Accuracy of automated software-guided detection of significant coronary artery stenosis by CT angiography: comparison with invasive catheterisation.

PURPOSE: True automated detection of coronary artery stenoses might be useful whenever expert evaluation is not available, or as a "second reader" to enhance diagnostic confidence. We evaluated the accuracy of a PC-based stenosis detection tool alone and combined with expert interpretation. METHODS: One hundred coronary CT angiography datasets were evaluated with the automated software alone, by manual interpretation (axial images, multiplanar reformations and maximum intensity projections in free double-oblique planes), and by expert interpretation aware of the automated findings. Stenoses ≥ 50 % were noted per-vessel and per-patient, and compared with invasive angiography. RESULTS: Automated post-processing was successful in 90 % of patients (88 % of vessels). When excluding uninterpretable datasets, per-patient sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89 %, 79 %, 74 % and 92 % (per-vessel: 82 %, 85 %, 48 % and 96 %). All 100 datasets were evaluable by expert interpretation. Per-patient sensitivity, specificity, PPV and NPV were 95 %, 95 %, 93 % and 97 % (per-vessel: 89 %,98 %, 88 % and 98 %). Knowing the results of automated interpretation did not improve the performance of expert readers. CONCLUSION: Automated off-line post-processing of coronary CT angiography shows adequate sensitivity, but relatively low specificity in coronary stenosis detection. It does not increase accuracy of expert interpretation. Failure of post-processing in 10 % of all patients necessitates additional manual image work-up. KEY POINTS: • Coronary CT angiography is increasingly used for detection of coronary artery stenosis • Computer assisted diagnosis might facilitate and speed up interpretation • Performance in properly segmented cases compared favourably with manual image interpretation • However, automated segmentation failed in about 10 % of cases • Manual reading is still mandatory; computer assisted diagnosis can provide a useful second read.

Image quality of ultra-low radiation exposure coronary CT angiography with an effective dose <0.1 mSv using high-pitch spiral acquisition and raw data-based iterative reconstruction.

OBJECTIVES: We evaluated the potential of prospectively ECG-triggered high-pitch spiral acquisition with low tube voltage and current in combination with iterative reconstruction to achieve coronary CT angiography with sufficient image quality at an effective dose below 0.1 mSv. METHODS: Contrast-enhanced coronary dual source CT angiography (2 × 128 × 0.6 mm, 80 kV, 50 mAs) in prospectively ECG-triggered high-pitch spiral acquisition mode was performed in 21 consecutive individuals (body weight <100 kg, heart rate ≤60/min). Images were reconstructed with raw data-based filtered back projection (FBP) and iterative reconstruction (IR). Image quality was assessed on a 4-point scale (1 = no artefacts, 4 = unevaluable). RESULTS: Mean effective dose was 0.06 ± 0.01 mSv. Image noise was significantly reduced in IR (128.9 ± 46.6 vs. 158.2 ± 44.7 HU). The mean image quality score was lower for IR (1.9 ± 1.1 vs. 2.2 ± 1.0, P < 0.0001). Of 292 coronary segments, 55 in FBP and 40 in IR (P = 0.12) were graded "unevaluable". In patients with a body weight ≤75 kg, both in FBP and in IR, the rates of fully evaluable segments were significantly higher in comparison to patients >75 kg. CONCLUSIONS: Coronary CT angiography with an estimated effective dose <0.1 mSv may provide sufficient image quality in selected patients through the combination of high-pitch spiral acquisition and raw data-based iterative reconstruction.

Additional diagnostic and prognostic value of copeptin ultra-sensitive for diagnosis of non-ST-elevation myocardial infarction in older patients presenting to the emergency department.

