Christian Herdeg

Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography

OBJECTIVES The aim of the present study was to evaluate the accuracy in determining coronary lesion configuration by multislice computed tomography (MSCT). The results were compared with the findings of intracoronary ultrasound (ICUS). BACKGROUND The risk of acute coronary syndromes caused by plaque disruption and thrombosis depends on plaque composition rather than stenosis severity. Thus, the reliable noninvasive assessment of plaque configuration would constitute an important step forward for risk stratification in patients with known or suspected coronary artery disease. Just recently, MSCT scanners became available for general purpose scanning. Due to improved spatial and temporal resolution, this new technology holds promise to allow for differentiation of coronary lesion configuration. METHODS The ICUS and MSCT scans (Somatom Volume Zoom, Siemens, Forchheim, Germany) were performed in 15 patients. Plaque composition was analyzed according to ICUS (plaque echogenity: soft, intermediate, calcified) and MSCT criteria (plaque density expressed by Hounsfield units [HU]). RESULTS Thirty-four plaques were analyzed. With ICUS, the plaques were classified as soft (n = 12), intermediate (n = 5) and calcified (n = 17). Using MSCT, soft plaques had a density of 14 +/- 26 HU (range -42 to +47 HU), intermediate plaques of 91 +/- 21 HU (61 to 112 HU) and calcified plaques of 419 +/- 194 HU (126 to 736 HU). Nonparametric Kruskal-Wallis test revealed a significant difference of plaque density among the three groups (p < 0.0001). CONCLUSIONS Our results indicate that coronary lesion configuration might be correctly differentiated by MSCT. Since also rupture-prone soft plaques can be detected by MSCT, this noninvasive method might become an important diagnostic tool for risk stratification in the near future.

Clinical studyNoninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography1

OBJECTIVES The aim of the present study was to evaluate the accuracy in determining coronary lesion configuration by multislice computed tomography (MSCT). The results were compared with the findings of intracoronary ultrasound (ICUS). BACKGROUND The risk of acute coronary syndromes caused by plaque disruption and thrombosis depends on plaque composition rather than stenosis severity. Thus, the reliable noninvasive assessment of plaque configuration would constitute an important step forward for risk stratification in patients with known or suspected coronary artery disease. Just recently, MSCT scanners became available for general purpose scanning. Due to improved spatial and temporal resolution, this new technology holds promise to allow for differentiation of coronary lesion configuration. METHODS The ICUS and MSCT scans (Somatom Volume Zoom, Siemens, Forchheim, Germany) were performed in 15 patients. Plaque composition was analyzed according to ICUS (plaque echogenity: soft, intermediate, calcified) and MSCT criteria (plaque density expressed by Hounsfield units [HU]). RESULTS Thirty-four plaques were analyzed. With ICUS, the plaques were classified as soft (n = 12), intermediate (n = 5) and calcified (n = 17). Using MSCT, soft plaques had a density of 14 +/- 26 HU (range -42 to +47 HU), intermediate plaques of 91 +/- 21 HU (61 to 112 HU) and calcified plaques of 419 +/- 194 HU (126 to 736 HU). Nonparametric Kruskal-Wallis test revealed a significant difference of plaque density among the three groups (p < 0.0001). CONCLUSIONS Our results indicate that coronary lesion configuration might be correctly differentiated by MSCT. Since also rupture-prone soft plaques can be detected by MSCT, this noninvasive method might become an important diagnostic tool for risk stratification in the near future.

Local Paclitaxel Delivery for the Prevention of Restenosis: Biological Effects and Efficacy In Vivo

