Andreas H. Mahnken

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.

Comparison of two-dimensional and three-dimensional imaging techniques for measurement of aortic annulus diameters before transcatheter aortic valve implantation

Aims Different two-dimensional (2D) and three-dimensional (3D) imaging techniques are used for procedure planning and selection of prosthesis size before transcatheter aortic valve implantation. This study sought to compare different 2D and 3D imaging techniques and determine the accuracy of 3D transoesophageal echocardiography (TEE) for accurate analysis of aortic annulus dimensions. Methods In 49 consecutive patients with severe aortic stenosis undergoing transcatheter aortic valve implantation angiography, 2D transthoracic echocardiography (TTE), 2D and 3D TEE, and dual-source CT (DSCT) were performed to determine aortic annulus diameters. TTE and 2D TEE provided only one diameter of the aortic annulus. Angiography, DSCT and 3D TEE allowed measurement of diameters in sagittal and coronal views. The distance between aortic annulus and left main coronary artery ostium was measured by angiography, DSCT and 3D TEE. Results Sagittal diameters determined by angiography, TTE, 2D TEE, 3D TEE and DSCT were smaller than coronal diameters determined by angiography, 3D TEE and DSCT. Coronal and sagittal diameters determined by 3D TEE were in high agreement with corresponding measurements by DSCT (23.60±1.89 vs 23.46±2.07 mm and 22.19±1.96 vs 22.27±2.01 mm, respectively; mean±SD). There was a high correlation between DSCT and 3D TEE for the definition of coronal and sagittal aortic annulus diameters (r=0.88, SEE=0.89 mm and r=0.77, SEE=1.26 mm, respectively). Correlation of 3D TEE (13.47±1.67 mm) and DSCT (13.64±1.82 mm) in the analysis of the distance between aortic annulus and left main coronary artery ostium was better (r=0.54, SEE=1.55 mm) than between angiography (14.85±3.84 mm) and DSCT (r=0.35, SEE=1.77 mm). Conclusions 3D imaging techniques should be used to evaluate aortic annulus diameters, as 2D imaging techniques, providing only a sagittal view, underestimate them. 3D TEE provides measurements of aortic annulus diameters similar to those obtained by DSCT.

Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation

BACKGROUND This study sought to examine a possible relationship between the severity of aortic valve calcification (AVC), the distribution of AVC and the degree of aortic valve regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). METHODS 57 patients (22 men, 81 ± 5 years) with symptomatic AS and with a logistic EuroSCORE of 24 ± 12 were included. 38 patients (67%) received a third (18F)-generation CoreValve® aortic valve prosthesis, in 19 patients (33%) an Edwards SAPIEN™ prosthesis was implanted. Prior to TAVI dual-source computed tomography for assessment of AVC was performed. To determine the distribution of AVC the percentage of the calcium load of the most severely calcified cusp was calculated. After TAVI the degree of AR was determined by angiography and echocardiography. The severity of AR after TAVI was related to the severity and distribution of AVC. RESULTS There was no association between the distribution of AVC and the degree of paravalvular AR after TAVI as assessed by angiography (r = -0.02, p = 0.88). Agatston AVC scores were significantly higher in patients with AR grade ≥ 3 (5055 ± 1753, n = 3) than in patients with AR grade < 3 (1723 ± 967, p = 0.03, n = 54). Agatston AVC scores > 3000 were associated with a relevant paravalvular AR and showed a trend for increased need for second manoeuvres. There was a significant correlation between the severity of AVC and the degree of AR after AVR (r = 0.50, p < 0.001). CONCLUSION Patients with severe AVC have an increased risk for a relevant AR after TAVI as well as a trend for increased need for additional procedures.

Multislice spiral computed tomography for the detection of coronary stent restenosis and patency