BACKGROUND: Identifying older patients with non-ST- elevation myocardial infarction (NSTEMI) within the very large proportion with elevated high-sensitive cardiac troponin T (hs-cTnT) is a diagnostic challenge because they often present without clear symptoms or electrocardiographic features of acute coronary syndrome to the emergency department (ED). We prospectively investigated the diagnostic and prognostic performance of copeptin ultra-sensitive (copeptin-us) and hs-cTnT compared to hs-cTnT alone for NSTEMI at prespecified cut-offs in unselected older patients. METHODS: We consecutively enrolled 306 non-surgical patients ≥70 years presenting to the ED. In addition to clinical examination, copeptin-us and hs-cTnT were measured at admission. Two cardiologists independently adjudicated the final diagnosis of NSTEMI after reviewing all available data. All patients were followed up for cardiovascular-related death within the following 12 months. RESULTS: NSTEMI was diagnosed in 38 (12%) patients (age 81±6 years). The combination of copeptin-us ≥14 pmol/L and hs-cTnT ≥0.014 µg/L compared to hs-cTnT ≥0.014 µg/L alone had a positive predictive value of 21% vs. 19% to rule in NSTEMI. The combination of copeptin-us <14 pmol/L and hs-cTnT <0.014 µg/L compared to hs-cTnT <0.014 µg/L alone had a negative predictive value of 100% vs. 99% to rule out NSTEMI. Hs-cTnT ≥0.014 µg/L alone was significantly associated with outcome. When copeptin-us ≥14 pmol/L was added, the net reclassification improvement for outcome was not significant (p=0.809). CONCLUSIONS: In unselected older patients presenting to the ED, the additional use of copeptin-us at predefined cut-offs may help to reliably rule out NSTEMI but may not help to increase predicted risk for outcome compared to hs-cTnT alone.

A myocardial ischemia- and reperfusion-induced injury is mediated by reactive oxygen species released from blood platelets.

In recent experimental studies, blood platelets have been found to exhibit some cardiodepressive effects in ischemic and reperfused guinea pig hearts independent of thrombus formation. These effects seemed to be mediated by reactive oxygen species (ROS). However, the source of these ROS - platelets or heart - remained still unknown. Isolated, buffer-perfused and pressure-volume work performing guinea pig hearts were exposed to a low-flow ischemia (1 ml/min) of 30 min duration and reperfused at a constant flow of 5 ml/min. Human thrombocytes were administered as 1 min bolus (20 000 thrombocytes/µl perfusion buffer) in the 15th min of ischemia or in the 1st or 5th min of reperfusion in the presence of thrombin (0.3 U/ml perfusion buffer). Recovery of external heart work (REHW) was expressed as ratio between postischemic and preischemic EHW in percent. Intracoronary platelet retention (RET) was quantified as percent of platelets applied. In a second set of experiments, thrombocytes were incubated with 10 µM of the irreversible NADPH oxidase blocker diphenyliodonium chloride and washed twice, thereafter, and administered according to the same protocol as described above. Hearts exposed to ischemia and reperfusion in the presence of thrombin but without application of platelets served as controls. Controls without application of platelets did not reveal a severe compromisation of myocardial function (REHW 85.5 ± 1%). However, addition of platelets during ischemia or in the 1st or 5th min of reperfusion led to a significant reduction of REHW as compared with controls (REHW 62.4 ± 6, 53.9 ± 3, 40.5 ± 3, respectively). Application of platelets pretreated with diphenyliodonium chloride did not reveal any cardiodepressive effects being significantly different from controls without platelet application. Moreover, treatment of platelets with diphenyliodonium chloride did not significantly decrease intracoronary platelet retention. In conclusion, these results demonstrate that cardiodepressive effects of human thrombocytes in ischemic and reperfused guinea pig hearts are mediated by ROS released from thrombocytes and not the heart.

Association of systemic inflammation markers with the presence and extent of coronary artery calcification.

