would also have induced a median score deviation of 0% [interquartile range: 0%–7% (AS), 0%–5% (MS), and 0%–3% (VS)]. Errors in calcium scores of more than 10% occur in around 10% of subjects for all 3 scoring algorithms. Dose savings increased with lower heart rates and shorter application of diagnostic dose. Conclusions:The optimum phases for dose modulation are 70% (mid-diastole) at heart rates below 70 bpm and 40% (end-systole) at heart rates above 70 bpm. Under these conditions dose saving is maximum and a median error of 0% is found for the various calcium scoring techniques with score errors of more than 10% in around 10% of subjects.

Mice lacking L1 have reduced CGRP fibre in-growth into spinal transection lesions

Repair strategies for spinal cord injury often focus on promoting regeneration of injured axons and stimulating subsequent functional recovery. Although many of these strategies have proven their merits, less is known about potential unwanted side-effects, such as sprouting of nociceptive CGRP immunoreactive axons, which may bring about pain-related behavior. Sprouting of CGRP axons into lesion sites spontaneously occurs after spinal cord injury (SCI). Using L1-deficient mice we show a reduction of such CGRP growth response. This reduction was specific for CGRP axons since the overall neurofilament positive fibre in-growth into the spinal lesion site was not affected. Our results may have important implications on the development and assessment of repair strategies that should not only stimulate functional recovery, but also prevent the development of pain or autonomic dysreflexia.

Relation Between Abdominal Obesity, Insulin Resistance and Left Ventricular Hypertrophy Diagnosed by Electrocardiogram and Magnetic Resonance Imaging in Hypertensive Patients

Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass (LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted β = -0.02, 95% confidence interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (β = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.

Comparison of Frequency of Calcified Versus Non-Calcified Coronary Lesions by Computed Tomographic Angiography in Patients With Stable Versus Unstable Angina Pectoris

Computed tomographic coronary angiography (CTCA) can noninvasively identify calcified and noncalcified coronary plaques. The aim of this study was to compare the phenotypes of all plaques and of culprit plaques between patients with unstable angina pectoris (UAP) and those with stable angina pectoris (SAP), because plaque characteristics may differ between these patients. In 110 patients with UAP and 189 with SAP from a multicenter study comparing 64-slice CTCA with conventional coronary angiography, the number and phenotypes (noncalcified, mixed, and calcified) of coronary plaques were compared. In a subanalysis in 50 patients with UAP and 64 with SAP, culprit plaque characteristics, including culprit plaque cross-sectional area relative to total vessel cross-sectional area, culprit plaque length, remodeling index, and spotty calcification, were determined. Odds ratios for the presence of UAP, adjusted for clinical variables and the total number of plaques, were calculated for plaque characteristics on CTCA. Although the number of plaques was similar for patients with UAP and those with SAP, plaques in patients with UAP were more frequently noncalcified than in patients with SAP. The odds ratio for UAP was 1.3 (95% confidence interval [CI] 1.1 to 1.5) per noncalcified plaque. In the culprit plaque subanalysis, odds ratios for UAP were 0.99 (95% CI 0.96 to 1.01) per millimeter culprit plaque length, 2.7 (95% CI 1.2 to 6.4) for noncalcified culprit plaque, and 1.06 (95% CI 0.99 to 1.13) per percentage relative culprit plaque cross-sectional area. No significant relation was found between remodeling index or spotty calcification and UAP. In conclusion, noncalcified plaques and large noncalcified culprit plaques are more frequently found in patients with UAP than in those with SAP.

Relationship between myocardial bridges and reduced coronary atherosclerosis in patients with angina pectoris.

BACKGROUND A myocardial bridge (MB) is a band of myocardium covering a coronary artery segment, typically located in the left anterior descending coronary artery (LAD). Bridged segments of the coronary artery are isolated from the influence of perivascular adipose tissue. The aims of this study were to investigate the relationship between MBs and atherosclerosis in bridged LAD segments and to evaluate whether perivascular adipose tissue is involved in this relationship. METHODS MBs were identified in the coronary arteries of patients referred for diagnostic cardiac CT. The calcium score of MBs of the LAD or, in patients without LAD-MBs, of a corresponding LAD segment at the same distance from its origin and over the same length was measured. RESULTS Of 128 patients, 56 (44%) had in total 73 MBs. The mean MB length was 22 ± 14 mm and the median MB thickness was 0.8mm (interquartile range 0.3-2.1mm). MBs in the LAD were present in 40 patients (31%). The calcium score was 0 in 95% of the LAD segments with MBs compared with 52% of the corresponding LAD segments without MBs. The association between LAD-MBs and calcium score (OR 0.06, 95% CI 0.01-0.25) was not influenced by age and gender, but was attenuated by local perivascular adipose tissue thickness (OR 0.35, 95% CI 0.04-2.70). CONCLUSIONS Coronary artery segments covered with an MB have a lower calcium score than segments without an MB. The association between MBs and calcium scores was influenced by local perivascular adipose tissue thickness.