BACKGROUND Multislice spiral computed tomography (MSCT) has evolved as a new promising method for non-invasive visualization of the coronary arteries and detection of native coronary artery stenosis. We determined the value of MSCT to non-invasively detect significant in-stent restenosis after coronary artery stenting. METHODS Twenty patients (age 56.3+/-8.6 years) were investigated by MSCT (4x1 mm cross-sections, 500 ms tube rotation, table feed 1.5 mm/rotation, intravenous contrast agent, retrospectively ECG-gated image reconstruction) at a mean interval of 9.6+/-4.2 months after coronary stent implantation. Results were compared with conventional quantitative coronary angiography (QCA). A total number of 32 stents were studied, four different stent types were evaluated. RESULTS QCA showed in-stent restenosis >50% diameter stenosis in five (16%) stents. Using MSCT it was impossible in all stents, irrespective of stent type or diameter, to directly visualize the stent lumen due to partial volume effects and beam hardening. MSCT allowed the visualization of the coronary vessel proximal and distal to the stent. This allowed confirmation of stent patency in 18/18 cases and correct identification of total stent occlusion in two patients. CONCLUSIONS MSCT allows no direct visualization of coronary in-stent restenosis, but it correctly differentiates between stent patency and stent occlusion. The reasons are mainly partial volume effects and beam hardening, which are induced by the stent material.

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.

Image fusion in dual energy computed tomography: effect on contrast enhancement, signal-to-noise ratio and image quality in computed tomography angiography.

Objective:The aim of this study was to evaluate the influence of different weighting factors on contrast enhancement, signal-to-noise ratio (SNR), and image quality in image fusion in dual energy computed tomography (DECT) angiography. Material and Methods:Fifteen patients underwent a CT angiography of the aorta with a SOMATOM Definition Dual Source CT (DSCT; Siemens, Forchheim, Germany) in dual energy mode (DECT) (tube voltage: 80 and 140 kVp; tube current: 297 eff. mA and 70 eff. mA; collimation, 14 × 1.2 mm). Raw data were reconstructed using a soft convolution kernel (D30f). Fused images were calculated using a spectrum of weighting factors (0.0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1.0) generating different ratios between the 80- and 140-kVp images (eg, factor 0.5 corresponds to 50% image information from the 140- and the 80-kVp image). Both CT values and SNR were measured in the descending aorta (levels of celiac trunk, renal arteries, and aortic bifurcation), in the right and left common iliac artery and in paraaortal fat. Image quality was evaluated using a 5-point grading scale. Results were compared using paired t-tests and nonparametric paired Wilcoxon tests. Results:Statistically significant increases in mean CT values were seen in vessels when increasing weighting factors were used (all P ≤ 0.001). For example, mean CT values derived from the aorta at the level of the celiac trunk were 273.8 ± 25.8 Hounsfield units (HU), 304.0 ± 24.3 HU, 361.4 ± 22.5 HU, 418.3 ± 25.8 HU, 477.8 ± 32.2 HU, 536.2 ± 41.2 HU, 564.6 ± 45.3 HU, when the weighting factors 0.0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1.0 were used. The highest SNR values were found in vessels when the weighting factor 0.5 was used. The highest SNR values of the paraaortal fat were obtained for the weighting factors 0.3 and 0.5. Visual image assessment for image quality showed the highest score for the data reconstructed using the weighting factor 0.5. Conclusion:Different weighting factors used to create fused images in DECT cause statistically significant differences in CT value, SNR, and image quality. Best results were obtained using the weighting factor 0.5, which we recommend for image fusion in DECT angiography.

Quantitative Whole Heart Stress Perfusion CT Imaging as Noninvasive Assessment of Hemodynamics in Coronary Artery Stenosis: Preliminary Animal Experience

Purpose:To quantify differences in regional myocardial perfusion in coronary artery stenosis by the use of dual source computed tomography (DSCT) in an animal model. Material and Methods:In 5 pigs, an 80% stenosis of the left anterior descending artery was successfully induced by partial balloon occlusion (ischemia group). Five animals served as control group. All animals underwent contrast enhanced whole heart DSCT (Definition Flash, Siemens, Germany) perfusion imaging using a prototype electrocardiogram -triggered dynamic scan mode. Imaging was performed at rest as well as under stress conditions during continuous infusion of adenosine (240 mg/kg/min). For contrast enhancement 60 mL Iopromide 300 (Ultravist 300, Bayer-Schering Pharma, Berlin, Germany) were injected at a rate of 6 mL/s. Myocardial blood flow (MBF), first pass distribution volume, and intravascular blood volume were volumetrically quantified. Results:In the control group MBF increased significantly from 98.2 mL/100 mL/min to 134.0 mL/100 mL/min if adenosine was administered (P = 0.0153). There were no significant differences in the perfusion parameters comparing the control and ischemia group at rest. In the ischemia group MBF under stress was 74.0 ± 21.9 mL/100 mL/min in the poststenotic myocardium and 117.4 ± 18.6 mL/100 mL/min in the remaining normal myocardium (P = 0.0024). Conclusion:DSCT permits quantitative whole heart perfusion imaging. As this technique is able to show the hemodynamic effect of high grade coronary artery stenosis, it exceeds the present key limitation of cardiac computed tomography, which currently only allows a morphologic assessment of coronary artery stenosis.

