Joachim E. Wildberger

Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study

BACKGROUND Vascular calcification is the most prominent underlying pathological finding in patients with uraemia, and is a predictor of mortality in this population. Fetuin-A (alpha2-Heremans Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response. We aimed to investigate the hypothesis that AHSG deficiency is directly related to uraemic vascular calcification. METHODS We did a cross-sectional study in 312 stable patients on haemodialysis to analyse the inter-relation of AHSG and C-reactive protein (CRP) and their predictive effect on all-cause and cardiovascular mortality, over a period of 32 months. Subsequently, we tested the capacity of serum to inhibit CaxPO4 precipitation in patients on long-term dialysis (n=17) with apparent soft-tissue calcifications, and in those on short-term dialysis (n=8) without evidence of calcifications and cardiovascular disease. FINDINGS AHSG concentrations in serum were significantly lower in patients on haemodialysis (mean 0.66 g/L [SD 0.28]) than in healthy controls (0.72 [0.19]). Low concentrations of the glycoprotein were associated with raised amounts of CRP and with enhanced cardiovascular (p=0.031) and all-cause mortality (p=0.0013). Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit CaxPO4 precipitation (mean IC50: 9.0 microL serum [SD 3.1] vs 7.5 [0.8] in short-term patients and 6.4 [2.6] in controls). Reconstitution of sera with purified AHSG returned this impairment to normal. Interpretation AHSG deficiency is associated with inflammation and links vascular calcification to mortality in patients on dialysis. Activated acute-phase response and AHSG deficiency might account for accelerated atherosclerosis in uraemia.

Diagnostic Performance of Noninvasive Myocardial Perfusion Imaging Using Single-Photon Emission Computed Tomography, Cardiac Magnetic Resonance, and Positron Emission Tomography Imaging for the Detection of Obstructive Coronary Artery Disease: A Meta-Analysis

OBJECTIVES This study aimed to determine the diagnostic accuracy of the 3 most commonly used noninvasive myocardial perfusion imaging modalities, single-photon emission computed tomography (SPECT), cardiac magnetic resonance (CMR), and positron emission tomography (PET) perfusion imaging for the diagnosis of obstructive coronary artery disease (CAD). Additionally, the effect of test and study characteristics was explored. BACKGROUND Accurate detection of obstructive CAD is important for effective therapy. Noninvasive myocardial perfusion imaging is increasingly being applied to gauge the severity of CAD. METHODS Studies published between 1990 and 2010 identified by PubMed search and citation tracking were examined. A study was included if a perfusion imaging modality was used as a diagnostic test for the detection of obstructive CAD and coronary angiography as the reference standard (≥50% diameter stenosis). RESULTS Of the 3,635 citations, 166 articles (n = 17,901) met the inclusion criteria: 114 SPECT, 37 CMR, and 15 PET articles. There were not enough publications on other perfusion techniques such as perfusion echocardiography and computed tomography to include these modalities into the study. The patient-based analysis per imaging modality demonstrated a pooled sensitivity of 88% (95% confidence interval [CI]: 88% to 89%), 89% (95% CI: 88% to 91%), and 84% (95% CI: 81% to 87%) for SPECT, CMR, and PET, respectively; with a pooled specificity of 61% (95% CI: 59% to 62%), 76% (95% CI: 73% to 78%), and 81% (95% CI: 74% to 87%). This resulted in a pooled diagnostic odds ratio (DOR) of 15.31 (95% CI: 12.66 to 18.52; I(2) 63.6%), 26.42 (95% CI: 17.69 to 39.47; I(2) 58.3%), and 36.47 (95% CI: 21.48 to 61.92; I(2) 0%). Most of the evaluated test and study characteristics did not affect the ranking of diagnostic performances. CONCLUSIONS SPECT, CMR, and PET all yielded a high sensitivity, while a broad range of specificity was observed. SPECT is widely available and most extensively validated; PET achieved the highest diagnostic performance; CMR may provide an alternative without ionizing radiation and a similar diagnostic accuracy as PET. We suggest that referring physicians consider these findings in the context of local expertise and infrastructure.

