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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 β-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.

Recent data have suggested a relation among long-term endurance sport practice, left atrial remodeling, and atrial fibrillation. We investigated the influence of an increased vagal tone, represented by the early repolarization (ER) pattern, on diastolic function and left atrial size in professional soccer players. Fifty-four consecutive athletes underwent electrocardiography, echocardiography, and exercise testing as part of their preparticipation screening. Athletes were divided into 2 groups according to presence or absence of an ER pattern, defined as a ST-segment elevation at the J-point (STE) > or =0.1 mm in 2 leads. For linear comparisons average STE was calculated. Mean age was 24 +/- 4 years. Twenty-five athletes (46%) showed an ER pattern. Athletes with an ER pattern had a significant lower heart rate (54 +/- 9 vs 62 +/- 11 beats/min, p = 0.024), an increased E/e' ratio (6.1 +/- 1.2 vs 5.1 +/- 1.0, p = 0.002), and larger volumes of the left atrium (25.6 +/- 7.3 vs 21.8 +/- 5.0 ml/m(2), p = 0.031) compared to athletes without an ER pattern. There were no significant differences concerning maximum workload, left ventricular dimensions, and systolic function. Univariate regression analysis revealed significant correlations among age, STE, and left atrial volume. In a stepwise multivariate regression analysis age, STE and e' contributed independently to left atrial size (r = 0.659, p <0.001). In conclusion, athletes with an ER pattern had an increased E/e' ratio, reflecting a higher left atrial filling pressure, contributing to left atrial remodeling over time.

Aims: Regional myocardial function may change differently in different pathology. Speckle tracking echocardiography (STE) was applied to evaluate longitudinal, radial, and circumferential function in patients with aortic stenosis (AS) before, within 1 week, and 6 months after aortic valve replacement (AVR)., Methods and Results: In 40 consecutive patients with severe AS, we acquired apical four-, three-, and two-chamber views and standard short-axis view pre- and post-AVR and after 6 months. Longitudinal, radial, and circumferential (LS, RS, and CS) were calculated by commercial STE software. Further, we analysed diastolic myocardial function by measuring E/e' ratio. With AVR, valve area increased and remained stable at 6 months follow-up. Left ventricular mass was unchanged 1 week after AVR (270 +/- 58 g vs. 267 +/- 58 g, n.s.) but decreased significantly during the next 6 months (219 +/- 50 g, P < 0.05). Left ventricular ejection fraction remained unchanged. Strain values did not change significantly within 1 week after AVR but increased significantly after 6 months (LS by 16%, RS by 21%, and CS by 28% of baseline values). E/e' ratio was highly augmented before AVR (26.1 +/- 12.5) and decreased significantly 6 months after AVR (15.9 +/- 5.9)., Conclusion: Myocardial function significantly recovers after replacing the stenosed aortic valve. However, there is a considerable difference between the response of longitudinal, radial, and circumferential function. Our data suggest that echocardiographic assessment of regional function is feasible and of potential clinical importance.

Objective: We analyzed typical morphological features of coronary atherosclerotic plaques in acute coronary syndromes (ACS) using contrast-enhanced coronary Dual-Source CT angiography (CTA) in comparison to stable coronary lesions., Patients and Methods: Fifty-five patients with ACS and 55 controls with stable angina pectoris (SAP) with similar atherosclerotic risk profile were studied. CT angiography was performed using a Dual-Source CT scanner (330 ms rotation, 2 x 64 x 0.6mm collimation, 60-80 mL contrast agent i.v. at 6 mL/s) before invasive catheterization. We analyzed plaque volume (mm(3)), mean and minimal CT density (HU), remodeling index, plaque type (calcified/non-calcified/mixed) and presence of "spotty" calcifications as well as presence of contrast rims., Results: In patients with ACS and SAP, 28 and 10 lesions showed both calcified and non-calcified components, but in a greater proportion of non-calcified material, 6 and 23 lesions showed a greater proportion of calcified material and 21 and 8 lesions were completely non-calcified, respectively. None of the culprit plaques in ACS and 14 of the lesions in SAP were completely calcified. A "spotty" pattern of calcification within the plaque and a central filling defect surrounded by a rim of contrast were present in 11 and 14 of 55 ACS cases, but never in SAP lesions. For culprit lesions in ACS and for lesions in patients with SAP, mean plaque volumes were 192.8 + or - 114.9 mm(3) and 103.8+/-51.8 mm(3) (p=0.001), mean and minimal CT densities were 85.6 + or - 45.1HU and 47.2 + or - 33.7 HU versus 143.8 + or - 104.1 HU and 95.9 + or - 84.0 HU (p<0.01) and mean remodeling indices were 1.6 + or - 0.4 and 0.97 + or - 0.17 (p<0.001), respectively., Conclusion: Plaques of culprit lesions in ACS show specific morphologic characteristics in non-invasive coronary CT angiography. As compared to stable lesions, culprit lesions in ACS display greater proportion of non-calcified material and presence of "spotty" calcifications/contrast rims as well as larger plaque volumes, lower CT attenuation and higher remodeling indices., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The quantification of non-calcified coronary plaques using multidetector computed tomography has not been extensively investigated., Objective: To evaluate the ability of dual-source computed tomography (DSCT) to quantify non-calcified plaque volumes using intravascular ultrasound (IVUS) as the standard of reference., Methods: The datasets of 70 patients with suspected or known coronary artery disease who underwent DSCT (330 ms gantry rotation, 2 x 64 x 0.6 mm collimation, 60-90 ml contrast agent) were analysed before invasive coronary angiography, with IVUS performed as part of the diagnostic procedure. 100 individual non-calcified coronary atherosclerotic plaques (one to three plaques per patient) with suitable fiducial markers were matched and selected for plaque volume measurements using manual segmentation. Only DSCT datasets with good or excellent image quality were considered for analysis., Results: Intra and interobserver variability for plaque volume measurements by DSCT were 6+/-5% and 11+/-7%, respectively. Mean total plaque volume by DSCT was 89+/-66 mm(3) (range 14-400 mm(3)). Mean total plaque volume by IVUS was 90+/-73 mm(3) (range 16-409 mm(3)). The mean difference between DSCT and IVUS was 1+/-34 mm(3) (range -131-85 mm(3)). Despite the good correlation for plaque volume measurements (r=0.89, p<0.001), agreement between the two methods was only modest (Bland-Altman limits of agreement -67 to +65 mm(3)). CONCLUSIONS ; Non-calcified plaque volumes as determined by DSCT yielded good correlation but only modest agreement in comparison with IVUS.

