37 research outputs found

    Computed Tomography of the Coronary Arteries

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    Non-invasive coronary computed tomography angiography (CCTA) has become an important tool for visualisation of coronary arteries since the introduction of 64-channel detector CCTA in 2004. It has been proved to be especially beneficial for ruling out coronary artery disease (CAD) in selected patient populations, due to the high negative predictive value (NPV). The aim of this thesis was to study some aspects of the introduction, establishment and development of a new method, retrospectively ECG-gated CCTA with 64-channel detector, to evaluate coronary arteries. In study I the diagnostic capacity and limitation of CCTA was compared to that of invasive coronary angiography (ICA) in a newly established CCTA team. CCTA had a very high NPV but the number of non-diagnostic scans was also high. The main limitations were motion artifacts and vessel calcifications, while short experience in reading CCTA did not affect image interpretation. Study II described the learning-curve effect of the interpretation of 100 CCTA and also compared the diagnostic accuracy of both radiologists and radiographers, after a common introduction. The review time for novices was approximately halved during the first 100 cases, with maintained diagnostic accuracy. There was a learning-curve effect in positive predictive value (PPV) for radiologists, but not for the radiographers. However, the diagnostic accuracy of dedicated radiographers indicated that they might be considered as part of the evaluation team. Study III compared the radiation exposure in retrospectively ECG-gated CCTA and ICA in the same population. Both mean estimated effective dose (ED) and organ doses (skin, breast, lung and oesophagus) were higher in CCTA when compared to ICA. The relatively high radiation dose to breast indicates that bismuth shielding should be used in women when performing CCTA. When using the updated tissue weighting factors provided in ICRP 103 the calculated ED from CCTA were significantly higher than those obtained using outdated ICRP 60. In study IV the image quality and radiation doses were compared when decreasing X-ray tube peak kilovoltage (kVp) from 120 to 100 kVp in patients undergoing CCTA. By reduction of tube voltage the radiation dose was almost halved while the diagnostic image quality was kept at a clinically acceptable level. In conclusion, CCTA is increasingly available throughout the world as an alternative to gold standard ICA, especially due to the excellent capability to rule out CAD. Still, retrospectively ECG-gated 64-channel detector CCTA has limitations such as motion artifacts and vessel calcifications. Another limitation is the high radiation doses required for CCTA compared to ICA. By lowering the kVp from traditionally 120 kVp to 100 kVp the radiation dose is halved while retaining diagnostic accuracy. There is a learning curve effect (regarded PPV and review time) of the interpretation of CCTA. However, more than 100 reviewed CCTA cases are necessary to reach a diagnostic accuracy that is acceptable

    Preface and Acknowledgement

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    Background. The choice of treatment strategy for coronary artery disease is often based on: 1) anatomical information on stenosis locations, and 2) functional information on their haemodynamic relevance, e.g. myocardial deformation or perfusion. Inspecting a single fused image containing both anatomical and functional information, as opposed to viewing separate images side-by-side, facilitates this treatment choice. The aim of this study is to develop a novel cardiac fusion imaging technique to combine 3D+time echocardiography (3DE) (functional information) with coronary computed tomography angiography (CCTA) (anatomical information). Method. 3DE and CCTA data sets were obtained from 20 patients with suspected coronary artery disease. The coronary artery tree was segmented from the CCTA images. A semi-automatic fusion algorithm was developed to perform the following steps: The left ventricle (LV) 3D surfaces were segmented in the CCTA image and 3DE images and used to align the two data sets. The moving 3DE LV was then visualized along with the CCTA coronary arteries. Myocardial strain was estimated and visualized on the LV surface. Results. Preliminary fusion results from images of one patient have been obtained. The figure shows the CCTA coronary artery tree aligned with a) 3DE LV endocardium in end-systole, b) 3DE LV endocardium in end-diastole, and c) 3DE LV with colour-coded instantaneous longitudinal strain. Discussion. Preliminary results show that fusion of CCTA and 3DE images is feasible. However, the algorithm needs to be further developed to increase automation and include other functional parameters, such as myocardial perfusion. Moreover, a validation study to assess algorithm performance and diagnostic value in multiple patients will be performed. QC 20150122</p

    CDKN2A/p16INK4a expression is associated with vascular progeria in chronic kidney disease