Coronary artery stents in multislice computed tomography: in vitro artifact evaluation.

Rationale and ObjectiveThe aim of this study was to systematically compare the ability to assess the coronary artery lumen in the presence of coronary artery stents in multislice spiral CT (MSCT). MethodsTen different coronary artery stents were examined with 4- and 16-detector row MSCT scanners. For image reconstruction, a standard and a dedicated convolution kernel for coronary artery stent visualization were used. Images were analyzed regarding lumen visibility, intraluminal attenuation, and artifacts outside the stent lumen. Results were compared using repeated-measure analysis of variance. ResultsDepending on stent type, scanner hardware, and convolution kernel, artificial lumen narrowing ranged from 20% to 100%. The convolution kernel had the most significant influence on the visibility of the stent lumen. Artificial lumen narrowing and intraluminal attenuation changes decreased significantly using the dedicated convolution kernel. In general, most severe artifacts were caused by gold or gold-coated stents. ConclusionsIndependent of the scanner hardware or dedicated convolution kernels, routine evaluation of most coronary artery stents is not yet feasible using MSCT.

The Extent of Coronary Atherosclerosis Is Associated With Increasing Circulating Levels of High Sensitive Cardiac Troponin T

Objective—This study explored the relationship between coronary atherosclerotic plaque burden and quantifiable circulating levels of troponin measured with a recently introduced high sensitive cardiac troponin T (hs-cTnT) assay. Methods and Results—Cardiac patients suspected of having coronary artery disease (CAD) but without acute coronary syndrome were studied. Cardiac troponin T levels were assessed using the fifth-generation hs-cTnT assay. All patients (n=615) underwent cardiac computed tomographic angiography (CCTA). On the basis of CCTA, patients were classified as having no CAD or mild (<50% lesion), moderate (50% to 70% lesion), severe (>70% lesion), or multivessel CAD (multiple >70% lesions). As a comparison, high-sensitivity C-reactive protein levels were measured. Progressively increasing hs-cTnT levels were found in patients with mild (median, 4.5 ng/L), moderate (median, 5.5 ng/L), severe (median, 5.7 ng/L), and multivessel (median, 8.6 ng/L) CAD compared with patients without CAD (median, 3.7 ng/L) (all P<0.01). For high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide, no such relationship was observed. In patients without CAD, 11% showed hs-cTnT levels in the highest quartile, compared with 62% in the multivessel disease group (P<0.05). Multivariance analysis identified hs-cTnT as an independent risk factor for the presence of CAD. Conclusion—In patients without acute coronary syndrome, even mild CAD is associated with quantifiable circulating levels of hs-cTnT.

Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients

AIMS Vitamin K antagonists (VKA) are currently the most frequently used drug to prevent ischaemic stroke in atrial fibrillation (AF) patients. However, VKA use has been associated with increased vascular calcification. The aim of this study was to investigate the contribution of VKA use to coronary artery calcification in low-risk AF patients. METHODS AND RESULTS A prospective coronary calcium scan was performed in 157 AF patients without significant cardiovascular disease (108 males; mean age 57 ± 9 years). A total of 71 (45%) patients were chronic VKA users. The duration of VKA treatment varied between 6 and 143 months (mean 46 months). No significant differences in clinical characteristics were found between patients on VKA treatment and non-anticoagulated patients. However, median coronary artery calcium scores differed significantly between patients without and patients with VKA treatment [0, inter-quartile range (IQR) 0-40, vs. 29, IQR 0-184; P = 0.001]. Mean coronary calcium scores increased with the duration of VKA use (no VKA: 53 ± 115, 6-60 months on VKA: 90 ± 167, and >60 months on VKA: 236 ± 278; P < 0.001). Multivariable logistic regression analysis revealed that age and VKA treatment were significantly related to increased coronary calcium score. CONCLUSION Patients using VKA show increased levels of coronary calcification. Age and VKA treatment were independently related to increased coronary calcium score.

Low tube voltage improves computed tomography imaging of delayed myocardial contrast enhancement in an experimental acute myocardial infarction model.