Background: The computed tomographic (CT) attenuation of coronary atherosclerotic plaque has been proposed as a marker for tissue characterization and may thus potentially contribute to the assessment of plaque instability., Objective: We analyzed the influence of reconstruction parameters on CT attenuation measured within noncalcified coronary atherosclerotic lesions., Methods: Seventy-two patients were studied by contrast-enhanced dual-source CT coronary angiography (330 millisecond rotation time, 2 x 64 x 0.6 mm collimation, 120 kV, 400 mAs, 80 mL contrast agent intravenously at 6 mL/s), and a total of 100 distinct noncalcified coronary atherosclerotic plaques were identified. Image data sets were reconstructed with a soft (B20f), medium soft (B26f), and sharp (B46f) reconstruction kernel. With the medium soft kernel, image data sets were reconstructed with a slice thickness/increment of 0.6/0.3 mm, 0.75/0.4 mm, and 1.0/0.5mm. Within each plaque, CT attenuation was measured., Results: Mean CT attenuation using the medium soft kernel was 109 +/- 58 HU (range, -16 to 168 HU). Using the soft kernel, mean density was 113 +/- 57 HU (range, -13 to 169 HU), and using a sharp kernel, mean density was 97 +/- 49 HU (range, -23 to 131 HU). Similarly, reconstructed slice thickness had a significant influence on the measured CT attenuation (mean values for medium soft kernel: 102 +/- 52 HU versus 109 +/- 58 HU versus 113 +/- 57 HU for 0.6-mm, 0.75-mm, and 1.0-mm slice thickness). The differences between 0.75-mm and 0.6-mm slice thickness (P = 0.05) and between medium sharp and sharp kernels (P = 0.02) were statistically significant., Conclusions: Image reconstruction significantly influences CT attenuation of noncalcified coronary atherosclerotic plaque. With decreasing spatial resolution (softer kernel or thicker slices), CT attenuation increases significantly. Using absolute CT attenuation values for plaque characterization may therefore be problematic., (Copyright 2010 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Dendritic cells (DC) are crucial for T cell mediated immune responses. Recently, we observed a significant decrease in circulating myeloid DC precursors in patients with acute myocardial infarction (AMI). The aim of the present study was to investigate whether myeloid DC are present in infarcted myocardium. Myocardial specimens of 10 patients with AMI and 7 accident victims (controls) were collected after autopsy. In immunostainings the presence of DC (CD209(+), fascin(+)), T cells (CD3(+)), macrophages (CD68(+)), and HLA-DR expression was analyzed. Significantly higher numbers of CD209(+)-DC (97 vs. 44 cells/0.25 mm(2), p=0.03), fascin(+)-DC (54 vs. 8 cells/0.25 mm(2), p=0.02), T cells (27 vs. 6 cells/0.25 mm(2), p=0.02), and macrophages (44 vs. 6 cells/0.25 mm(2), p=0.01) associated with high HLA-DR expression were detected in infarcted myocardium. Frequent colocalizations of DC and T cells were observed. In occluded coronary arteries numerous DC, T cells, macrophages and high HLA-DR expression were found. We show that DC are present in infarcted myocardium after AMI. High HLA-DR expression and the colocalization with T cells suggest that they might trigger an immune response leading to further myocardial damage.

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

Background: Atherosclerotic plaques develop at arterial regions subjected to non-uniform shear stress, and are initiated by increased leukocyte-endothelial interactions. In this study, we investigated the effects of distinct shear stress patterns on endothelial recruitment of monocytic cells., Methods: Human umbilical vein endothelial cells (ECs) were exposed to laminar or non-uniform shear stress in bifurcating flow-through slides, followed by 2 h stimulation with TNF-α. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells for 1 h. Endothelial protein expression was determined by immunofluorescence., Results: Exposure to non-uniform shear stress and TNF-α lead to progressive induction of adhesion molecules and increase in monocytic cell adhesion observed over 0.5-3 h. To investigate the relative role of the shear stress patterns in monocytic cell recruitment, ECs were exposed to reduced levels of shear stress, resulting in a reduced gradient steepness in the non-uniform shear stress regions. Lowering the shear stress from 10 to 5 and 2 dyne/cm2 resulted in increased monocytic cell adhesion under laminar shear stress. However, in these conditions, adherent monocytic cells under non-uniform shear stress were strongly reduced. Moreover, in the region exposed to shear stress gradient parallel to flow direction, monocytic cell adhesion was significantly lower than in the region of non-uniform shear stress, characterized by transversal gradient., Conclusion: Exposure to non-uniform shear stress results in progressive induction of adhesion molecules and monocytic cell recruitment in response to circulating TNF-α. Enhanced monocytic cell recruitment at bifurcations is affected not only by the magnitude and steepness of shear stress gradient, but also by its direction in relation to the flow.

We compared the measurements of the aortic valve area (AVA) using dual-source computed tomography (DSCT) in patients with mid to severe aortic stenosis to measurements using transthoracic echocardiography (TTE) and invasive hemodynamic assessment. A total of 50 patients (mean age 73 +/- 10 years) with suspected aortic stenosis were included. The computed tomographic data were acquired using DSCT with standardized scan parameters (2 x 64 x 0.6 mm collimation, 330-ms rotation, 120-kV tube voltage, 560 mA/rot tube current). After injection of 35 ml contrast agent (flow rate 5 ml/s), a targeted volume data set, ranging from the top of the leaflets to the infundibulum, was acquired. Ten cross-sectional data sets (slice thickness 1 mm, no overlap, increment 0.6 mm) were reconstructed during systole in 5% increments of the R-R interval. The AVA determined in systole by planimetry was compared to the calculated AVA values using the continuity equation on TTE and the Gorlin formula on catheterization. DSCT allowed the planimetry of the AVA in all patients. The mean AVA using DSCT was 1.16 +/- 0.47 cm(2) compared to a mean AVA of 1.04 +/- 0.45 cm(2) using TTE and 1.06 +/- 0.45 cm(2) using catheterization, with a significant correlation between DSCT/TTE (r = 0.93, p <0.001) and DSCT/cardiac catheterization (r = 0.97, p <0.001). However, DSCT demonstrated a slight, but significant, overestimation of the AVA compared to TTE (+0.12 +/- 0.17 cm) and catheterization (+0.10 +/- 0.12 cm(2)). In conclusion, DSCT permits one to assess the AVA with a high-image quality and diagnostic accuracy compared to TTE and invasive determination.