OBJECTIVE The aim of this study was to evaluate the potential of paclitaxel to prevent restenosis in vivo. BACKGROUND Paclitaxel (Taxol) is a microtubule-stabilizing compound with potent antitumor activity. It influences the cytoskeleton equilibrium by increasing the assembly of altered microtubules, thereby inducing cellular modifications that result in reduced proliferation, migration and signal transduction. METHODS Before the in vivo study, delivery efficiency was determined with radiolabeled paclitaxel in porcine hearts. After induction of a defined plaque in the right carotid arteries of 76 New Zealand rabbits by electrical stimulation, 27 animals underwent balloon dilation and subsequent local paclitaxel delivery (10 ml, 10 micromol/liter) with a double-balloon catheter. Twenty-nine animals served as control with angioplasty only, 10 animals underwent local delivery of vehicle only (0.9% NaCl solution) and 10 animals were solely electrostimulated. Vessels were excised one, four, and eight weeks after intervention. RESULTS The extent of stenosis in paclitaxel-treated animals was significantly reduced compared with balloon-dilated control animals (p = 0.0012, one, four and eight weeks after intervention: 14.6%, 24.6% and 20.5%, vs. 24.9%, 33.8% and 43.1%, respectively). Marked vessel enlargement compared with balloon-dilated control animals could be observed (p = 0.0001, total vessel area after one, four and eight weeks: paclitaxel group: 1.983, 1.700 and 1.602 mm2, control: 1.071, 1.338 and 1.206 mm2, respectively). Tubulin staining and electron microscopy revealed changes in microtubule assembly, which were limited to the intimal area. Vasocontractile function after paclitaxel treatment showed major impairment. CONCLUSIONS Local delivery of paclitaxel resulted in reduced neointimal stenosis and enlargement in vessel size. Both these effects contribute to a preservation of vessel shape and are likely to be caused by a structural alteration of the cytoskeleton.

Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: Pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging

BACKGROUND Peripheral endothelial dysfunction (ED) quantified by the determination of flow-mediated dilation (FMD%) of the brachial artery with the use of high-resolution ultrasound is an early marker of atherosclerosis. Although a positive correlation with coronary artery disease (CAD) has been reported, the unanswered clinical question is the validity of FMD% as a screening test in patients with clinical suspicion of CAD. Thus the aim of this study was to determine the predictive value of FMD% compared with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. METHODS AND RESULTS In this pilot study, we measured ED in 122 patients scheduled for coronary angiography by using high-resolution ultrasound (13 MHz). We defined ED as FMD% </=4.5%. The presence of CAD was defined as angiographically detectable atherosclerotic vessel alterations of any degree. Exercise electrocardiography and myocardial perfusion imaging had been performed on an outpatient basis. Statistical analysis was conducted by analysis of variance and Mantel-Haenszel chi-square test. Patients with CAD (n = 101) had a significantly lower FMD% than patients without CAD (n = 21; 3.7% +/- 4.1% vs 7.01% +/- 3.5%, P <.001). A sensitivity of 71%, a specificity of 81% with a positive predictive value of 0.95 (72 of 76), and a negative predictive value of 0.41 (17 of 46) was calculated. In comparison to angina pectoris (sensitivity 95%, specificity 47.6%), exercise electrocardiography (sensitivity 82.4%, specificity 57.1%) and myocardial perfusion imaging (sensitivity in our study group 100%) had the best specificity, and a high sensitivity for FMD% was found. CONCLUSIONS The determination of ED was found to be a sensitive and specific screening test to predict the presence of CAD. Because this is a noninvasive, nonradioactive, and cost-effective approach, it warrants further evaluation to determine its value in daily clinical practice as an additional screening test in the diagnosis of CAD.

Reliability of differentiating human coronary plaque morphology using contrast-enhanced multislice spiral computed tomography : A comparison with histology

Background: Initial clinical results indicate that multislice spiral computed tomography (MDCT) might be useful for the noninvasive characterization of human coronary plaque morphology by determining tissue density within the lesions. This seems to be of clinical relevance, because coronary artery disease might be detected at an early stage before calcifications occur and noncalcified plaques that may be more likely to rupture could also be visualized noninvasively. The aim of the present study was to evaluate the reliability of contrast-enhanced MDCT in differentiating human atherosclerotic coronary plaque morphology by comparing it with the histopathologic gold standard. Methods and Results: Twelve human hearts were scanned postmortem using an MDCT (Somatom Volume Zoom; Siemens, Forchheim, Germany) high-resolution computed tomography scanner to detect atherosclerotic coronary plaques. Density measurements were performed within detected plaque areas. The exact location of each plaque was marked at the surface of the heart to assure accurate histopathologic sectioning of these lesions. The plaques were classified according to a modified Stary classification. Seventeen plaques were identified by MDCT. Six plaques were histopathologically classified as lipid rich (Stary III/IV), 6 plaques as intermediate (Stary V), and 5 plaques as calcific (Stary VII). Lipid-rich plaques had a mean density on MDCT of 42 ± 22 Hounsfield units (HU), intermediate plaques had a mean density of 70 ± 21 HU, and calcific plaques had a mean density of 715 ± 328 HU. ANOVA analysis revealed a significant difference in plaque density between the 3 groups (P < 0.0001). Conclusions: The comparison with histopathology confirms that tissue density as determined by contrast-enhanced MDCT might be used to differentiate atherosclerotic plaque morphology.