BACKGROUND: Coronary artery calcification (CAC) is a marker for the presence and extent of coronary atherosclerotic plaques and can be detected non-invasively by multi-detector row CT (MDCT). Well known predictors of CAC are age, gender, and the classical atherogenic risk factors. CAC is associated with atherosclerotic plaque burden, but it is still elusive if atherosclerosis-relevant cytokines and chemokines are also associated with CAC. METHODS: We conducted a clinical study among 455 consecutive individuals who underwent coronary calcium assessment performed by MDCT. Before MDCT, blood was drawn and subsequently analyzed for 20 different atherosclerosis-relevant cytokines and chemokines using a Luminex-laser-based fluorescence analysis. RESULTS: Using univariate analyses, CAC patients revealed significantly higher levels of the chemokines IP-10 (P=0.047) and eotaxin (P=0.031) as compared to non-CAC patients. In multivariate analyses using common thresholds for calcium burden, the three cytokines interleukin-6 (P=0.028), interleukin-8 (P=0.009), and interleukin-13 (P=0.024) were associated with high coronary calcium levels after adjustment for classical variables and risk factors. CONCLUSIONS: In a large group of individuals with atypical chest pain and a low to intermediate likelihood for coronary artery disease elevated plasma levels of IL-6 and reduced levels of IL-8 and IL-13 were predictive for distinct coronary artery calcification. These findings support a specific role of these cytokines in coronary calcification.

Interobserver agreement for the detection of atherosclerotic plaque in coronary CT angiography: comparison of two low-dose image acquisition protocols with standard retrospectively ECG-gated reconstruction.

BACKGROUND: We compared the interobserver variability concerning the detection of calcified and non-calcified plaque in two different low-dose and standard retrospectively gated protocols for coronary CTA. METHODS: 150 patients with low heart rates and less than 100 kg body weight were randomised and examined by contrast-enhanced dual-source CT coronary angiography (100 kV, 320 mAs). 50 patients were examined with prospectively ECG-triggered axial acquisition, 50 patients with prospectively ECG-triggered high pitch spiral acquisition, and 50 patients using spiral acquisition with retrospective ECG gating. Two investigators independently analysed the datasets concerning the presence of calcified and non-calcified plaque on a per-segment level. RESULTS: Mean effective dose was 1.4 ± 0.2 mSv for axial, 0.8 ± 0.07 mSv for high-pitch spiral, and 5.3 ± 2.6 mSV for standard spiral acquisition (P < 0.0001). In axial acquisition, interobserver agreement concerning the presence of atherosclerotic plaque was achieved in 650/749 coronary segments (86.8%). In high-pitch spiral acquisition, agreement was achieved in 664/748 segments (88.8%, n.s.). In standard spiral acquisition, agreement was achieved in 672/738 segments (91.0%, P < 0.0001). Interobserver agreement was significantly higher for calcified than for non-calcified plaque in all data acquisition modes. CONCLUSION: Low-dose coronary CT angiography permits the detection of coronary atherosclerotic plaque with good interobserver agreement. KEY POINTS: • Low-dose CT protocols permit coronary plaque detection with good interobserver agreement. • Image noise is a major predictor of interobserver variability. • Interobserver agreement is significantly higher for calcified than for non-calcified plaque.

Cardiac imaging after myocardial infarction.

After myocardial infarction, optimal clinical management depends critically on cardiac imaging. Remodelling and heart failure, presence of inducible ischaemia, presence of dysfunctional viable myocardium, future risk of adverse events including risk of ventricular arrhythmias, need for anticoagulation, and other questions should be addressed by cardiac imaging. Strengths and weaknesses, recent developments, choice, and timing of the different non-invasive techniques are reviewed for this frequent clinical scenario.

Carotid plaque vulnerability: a positive feedback between hemodynamic and biochemical mechanisms.

BACKGROUND AND PURPOSE: Rupture of atherosclerotic plaques is one of the main causes of ischemic strokes. The aim of this study was to investigate carotid plaque vulnerability markers in relation to blood flow direction and the mechanisms leading to plaque rupture at the upstream side of carotid stenoses. METHODS: Frequency and location of rupture, endothelial erosion, neovascularization, and hemorrhage were determined in longitudinal sections of 80 human carotid specimens. Plaques were immunohistochemically analyzed for markers of vulnerability. Plaque geometry was measured to reconstruct shape profiles of ruptured versus stable plaques and to perform computational fluid dynamics analyses. RESULTS: In 86% of ruptured plaques, rupture was observed upstream. In this region, neovascularization and hemorrhage were increased, along with increased immunoreactivity of vascular endothelial and connective tissue growth factor, whereas endothelial erosion was more frequent downstream. Proteolytic enzymes, mast cell chymase and cathepsin L, and the proapoptotic protein Bax showed significantly higher expression upstream as compared with the downstream shoulder of atherosclerotic lesions. Comparison of geometric profiles for ruptured and stable plaques showed increased longitudinal asymmetry of fibrous cap and lipid core thickness in ruptured plaques. The specific geometry of plaques ruptured upstream induced increased levels of shear stress and increased pressure drop between the upstream and the downstream plaque shoulders. CONCLUSIONS: Vulnerability of the upstream plaque region is associated with enhanced neovascularization, hemorrhage, and cap thinning induced by proteolytic and proapoptotic mechanisms. These processes are reflected in structural plaque characteristics, analyses of which could improve the efficacy of vascular diagnostics and prevention.

