Matthew Matheson

Myocardial CT Perfusion Imaging and SPECT for the Diagnosis of Coronary Artery Disease: A Head-to-Head Comparison from the CORE320 Multicenter Diagnostic Performance Study

PURPOSE To compare the diagnostic performance of myocardial computed tomographic (CT) perfusion imaging and single photon emission computed tomography (SPECT) perfusion imaging in the diagnosis of anatomically significant coronary artery disease (CAD) as depicted at invasive coronary angiography. MATERIALS AND METHODS This study was approved by the institutional review board. Written informed consent was obtained from all patients. Sixteen centers enrolled 381 patients from November 2009 to July 2011. Patients underwent rest and adenosine stress CT perfusion imaging and rest and either exercise or pharmacologic stress SPECT before and within 60 days of coronary angiography. Images from CT perfusion imaging, SPECT, and coronary angiography were interpreted at blinded, independent core laboratories. The primary diagnostic parameter was the area under the receiver operating characteristic curve (Az). Sensitivity and specificity were calculated with use of prespecified cutoffs. The reference standard was a stenosis of at least 50% at coronary angiography as determined with quantitative methods. RESULTS CAD was diagnosed in 229 of the 381 patients (60%). The per-patient sensitivity and specificity for the diagnosis of CAD (stenosis ≥50%) were 88% (202 of 229 patients) and 55% (83 of 152 patients), respectively, for CT perfusion imaging and 62% (143 of 229 patients) and 67% (102 of 152 patients) for SPECT, with Az values of 0.78 (95% confidence interval: 0.74, 0.82) and 0.69 (95% confidence interval: 0.64, 0.74) (P = .001). The sensitivity of CT perfusion imaging for single- and multivessel CAD was higher than that of SPECT, with sensitivities for left main, three-vessel, two-vessel, and one-vessel disease of 92%, 92%, 89%, and 83%, respectively, for CT perfusion imaging and 75%, 79%, 68%, and 41%, respectively, for SPECT. CONCLUSION The overall performance of myocardial CT perfusion imaging in the diagnosis of anatomic CAD (stenosis ≥50%), as demonstrated with the Az, was higher than that of SPECT and was driven in part by the higher sensitivity for left main and multivessel disease.

Neurocognitive Functioning of Children and Adolescents with Mild-to-Moderate Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Few data exist on the neurocognitive functioning of children with mild-to-moderate chronic kidney disease (CKD). The primary objectives of this paper are (1) to determine the neurocognitive status in this population and (2) to identify sociodemographic and health-status variables associated with neurocognitive functioning. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional study of 368 children, aged 6 to 16 years, from the Chronic Kidney Disease in Children (CKiD) cohort. Median iGFR was 43 ml/min per 1.73 m(2), and the median duration of CKD was 8.0 years. Approximately 26% had underlying glomerular disease. Measures of intelligence, academic achievement, attention regulation, and executive functioning were obtained at study entry. The prevalence of neurocognitive deficits was determined by comparing participant scores on each measure of neurocognitive functioning with normative data. The association between hypothesized predictors of neurocognitive dysfunction was evaluated using multivariate regression analyses. RESULTS Neurocognitive functioning was within the average range for the entire group; however, 21% to 40% of participants scored at least one SD below the mean on measures of intelligence quotient (IQ), academic achievement, attention regulation, or executive functioning. Higher iohexol-based GFR (iGFR) predicted a lesser risk for poor performance on measures of executive function. Participants having elevated proteinuria (i.e., urine protein/creatinine >2) scored lower on verbal IQ, full-scale IQ, and attention variability than those without elevated proteinuria. CONCLUSIONS Whereas most children with mild-to-moderate CKD have no major neurocognitive deficits, a substantial percentage did show neurocognitive dysfunction that places them at risk for poor long-term educational and occupational outcomes.

The impact of short stature on health-related quality of life in children with chronic kidney disease

OBJECTIVES To compare the health-related quality of life (HRQoL) of children with chronic kidney disease (CKD) and short stature (SS) with that of children with CKD and normal height (NH), to evaluate the impact of catch-up growth and growth hormone (GH) use on HRQoL, and to describe the concordance of perceptions of HRQoL between children with SS and NH and their parents. STUDY DESIGN Four hundred eighty-three children and/or parents enrolled in the multicenter Chronic Kidney Disease in Children study who had completed the Pediatric Quality of Life Inventory (Version 4.0) on at least 2 Chronic Kidney Disease in Children study visits composed this substudy population. Participants were dichotomized into NH or SS groups. The demographic characteristics that varied at baseline (sex, glomerular filtration rate, and parent education) were controlled for in the main analysis evaluating the impact of catch-up growth and use of GH on HRQoL. RESULTS Multivariate modeling (controlling for confounding variables) revealed a significant association between both catch-up growth and GH use on parent-proxy reports of child physical functioning (P < .05) and social functioning (P < .05). Older children with CKD (15-17 years old) had significantly higher ratings than their parents on the Pediatric Quality of Life Inventory Physical, Emotional, Social, and School Functioning scales compared with younger children (8-14 years old). CONCLUSION The finding that height gains and GH use are associated with increases in physical and social functioning by parent report provides additional support for interventions to improve height in children with CKD. The importance of evaluating both the parent and child perceptions of HRQoL is supported by our results.

