Combined Assessment of High-Sensitivity Troponin T and Noninvasive Coronary Plaque Composition for the Prediction of Cardiac Outcomes.

PURPOSE: To determine the risk-stratification ability of plaque volume and composition assessment with cardiac computed tomographic (CT) angiography and high-sensitivity troponin T (hsTnT) in patients at intermediate risk for coronary artery disease (CAD). MATERIALS AND METHODS: The study complied with the Declaration of Helsinki and was approved by the local ethics committee. All patients gave written informed consent. Five hundred twenty-one consecutive patients (mean age ± standard deviation, 62 years ± 10; 256 men and 265 women) were included in this prospective, observational, longitudinal, single-center study. Quantitative cardiac CT angiography analysis was performed in all patients (for 7690 coronary segments), whereas biomarkers (hsTnT and high-sensitivity C-reactive protein) were available in 408 patients (78%). To evaluate the incremental value of cardiac CT angiography and hsTnT for the prediction of cardiovascular events, multivariate Cox regression and integrated discrimination improvement analysis were applied. RESULTS: In 521 patients, 13 hard cardiac events occurred during a mean follow-up period of 2.3 years ± 1.1 (median, 2.4 years; range, 0.5-4.5 years), while 23 patients underwent late coronary revascularization. The Duke clinical score was 51% ± 30, indicating intermediate risk. The presence of no plaques or purely calcified versus noncalcified plaques, plaque volume according to tertiles, and increased hsTnT (≥14 pg/mL) was independently associated with hard cardiac events (hazard ratio [HR] = 26.08, 95% confidence interval [CI]: 2.78, 244.99; HR = 12.14, 95% CI: 1.87, 78.74; and HR = 10.31, 95% CI: 2.72, 39.0, respectively; P < .01 for all). Patients with increased hsTnT and plaque burden (n = 53) showed the highest incidence for hard cardiac events (annual rate, 12.7%), followed by those with either increased hsTnT or plaque burden (n = 145; annual rate = 0.44%, P < .03), while those with lower hsTnT and plaque burden exhibited excellent outcomes and no hard event during the follow-up duration (n = 210; annual rate = 0%, P < .001). CONCLUSION: Use of hsTnT as a marker of myocardial microinjury and cardiac CT angiography as a marker of the total atherosclerotic burden improves the prediction of cardiac outcome in patients with presumably stable CAD and may aid in personalized risk stratification in patients at intermediate risk.

Steady-state equilibrium phase inversion recovery ON-resonant water suppression (IRON) MR angiography in conjunction with superparamagnetic nanoparticles. A robust technique for imaging within a wide range of contrast agent dosages.

PURPOSE: To investigate the ability of inversion recovery ON-resonant water suppression (IRON) in conjunction with P904 (superparamagnetic nanoparticles which consisting of a maghemite core coated with a low-molecular-weight amino-alcohol derivative of glucose) to perform steady-state equilibrium phase MR angiography (MRA) over a wide dose range. MATERIALS AND METHODS: Experiments were approved by the institutional animal care committee. Rabbits (n = 12) were imaged at baseline and serially after the administration of 10 incremental dosages of 0.57-5.7 mgFe/Kg P904. Conventional T1-weighted and IRON MRA were obtained on a clinical 1.5 Tesla (T) scanner to image the thoracic and abdominal aorta, and peripheral vessels. Contrast-to-noise ratios (CNR) and vessel sharpness were quantified. RESULTS: Using IRON MRA, CNR and vessel sharpness progressively increased with incremental dosages of the contrast agent P904, exhibiting constantly higher contrast values than T1 -weighted MRA over a very wide range of contrast agent doses (CNR of 18.8 ± 5.6 for IRON versus 11.1 ± 2.8 for T1 -weighted MRA at 1.71 mgFe/kg, P = 0.02 and 19.8 ± 5.9 for IRON versus -0.8 ± 1.4 for T1-weighted MRA at 3.99 mgFe/kg, P = 0.0002). Similar results were obtained for vessel sharpness in peripheral vessels, (Vessel sharpness of 46.76 ± 6.48% for IRON versus 33.20 ± 3.53% for T1-weighted MRA at 1.71 mgFe/Kg, P = 0.002, and of 48.66 ± 5.50% for IRON versus 19.00 ± 7.41% for T1-weighted MRA at 3.99 mgFe/Kg, P = 0.003). CONCLUSION: Our study suggests that quantitative CNR and vessel sharpness after the injection of P904 are consistently higher for IRON MRA when compared with conventional T1-weighted MRA. These findings apply for a wide range of contrast agent dosages.