Coronary vessel and luminal area measurement using dual-source computed tomography in comparison with intravascular ultrasound: effect of window settings on measurement accuracy.

BACKGROUND: Image display settings (window and level) have a substantial impact on measurements of coronary artery and plaque dimensions in computed tomography (CT), and their influence on measurement accuracy has not been systematically evaluated. We analyzed the influence of window width/level settings on the accuracy for determining cross-sectional lumen and outer vessel diameters in contrast-enhanced CT angiography compared with intravascular ultrasound (IVUS). METHODS: We evaluated the data sets of 35 patients. Coronary CT angiography was performed as part of a research protocol before invasive coronary angiography. A contrast-enhanced volume data set was acquired using a dual-source CT (DSCT) scanner (Siemens Healthcare, Forchheim, Germany). Intravascular ultrasound was performed using a 40-MHz IVUS catheter (Atlantis, Boston Scientific Corporation, Natick, Mass) and motorized pullback at 0.5 mm/s. One hundred exactly corresponding sites within the coronary artery system were identified in both DSCT and IVUS using bifurcation points as fiducial markers. In DSCT data sets, multiplanar reconstructions (0.75-mm slice thickness) were rendered orthogonally to the centerline of the coronary artery at each of the 100 sites. Computed tomographic images were displayed using 4 previously published settings (700/200, 700/140, and 500/150 Hounsfield units [HU], and 1 HU/65% of the mean luminal intensity [HU] and 155%/65% of the mean luminal intensity [HU] for window width/level) as well as with a visually adjusted setting for subjectively optimal lumen and outer vessel area measurement. Coronary lumen and cross-sectional vessel areas were manually traced using all 5 display settings and compared with IVUS measurements. RESULTS: Concerning cross-sectional vessel area measurements, correlation was close and significant compared with IVUS using all settings (r ≥ 0.93, P = 0.01 for all settings). Bland-Altman analysis revealed a good agreement between both modalities with a systematic bias toward overestimation in CT. Least bias was demonstrated using the setting 155%/65% of the mean luminal intensity for window width/level, with a mean (SD) difference of 0.2 (1.73) mm2. For the measurement of the luminal area, the window setting using a width of 1 HU and a level of 65% of the mean luminal intensity showed the lowest correlation to IVUS (r = 0.85), with a systematic bias toward underestimation of the lumen in CT. Bland-Altman analysis revealed a moderate agreement with a mean (SD) difference of -2.1 (1.6) mm2. For all other settings, a very close correlation was observed (r > 0.9, P = 0.01), and Bland-Altman analysis revealed a slight trend toward lumen underestimation in CT, yet with a good agreement. The least bias was demonstrated using the setting 700/200 HU for window width/level with a mean (SD) difference of -0.1 (0.9) mm2. CONCLUSION: Previously published window settings and visually adjusted window setting correlate very well with IVUS measurements regarding coronary artery cross-sectional and luminal area, with a better agreement for luminal area measurements. A systematic bias toward overestimation of vessel area in CT was observed as well as a slight trend toward lumen underestimation. This bias was least for vessel area measurement using 155%/65% of the mean luminal intensity (HU) for window width/level, whereas for luminal area measurement, the setting 700/200 HU for window width/level yielded the least bias.