MRI-measured regression of carotid atherosclerosis induced by statins with and without niacin in a randomised controlled trial: the NIA plaque study

Objective To evaluate the benefit of niacin in addition to statin therapy on plaque regression among older individuals with established atherosclerosis. Design Randomised, controlled, double-blind clinical trial. Setting University outpatient center. Patients 145 patients older than 65 years, half of them older than 75 years of age, with established atherosclerosis were enrolled. Interventions Participants received either extended release niacin (1500 mg daily) or placebo in addition to statin therapy to reach their National Cholesterol Education Program-defined low density lipoprotein (LDL) cholesterol target. Main Outcome Measures The primary endpoint was reduction in the wall volume of the internal carotid artery (ICA) measured by MRI. Results After 18 months, high density lipoprotein cholesterol was higher with statins plus niacin compared with statins alone (1.6±0.4 vs 1.4±0.4 mmol/L p<0.001). Both groups had significant decreases in the main outcome measure of ICA wall volume, which regressed at 0.5%/month (SEM 0.2, p=0.004) in the statins plus placebo group and at 0.7%/month in the statins plus niacin group (SEM 0.2, p<0.001). There was no difference in the rate of regression between groups (p=0.49). Conclusions Treatment with statin therapy to presently recommended LDL levels, with or without niacin, resulted in significant atherosclerosis reduction.

Lack of Association Between Epicardial Fat Volume and Extent of Coronary Artery Calcification, Severity of Coronary Artery Disease, or Presence of Myocardial Perfusion Abnormalities in a Diverse, Symptomatic Patient Population Results From the CORE320 Multicenter Study

Background—Epicardial fat may play a role in the pathogenesis of coronary artery disease (CAD). We explored the relationship of epicardial fat volume (EFV) with the presence and severity of CAD or myocardial perfusion abnormalities in a diverse, symptomatic patient population. Methods and Results—Patients (n=380) with known or suspected CAD who underwent 320-detector row computed tomographic angiography, nuclear stress perfusion imaging, and clinically driven invasive coronary angiography for the CORE320 international study were included. EFV was defined as adipose tissue within the pericardial borders as assessed by computed tomography using semiautomatic software. We used linear and logistic regression models to assess the relationship of EFV with coronary calcium score, stenosis severity by quantitative coronary angiography, and myocardial perfusion abnormalities by single photon emission computed tomography (SPECT). Median EFV among patients (median age, 62.6 years) was 102 cm3 (interquartile range: 53). A coronary calcium score of ≥1 was present in 83% of patients. Fifty-nine percent of patients had ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography, and 49% had abnormal myocardial perfusion results by SPECT. There were no significant associations between EFV and coronary artery calcium scanning, presence severity of ≥50% stenosis by quantitative coronary angiography, or abnormal myocardial perfusion by SPECT. Conclusions—In a diverse population of symptomatic patients referred for invasive coronary angiography, we did not find associations of EFV with the presence and severity of CAD or with myocardial perfusion abnormalities. The clinical significance of quantifying EFV remains uncertain but may relate to the pathophysiology of acute coronary events rather than the presence of atherosclerotic disease.

Duration of chronic kidney disease reduces attention and executive function in pediatric patients

Chronic kidney disease (CKD) in childhood is associated with neurocognitive deficits. Affected children show worse performance on tests of intelligence than their unaffected siblings and skew toward the lower end of the normal range. Here we further assessed this association in 340 pediatric patients (ages 6 to 21) with mild-moderate CKD in The Chronic Kidney Disease in Childhood cohort from 48 pediatric centers in North America. Participants underwent a battery of age-appropriate tests including Conner’s Continuous Performance Test-II (CPT-II), Delis- Kaplan Executive Function System Tower task, and the Digit Span Backwards task from the age-appropriate Wechsler Intelligence Scale. Test performance was compared across the range of estimated GFR and duration of CKD with relevant covariates including maternal education, household income, IQ, blood pressure and preterm birth. Among the 340 patients, 35% had poor performance (below the mean by1.5 or more standard deviations) on at least one test of executive function. By univariate nonparametric comparison and multiple logistic regression, longer duration of CKD was associated with increased odds ratio for poor performance on the CPT-II Errors of Commission, a test of attention regulation and inhibitory control. Thus, in a population with mild to moderate CKD, the duration of disease rather than estimated GFR was associated with impaired attention regulation and inhibitory control.

Incremental diagnostic accuracy of computed tomography myocardial perfusion imaging over coronary angiography stratified by pre-test probability of coronary artery disease and severity of coronary artery calcification: The CORE320 study.