Objective quantification of aortic valvular structures by cardiac computed tomography angiography in patients considered for transcatheter aortic valve implantation.

PURPOSE: To test the ability of a model-based segmentation of the aortic root for consistent assessment of aortic valve structures in patients considered for transcatheter aortic valve implantation (TAVI) who underwent 256-slice cardiac computed tomography (CT). METHODS: Consecutive patients (n = 49) with symptomatic severe aortic stenosis considered for TAVI and patients without aortic stenosis (n = 17) underwent cardiac CT. Images were evaluated by two independent observers who measured the diameter of the aortic annulus and its distance to both coronary ostia (1) manually and (2) software-assisted. All acquired measures were compared with each other and to (3) fully automatic quantification. RESULTS: High correlations were observed for 3D measures of the aortic annulus conducted on multiple oblique planes (r = 0.87 and 0.84 between observers and model-based measures, and r = 0.81 between observers). Reproducibility was further improved by software-assisted versus manual assessment for all the acquired variables (r = 0.98 versus 0.81 for annulus diameter, r = 0.94 versus 0.85 for distance to the left coronary ostium, P < 0.01 for both). Thus, using software-assisted measurements very low limits of agreement were observed for the annulus diameter (95%CI of -1.2 to 0.6 mm) and within very low time-spent (0.6 ± 0.1 min for software-assisted versus 1.6 ± 0.3 min per patient for manual assessment, P < 0.001). Assessment of the aortic annulus using the 3D model-based instead of manual 2D-coronal measurements would have modified the implantation strategy in 12 of 49 patients (25%) with aortic stenosis. Four of 12 patients with potentially modified implantation strategy yielded postprocedural moderate paravalvular regurgitation, which may have been avoided by implantation of a larger prosthesis, as suggested by automatic 3D measures. CONCLUSION: Our study highlights the usefulness of software-assisted preprocedural assessment of the aortic annulus in patients considered for TAVI.

Left ventricular diastolic function in type 2 diabetes mellitus is associated with myocardial triglyceride content but not with impaired myocardial perfusion reserve.

PURPOSE: To study myocardial perfusion reserve and myocellular metabolic alterations indicated by triglyceride content as possible causes of diastolic dysfunction in patients with type 2 diabetes mellitus, preserved systolic function, and without clinically evident coronary artery disease. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus (n = 42) underwent cardiac magnetic resonance (CMR) for quantification of 1) myocardial contractility by strain-encoded MR (SENC); 2) myocardial triglyceride content by proton magnetic resonance spectroscopy ((1) H-MRS); and 3) myocardial perfusion reserve during pharmacologic hyperemia. Age-matched healthy volunteers (n = 16) also underwent CMR to acquire normal values for myocardial strain and perfusion reserve. RESULTS: Stress CMR procedures were successfully performed in all subjects, and no regional inducible perfusion defects were observed in type 2 diabetes mellitus patients. Diastolic strain rate and myocardial perfusion reserve were significantly impaired in patients with type 2 diabetes mellitus compared to control subjects (P < 0.001 for both). Interestingly, impaired diastolic function in type 2 diabetes mellitus was not associated with impaired myocardial perfusion reserve (r = 0.12, P = NS). Conversely a significant association was observed between diastolic dysfunction and myocardial triglyceride content (r = -0.71, P < 0.001), which proved to be independent of age, gender, diabetes duration, blood pressure, and fasting blood glucose. CONCLUSION: Myocardial steatosis may represent an early marker of diabetic heart disease, triggering subclinical myocardial dysfunction irrespective of myocardial perfusion reserve.

A systematic report on non-coronary cardiac CTA in 1097 patients from the German cardiac CT registry.