This study evaluated the ability of dual-source computed tomography (DSCT) to detect coronary allograft vasculopathy (CAV) in heart transplant recipients using intravascular ultrasound (IVUS) as the standard of reference. Thirty patients with heart transplants (81% men, mean age 40 years) underwent DSCT (330-ms gantry rotation, 2 x 64 x 0.6-mm collimation, 60- to 80-ml contrast agent, no additional beta blockers) before invasive coronary angiography including IVUS of 1 vessel. Detection of CAV by DSCT was qualitatively defined as the presence of any coronary plaque. Mean heart rate during dual-source computed tomographic scanning was 80 +/- 14 beats/min. Four hundred fifty-nine segments with a vessel caliber >or=1.5 mm according to quantitative coronary angiography were evaluated in 30 patients. Of these, 96% were considered to have excellent or good image quality. IVUS detected CAV in 17 of 30 patients (57%) and in 41 of 110 coronary segments (37%). Compared to IVUS, sensitivity, specificity, positive and negative predictive values for the detection of CAV by DSCT were 85%, 84%, 76%, and 91%, respectively. In conclusion, DSCT permits the investigation of transplant recipients concerning the presence of CAV with good image quality and high diagnostic accuracy.

Background: A higher mortality risk for women with acute ST-elevation myocardial infarction (STEMI) has been a common finding in the past, even after acute percutaneous coronary intervention (PCI). We set out to analyze whether there are gender differences in real-world contemporary treatment and outcomes of STEMI., Patients and Methods: A retrospective analysis of all consecutive patients with STEMI and acute coronary angiography with the intention of performing a PCI at our center 6/1999-6/2006 was carried out (n = 566). Data were examined for gender-specific differences regarding patients' characteristics, referral patterns, timing of acute symptoms, angiographic findings, procedural details, and adverse events at 30 days after PCI., Results: Women (n = 161) were on average 8 years older than men (n = 405), had higher co-morbidity, were more often transported to the hospital by ambulance and presented less often to the emergency room on their own (4.2% vs. 12.6% in men, P = 0.02). The pre-hospital delay from symptom onset to admission was significantly longer for women (median 185 vs. 135 min, P < 0.02). There was no gender difference in time from admission to PCI (median 46 min vs. 48 min, P = 0.42). Both genders received PCI with similar frequency (88.8% vs. 92.4%, P = 0.19), with similar success rates (83.2% vs. 85.3%, P = 0.68). Thirty-day overall mortality for women was not significantly higher than for men (8.7% vs. 7.2%, P = 0.6). Re-infarction or stroke within 30 days were rare for both genders without gender-specific differences whereas bleeding necessitating blood replacement was significantly more frequent in women (16.8% vs. 5.9%, P < 0.001). In multivariate analysis, female gender was not independently associated with a higher risk of 30-day mortality (OR 0.964, P = 0.93)., Conclusions: Women underwent PCI therapy for STEMI with the same frequency and the same angiographic success as men. Despite their more advanced age and the higher prevalence of co-morbidities, they did not have a significantly higher 30-day mortality rate than men. Female gender was not an independent risk factor of 30-day mortality. Longer pre-hospital delays before hospital admission in women indicate that awareness of risk from coronary artery disease should be further raised in women.

Objective: Atherosclerotic plaque formation results from a combination of local shear stress patterns and inflammatory processes. This study investigated the endothelial response to shear stress in combination with the inflammatory cytokine TNF-alpha in a simplified model of arterial bifurcation., Methods: Human umbilical vein endothelial cells (ECs) were exposed to laminar or non-uniform shear stress in bifurcating flow-through slides, followed by stimulation with TNF-alpha. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Endothelial protein expression was determined by immunofluorescence., Results: Adhesion of monocytic cells to unstimulated ECs was nearly undetectable under laminar shear stress and was slightly increased under non-uniform shear stress. Exposure of ECs to non-uniform shear stress in combination with TNF-alpha induced a 12-fold increase in monocytic cell recruitment and a significant induction of endothelial E-selectin and VCAM-1 expression. Both these effects were prevented in ECs exposed to laminar shear stress. The significant differences in TNF-alpha-induced monocytic cell recruitment and adhesion molecule expression between laminar and non-uniform shear stress regions were abolished in the absence of shear stress preconditioning. Simvastatin (1 micromol/L) suppressed the non-uniform shear stress- and TNF-alpha-induced increase in monocytic cell adhesion by about 30% via inhibition of VCAM-1 expression. Resveratrol, the active component of red wine, inhibited the expression of both VCAM-1 and E-selectin, and reduced monocytic cell recruitment by 50% at 20 micromol/L., Conclusions: Non-uniform shear stress induces endothelial susceptibility to circulating TNF-alpha and adhesion of monocytic cells. Interference with this process may inhibit inflammatory response in atherosclerosis-prone regions.

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.