Accuracy of dual-source computed tomography to identify significant coronary artery disease in patients with atrial fibrillation: comparison with coronary angiography.

AIMS: It has been previously reported that the sensitivity and specificity of multislice computed tomography (CT) for detecting significant coronary artery disease (CAD) is high. However, regular sinus rhythm has been considered a prerequisite for an adequate examination, even though atrial fibrillation (AF) is common among patients evaluated for the presence of coronary heart disease. In this study, we investigated the sensitivity and specificity of dual-source CT (DSCT) to detect and rule out significant coronary stenoses in patients with AF referred for invasive coronary angiography. METHODS AND RESULTS: One hundred and ten consecutive patients with AF who were admitted for a first diagnostic coronary angiogram were screened for participation. Out of these, 50 patients were excluded either due to renal insufficiency, inability to maintain an adequate breath hold or due to rapid AF non-responsive to ß-blocker therapy (heart rate > 100 b.p.m.). Sixty remaining patients (mean age 71 ± 7 years) were included and subjected to CT angiography using DSCT within 24 h before invasive coronary angiography. A contrast-enhanced volume data set was acquired (330 ms gantry rotation, collimation 2 × 64 × 0.6 mm, retrospective electrocardiogram gating). Data sets were evaluated concerning the presence or absence of significant coronary stenoses and validated against invasive coronary angiography. A significant stenosis was assumed if the diameter reduction was ≥50%. Mean heart rate during CT was 70 ± 15 b.p.m. (range 32-107 b.p.m.). On a per-patient basis, the sensitivity and specificity for DSCT to detect significant coronary stenoses in vessels >1.5 mm diameter was 100% [14/14, 95% confidence interval (CI) 77-100] and 85% (39/46, 95% CI 71-94), respectively, with a negative predictive value (NPV) of 100% (39/39, 95% CI 91-100) and a positive predictive value (PPV) of 67% (14/21, 95% CI 43-85). On a per-artery basis, 240 vessels were evaluated (left main, left anterior descending, left circumflex, and right coronary artery in 60 patients, with 3 non-assessable vessels due to either severe calcification or motion artefacts which were considered positive for stenoses) with a sensitivity of 95% (21/22, 95% CI 77-100) and specificity of 94% (204/218, 95% CI 89-97); NPV was 99% (204/205, 95% CI 96-100), and PPV was 60% (21/35, 95% CI 38-80). CONCLUSION: Our study demonstrates high sensitivity, specificity, and NPV of DSCT to detect significant CAD in selected patients with rate controlled AF.

Coronary computed tomography angiography with a consistent dose below 1 mSv using prospectively electrocardiogram-triggered high-pitch spiral acquisition.

AIMS: We evaluated the feasibility and image quality of a new scan mode for coronary computed tomography angiography (CTA) with an effective dose of less than 1 mSv. METHODS AND RESULTS: In 50 consecutive patients (body weight

Prevalence of first-pass myocardial perfusion defects detected by contrast-enhanced dual-source CT in patients with non-ST segment elevation acute coronary syndromes.

OBJECTIVE: To investigate the prevalence and diagnostic value of first-pass myocardial perfusion defects (PD) visualised by contrast-enhanced multidetector computed tomography (MDCT) in patients admitted for a first acute coronary syndrome (ACS). METHODS: Thirty-eight patients with non-ST segment elevation myocardial infarction (NSTEMI) or unstable angina (UA) and scheduled for percutaneous coronary intervention underwent dual-source CT immediately before catheterisation. CT images were analysed for the presence of any PD by using a 17-segment model. Results were compared with peak cardiac troponin-I (cTnI) and angiography findings. RESULTS: PD were seen in 21 of the 24 patients with NSTEMI (median peak cTnI level 7.07 ng/mL; range 0.72-37.07 ng/mL) and in 2 of 14 patients with UA. PD corresponded with the territory of the infarct-related artery in 20 out of 22 patients. In a patient-based analysis, sensitivity, specificity, negative and positive predictive values of any PD for predicting NSTEMI were 88%, 86%, 80% and 91%. Per culprit artery, the respective values were 86%, 75%, 80% and 83%. CONCLUSION: In patients with non-ST segment elevation ACS, first-pass myocardial PD in contrast-enhanced MDCT correlate closely with the presence of myocardial necrosis, as determined by increases in cTnI levels.