PURPOSE: To prospectively evaluate contemporary indications, safety and diagnostic impact of cardiac CTA in patients undergoing cardiac CTA examinations for non-coronary clinical indications. METHOD: We analyzed 1097 consecutive patients from the German Cardiac CT Registry who underwent cardiac CTA between 2009 and 2014 due to clinically indicated non-coronary reasons using 64-slice or newer CT systems in twelve tertiary German heart centers in order to evaluate the impact of clinical indications on procedure-associated parameters. All participating centers electronically submitted patient and examination data including detailed indications, clinical symptoms, procedural parameters, complications and diagnostic results in a predefined template. RESULTS: The most frequent indication for non-coronary cardiac CTA was the evaluation of pulmonary vein anatomy (65.9 %, 723/1097). In the remaining cases, most frequent indications were planning before TAVI (44.5 %, 69/155), evaluation of valvular disease (31.6 %, 49/155), and evaluation of implants (5.8 %, 9/155). Non-coronary cardiac CTA required a median amount of iodinated contrast agent of 100.0 mL (IQR 95.0-110.0 mL). Prospectively ECG-triggered acquisition was the most frequently used protocol (74.0 %), followed by retrospectively ECG-gated acquisition with and without tube current modulation (19.9 % and 6.0 %, respectively), resulting in a mean estimated effective dose of 5.2 mSv (IQR 2.9-9.5 mSv, average conversion factor k = 0.026). Overall, complication rate was very low (1.5 %). Non-coronary cardiac CTA revealed a new clinical diagnostic aspect in 3.2 % of all patients, and a new main clinical diagnosis in 2.2 %. CONCLUSIONS: Non-coronary cardiac CTA as a routinely applied diagnostic modality is associated with a very low procedure-related rate of complications and reasonably low radiation exposure using contemporary CT systems.

Multimodality cardiac computed tomography angiography and magnetic resonance with clinical-grade scanners provide robust assessment of cardiac morphology and function in rabbits.

BACKGROUND: Non-invasive computer tomography (CT)- and magnetic resonance (MR)-based cardiac imaging still remains challenging in rodents. To investigate the robustness of non-invasive multimodality cardiac imaging in rabbits using clinical-grade CT and MR scanners. METHODS: A total of 16 rabbits (2.7-4.0 kg) serially underwent cardiac-gated imaging using a clinical-grade 256-row CT and a 1.5 Tesla MR-scanner at baseline and at 4-month follow-up (16±1 weeks). Image analysis included image quality (5-grade scale), left ventricular (LV) volumes, LV stroke volume, LV diameters, LV wall thickness and ejection fraction (LVEF). RESULTS: Cardiac MR (CMR) and CT angiography (CTA) provide images with an overall good image quality (excellent or good quality: CMR 82% vs. CTA 78%, P=0.68). Linear regression analysis demonstrated a good correlation of all diameters (diam.) and volumes (vol.) as assessed by CTA and CMR (diam.: r=0.9, 95% CI: 0.8-0.9; vol.: r=0.8, 95% CI: 0.6-0.9; P<0.0001 for both). CTA-based volumetric analysis revealed slightly higher LVEF values as compared to CMR (CTA: 64%±1%, CMR: 59%±1%, P=0.002). Analysis of inter-/intra-observer agreement demonstrated excellent agreements for diameters (CMR: 98.5%/98.7%; CTA: 98.2%/97.4%) and volumes (CMR: 99.9%/98.8%; CTA 98.7%/98.7%). Finally, serial CMR- and CTA-based assessment of cardiac diameters and volumes delivered excellent intersession agreements of baseline versus follow-up data (diam.: CMR: r=0.89; CTA: r=0.92; vol.: CMR: r=0.87; CTA: r=0.96, P<0.0001 for all). CONCLUSIONS: Multimodality non-invasive assessment of cardiac function and aortic hemodynamics is feasible and robust in rabbits using clinical-grade and MR and CT scanners. These imaging modalities could improve serial cardiac assessment for disease monitoring in preclinical settings.

Influence of irregular heart rhythm on radiation exposure, image quality and diagnostic impact of cardiac computed tomography angiography in 4,339 patients. Data from the German Cardiac Computed Tomography Registry.