Accuracy of Density measurements within plaques located in artificial coronary arteries by X-ray multislice CT: Results of a phantom study

Purpose Clinical studies indicate that coronary plaque morphology might be differentiated noninvasively using multislice CT by determining tissue density within the lesions. The aim of the present experimental study was to evaluate factors that influence density measurements within small vessels. Method A coronary phantom model was developed, consisting of silicon tubes (lumen diameter 4 mm) with two plaques of known density inside, simulating soft and intermediate lesions (Plaque 1: −39 HU; Plaque 2: 72 HU). Density measurement were conducted in three different contrast medium concentrations (1:30, 1:40, 1:50) and two different slice widths (4 × 2.5 mm, 4 × 1 mm). All scans were performed on a Somatom Volume Zoom (Siemens, Forchheim, Germany). Experimental results were compared with calculated data based on computer simulation. Results The two plaques could be clearly differentiated from each other on both collimations (4 × 2.5 mm: Plaque 1, 85 ± 61 HU vs. Plaque 2, 119 ± 26 HU, p < 0.0001; 4 × 1 mm: Plaque 1, 50 ± 54 HU vs. Plaque 2, 91 ± 17 HU, p < 0.0001). Significantly lower and more accurate results were achieved with 1.0 mm collimation (p < 0.0001). Contrast medium concentration contributed significantly to the measurements (p < 0.001). The experimental findings were confirmed by computer simulation, which revealed even more accurate results when using a 0.5 mm collimation (Plaque 1, 0.5 mm: −9 HU vs. 4 × 1 mm: 14 HU, Plaque 2, 4 × 0.5 mm: 83 HU vs. 4 × 1 mm: 93 HU). Conclusion Density measurements were found to be highly dependent on slice width and surrounding contrast enhancement. Our results indicate that standardization of methodology is required before the noninvasive differentiation of human plaque morphology by multislice CT can be applied in the clinical setting as a screening test for coronary soft plaques.

Early but not late stent thrombosis is influenced by residual platelet aggregation in patients undergoing coronary interventions

AIMS Recent studies suggest a relevant association of post-interventional residual platelet aggregation (RPA) under therapy with oral platelet inhibitors and the occurrence of atherothrombotic events. The influence of post-interventional RPA on the incidence of stent thrombosis (ST) has not been sufficiently evaluated in consecutive unselected cohorts of percutaneous coronary intervention (PCI) patients. The aim of this observational study was to investigate the impact of RPA on the incidence of ST within 3 months in patients treated with dual antiplatelet therapy. METHODS AND RESULTS The study population included a consecutive cohort of 1019 patients treated with PCI [n = 741 bare-metal stent (BMS) and n = 278 drug-eluting stent (DES)] due to symptomatic coronary artery disease. Residual platelet activity was assessed by adenosine disphosphate (20 micromol/L)-induced PA after 600 mg clopidogrel loading dose. Maximum RPA was measured as peak of aggregation, final RPA was measured 5 min after addition of agonist. The primary endpoint was the occurrence of ST within 3 months defined according to academic research consortium (ARC) criteria. Final and maximum RPA were independent predictors of ST after 3 months. In secondary analysis, the observed effects were independently associated with early ST (HR 1.05, 95% CI 1.01-1.08 and HR 1.05, 95% CI 1.01-1.09, P < 0.01, respectively). However, incidence of 3-month late stent thrombosis (LAT) was not influenced by post-interventional RPA in multivariable analysis. CONCLUSION Post-interventional RPA is associated with the occurrence of early ST in patients treated with either BMS or DES; however, there is no predictive value of RPA for the incidence of 3-month LAT, suggesting the involvement of other possible mechanisms like discontinuation of antiplatelet therapy.