Objective:We sought to evaluate the influence of tube voltage on the visualization of acute myocardial infarction (MI) in cardiac multislice spiral computed tomography (MSCT). Materials and Methods:Acute MI was induced in 12 domestic pigs by a 45-minute balloon occlusion of the left anterior descending artery. Delayed enhancement magnetic resonance imaging was performed 15 minutes after the injection of 0.2 mmol/kg Gd-DTPA. On the same day, retrospectively ECG-gated MSCT was performed at 120, 100, and 80 kV (16 × 0.75mm, 550mAseff.) 15 minutes after the injection of 140 mL of iopromide (1 g/iodine/kg). The pigs were killed and the hearts were excised and stained with 2,3,5-triphenyltetrazolium chloride. The area of acute MI, contrast-to-noise ratio (CNR), and percent signal difference were compared among the different imaging techniques by applying Bland-Altman plots and 2-way analysis of variance. Results:On MSCT at 120, 100, and 80 kV, the respective mean acute MI sizes were 18.4 ± 11.4%, 19.3 ± 11.5%, and 20.5 ± 11.6%. The mean MI sizes were 20.8 ± 12.2% and 20.1 ± 12.4% on magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. Analysis of variance did not show any statistically significant differences between the different techniques with respect to the size of acute MI (P = 0.9880). Comparing the different kV settings on MSCT, the highest percent signal difference (74.7 ± 12.1%) and the highest CNR (6.7 ± 1.8) between infarcted and healthy remote myocardium were achieved at 80 kV. Conclusions:When compared with routine scan protocols, low tube voltage MSCT allows for the assessment of the MI size with an improved CNR and contrast resolution. This technique appears to be advantageous for assessing myocardial viability from contrast enhanced late-phase MSCT.

Individually adapted examination protocols for reduction of radiation exposure in chest CT.

Wildberger JE, Mahnken AH, Schmitz-Rode T, et al. Individually adapted examination protocols for reduction of radiation exposure in chest CT. Invest Radiol 2001;36:604–611. rationale and objectives. To develop a simple directive for the reduction of radiation exposure without loss of diagnostic information in routine chest CT examinations. methods.Two hundred fifty adult patients (164 male, 86 female) were entered into a prospective trial. All examinations were performed with a multislice CT technique (Somatom Volume Zoom, Siemens). Four groups of 50 patients each were scanned with patient-related specific parameters: individual mA-s values were derived from the estimated body weight: kilograms + 10, ± 0, − 10, and − 20 mAs. The results were compared with those of 50 patients who were examined by a standard chest protocol by using the parameters 120 mAs and 140 kV. All other parameters including the tube voltage were kept constant. Subjective image quality was rated on a three-point scale: 1 = excellent, 2 = fair, 3 = nondiagnostic. In addition, objective criteria based on signal-to-noise measurements were assessed by using a region-of-interest methodology. results.Image quality was sufficient in all cases. Mean subjective gradings of image quality, based on soft-tissue window settings, were 1.1 for the 120-mAs protocol, 1.1 for the (body weight [kg] + 10) mAs protocol, 1.1 for the (body weight [kg] ± 0) mAs protocol, 1.3 for the (body weight [kg] − 10) mAs protocol, and 1.2 for the (body weight [kg] − 20) mAs protocol. Objective criteria based on noise measurements showed mean ± standard deviation values of 5.7 ± 0.8 Hounsfield units (HU) for the 120-mAs protocol. For the reduced-dose protocols, values were calculated as 7.6 ± 1.2 HU (group + 10), 7.9 ± 1.3 HU (group ± 0), 8.7 ± 1.2 HU (group − 10), and finally 9.1 ± 1.3 HU (group − 20). The best correlation for an entire subgroup was achieved with the − 10 protocol (body weight [kg] − 10) mAs, with nearly constant noise related to body weight in all patients. conclusions.By deriving mAs values from body weight estimation, an individually adapted protocol for chest CT can be recommended and easily employed in a clinical setting. With an adaptation of the tube current–time product based on the estimated body weight of the patient − 10 (body weight [kg] − 10 mAs), a well-balanced examination without significant loss of information, even in soft-tissue window settings, can be performed with this particular scanner. For this adapted mAs protocol, a mean reduction of radiation exposure of 45% was achievable, compared with the standard protocol. A maximum decrease per case down to 31 mAs was obtained, without relevant loss of image quality. Therefore, for other types of CT scanners, analogous protocols may be adapted.