BACKGROUND: Coronary computed tomography angiography (coronary CTA) provides non-invasive evaluation of the coronary arteries with high precision for the detection of significant coronary artery disease (CAD). AIM: To investigate whether irregular heart rhythm including atrial fibrillation and premature beats during data acquisition influences (i) radiation and contrast media exposure, (ii) number of non-evaluable coronary segments and (iii) diagnostic impact of coronary CTA. METHODS: Twelve tertiary care centers with ≥64 slice CT scanners and ≥5 years of experience with cardiovascular imaging participated in this registry. Between 2009 and 2014, 4339 examinations were analysed in patients who underwent clinically indicated coronary CTA for suspected CAD. Clinical and epidemiologic data were gathered from all patients. In addition, clinical presentation, heart rate and rhythm during the scan, Agatston score, radiation and contrast media exposure and the diagnostic impact of coronary CTA were systematically analysed. RESULTS: Of 4339 patients in total, 260 (6.0%) had irregular heart rhythm, whereas the remaining 4079 (94.0%) had stable sinus rhythm. Patients with irregular heart rhythm were older (63.2 ± 12.5yrs versus 58.6 ± 11.4yrs. p < 0.001), exhibited a higher rate of pathologic stress tests before CTA (37.1% versus 26.1%, p < 0.01) and higher heart rates during CTA compared to those with sinus rhythm (62.5 ± 11.6bpm versus 58.9 ± 8.5bpm, p < 0.001). Both contrast media exposure and radiation exposure were significantly higher in patients with irregular heart rhythm (90 mL (95%CI = 80-110 mL) versus 80 mL (95%CI = 70-90 mL) and 6.2 mSv (95%CI = 2.5-11.7) versus 3.3 mSv (95%CI = 1.7-6.9), p < 0.001 for both). Coronary CTA excluded significant CAD less frequently in patients with irregular heart rhythm (32.9% versus 44.8%, p < 0.001). This was attributed to the higher rate of examinations with at least one non-diagnostic coronary segment in patients with irregular heart rhythm (10.8% versus 4.6%, p < 0.001). Subsequent invasive angiography could be avoided in 47.2% of patients with irregular heart rhythm compared to 52.9% of patients with sinus rhythm (p = NS), whereas downstream stress testing was recommended in 3.2% of patients with irregular heart rhythm versus 4.0% of patients with sinus rhythm (p = NS). CONCLUSION: A significant number of patients scheduled for coronary CTA have irregular heart rhythm in a real-world clinical setting. In such patients, heart rate during coronary CTA is higher, possibly resulting in (i) higher radiation and contrast agent exposure and (ii) more frequent coronary CTA examinations with at least one non-diagnostic coronary artery segment. However, this does not seem to lead to increased downstream stress testing or subsequent invasive procedures.

Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas.

PURPOSE: To elicit a long-lasting antitumor immune response, CD8+ and CD4+ T cells should be activated. We attempted to isolate HLA-DR-presented peptides directly from dissected solid tumors, in particular from renal cell carcinoma, to identify MHC class II ligands from tumor-associated antigens (TAA) for their use in peptide-based immunotherapy. EXPERIMENTAL DESIGN: Tumor specimens were analyzed by immunohistochemical staining for their HLA class II expression. HLA class II peptides were subsequently isolated and identified by mass spectrometry. Gene expression analysis was done to detect genes overexpressed in tumor tissue. Peptides from identified TAAs were used to induce peptide-specific CD4+ T-cell responses in healthy donors and in tumor patients. RESULTS: In the absence of inflammation, expression of MHC class II molecules is mainly restricted to cells of the immune system. To our surprise, we were able to isolate and characterize hundreds of class II peptides directly from primary dissected solid tumors, especially from renal cell carcinomas, and from colorectal carcinomas and transitional cell carcinomas. Infiltrating leukocytes expressed MHC class II molecules and tumor cells, very likely under the influence of IFNgamma. Our list of identified peptides contains ligands from several TAAs, including insulin-like growth factor binding protein 3 and matrix metalloproteinase 7. The latter bound promiscuously to HLA-DR molecules and were able to elicit CD4+ T-cell responses. CONCLUSIONS: Thus, our direct approach will rapidly expand the limited number of T-helper epitopes from TAAs for their use in clinical vaccination protocols.

Image quality and contrast agent exposure in cardiac computed tomography angiography prior to transcatheter aortic valve implantation procedures using different acquisition protocols.

BACKGROUND: ECG-gated cardiac computed tomography angiography (CCTA) has found widespread use for prosthesis sizing before transcatheter aortic valve implantation (TAVI). However, still little data exists on the optimal scan-strategy in such patients. We hypothesized that prospectively triggered CCTA can enable the visualization of aortic valve structures and peripheral arteries with lower radiation and contrast agent exposure in patients considered for TAVI compared to retrospectively gated protocols. METHODS: All studies were performed using a 256 multi-detector single source CT (iCT Philips, Best, Netherlands). With the prospective protocol the whole volume from the heart to the iliofemoral arteries scanned using prospective triggering. With the retrospective protocol a first retrospectively gated scan was performed for the heart and the iliofemoral part was subsequently scanned using a second non-triggered scan. Image quality was assessed semi-quantitatively and signal-to-noise- (SNR) and contrast-to-noise-ratios (CNR) were obtained for all scans. RESULTS: Prospective CCTA was performed in 74 and in 34 patients, respectively using non-tailored and BMI adapted scans, whereas retrospective CCTA was performed in 57 patients. Prospective scans required lower contrast agent administration compared to retrospective scans (71 ± 8 mL versus 91 ± 15 mL, p < 0.01) and resulted in lower radiation exposure (26 ± 7mSv for retrospective versus 15 ± 3mSv for non-tailored prospective versus 8 ± 4mSv for BMI-adapted prospective scans, p < 0.01). Visual image quality was better for the evaluation of aortic valve structures and similar for the assessment of iliofemoral anatomy with prospective versus retrospective scans. In addition, contrast density, SNR and CNR were higher in the ascending aorta with prospective versus retrospective CCTA (434 ± 98HU versus 349 ± 112HU; 35 ± 14 versus 24 ± 9 and 31 ± 11 versus 16 ± 7, p < 0.001 for all). Subsection analysis by heart rate groups demonstrated that both image quality and CNR were significantly higher in patients with prospective versus retrospective CCTA, irrespective of the heart rate during image acquisition. CONCLUSION: Prospectively triggered CCTA allows for improved visualization of aortic valve structures and peripheral arteries in patients scheduled for TAVI with simultaneously reduced contrast agent dose and radiation exposure. Therefore, this acquisition mode seems to be the preferred for the evaluation of patients considered for TAVI.

Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas.

AIMS: To evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque. METHODS AND RESULTS: Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001). CONCLUSION: Low ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.

Limits of the possible: diagnostic image quality in coronary angiography with third-generation dual-source CT.

BACKGROUND: The usage of coronary CT angiography (CTA) is appropriate in patients with acute or chronic chest pain; however the diagnostic accuracy may be challenged with increased Agatston score (AS), increased heart rate, arrhythmia and severe obesity. Thus, we aim to determine the potential of the recently introduced third-generation dual-source CT (DSCT) for CTA in a 'real-life' clinical setting. METHODS: Two hundred and sixty-eight consecutive patients (age: 67 ± 10 years; BMI: 27 ± 5 kg/m²; 61% male) undergoing clinically indicated CTA with DSCT were included in the retrospective single-center analysis. A contrast-enhanced volume dataset was acquired in sequential (SSM) (n = 151) or helical scan mode (HSM) (n = 117). Coronary segments were classified in diagnostic or non-diagnostic image quality. A subset underwent invasive angiography to determine the diagnostic accuracy of CTA. RESULTS: SSM (96.8 ± 6%) and HSM (97.5 ± 8%) provided no significant differences in the overall diagnostic image quality. However, AS had significant influence on diagnostic image quality exclusively in SSM (B = 0.003; p = 0.0001), but not in HSM. Diagnostic image quality significantly decreased in SSM in patients with AS ≥2,000 (p = 0.03). SSM (sensitivity: 93.9%; specificity: 96.7%; PPV: 88.6%; NPV: 98.3%) and HSM (sensitivity: 97.4%; specificity: 94.3%; PPV: 86.0%; NPV: 99.0%) provided comparable diagnostic accuracy (p = n.s.). SSM yielded significantly lower radiation doses as compared to HSM (2.1 ± 2.0 vs. 5.1 ± 3.3 mSv; p = 0.0001) in age and BMI-matched cohorts. CONCLUSION: SSM in third-generation DSCT enables significant dose savings and provides robust diagnostic image quality in patients with AS ≤2000 independent of heart rate, heart rhythm or obesity.

Off-resonance magnetic resonance angiography improves visualization of in-stent lumen in peripheral nitinol stents compared to conventional T1-weighted acquisitions: an in vitro comparison study.

To compare the value of inversion recovery with on-resonant water suppression (IRON) to conventional T1-weighted (T1w) MRA and computed tomography angiography (CTA) for visualization of peripheral nitinol stents. We visualized 14 different peripheral nitinol stents in vitro both using Gadolinium (Gd) and ultrasmall superparamagnetic iron nanoparticles (USPIOs) for conventional T1w and IRON-MRA using clinical grade 1.5T MR scanner and iodinated contrast material for CTA using a 256-slice CT scanner. Parameter assessment included signal- and contrast-to-noise ratio (S/CNR), relative in-stent signal and artificial lumen narrowing. X-ray angiography served as gold standard for diameter assessment. Gd-enhanced IRON-MRA exhibited highest in-stent SNR and CNR values compared to conventional T1w MRA (IRON (Gd/USPIO): SNR = 30 ± 3/21 ± 2, CNR = 23 ± 2/14 ± 1; T1w: SNR = 16 ± 1/14 ± 2, CNR = 12 ± 1/10 ± 1, all p < 0.05). Furthermore, IRON-MRA achieved highest relative in-stent signal both using Gd and USPIO (IRON (Gd/USPIO): 121 ± 8 %/103 ± 6 %; T1w: 73 ± 2 %/66 ± 4 %; CTA: 84 ± 6 %, all p < 0.05). However, artificial lumen narrowing appeared similar in all imaging protocols (IRON (Gd/USPIO): 21 ± 3 %/21 ± 2 %; T1w: 16 ± 4 %/17 ± 3 %; CTA: 19 ± 2 %, all p = NS). Finally, IRON-MRA provided improvement of the in-stent lumen visualization with an 'open-close-open' design, which revealed a complete in-stent signal loss in T1w MRA. IRON-MRA improves in-stent visualization in vitro compared to conventional T1w MRA and CTA. In light of the in vitro results with Gd-enhanced IRON-MRA, the clinical implementation of such an approach appears promising.

