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.

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.

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.

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.

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.

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.

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.