Radiation exposure and image quality in staged low-dose protocols for coronary dual-source CT angiography: a randomized comparison.

OBJECTIVE: To evaluate staged low-dose approaches for coronary CT angiography (CTA) in which a standard sequence was added if the low-dose sequence did not allow reliable rule-out of coronary stenosis. PATIENTS AND METHODS: A total of 176 consecutive patients referred for dual-source CTA were randomized to three protocols: group 1 using prospective ECG-triggering (100 kV, 330 mAs), group 2 a retrospectively gated "MinDose" sequence (100 kV, 330 mAs) and group 3 a standard spiral sequence (120 kV, 400 mAs). If image quality in low-dose groups 1 or 2 was non-diagnostic, an additional standard CT examination (as in group 3) was performed. RESULTS: Non-diagnostic image quality was found in 11/56, 4/55, and 2/65 patients (46/896, 4/880 and 3/1,040 coronary segments) in groups 1, 2 and 3, respectively. Median (interquartile ranges) volumes of contrast material, CTDI(vol), DLP and effective dose for low-dose groups 1 and 2 and for standard group 3 were 92.5 (11.3), 75.0 (2.5) and 75.0 (9.0) ml; 8.0 (1.4), 16.8 (4.8) and 48.1 (14.2) mGy; 108.0 (27.3), 246.0 (93.0) and 701.0 (207.8) mGy cm; and 1.5 (0.4), 3.4 (1.3) and 9.8 (2.9) mSv, respectively. CONCLUSION: A staged coronary CTA protocol with an initial low-dose approach and addition of a standard sequence--should image quality be too low--can lead to a substantial reduction in radiation exposure.

Apical transverse motion as surrogate parameter to determine regional left ventricular function inhomogeneities: a new, integrative approach to left ventricular asynchrony assessment.

AIMS: Left ventricular (LV) asynchrony assessment is mostly based on delays between regional myocardial velocity peaks. Regional function is barely considered. We propose apical transverse motion (ATM) as a new parameter integrating both temporal and functional information, which was tested in different conduction delays. METHODS AND RESULTS: We examined 67 patients, 11 patients with post-infarct ischaemic left bundle branch blocks (iLBBB) and 25 patients with non-ischaemic left bundle branch block (nLBBB), 12 patients with right bundle branch block (RBBB), and 19 normal healthy volunteers (NORM). Longitudinal colour tissue Doppler data were used to calculate the total transverse apex motion (ATM), the transverse motion in the four-chamber view plane alone (ATM(4CV)) as well as regional myocardial deformation and conventional LV asynchrony parameters. Median ATM was 1.8 mm in NORM, 1.5 mm in RBBB (P = 0.999), 2.4 mm in iLBBB (P = 0.183), and 4.3 mm in nLBBB (P < 0.001 vs. NORM and RSB). ATM(4CV) behaved similarly, showed a good correlation with regional deformation data, and distinguished well between NORM and LBBB (AUC = 0.87). CONCLUSION: Apical transverse motion is a new and simple parameter integrating information on both regional and temporal function inhomogeneities of the LV. It has a potential role in assessing LV asynchrony in the clinical context.

Predictive value of the decrease in circulating dendritic cell precursors in stable coronary artery disease.