Objective: Assessment of left ventricular function is possible in contrast-enhanced cardiac CT data sets. However, rapid ventricular motion especially in systole can lead to artifacts. Dual Source Computed Tomography (DSCT) has high temporal resolution which effectively limits motion artifact. We therefore assessed the accuracy of DSCT to detect regional left ventricular wall motion abnormalities in comparison to invasive cine angiocardiography., Methods: We analyzed DSCT data sets of 50 patients (39 male, 11 female, mean age: 61+/-10 years) which were acquired after intravenous injection of 55-70 mL contrast agent (rotation time: 330 ms, collimation: 2 mm x 64 mm x 0.6 mm, 120 kV, 380 mAs, ECG-correlated tube current modulation). 10 data sets consisting of transaxial slices with a slice thickness of 1.5 mm, an increment of 1.0 mm and a matrix of 256 x 256 pixels were reconstructed at 10 time instants during the cardiac cycle (0-90% in 10% increments). The data sets were analyzed visually by two independent readers, using standard left ventricular planes, concerning regional wall motion abnormalities. DSCT was verified in a blinded fashion against cine ventriculography performed during cardiac catheterization (RAO and LAO projection), using a 7-segment model. Analysis was performed on a per-patient (presence of at least one hypo-, a- or dyskinetic segment) and on a per-segment basis., Results: Concerning the presence of a wall motion abnormality, the two observers agreed in 340/350 segments (97%) and 48/50 patients (96%). In invasive cine angiocardiography, 22 of 50 patients displayed at least one segment with abnormal contraction. To detect these patients, DSCT showed a sensitivity of 95% (21/22), specificity of 96% (27/28), positive predictive value of 95% and negative predictive value of 96%. Out of a total of 350 left ventricular segments, 66 segments had abnormal contraction in cine angiocardiography (34 hypokinetic, 26 akinetic, 6 dyskinetic). For detection of these segments, DSCT had a sensitivity of 88% (58/66), specificity of 98% (278/284), positive predictive value of 91% (58/64) and negative predictive value of 97% (278/286)., Conclusion: DSCT allows the detection of regional wall motion abnormalities with high interobserver agreement as well as high sensitivity and specificity. Whereas sensitivity and positive predictive value were higher in a per-patient- in comparison to a per-segment-based analysis, specificity, negative predictive value and interobserver agreement did not differ considerably between both analyzing methods.

Objective: Identification of clinically relevant determinants for acute coronary syndromes (ACS) promises reduction of ACS-associated mortality. C-reactive protein (CRP) has proved to be useful identifying people at risk for cardiovascular events. However, it is unknown whether genetic variants at Fcgamma receptor IIa (FcgammaRIIa), the main receptor for CRP, are involved in CRP-related cardiovascular risk. We evaluated the potential impact of FcgammaRIIa through a genetic association study in patients with ACS., Methods and Results: We conducted a genetic association study among 701 consecutive patients with first event of ACS compared to 467 patients with stable angina pectoris. All patients were genotyped for a frequent functional variant at position 131 of the mature FcgammaRIIa, where the arginine (R) allele results in an increased signal transduction upon CRP binding. In our study, the R/R131 genotype was significantly associated with ACS as the first manifestation of coronary artery disease (P=1.2x10(-9), odds ratio 2.86, 95% CI: 2.06-3.99) compared to the non-R/R131 genotype., Conclusions: Our data show a genetic association of the FcgammaRIIa R/R131 genotype with a more frequent occurrence of ACS as the first manifestation of coronary artery disease, probably mediated via its interaction with CRP. Genotyping of this FcgammaRIIa variant could help to improve risk stratification in the course of coronary disease in the future.

Objective and Design: Atherosclerosis, as an inflammatory disease, is characterized by pathologically altered levels of cytokines. We investigated whether smoking affects the CD40/CD154 system and pro-inflammatory cytokines in young males without other risk factors for atherosclerosis., Subjects: Young male smokers (n=13) and 14 non-smoking controls were investigated., Methods: The differences in CD40/CD154 system and serum cytokines between the groups were measured using flow cytometry and ELISA., Results: In smokers, there was a strong trend (P<0.06) for increased CD40 expression on platelets as compared with non-smokers. However, there were no significant differences in CD40 expression on monocytes or in CD154 expression on platelets and T-cells between smokers and non-smokers. There was a strong trend for increased platelet-monocyte aggregates in smokers (P<0.06). Also, smokers had slightly but not significantly elevated hsCRP and IL-6 levels, and slightly decreased TNF-alpha and MCP-1. Interestingly, IL-18, a cytokine which has the ability to promote both Th1 and Th2 responses, was significantly decreased in smokers group (P=0.03 vs controls)., Conclusions: In young healthy males, smoking is not associated with dramatic changes in CD40/CD154 system. However, cigarette smoke alters the secreted cytokine profile, leading to significant decrease in systemic IL-18 levels.

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

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.

Purpose: Spiral CT angiography (CTA) of the coronaries using low-pitch scanning and ECG-gated image reconstruction is a robust method for detecting or excluding relevant coronary plaque. However, the resulting dose exposure is considerable. The aim of the present study was to evaluate image quality and artifacts as well as to record dose values for sequential coronary CTA using a 128-slice scanner with a temporal resolution of 150 ms., Materials and Methods: 20 patients with a regular heart rate and without contraindications for oral/I.V. beta blockers, who were referred for CTA of the coronaries for exclusion or detection of relevant plaques, were examined by sequential CTA with the following parameters: 120 kV, 200 ref mAs, collimation 2 x 64 x 0.6, table feed of 34.5 mm at a detector width of 38.4 mm. A total acquisition time of 380 ms per table position allowed for mild shifting of the reconstruction window within the cardiac cycle of +/- 5 %. 50 ml of contrast agent were injected at 5 ml/s followed by a 50 ml split bolus (20 % contrast). The individual start delay was determined by a test bolus scan (10 ml contrast + 50 ml saline flush at 5 ml/s). The image quality for each segment, coronary artery, and patient was determined on a 4-point scale. Dose values were estimated based on the individual dose length product as provided by the scanner's patient protocol. Artifacts were evaluated to determine the cause (calcium vs. motion)., Results: All patients received beta blocker pretreatment. The mean heart rate was 62 +/- 5 beats/min. 5 % (13 / 286) of all segments in 5 / 20 patients were rated as non-diagnostic. The mean dose length product was 213 mGy x cm, and the mean effective dose was 3.6 mSv. Calcifications were the major cause of non-diagnostic images. However breathing or other motion artifacts occurred as well., Conclusion: In select patients with effective heart rate control and thorough instruction for breath hold compliance, sequential CTA of the coronaries using a 128-slice scanner with a temporal resolution of 150 ms is technically feasible. The resulting effective dose values are clearly below those of spiral coronary CT scans.

Assessment of coronary artery stents using computed tomographic angiography has been challenging. The technology of dual-source computed tomography (DSCT) provides higher temporal resolution that may allow more accurate evaluation of coronary stents. This study evaluated the accuracy of DSCT for the assessment of coronary artery in-stent restenosis. A total of 112 patients with 150 previously implanted coronary stents (diameter > or = 3.0 mm) were examined using DSCT (Definition; Siemens Medical Solutions, Forchheim, Germany) before conventional coronary angiography. Each stent was classified as assessable or not assessable. All assessable stents were further classified for the absence or presence of in-stent restenosis (>50% diameter reduction) using DSCT, and results were compared with those using quantitative coronary angiography. Mean stent diameter was 3.27 +/- 0.35 mm. Fifteen of 80 stents (19%) with a diameter of 3.0 mm were not assessable, and all 70 stents >3.0 mm were assessable. DSCT correctly identified 16 of 19 in-stent restenoses in 135 assessable stents, as well as the absence of in-stent restenosis in 110 of 116 stents (sensitivity 84%, specificity 95%, positive predictive value 73%, and negative predictive value 97% in assessable stents). In conclusion, DSCT may be useful to noninvasively detect in-stent restenosis, especially in stents with a relatively large diameter.