Radiomics: the bridge between medical imaging and personalized medicine

Radiomics, the high-throughput mining of quantitative image features from standard-of-care medical imaging that enables data to be extracted and applied within clinical-decision support systems to improve diagnostic, prognostic, and predictive accuracy, is gaining importance in cancer research. Radiomic analysis exploits sophisticated image analysis tools and the rapid development and validation of medical imaging data that uses image-based signatures for precision diagnosis and treatment, providing a powerful tool in modern medicine. Herein, we describe the process of radiomics, its pitfalls, challenges, opportunities, and its capacity to improve clinical decision making, emphasizing the utility for patients with cancer. Currently, the field of radiomics lacks standardized evaluation of both the scientific integrity and the clinical relevance of the numerous published radiomics investigations resulting from the rapid growth of this area. Rigorous evaluation criteria and reporting guidelines need to be established in order for radiomics to mature as a discipline. Herein, we provide guidance for investigations to meet this urgent need in the field of radiomics.

Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial

BACKGROUND Intravenous saline is recommended in clinical practice guidelines as the cornerstone for preventing contrast-induced nephropathy in patients with compromised renal function. However, clinical-effectiveness and cost-effectiveness of this prophylactic hydration treatment in protecting renal function has not been adequately studied in the population targeted by the guidelines, against a group receiving no prophylaxis. This was the aim of the AMACING trial. METHODS AMACING is a prospective, randomised, phase 3, parallel-group, open-label, non-inferiority trial of patients at risk of contrast-induced nephropathy according to current guidelines. High-risk patients (with an estimated glomerular filtration rate [eGFR] of 30-59 mL per min/1·73 m2) aged 18 years and older, undergoing an elective procedure requiring iodinated contrast material administration at Maastricht University Medical Centre, the Netherlands, were randomly assigned (1:1) to receive intravenous 0·9% NaCl or no prophylaxis. We excluded patients with eGFR lower than 30 mL per min/1·73 m2, previous dialysis, or no referral for intravenous hydration. Randomisation was stratified by predefined risk factors. The primary outcome was incidence of contrast-induced nephropathy, defined as an increase in serum creatinine from baseline of more than 25% or 44 μmol/L within 2-6 days of contrast exposure, and cost-effectiveness of no prophylaxis compared with intravenous hydration in the prevention of contrast-induced nephropathy. We measured serum creatinine immediately before, 2-6 days, and 26-35 days after contrast-material exposure. Laboratory personnel were masked to treatment allocation. Adverse events and use of resources were systematically recorded. The non-inferiority margin was set at 2·1%. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT02106234. FINDINGS Between June 17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to receive no prophylaxis (n=332) or intravenous hydration (n=328). 2-6 day serum creatinine was available for 307 (92%) of 332 patients in the no prophylaxis group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast-induced nephropathy was recorded in eight (2·6%) of 307 non-hydrated patients and in eight (2·7%) of 296 hydrated patients. The absolute difference (no hydration vs hydration) was -0·10% (one-sided 95% CI -2·25 to 2·06; one-tailed p=0·4710). No hydration was cost-saving relative to hydration. No haemodialysis or related deaths occurred within 35 days. 18 (5·5%) of 328 patients had complications associated with intravenous hydration. INTERPRETATION We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration according to current clinical practice guidelines. FUNDING Stichting de Weijerhorst.

Imaging of the Cardiac Venous System: Comparison of MDCT and Conventional Angiography

OBJECTIVE Diagnostic and therapeutic strategies in electrophysiology and interventional cardiology include the coronary venous system. The purpose of this study was to compare MDCT angiography with conventional coronary sinus angiography in terms of detailed anatomic display of the coronary veins. CONCLUSION MDCT angiography is a reliable alternative to conventional coronary sinus angiography for detailed anatomic display of the coronary veins.