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    Patients with chronic kidney disease (CKD) display a progeric vascular phenotype linked to apoptosis, cellular senescence and osteogenic transformation. This has proven intractable to modelling appropriately in model organisms. We have therefore investigated this directly in man, using for the first time validated cellular biomarkers of ageing (CDKN2A/p16INK4a, SA-β-Gal) in arterial biopsies from 61 CKD patients undergoing living donor renal transplantation. We demonstrate that in the uremic milieu, increased arterial expression of CDKN2A/p16INK4a associated with vascular progeria in CKD, independently of chronological age. The arterial expression of CDKN2A/p16INK4a was significantly higher in patients with coronary calcification (p=0.01) and associated cardiovascular disease (CVD) (p=0.004). The correlation between CDKN2A/p16INK4a and media calcification was statistically significant (p=0.0003) after correction for chronological age. We further employed correlate expression of matrix Gla protein (MGP) and runt-related transcription factor 2 (RUNX2) as additional pathognomonic markers. Higher expression of CDKN2A/p16INK4a, RUNX2 and MGP were observed in arteries with severe media calcification. The number of p16INK4a and SA-β-Gal positive cells was higher in biopsies with severe media calcification. A strong inverse correlation was observed between CDKN2A/p16INK4a expression and carboxylated osteocalcin levels. Thus, impaired vitamin K mediated carboxylation may contribute to premature vascular senescence

    Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5

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    Background: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30– 70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. Methods: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography. Results: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman’s rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. Conclusions: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.Baxter HealthcareKarolinska Institutet Diabetes Theme CenterHeart and Lung FoundationNjurfondenWestmans FoundationEuropean Union’s Horizon 2020 research and innovation program, Marie Sklodowska-Curie (grant agreement No 722609)Publishe

    CDKN2A/p16INK4a expression is associated with vascular progeria in chronic kidney disease

    Get PDF
    Patients with chronic kidney disease (CKD) display a progeric vascular phenotype linked to apoptosis, cellular senescence and osteogenic transformation. This has proven intractable to modelling appropriately in model organisms. We have therefore investigated this directly in man, using for the first time validated cellular biomarkers of ageing (CDKN2A/p16INK4a, SA-β-Gal) in arterial biopsies from 61 CKD patients undergoing living donor renal transplantation. We demonstrate that in the uremic milieu, increased arterial expression of CDKN2A/p16INK4a associated with vascular progeria in CKD, independently of chronological age. The arterial expression of CDKN2A/p16INK4a was significantly higher in patients with coronary calcification (p=0.01) and associated cardiovascular disease (CVD) (p=0.004). The correlation between CDKN2A/p16INK4a and media calcification was statistically significant (p=0.0003) after correction for chronological age. We further employed correlate expression of matrix Gla protein (MGP) and runt-related transcription factor 2 (RUNX2) as additional pathognomonic markers. Higher expression of CDKN2A/p16INK4a, RUNX2 and MGP were observed in arteries with severe media calcification. The number of p16INK4a and SA-β-Gal positive cells was higher in biopsies with severe media calcification. A strong inverse correlation was observed between CDKN2A/p16INK4a expression and carboxylated osteocalcin levels. Thus, impaired vitamin K mediated carboxylation may contribute to premature vascular senescence

    Assessment of left ventricular volumes using simplified 3-D echocardiography and computed tomography – a phantom and clinical study

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    <p>Abstract</p> <p>Objectives</p> <p>To compare the accuracy of simplified 3-dimensional (3-D) echocardiography vs. multi-slice computed tomography (MSCT) software for the quantification of left ventricular (LV) volumes.</p> <p>Design</p> <p>Three-D echocardiography (3-planes approach) and MSCT-CardIQ software were calibrated by measuring known volumes of 10 phantoms designed to closely mimic blood-endocardium interface. Subsequently, LV volumes were measured with both the methods in 9 patients referred routinely for coronary angiography and the agreement between the measurements was evaluated.</p> <p>Results</p> <p>Simplified 3D-echocardiography provided higher degree of agreement between the measured and true phantom volumes (mean difference 0 ± 1 ml, variation range +4 to -4 ml) than MSCT software (mean difference 6 ± 5 ml; variation range +22 to -10 ml). The agreement between LV measurements in the patients was considerably poorer, with significantly larger volumes produced by MSCT (mean difference -23 ± 40 ml, variation between +93 and -138 ml).</p> <p>Conclusion</p> <p>Simplified 3-D echocardiography provides more accurate assessment of phantom volumes than MSCT-CardIQ software. The discrepancy between the results of LV measurements with the two methods is even greater and does not warrant their interchangeable diagnostic use.</p

    Coronary artery calcification and aortic valve calcification in patients with kidney failure : a sex-disaggregated study

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    Background: Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF. Methods: KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables. Results: Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010). Conclusions: In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF
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