Coronary CT angiography allows high-quality imaging of the coronary arteries when state-of-the-art CT systems are used. However, radiation exposure has been a concern. We describe a new scan mode that uses a very high-pitch spiral acquisition, "Flash Spiral," which has been developed specifically for low-dose imaging with dual-source CT. The scan mode uses a pitch of 3.2 to acquire a spiral CT data set, while covering the entire volume of the heart in one cardiac cycle. Data acquisition is prospectively triggered by the electrocardiogram and starts in late systole to be completed within one cardiac cycle. Images are reconstructed with a temporal resolution that corresponds to one-quarter of the gantry rotation time. Throughout the data set, subsequent images are reconstructed at later time instants in the cardiac cycle. In a patient with a heart rate of 49 beats/min, the Flash Spiral scan mode was used with a first-generation dual-source CT system and allowed artifact-free visualization of the coronary arteries with a radiation exposure of 1.7 mSv for a 12-cm scan range at 120 kVp tube voltage.

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.

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.

Background: Data on contemporary real-world outcomes of interventional revascularization in patients > or = 75 y of age with ST elevation infarction (STEMI) are limited., Methods: We analyzed all 504 consecutive patients who underwent angiography for acute STEMI between 1999 and 2005 at our center, and followed them up over one year. Outcomes in patients > or = 75 y of age were compared with younger patients., Results: Patients > or = 75 y of age (n = 115) were majority females (55% versus 21%, p < 0.001), more cases of diabetes (42% versus 27%, p = 0.004), hypertension (78% versus 65%, p = 0.03) and a history of coronary events (25% versus 15%, p = 0.002). Younger patients were more often smokers (63% versus 30%, p < 0.001). After coronary angiography patients > or = 75 y of age underwent less frequent intervention (PCI; 84% versus 93%, p = 0.01). However, if PCI was performed, technical success rates were similar to younger patients (84% versus 86%). The 30-d mortality was 13% versus 6.4% (p = 0.03), but after successful PCI, the 30-d mortality rate was not significantly higher in old patients (7.4% versus 3.9%, p = 0.23). Bleeding complications were very low in both age groups if the radial access route was chosen. Multivariate predictors of 30-d mortality were cardiogenic shock/survived cardiac arrest, ejection fraction < 30%, conservative treatment or unsuccessful PCI (OR 3.01), renal insufficiency, diabetes, and age. One-y mortality was higher in the elderly (24.3% versus 9.9%, p < 0.001). Among 30-d-survivors, only multivessel disease and age were multivariate predictors of 1-y mortality., Conclusion: Patients > or = 75 y of age benefit from PCI in STEMI, and failed or unattempted PCI worsens prognosis in the old as well as in younger patients.

Background: Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Vascular endothelial cell growth factor (VEGF) is currently discussed as a possible mediator of inflammation. To investigate the hypothesis that VEGF plays a role as an inflammatory mediator in EH we performed the present pilot study of young patients in a very early stage of EH., Materials and Methods: 15 young patients with mild EH [33.8 +/- 7.3 years, systolic blood pressure (SBP): 143.8 +/- 10.5 mmHg, diastolic blood pressure (DBP): 88.2 +/- 11.1 mmHg, mean arterial pressure (MAP) 106.6 +/- 10.4 mmHg] and 15 healthy controls (31.7 +/- 10.6 years) were examined. Blood was drawn from a peripheral vein and serum levels of VEGF, monocyte-chemoattractant-protein (MCP)-1, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and tumour-necrosis-factor (TNF)-alpha were measured via commercially available enzyme-linked immunoassays., Results: Hypertensives showed increased plasma levels of VEGF (P < 0.05) and MCP-1 (P < 0.05). VEGF positively correlated with MAP (r = 0.46, P < 0.05) and MCP-1 (r = 0.63, P < 0.01). Multivariate analysis demonstrated VEGF to be an independent predictor of MCP-1 levels. Furthermore, hypertensives had higher levels of hsCRP (P < 0.01), IL-6 (P < 0.001) and TNF-alpha (P < 0.05). IL-6 levels correlated with SBP (r = 0.59, P < 0.001), DBP (r = 0.67, P < 0.001) and MAP (r = 0.46, P < 0.001). A significant positive correlation was also found between hsCRP levels and SBP (r = 0.39, P < 0.05)., Conclusions: This pilot study demonstrates that in an early state of EH, inflammatory pathways have already been activated. Besides classical pro-inflammatory cytokines, VEGF serum levels are significantly elevated. The positive correlation of VEGF with MCP-1 is suggestive for the already described induction of MCP-1 via VEGF.

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.

Endothelial cells are maintaining atherosclerotic signaling mediated by Extracellular Regulated Kinases 1 and 2 (ERK). Signaling gets activated upon stimulation of G protein-coupled receptors mediated by G(q) and G(i/o) proteins subjected to regulation by RGS proteins. The goal of the study was to delineate the specificity of RGS proteins modulating induced ERK phosphorylation. We used stimulated HUVEC, silenced specifically RGS proteins and compared assessed ERK 1/2 activation with immunohistochemical stainings on atherosclerotic plaques. Increased ERK phosphorylation was detected upon stimulation with Phenylephrine (2.6+/-0.1 times over basal), Endothelin-1 (1.8+/-0.2), Dopamine (5.1+/-0.2), TNF (9.8+/-0.7) or IL-4 (3.1+/-0.3). RGS silencing increased activation of ERK 1/2: Phen (RGS3, 5), ET-1 (RGS3, 4), Dopa (RGS3), TNF (RGS2, 3, 4) or IL-4 (RGS2, 3, 4). Immunohistochemically, increased ERK activation was detected on atherosclerotic plaques. This data supports the role of RGS proteins on ERK activation in human atherosclerosis which identifies RGS proteins as new therapeutical targets.