Epicardial Adipose Tissue Is Associated with Plaque Burden and Composition and Provides Incremental Value for the Prediction of Cardiac Outcome. A Clinical Cardiac Computed Tomography Angiography Study.

OBJECTIVES: We sought to investigate the association of epicardial adipose tissue (eCAT) volume with plaque burden, circulating biomarkers and cardiac outcomes in patients with intermediate risk for coronary artery disease (CAD). METHODS AND RESULTS: 177 consecutive outpatients at intermediate risk for CAD and completed biomarker analysis including high-sensitive Troponin T (hs-TnT) and hs-CRP underwent 256-slice cardiac computed tomography angiography (CCTA) between June 2008 and October 2011. Patients with lumen narrowing ≥50% exhibited significantly higher eCAT volume than patients without any CAD or lumen narrowing <50% (median (interquartile range, IQR): 108 (73-167) cm3 vs. 119 (82-196) cm3, p = 0.04). Multivariate regression analysis demonstrated an independent association eCAT volume with plaque burden by number of lesions (R2 = 0.22, rpartial = 0.29, p = 0.026) and CAD severity by lumen narrowing (R2 = 0.22, rpartial = 0.23, p = 0.038) after adjustment for age, diabetes mellitus, hyperlidipemia, body-mass-index (BMI), hs-CRP and hs-TnT. Univariate Cox proportional hazards regression analysis identified a significant association for both increased eCAT volume and maximal lumen narrowing with all cardiac events. Multivariate Cox proportional hazards regression analysis revealed an independent association of increased eCAT volume with all cardiac events after adjustment for age, >3 risk factors, presence of CAD, hs-CRP and hs-TnT. CONCLUSION: Epicardial adipose tissue volume is independently associated with plaque burden and maximum luminal narrowing by CCTA and may serve as an independent predictor for cardiac outcomes in patients at intermediate risk for CAD.

Low levels of natural IgM antibodies against phosphorylcholine are independently associated with vascular remodeling in patients with coronary artery disease.

Low anti-phosphorylcholine (PC) IgM plasma levels have been associated with increased incidence of adverse events in coronary artery disease (CAD). The underlying mechanisms are unclear. We hypothesized that atheroprotection mediated by anti-PC IgM antibodies is associated with reduced vascular remodeling and therefore tested whether anti-PC IgM plasma levels independently predict vascular remodeling. In a prospective cross-sectional study, anti-PC IgM plasma levels were measured in 175 consecutive patients with suspected CAD undergoing cardiac computed tomography angiography. Plaque morphology was thoroughly analyzed. Vascular remodeling was defined by a change in the vessel diameter at the plaque site in comparison to the reference segment proximal to the lesion (reference diameter) of ≥10%. Mean age of the patients was 64.8 ± 10.7 years, 48.6% were female. In 98 patients CAD was diagnosed, 57 (58.2%) of which displayed non-obstructive CAD (stenosis <50%), whereas 41 (41.8%) exhibited obstructive CAD (stenosis ≥50%). In 34 of 98 (34.7%) CAD patients vascular remodeling was present. Mean anti-PC IgM levels did not differ between patients with and without CAD (70.8 ± 52.7 vs. 69.1 ± 55.1 U/mL). However, anti-PC IgM levels were significantly lower in CAD patients compared to those without vascular remodeling (46.6 ± 31.6 vs. 73.3 ± 58.5 U/mL, P = 0.024). Using multivariate logistic regression, anti-PC IgM plasma levels independently predicted coronary vascular remodeling (HR 0.322, 95% confidence interval 0.121-0.856, P = 0.023). In conclusion, low anti-PC IgM levels are independently associated with coronary vascular remodeling. These findings may represent the link between in vitro studies demonstrating atheroprotective effects of anti-PC IgM and clinical data demonstrating that low anti-PC IgM levels are associated with adverse outcome in CAD patients.