BACKGROUND Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis. OBJECTIVES To assess the diagnostic performance of CTA and CTP alone versus combined CTA-CTP stratified by Morises pre-test probability and coronary artery calcium (CAC, Agatston) score. METHODS 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1-399 and ≥400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA≥50% stenosis+corresponding SPECT summed stress score ≥1. RESULTS In both pre-test risk groups with an Agatston score of 1-399, AUCs of CTA-CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1-399, AUC for CTA-CTP (89) was higher than that for CTP (76, p=0.003) alone. In the same group with CAC score ≥400, AUCs were higher for CTA-CTP (97) than that for CTA (88, p=0.030) and CTP (83, p=0.033). In high risk/known CAD patients with CAC 1-399, diagnostic performance for CTA-CTP (77) was superior to CTP (71, p=0.037) alone. In the high risk/known CAD group with CAC score ≥400, AUCs for combined imaging were higher (86) than that for CTA (75, p<0.001) as well as CTP (78, p=0.020). CONCLUSIONS The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score≥400), combined CTA-CTP has better diagnostic accuracy than CTA and CTP alone.

A comparison of the generalized gamma and exponentiated Weibull distributions.

This paper provides a comparison of the three-parameter exponentiated Weibull (EW) and generalized gamma (GG) distributions. The connection between these two different families is that the hazard functions of both have the four standard shapes (increasing, decreasing, bathtub, and arc shaped), and in fact, the shape of the hazard is the same for identical values of the three parameters. For a given EW distribution, we define a matching GG using simulation and also by matching the 5 (th) , 50 (th) , and 95 (th) percentiles. We compare EW and matching GG distributions graphically and using the Kullback-Leibler distance. We find that the survival functions for the EW and matching GG are graphically indistinguishable, and only the hazard functions can sometimes be seen to be slightly different. The Kullback-Leibler distances are very small and decrease with increasing sample size. We conclude that the similarity between the two distributions is striking, and therefore, the EW represents a convenient alternative to the GG with the identical richness of hazard behavior. More importantly, these results suggest that having the four basic hazard shapes may to some extent be an important structural characteristic of any family of distributions.

Comprehensive Assessment of Radiation Dose Estimates for the CORE320 Study

OBJECTIVE. The purpose of this study was to comprehensively study estimated radiation doses for subjects included in the main analysis of the Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography (CORE320) study ( ClinicalTrials.gov identifier NCT00934037), a clinical trial comparing combined CT angiography (CTA) and perfusion CT with the reference standard catheter angiography plus myocardial perfusion SPECT. SUBJECTS AND METHODS. Prospectively acquired data on 381 CORE320 subjects were analyzed in four groups of testing related to radiation exposure. Radiation dose estimates were compared between modalities for combined CTA and perfusion CT with respect to covariates known to influence radiation exposure and for the main clinical outcomes defined by the trial. The final analysis assessed variations in radiation dose with respect to several factors inherent to the trial. RESULTS. The mean radiation dose estimate for the combined CTA and perfusion CT protocol (8.63 mSv) was significantly (p < 0.0001 for both) less than the average dose delivered from SPECT (10.48 mSv) and the average dose from diagnostic catheter angiography (11.63 mSv). There was no significant difference in estimated CTA-perfusion CT radiation dose for subjects who had false-positive or false-negative results in the CORE320 main analyses in a comparison with subjects for whom the CTA-perfusion CT findings were in accordance with the reference standard SPECT plus catheter angiographic findings. CONCLUSION. Radiation dose estimates from CORE320 support clinical implementation of a combined CT protocol for assessing coronary anatomy and myocardial perfusion.

Neurocognition in children with autosomal recessive polycystic kidney disease in the CKiD cohort study

BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is an inherited disorder characterized by enlarged, cystic kidneys with progressive chronic kidney disease (CKD), systemic hypertension, and congenital hepatic fibrosis. Children with ARPKD can have early onset CKD and severe hypertension, both of which are known to have adverse neurocognitive effects. The objectives of this study were (1) to determine whether ARPKD patients have greater neurocognitive deficits compared to that of children with other causes of CKD, and (2) to examine the relative prevalence of hypertension in ARPKD, a known risk factor for neurocognitive dysfunction.MethodsWe performed a cross-sectional, control-matched analysis of 22 ARPKD patients with mild-to-moderate CKD in the Chronic Kidney Disease in Children (CKiD) cohort study, compared with a control group of 44 children with other causes of CKD, matched based on glomerular filtration rate, age at study entry, and age at diagnosis.ResultsChildren with ARPKD in this cohort had neurocognitive functioning comparable to children with other causes of CKD in domains of intellectual functioning, academic achievement, attention regulation, executive functioning, and behavior. Blood pressure parameters were similar between the two groups; however, ARPKD patients required a significantly greater number of antihypertensive medications to achieve similar BP levels.ConclusionsARPKD patients are potentially at risk for neurocognitive dysfunction due to early onset CKD and more severe hypertension. However, this study of children with mild-to-moderate CKD in the CKiD cohort did not demonstrate increased risk in children with ARPKD compared to children with other causes of CKD. Further studies are needed to determine if these findings are applicable to children with more severe manifestations of ARPKD.