Invasive catheterization can lead to mechanically induced spasm of coronary arteries. In this case report, CT angiography allowed us to unmask catheter-induced coronary spasm as the underlying reason for isolated left main coronary artery stenosis seen in invasive angiography.

In myocardial contrast echocardiography (MCE), power modulation technique may quantify myocardial perfusion in real-time. However, constant infusion of the contrast agent (CA) complicates handling. This pilot study sought for the clinical feasibility of quantitative MCE by a CA bolus application during Adenosine stress echocardiography to diagnose coronary artery disease (CAD). Twenty-four consecutive patients (pts) with contemporary coronary angiography underwent rest and maximum Adenosine stress. Signal intensity could be calculated in 316/348 left ventricular (LV) segments (91%) (18-segment model). At rest, gamma-variate (alpha) as well as saturation function (beta) was not significantly different in healthy men (n = 268) as well as CAD pts (n = 48) (alpha: 0.34 s(-1) versus 0.40 s(-1), n.s.; beta: 0.31 s(-1) versus 0.35 s(-1), n.s.). During Adenosine infusion both values increased in healthy men (alpha: 0.34 +/- 0.37 s(-1) versus 0.44 +/- 0.45 s(-1), p < 0.05; beta: 0.31 +/- 0.33 s(-1) versus 0.40 +/- 0.40 s(-1), p < 0.01), but not in CAD (alpha: 0.40 +/- 0.35 s(-1) versus 0.29 +/- 0.29 s(-1), n.s.; beta: 0.35 +/- 0.32 s(-1) versus 0.27 +/- 0.30 s(-1), n.s.). Sensitivity of alpha/beta reserve

The ability of contrast-enhanced CT to detect "late enhancement" in a fashion similar to magnetic resonance imaging has been reported previously. Typical myocardial distribution patterns of "late enhancement" have been described for MRI. The same patterns can be observed in CT imaging, albeit at a lower signal to noise ratio. We report a case of cardiac amyloidosis with a typical pattern of subendocardial, circumferential late enhancement in all four cardiac chambers.

Aims: The transradial (TR) approach has potentially lower complication rates than transfemoral (TF) approach coronary angiography. However, it may be technically more challenging, especially in elderly patients with alterations in vascular anatomy. We thus determined success rates, procedural data, and complication rates of TR angiography in comparison to the TF approach in elderly patients in a randomized, prospective trial., Methods and Results: Four hundred consecutive patients >or=75 years with known or suspected coronary artery disease were included in the study. After exclusion of 93 patients with contraindications to the radial approach, 152 patients were randomized to the TR and 155 to TF coronary angiography and intervention. In 13 patients randomized to TR, cross-over to TF was necessary (9%). Total examination time was significantly longer for the TR approach (18.1 vs. 15.0 min, P = 0.009), but no difference was found for fluoroscopy time, number of catheters used, or amount of contrast agent. The rate of major complications (bleeding requiring surgery or transfusion, stroke) was 0% for TR and 3.2% for TF approach (P < 0.001). Minor complications occurred in 1.3% versus 5.8% of patients (P < 0.001)., Conclusion: In elderly patients, TR coronary angiography and intervention has a high technical success rate and lower complication rates than the TF approach., ((c) 2008 Wiley-Liss, Inc.)

The signal transduction activating extracellular-regulated kinases (ERK) is triggered by G protein-coupled receptors (GPCR). In turn, the GPCR are mediated by G(q) and G(i/o) proteins subjected to regulation of regulators of G protein-mediated signaling (RGS) proteins. This network compiles extracellular growth signals to intracellular targets of sclerosis on calcified and stenotic human aortic valves (CSAV). Statins are known as partial inhibitors of atherosclerotic inflammation on CSAV. This study identifies descriptively the role of statins on RGS subjected ERK activation on CSAV. We collected human CSAV with (n=10, CSAV+) or without (n=10, CSAV-) at least 4 weeks of statin pre-treatment and investigated gene-profiling of RGS proteins, intermediaries and ERK using microarray technique, real-time and semi-quantitative PCR. Human non-calcified aortic valves were controls (n=6, C). Immunohistochemical stainings defined activation of expressed ERK 1/2 on CSAV (+/-) or C. As compared to C, in CSAV- several cardiac expressed RGS proteins were translationally upregulated: RGS1 (2.6 compared C), RGS3 (3.1), RGS5 (2.1) and RGS8 (2.5). In CSAV+, statins neutralized observed RGS expression. ERK expression was found unchanged in all valves: CSAV-, CSAV+ or C. In contrast, immunohistochemically we found enhanced activation of phosphorylated ERK in CSAV+ as compared to CSAV- or control. This study shows reduced RGS protein expression through statins leading to increased activation of ERK on human CSAV. In regard to known studies, the partial therapeutical failure of statins on severe end-stage CSAV is due to the induction of ERK activation which offers the need for more investigation.

Evidence has shown that pro-inflammatory cytokines, especially TNF-alpha, are involved in the inflammatory response in the remodelling process after myocardial infarction (MI). Although IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha, little is known about its role in post-MI left ventricular (LV) dysfunction. The aim of the present study was to investigate whether a therapy with rhIL-10 could be beneficial in an animal model of post-MI heart failure (HF). Rats with experimental MI were treated with rhIL-10 (75 microg/kg/d sc) starting directly after MI induction, and continuing for 4 weeks. Controls were untreated MI and sham-operated rats. 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, the ratio of TNF-alpha to IL-10, serum levels of MCP-1 as well as myocardial macrophage infiltration, were analyzed. Treatment with rhIL-10 significantly improved post-MI LV function (FS +127%;, dP/dt(max) +131%; LVEDP -36%). This effect was associated with a significant decrease in pro-inflammatory cytokine and chemokine levels (TNF-alpha, IL-6, MCP-1) and furthermore resulted in a reduced myocardial infiltration of macrophages.

Cardiac computed tomography (CT) angiography permits detection of myocardial scars through "late enhancement." We report the case of a patient with suspected cardiac sarcoidosis. Because of implanted defibrillator leads, magnetic resonance imaging was not possible. Dual-source CT with intravenous contrast injection was used as an alternative technique to detect late myocardial enhancement. A typical pattern of myocardial scarring allowed us to establish the diagnosis of cardiac sarcoidosis. CT imaging may be an alternative diagnostic tool to visualize late enhancement in patients with contraindications to magnetic resonance imaging.