Assessment of coronary artery disease using coronary computed tomography angiography and biochemical markers.

Chronic inflammatory mechanisms in the arterial wall lead to atherosclerosis, and include endothelial cell damage, inflammation, apoptosis, lipoprotein deposition, calcification and fibrosis. Cardiac computed tomography angiography (CCTA) has been shown to be a promising tool for non-invasive assessment of theses specific compositional and structural changes in coronary arteries. This review focuses on the technical background of CCTA-based quantitative plaque characterization. Furthermore, we discuss the available evidence for CCTA-based plaque characterization and the potential role of CCTA for risk stratification of patients with coronary artery disease.

Cardiac magnetic resonance and computed tomography angiography for clinical imaging of stable coronary artery disease. Diagnostic classification and risk stratification.

Despite advances in the pharmacologic and interventional treatment of coronary artery disease (CAD), atherosclerosis remains the leading cause of death in Western societies. X-ray coronary angiography has been the modality of choice for diagnosing the presence and extent of CAD. However, this technique is invasive and provides limited information on the composition of atherosclerotic plaque. Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have emerged as promising non-invasive techniques for the clinical imaging of CAD. Hereby, CCTA allows for visualization of coronary calcification, lumen narrowing and atherosclerotic plaque composition. In this regard, data from the CONFIRM Registry recently demonstrated that both atherosclerotic plaque burden and lumen narrowing exhibit incremental value for the prediction of future cardiac events. However, due to technical limitations with CCTA, resulting in false positive or negative results in the presence of severe calcification or motion artifacts, this technique cannot entirely replace invasive angiography at the present time. CMR on the other hand, provides accurate assessment of the myocardial function due to its high spatial and temporal resolution and intrinsic blood-to-tissue contrast. Hereby, regional wall motion and perfusion abnormalities, during dobutamine or vasodilator stress, precede the development of ST-segment depression and anginal symptoms enabling the detection of functionally significant CAD. While CT generally offers better spatial resolution, the versatility of CMR can provide information on myocardial function, perfusion, and viability, all without ionizing radiation for the patients. Technical developments with these 2 non-invasive imaging tools and their current implementation in the clinical imaging of CAD will be presented and discussed herein.

When do we really need coronary calcium scoring prior to contrast-enhanced coronary computed tomography angiography? Analysis by age, gender and coronary risk factors.

AIMS: To investigate the value of coronary calcium scoring (CCS) as a filter scan prior to coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Between February 2008 and April 2011, 732 consecutive patients underwent clinically indicated CCTA. During this 'control phase', CCS was performed in all patients. In patients with CCS≥800, CCTA was not performed. During a subsequent 'CCTA phase' (May 2011-May 2012) another 200 consecutive patients underwent CCTA, and CCS was performed only in patients with increased probability for severe calcification according to age, gender and atherogenic risk factors. In patients where CCS was not performed, calcium scoring was performed in contrast-enhanced CCTA images. Significant associations were noted between CCS and age (r = 0.30, p<0.001) and coronary risk factors (χ2 = 37.9; HR = 2.2; 95%CI = 1.7-2.9, p<0.001). Based on these associations, a ≤3% pre-test probability for CCS≥800 was observed for males <61 yrs. and females <79 yrs. According to these criteria, CCS was not performed in 106 of 200 (53%) patients during the 'CCTA phase', including 47 (42%) males and 59 (67%) females. This resulted in absolute radiation saving of ∼1 mSv in 75% of patients younger than 60 yrs. Of 106 patients where CCS was not performed, estimated calcium scoring was indeed <800 in 101 (95%) cases. Non-diagnostic image quality due to calcification was similar between the 'control phase' and the 'CCTA' group (0.25% versus 0.40%, p = NS). CONCLUSION: The value of CCS as a filter for identification of a high calcium score is limited in younger patients with intermediate risk profile. Omitting CCS in such patients can contribute to further dose reduction with cardiac CT studies.

Body mass index-adapted prospective coronary computed tomography angiography. Determining the lowest limit for diagnostic purposes.