DCs (dendritic cells) are present in atherosclerotic lesions leading to vascular inflammation, and the number of vascular DCs increases during atherosclerosis. Previously, we have shown that the levels of circulating DCPs (DC precursors) are reduced in acute coronary syndromes through vascular recruitment. In the present study, we have investigated whether DCP levels are also reduced in stable CAD (coronary artery disease). The levels of circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs) and tDCP (total DCPs) were investigated using flow cytometry in 290 patients with suspected stable CAD. A coronary angiogram was used to evaluate a CAD score for each patient as follows: (i) CAD excluded (n=57); (ii) early CAD (n=63); (iii) moderate CAD (n=85); and (iv) advanced CAD (n=85). Compared with controls, patients with advanced stable CAD had lower HDL (high-density lipoprotein)-cholesterol (P=0.03) and higher creatinine (P=0.003). In advanced CAD, a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.001). A significant inverse correlation was observed between the CAD score and mDCPs, pDCPs or tDCPs (each P<0.001). Patients who required percutaneous coronary intervention or coronary artery bypass grafting had less circulating mDCPs, pDCPs and tDCPs than controls (each P<0.001). Multiple stepwise logistic regression analysis suggested mDCPs, pDCPs and tDCPs as independent predictors of CAD. In conclusion, we have shown that patients with stable CAD have significantly lower levels of circulating DCPs than healthy individuals. Their decrease appears to be an independent predictor of the presence of, and subsequent therapeutic procedure in, stable CAD.

Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction.

LV (left ventricular) remodelling is the basic mechanism of HF (heart failure) following MI (myocardial infarction). Although there is evidence that pro-inflammatory cytokines [including TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6)] are involved in the remodelling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. As accumulating evidence has revealed that statins possess anti-inflammatory properties, the aim of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent LAD (left anterior descending) branch coronary artery ligation, were treated for 4 weeks with atorvastatin (10 mg x kg(-1) of body weight x day(-1) via oral gavage) starting on the first day after induction of MI. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10 protein, the TNF-alpha/IL-10 ratio, serum levels of MCP-1 (monocyte chemoattractant protein-1) as well as myocardial macrophage infiltration were analysed. Treatment with atorvastatin significantly improved post-MI LV function (fractional shortening, +120%; dP/dt(max), +147%; and LV end-diastolic pressure, -27%). Furthermore atorvastatin treatment markedly decreased the levels of TNF-alpha, IL-6 and MCP-1, reduced myocardial infiltration of macrophages and significantly increased myocardial and serum levels of the anti-inflammatory cytokine IL-10. Thus the balance between pro-inflammatory and anti-inflammatory cytokines was shifted in the anti-inflammatory direction, as shown by a significantly decreased TNF-alpha/IL-10 ratio. Atorvastatin ameliorated early LV remodelling and improved LV function in rats with HF subsequent to MI. Our study suggests that the modulation of the balance between pro- and anti-inflammatory cytokines towards the anti-inflammatory cytokine IL-10 is one salutary mechanism underlying how atorvastatin influences post-MI remodelling and thus improves LV function.

Transient decrease in circulating dendritic cell precursors after acute stroke: potential recruitment into the brain.

The role of DCs (dendritic cells) as potent mediators of inflammation has not been sufficiently investigated in stroke. Therefore, in the present study, circulating mDCPs (myeloid DC precursors), pDCPs (plasmacytoid DCPs) and tDCPs (total DCPs) were analysed by flow cytometry in (i) healthy controls (n=29), (ii) patients with ACI-S (asymptomatic cerebral infarction stenosis; n=46), (iii) patients with TIA (transient ischaemic attack; n=39), (iv) patients with AIS (acute ischaemic stroke; n=73), and (v) patients with AHS (acute haemorrhagic stroke; n=31). The NIHSS (National Institutes of Health Stroke Scale) and infarction size on a CT (computer tomography) scan were evaluated after stroke. In a patient subgroup, post-mortem immunohistochemical brain analyses were performed to detect mDCs (CD209), pDCs (CD123), T-cells (CD3) and HLA-DR. In AIS and AHS, the numbers of circulating mDCPs (P<0.005), pDCPs (P<0.005) and tDCPs (P<0.001) were significantly reduced. A significant inverse correlation was found between the NIHSS and circulating DCPs (P<0.02), as well as between hsCRP (high-sensitivity C-reactive protein) and circulating DCPs (P<0.001). Patients with large stroke sizes on a CT scan had significantly lower numbers of mDCPs (P=0.007), pDCPs (P=0.05) and tDCPs (P=0.01) than those with smaller stroke sizes. Follow-up analysis showed a significant recovery of circulating DCPs in the first few days after stroke. In the infarcted brain, a dense infiltration of mDCs co-localized with T-cells, single pDCs and high HLA-DR expression were observed. In conclusion, acute stroke leads to a decrease in circulating DCPs. Potentially, circulating DCPs are recruited from the blood into the infarcted brain and probably trigger cerebral immune reactions there.