Background: Epidemiological studies support the protective effect of omega-3 fatty acids on sudden cardiac death. However, patients with structural heart disease and an implantable cardioverter defibrillator (ICD) showed no effect or even a proarrhythmic response to fish oil supplementation. Animal studies suggest different electrophysiologic effects of circulating and incorporated omega-3 fatty acids., Methods: In 102 ICD patients in New York Health Association functional class II or III, the fatty acid composition of red blood cells was analyzed by gas chromatography. The omega-3 index was calculated from eicosapentaenoic acid and docosahexaenoic acid. Patients were followed for 1 year, and ventricular arrhythmias requiring antitachycardic therapy were analyzed. Twenty-five healthy subjects served as control., Results: In ICD patients, the fatty acid profile was significantly altered and the baseline omega-3 index was significantly elevated, as compared to control subjects (5.12% +/- 0.87% vs 4.24% +/- 0.96%, P < .001). Kaplan-Meier estimates of probability of ventricular arrhythmias showed significant differences among quartiles of the omega-3 index. Twelve percent of patients in the lowest quartile had ventricular arrhythmias, as compared to 54% of patients in the highest quartile (P = .022). In a multivariate analysis, the omega-3 index was the only independent predictor for ventricular arrhythmias up to 9 months. At 12 months, a reduced ejection fraction was an additional risk predictor., Conclusions: In heart failure patients, the red blood cell fatty acid profile is altered. Omega-3 fatty acids are elevated and predict the risk of ventricular arrhythmias.

Multidetector computed tomography (MDCT) permits the visualization of the coronary arteries and of coronary atherosclerotic plaques. The natural course of noncalcified plaque is not known. This study was conducted to measure the change in noncalcified coronary plaque volume in the left main coronary artery and in the proximal left anterior descending coronary artery over time using 64-slice MDCT. Fifty patients in whom noncalcified lesions had been detected on baseline MDCT received follow-up scans after an interval of 17 +/- 6 months. Plaque areas were traced manually in serial multiplanar reconstructions to determine overall volume. The mean plaque volumes were 92 +/- 81 mm(3) on baseline MDCT and 115 +/- 110 mm(3) on follow-up MDCT (p <0.001). The mean annualized volume change was 22% (95% confidence interval 14.7% to 29.7%). A weak but significant correlation with low-density lipoprotein cholesterol level was observed for the amount of baseline plaque volume (r = 0.37, p <0.001). In conclusion, the quantification of noncalcified plaque volume is possible on repeated 64-slice MDCT. A significant increase of the amount of noncalcified plaque was observed over a mean interval of 17 months. Contrast-enhanced MDCT may therefore be a tool to study the progression of coronary atherosclerosis.

Unlabelled: Multi-detector CT (MDCT) permits non-invasive visualization of the coronary arteries. Coronary plaque can be visualized, and earlier studies have indicated that the CT attenuation measured in atherosclerotic plaques is influenced by plaque composition. Also, MDCT has been shown to permit assessment of remodeling of coronary atherosclerotic lesions. It is assumed that both lipid-rich plaques and those that display positive remodeling are more prone to rupture and erosion. We thus evaluated the relationship between remodeling and CT attenuation of coronary atherosclerotic plaque by MDCT., Methods: Seventy-six patients were investigated by contrast-enhanced 64-slice CT. One-hundred twelve atherosclerotic lesions without substantial calcification and visualized with high image quality were selected. Multiplanar reconstructions orthogonal to the coronary artery were rendered at the lesion and the proximal reference site. Cross-sectional vessel areas were measured to determine the remodeling index (RI: lesion vessel area/reference vessel area) and the CT attenuation of plaque was measured by fitting a region of interest to the plaque area. CT attenuation of plaque was correlated to the presence of positive remodeling index (RI>1.05)., Results: The mean cross-sectional vessel area in the lesion was 0.25+/-0.08 cm(2), the mean reference vessel area was 0.22+/-0.09 cm(2). The mean CT attenuation of the atherosclerotic plaque in the lesions was 71+/-26 HU. CT attenuation of plaque was significantly lower in 72 lesions that displayed positive remodeling (59+/-22 HU) than in 40 lesions with no or with negative remodeling (91+/-20 HU, p<0.001)., Conclusions: Positive remodeling of coronary atherosclerotic lesions correlates to lower CT attenuation of plaque, which has been demonstrated to be associated with lipid-rich plaque. Both characteristics indicate increased risk for plaque rupture and subsequent events and could thus prove useful when the use of CT imaging for the detection of "vulnerable plaque" is considered.

Velocity and deformation imaging by Doppler and newer techniques based on "speckle tracking" in 2-D datasets have substantially added to the ability of echocardiography to detect myocardial ischemia. Typical parameters include tissue velocities and regional deformation ("strain") and deformation rate ("strain rate"), which with the Doppler-independent new techniques ("2-D strain", "velocity vector imaging") can be measured in several directions, largely independent of insonation angle. All of these techniques can be readily combined with stress echocardiography; so far, published results are mostly based on the combination with dobutamine echocardiography. Typical signs of myocardial ischemia include a decrease in tissue velocities, deformation rates, and deformation. Additionally, systolic deformation occurs later in systole and often still goes on after aortic valve closure (postsystolic deformation). While tissue velocities are unable to clearly identify regional ischemia because of tethering of the neighboring wall segments and a physiological variation in regional tissue velocities, deformation parameters are better suited to detect regional ischemia. The limited literature on the detection of myocardial ischemia by these techniques clearly shows a value of velocity and deformation imaging especially in those cases where qualitative visual assessment of wall motion remains ambiguous. Due to rapid evolution of these techniques, a final assessment of their potential is not possible yet.