PURPOSE: To investigate the value of 4 different protocols for prospectively triggered 256-slice coronary computed tomography angiography (coronary CTA). METHODS: Two hundred and ten patients underwent prospectively triggered coronary CTA for suspected or known coronary artery disease (CAD). Patients with heart rate >75 bps before the scan despite ß-blocker administration and with arrhythmia were excluded. From January to September 2010, 60 patients underwent coronary CTA using a non-tailored protocol (120 kV; 200 mAs) and served as our 'control' group. From September 2010 to April 2012, based on the body mass index (BMI) of the examined patients (BMI subgroups of <25; 25-28; 28-30, and ≥ 30 kg/m(2)) current tube voltage and tube current were: (1) slightly, (2) moderately or (3) strongly reduced, resulting into the 3 following BMI-adapted acquisition groups: (1) a 'standard' (100/120 kV; 100-200 mAs; n=50), 2) a 'low dose' (100/120 kV; 75-150 mAs; n=50), and 3) an 'ultra-low dose' (100/120 kV; 50-100 mAs; n=50) protocol. RESULTS: Patients examined using the non-tailored protocol exhibited the highest radiation exposure (3.2 ± 0.4 mSv), followed by the standard (1.6 ± 0.7 mSv), low-dose (1.2 ± 0.6 mSv) and ultra-low dose protocol (0.7 ± 0.3 mSv) (radiation savings of 50%, 63% and 78% respectively). Overall image quality was similar with standard dose (1.9 ± 0.6) and low-dose (2.0 ± 0.5) compared to the non-tailored group (1.9 ± 0.5) (p=NS for all). In the ultra-low dose group however, image quality was significant reduced (2.7 ± 0.6), p<0.05 versus all other groups). CONCLUSION: Using BMI-adapted low dose acquisitions image quality can be maintained with simultaneous radiation savings of ∼65% (dose of ∼1 mSv). This appears to be the lower limit for diagnostic coronary CTA, whereas ultra-low dose acquisitions result in significant image degradation.

HMGB1 is associated with atherosclerotic plaque composition and burden in patients with stable coronary artery disease.

OBJECTIVES: The role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1), an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD). DESIGN: HMGB1, high sensitive troponin T (hsTnT) and high sensitive C-reactive protein (hsCRP) were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA). Using CCTA, we assessed 1) coronary calcification, 2) non-calcified plaque burden and 3) the presence of vascular remodeling in areas of non-calcified plaques. RESULTS: Using univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively). By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively), whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07). By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively) was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately. CONCLUSIONS: In addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque.

Reduction of radiation exposure and improvement of image quality with BMI-adapted prospective cardiac computed tomography and iterative reconstruction.

PURPOSE: To assess the impact of body mass index (BMI)-adapted protocols and iterative reconstruction algorithms (iDose) on patient radiation exposure and image quality in patients undergoing prospective ECG-triggered 256-slice coronary computed tomography angiography (CCTA). METHODS: Image quality and radiation exposure were systematically analyzed in 100 patients. 60 Patients underwent prospective ECG-triggered CCTA using a non-tailored protocol and served as a 'control' group (Group 1: 120 kV, 200 mAs). 40 Consecutive patients with suspected coronary artery disease (CAD) underwent prospective CCTA, using BMI-adapted tube voltage and standard (Group 2: 100/120 kV, 100-200 mAs) versus reduced tube current (Group 3: 100/120 kV, 75-150 mAs). Iterative reconstructions were provided with different iDose levels and were compared to filtered back projection (FBP) reconstructions. Image quality was assessed in consensus of 2 experienced observers and using a 5-grade scale (1=best to 5=worse), and signal- and contrast-to-noise ratios (SNR and CNR) were quantified. RESULTS: CCTA was performed without adverse events in all patients (n=100, heart rate of 47-87 bpm and BMI of 19-38 kg/m2). Patients examined using the non-tailored protocol in Group 1 had the highest radiation exposure (3.2±0.4 mSv), followed by Group 2 (1.7±0.7 mSv) and Group 3 (1.2±0.6 mSv) (radiation savings of 47% and 63%, respectively, p<0.001). Iterative reconstructions provided increased SNR and CNR, particularly when higher iDose level 5 was applied with Multi-Frequency reconstruction (iDose5 MFR) (14.1±4.6 versus 21.2±7.3 for SNR and 12.0±4.2 versus 18.1±6.6 for CNR, for FBP versus iDose5 MFR, respectively, p<0.001). The combination of BMI adaptation with iterative reconstruction reduced radiation exposure and simultaneously improved image quality (subjective image quality of 1.4±0.4 versus 1.9±0.5 for Group 2 reconstructed using iDose5 MFR versus Group 1 reconstructed using FBP, p<0.05). CONCLUSIONS: Prospective ECG-triggered 256-slice CCTA allows for visualization of the coronary artery tree with high image quality within a wide range of heart rates and BMIs. The combination of BMI-adapted protocols with iterative reconstruction algorithms can reduce radiation exposure for the patients and simultaneously improve image quality.