Prospectively ECG-triggered high-pitch spiral acquisition for coronary CT angiography using dual source CT: technique and initial experience.

OBJECTIVE: We evaluated radiation exposure and image quality of a new coronary CT angiography protocol, high-pitch spiral acquisition, using dual source CT (DSCT). MATERIAL AND METHODS: Coronary CTAwas performed in 25 consecutive patients with a stable heart rate of 60 bpm or less after premedication, using 2 x 128 0.6-mm sections, 38.4-mm collimation width and 0.28-s rotation time. Tube settings were 100 kV/320 mAs and 120 kV/400 mAs for patients below and above 100-kg weight, respectively. Data acquisition was prospectively ECG-triggered at 60% of the R-R interval using a pitch of 3.2 (3.4 for the last 10 patients). Images were reconstructed with 75-ms temporal resolution, 0.6-mm slice thickness and 0.3-mm increment. Image quality was evaluated using a four-point scale (1 = excellent, 4 = unevaluable). RESULTS: Mean range of data acquisition was 113 +/- 22 mm, mean duration was 268 +/- 23 ms. Of 363 coronary artery segments, 327 had an image quality score of 1, and only 2 segments were rated as "unevaluable". Mean dose-length product (DLP) was 71 +/- 23 mGy cm, mean effective dose was 1.0 +/- 0.3 mSv (range 0.78-2.1 mSv). For 21 patients with a body weight below 100 kg, mean DLP was 63 +/- 5 mGy cm (0.88 +/- 0.07 mSv; range 0.78-0.97 mSv). CONCLUSION: Prospectively ECGtriggered high-pitch spiral CT acquisition provides high and stable image quality at very low radiation dose.

Atherosclerotic inflammation triggers osteogenic bone transformation in calcified and stenotic human aortic valves: still a matter of debate.

Sclerotic calcification of the aortic valve is a common disease in advanced age. However, pathophysiologic processes leading to valve calcifications are poorly understood. Transformation of atherosclerotic triggers to osteogenic differentiation is controversially discussed and is thought as a trigger of bone transformation in end stage disease. This study focuses on the transcriptional gene-profiling of severe calcified stenotic human aortic valves to clarify the molecular basis of the pathophysiological process. We collected severely calcified and stenotic human aortic valves (CSAV) with (CSAV+, n=10) and without (CSAV-, n=10) at least 4 weeks of statin pre-treatment prior to valve replacement and investigated transcriptional steady-state gene-profiling by using micro array technique and GAPDH-adjusted PCR for confirmation. Results were compared with findings in non-sclerotic aortic valves: C (n=6). Various parameters of inflammation were significantly up regulated as compared to C: eotaxin3, monokine induced by gamma-interferon, vascular adhesion protein-1 (VAP-1), peroxisome proliferative activated receptor-alpha or transforming growth factor beta 1 (TGF beta 1). Except for TGF beta 1 and VAP-1, statin pre-treatment neutralized altered gene expression. Genes of osteogenic bone transformation (tenascin C, bone sialoprotein, Cbfa1, Osteocalcin, Beta-catenin, Sox- and Cyclin-genes) were found unaltered in their expression in both, CSAV- or CSAV+ in comparison to C. This study shows continuing atherosclerotic inflammation on CSAV. Additionally, no evidence of initiated osteoblastic differentiation process was found. Pre-treatment of patients with statins partially neutralized the gene pattern of inflammation on the aortic valves. This suggests that there are potent benefits of statins on early development of inflammation on calcified aortic valves.

Image quality in a low radiation exposure protocol for retrospectively ECG-gated coronary CT angiography.

OBJECTIVE: The purpose of our study was to systematically compare the image quality of dual-source CT coronary angiography using 100 kV instead of 120 kV. SUBJECTS AND METHODS: One hundred patients with a body weight