Evaluation of aortic root for definition of prosthesis size by magnetic resonance imaging and cardiac computed tomography: Implications for transcatheter aortic valve implantation

BACKGROUND This study sought to compare cardiac magnetic resonance imaging (CMR) with dual source computed tomography (DSCT) for analysis of aortic root dimensions prior to transcatheter aortic valve implantation (TAVI). In addition, the potential impact of CMR and DSCT measurements on TAVI strategy defined by 2D-transesophageal echocardiography (TEE) was evaluated. METHODS Aortic root dimensions were measured using CMR and DSCT in 58 patients referred for evaluation of TAVI. The TAVI strategy (choice of prosthesis size and decision to implant) was based on 2D-TEE annulus measurements. RESULTS CMR and DSCT aortic root measurements showed an overall good correlation (r=0.86, p<0.001 for coronal aortic annulus diameters). There was also a good correlation between TEE and CMR as well as between TEE and DSCT for measurement of sagittal aortic annulus diameters (r=0.69, p<0.001). However, annulus diameters assessed by TEE (22.1±2.3mm) were significantly smaller than coronal aortic annulus diameters assessed by CMR (23.4±1.8mm, p<0.001) or DSCT (23.6±1.8, p<0.001). Regarding TAVI strategy, the agreement between TEE and sagittal CMR (kappa=0.89) as well as sagittal DSCT measurements (kappa=0.87) was statistically perfect. However, decision based on coronal CMR- or MSCT measurements would have modified TAVI strategy as compared to a TEE based choice in a significant number of patients (22% to 24%). CONCLUSION In patients referred for TAVI, CMR measurements of aortic root dimensions show a good correlation with DSCT measurements and thus CMR may be an alternative 3D-imaging modality. Aortic annulus measurements using TEE, CMR and DSCT were close but not identical and the method used has important potential implications on TAVI strategy.

A feasibility study of contrast enhancement of acute myocardial infarction in multislice computed tomography: comparison with magnetic resonance imaging and gross morphology in pigs.

Introduction:Late enhancement magnetic resonance imaging (MRI) of myocardial infarction (MI) is clinically established. There are no reports on MI assessment using state-of-the-art multislice CT technology. For this reason, animal experiments were conducted to examine the applicability of contrast-enhanced ECG-gated multislice computed tomography (MSCT) for the detection of acute MI. The results were correlated with MRI and postmortem tissue staining. Material and Methods:Acute MI was induced in 14 pigs by balloon occlusion of the LAD. In 8 animals, the LAD was reperfused after 45 minutes. In 6 animals, the LAD was permanently blocked. MR imaging was performed 15 minutes after the administration of 0.2 mmol Gd-DTPA/kg/bodyweight. Subsequently, 16-slice MSCT was performed at various timepoints after injecting 120 mL of iodinated contrast medium. 2,3,5-Triphenyltetrazolin-chloride (TTC) staining was acquired for all hearts investigated. Correlation analysis was applied to compare the area of MI derived from MRI, MSCT, and TTC. The reperfused infarcts were compared with the nonreperfused infarcts using an unpaired t test. Results:Mean infarct area as measured by TTC staining was 18.3% ± 7.8% of the left ventricular area. Good correlation of the spatial extent of the infarcted area was found for TTC and MRI as well as for TTC and MSCT data obtained 5 minutes postcontrast injection. MSCT imaging demonstrated a significant difference in density (P < 0.001) between nonreperfused (47.0 ± 6.6 HU) and reperfused (116.4 ± 19.8 HU) infarction. Conclusion:In our pilot study, contrast-enhanced MSCT was feasible to assess myocardial viability in pigs. MSCT also affords differentiation of nonreperfused and reperfused acute MI. MI sizes derived from MSCT imaging correlate well to those obtained with MRI and TTC.

Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification

Matrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant; OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 191 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 +/- 123.1 nM) compared to the control group (571.6 +/- 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGP, resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.