Objectives: The purpose of this study was to analyze the influence of a systematic approach to lower heart rate for coronary computed tomography (CT) angiography on diagnostic accuracy of 64-slice single- and dual-source CT., Background: Coronary CT angiography is often impaired by motion artifacts, so that routine lowering of heart rate is usually recommended. This is often conceived as a major limitation of the technique. It is expected that higher temporal resolution, such as with dual-source 64-slice CT, would allow diagnostic imaging even without systematic pre-treatment for lowering the heart rate., Methods: Two hundred patients with suspected coronary artery disease were first randomized to either 64-slice single-source CT (n = 100) or dual-source CT (n = 100) for contrast-enhanced coronary artery evaluation. In each group, patients were further randomized to either receive systematic heart rate control (oral and intravenous beta-blockade for a target heart rate < or =60 beats/min) or receive no premedication. Evaluability of datasets and diagnostic accuracy were compared between groups against the results obtained from invasive angiography., Results: Systematic pre-treatment lowered heart rate during CT coronary angiography by 10 beats/min. Heart rate control significantly improved evaluability in single-source CT (93% vs. 69% on a per-patient basis, p = 0.005), whereas it did not in dual-source CT (96% vs. 98%). In evaluable patients, sensitivity to detect the presence of at least 1 coronary stenosis by single-source CT was 86% and 79%, respectively, with and without heart rate control (p = NS). For dual-source CT, it was 100% and 95%, respectively (p = NS). The rate of correctly classified patients, defined as evaluable and correct classification as to the presence or absence of at least 1 coronary artery stenosis, was significantly improved by heart rate control in single-source CT (78% vs. 57%, p = 0.04), whereas there was no such influence in dual-source CT (87% vs. 93%)., Conclusions: Systematic heart rate control significantly improves image quality for coronary visualization by 64-slice single-source CT, whereas image quality and diagnostic accuracy remain unaffected in dual-source CT angiography. Improved temporal resolution obviates the need for heart rate control.

Background: Increasing scientific data suggest a role for inflammation in chronic heart failure (CHF), but up to now the exact mechanisms are still not clear. Recently, platelets were identified as inducing inflammation partly by releasing cytokines. This new aspect necessitates further studies about the contribution of platelets for the inflammatory setting of CHF., Methods: 50 CHF patients (mean 66.9 (SD 12.6) years, mean EF 22.1% (SD 9.1)) and 25 healthy controls (mean 63.6 (SD 10.2) years) were examined. MCP-1 serum levels were measured via EIA, expression of platelet CD154 by flow cytometry. In in-vitro experiments activated platelets were cocultured with human umbilical vein endothelial cells (HUVEC) in the presence and absence of anti-CD154 antibodies. MCP-1 in the supernatants was measured by EIA., Results: CHF patients showed significantly enhanced MCP-1 levels (median: 191.8; 25th centile: 153.7; 75th centile: 227.1 pg/ml vs median: 101.0; 25th centile: 86.7; 75th centile: 117.5 pg/ml, p<0.001). MCP-1 levels positively correlated with severity of CHF. In the cell coculture model activated platelets were able to significantly induce MCP-1 release from HUVEC in a CD154-dependent manner. Furthermore, CHF patients showed enhanced platelet CD154 expression with a positive correlation with MCP-1 levels. Aspirin therapy had no influence on either CD154 expression or MCP-1 levels., Conclusions: Platelets can contribute to enhanced MCP-1 levels in CHF. MCP-1 is markedly elevated in serum of CHF patients showing a direct correlation with the severity of symptoms and the degree of left ventricular dysfunction. Further studies are required to test whether MCP-1 blocking or sophisticated anti-platelet strategies may represent new therapeutic options in CHF.

Shear stress changes play an important role in atheroma formation. This study focussed on atherogenic protein expression under non-uniform shear stress and the pharmacological modulation of shear-related endothelial dysfunction. Bifurcating flow-through cell culture slides were used to expose HUVECs to steady laminar or non-uniform shear stress for 18 h at 10 dyn/cm(2). Protein expression was determined by immunofluorescence, and quantified using MetaVue software. Laminar shear stress resulted in cell alignment, reduced F-actin fibers, and significant induction of endothelial nitric oxide synthase expression. Under non-uniform shear stress at bifurcations, minor upregulation of adhesion molecules was observed. Connective tissue growth factor (CTGF) was significantly downregulated by laminar shear stress and induced in cells exposed to non-uniform shear stress. CTGF upregulation by non-uniform shear stress was RhoA-dependent, because it was almost completely inhibited in cells transfected with dominant negative RhoA-N19, and when cells were treated with 1 micromol/L simvastatin during flow. Pre-incubation of HUVECs with inhibitors of Rho-associated kinase before exposure to flow significantly suppressed the CTGF induction in regions of non-uniform shear stress. In conclusion, non-uniform shear stress-dependent CTGF expression requires active RhoA and can be prevented pharmacologically. Interference with shear stress-induced protein expression may inhibit endothelial dysfunction in atheroprone vessel regions.

Real-time myocardial contrast echocardiography (MCE) is a noninvasive perfusion imaging method, whereas technical and resolution problems impair its application in small animals. Hence, we investigated the feasibility of MCE in experimental cardiovascular set-ups involving healthy and infarcted myocardium in rats. Twenty-five male Wistar rats were examined under volatile anesthesia (2.5% isoflurane) with high-resolution conventional 2-D echocardiography (2DE) and real-time MCE (Sonos 7,500 with 15MHz-transducer, Philips Medical Systems, Andover, MA, USA) in short-axis view. Contrast agent (SonoVue, Bracco, Milan, Italy) was infused as a bolus into a sublingual vein. Background-subtracted contrast signal intensity (SI) was measured off-line in six end-systolic segments and fitted to an exponential curve (gamma variate). Derived peak SI was subsequently calculated and compared with wall motion and common functional measured quantities (left ventricular end-diastolic diameter [LVEDD], area shortening [AS]). Recordings were performed before and 14 days after left anterior descending (LAD) ligature. Infarction induced anterior wall motion abnormalities (WMA) in all animals (16 akinetic, 9 hypokinetic), increased LVEDD (9.1 +/- 0.6 vs. 7.9 +/- 0.6 mm, p < 0.001), reduced AS (36.1 +/- 10.0 vs. 59.5 +/- 4.1%, p < 0.001) and reduced anterior segmental SI (0.4 +/- 0.4 dB akinetic / 1.7 +/- 1.7 dB hypokinetic vs. 15.8 +/- 10.9 dB preinfarct, p < 0.001 / p < 0.001). Segmental SI in normokinetic segments remained unchanged. Area at risk (perfusion defect) correlated well with WMA (r = 0.838). These data confirmed high-resolution real-time MCE as a rational tool for assessing myocardial perfusion of Wistar rats. It may therefore be a useful diagnostic tool for in-vivo cardiovascular research in small animals.