Residual platelet activity is increased in Clopidogrel- and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary artery disease

Objective: To evaluate residual platelet activity in a consecutive cohort of patients treated with dual antiplatelet therapy after coronary stent implantation Design: Prospective single-centre cohort study. Setting: University hospital in Germany. Patients: 480 patients with symptomatic coronary artery disease (n = 221 (46%) or acute coronary syndrome (ACS; n = 259 (54%) stable angina) were studied. Platelet activity was measured by collagen- (5 µg/ml) and adenosine diphosphate- (ADP; 20 µmol/l) induced platelet aggregation to assess post-treatment activity in patients treated with acetylsalicylic acid (500 mg bolus intravenously followed by 100 mg once a day) and clopidogrel (600 mg loading dose followed by 75 mg once a day) Main outcome measures: Increased residual platelet activity (IRPA) was defined if platelet aggregation was in the upper tertile of values in the patient collective. Association of epidemiological factors with IRPA was evaluated in a multivariate logistic regression analysis. Results: IRPA-ADP was found in 53 patients (11.0%) and IRPA-collagen in 42 patients (8.8%). ACS was associated with IRPA independently from other factors (for IRPA-collagen: odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2 to 4.5, p<0.05; for IRPA-ADP: OR = 2.4; 95% CI 1.3 to 4.4, p<0.01; for IRPA-ADP/collagen: OR = 4.5, 95% CI 1.2 to 16.9, p<0.05). Conclusions: The data suggest that ACS is independently associated with IRPA despite conventional antiplatelet therapy. Further studies are warranted to demonstrate the effects of intensified antiplatelet therapy for patients with acute coronary events.

Influence of vessel size, age and body mass index on the flow-mediated dilatation (FMD%) of the brachial artery

BACKGROUND The non-invasive determination of the endothelial dysfunction (ED) of the brachial artery is a widely used method in clinical research. It remained, however, unclear, whether the test-results are influenced by the anatomical vessel size, the patients age, body mass index (BMI) or gender. METHODS The flow-mediated vasodilatation (FMD%) of the brachial artery was determined in 122 consecutive (88 male, 34 female) patients. FMD% was measured using high resolution ultrasound (13 Mhz) at rest, during reactive hyperaemia and after the sublingual administration of glycerolnitrate (GTN%). RESULTS Lumen diameters at rest varied from 2.48 mm to 6.33 mm (4.46+/-0.74 mm). The extent of FMD% as well as of GTN% showed an inverse correlation to the resting lumen diameters (r=-0.33, P<0.001/r=-0.51, P<0.001). This correlation was even more distinct in females (females: FMD% r=-0.54, P<0.001; GTN% r=-0.64, P<0.001 vs. males: FMD% -0.23, P<0.001; GTN% -0.59, P<0. 001). No significant influence of age (61+/-9 years, FMD%: r=-0.04, P=0.68, GTN%: r=-0.18, P=0.05) and BMI (27.03+/-3.43 kg/m(2), FMD%: r=0.16, P=0.08, GTN%: r=0.09, P=0.3) on the test results were found. CONCLUSIONS FMD% was found to be rather independent of age or BMI. The anatomical vessel size had an influence on the test results, which was more obvious in female patients. Our data indicate the necessity of further methodological studies, in larger, community-based populations. In particular, it needs to be clarified, whether vessel size or even gender-specific correction factors are required when using this technique in routine clinical practice.

Non-invasive evaluation of coronary artery bypass grafts using multi-slice computed tomography: initial clinical experience

Recurrence of angina pectoris in patients with previous coronary artery bypass graft (CABG) surgery due to severe coronary artery disease (CAD) is a common problem. Non-invasive imaging of coronary artery bypass grafts by computed tomography was first described in the early 1980s. Meanwhile, multi-slice computed tomography (MSCT) is now available. This new technique allows detection of coronary lesions with good sensitivity and specificity due to continuous improvement and modification of this method. The aim of this study was to investigate whether stenosis or occlusion of CABG can be detected by MSCT. Ten consecutive male patients (mean age 61+/-9.1 years) with previous CABG surgery and 21 bypass grafts (14 venous grafts, seven arterial grafts) were included in this study. Conventional coronary angiography and MSCT angiography (MSCTA) were performed in all patients. MSCTA results were compared with coronary angiography in regard of visualization and lesion detection in CABG. The analysis of MSCTA was performed blinded to the angiographic results. It was found that 18 of 21 bypass grafts (86%) were analyzable by MSCTA: seven of 21 (33%) grafts showed a significant stenosis (>75%), while six of them were detected by MSCTA (sensitivity: 86%, positive predictive value: 0.75). Dissection of one arterial graft could not be evaluated by MSCTA. Twelve of 13 grafts without severe lesion showed no significant stenosis in MSCTA (negative predictive value: 0.86). All grafts without severe lesions by MSCT showed no significant lesion in X-ray angiography (specificity: 100%). MSCTA is a promising new method for the detection of lesions in coronary artery bypass grafts. However, these data based on a small number has to be reevaluated by larger studies.