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Abstract Background Long acquisition times and complex breathing motion patterns lead to suboptimal image quality in whole heart coronary magnetic resonance angiography (WHCMRA). To overcome this problem, an abdominal belt (BELT) has been suggested by a Japanese group. However, its applicability in a Western population has not been previously demonstrated. The purpose of this study was to investigate 1) how the application of a BELT alters breathing patterns during MR scanning and 2) whether the BELT has a similar impact on breathing patterns in UK and Japanese patient populations. Methods 30 patients (15 in the UK and 15 in Japan) were studied at 1.5 Tesla (Achieva, Philips Healthcare). Real time navigator positioned through the right diaphragm in cranio-caudal direction was evaluated. Measurements were performed in the supine position with free breathing for one minute before and after a tight-fitting BELT was positioned around the patient's abdomen. End expiratory position (EEP), end inspiratory position (EIP), end expiratory duration (EED) for the right diaphragm and respiratory rate (RR) were obtained. Scan efficiency (SE) was calculated as follows; SE = [the duration within 5 mm gating window per minutes]/[RR interval]/[heart rate]. Results Height and weight of UK patients were significantly larger than in the Japanese population (171.2 ± 10.8 cm vs 160.8 ± 8.5 cm, p = 0.007; 80.5 ± 22.5 kg vs 59.9 ± 7.7 kg, p = 0.004). After fitting the BELT, EEP-EIP decreased (all patients, 14.9 ± 6.2 mm to 9.4 ± 3.8 mm, p < 0.001; UK patients, 15.9 ± 6.0 mm to 9.7 ± 3.1 mm, p = 0.001; Japanese patients, 14.0 ± 6.4 mm to 9.1 ± 4.6 mm, p = 0.001), RR increased (all patients, 10.0 ± 3.1 min-1 to 11.2 ± 3.0 min-1, p = 0.003; UK patients, 9.5 ± 2.8 min-1 to 10.7 ± 2.8 min-1, p = 0.038; Japanese patients, 10.4 ± 3.5 min-1 to 11.8 ± 3.1 min-1, p = 0.036), and calculated scan efficiency increased (all patients, 45.3 ± 11.4% to 58.6 ± 17.0%, p < 0.001; UK patients, 44.2 ± 10.8% to 55.7 ± 16.7%, p = 0.004; Japanese patients, 46.3 ± 32.2% to 61.0 ± 17.6%, p = 0.001). No significant differences were found between UK and Japanese patients before and after administration of the BELT. Conclusion Using a BELT significantly increases whole-heart coronary MR angiography scan efficiency in both UK and Japanese patients.

Abstract Background Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics. We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR. Methods 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; Tomtec; Germany). Right ventricular (RV) and left ventricular (LV) longitudinal strain (EllRV and EllLV) and LV long-axis radial strain (ErrLAX) were derived from a 4-chamber view at rest. LV short-axis circumferential strain (EccSAX) and ErrSAX; LV ejection fraction (EF) and volumes were analyzed at rest and during dobutamine stress (10 and 20 μg · kg-1· min-1). Results In all volunteers strain parameters could be derived from the SSFP images at rest and stress. EccSAX values showed significantly increased contraction with DSMR (rest: -24.1 ± 6.7; 10 μg: -32.7 ± 11.4; 20 μg: -39.2 ± 15.2; p < 0.05). ErrSAX increased significantly with dobutamine (rest: 19.6 ± 14.6; 10 μg: 31.8 ± 20.9; 20 μg: 42.4 ± 25.5; p < 0.05). In parallel with these changes; EF increased significantly with dobutamine (rest: 56.9 ± 4.4%; 10 μg: 70.7 ± 8.1; 20 μg: 76.8 ± 4.6; p < 0.05). Observer variability was best for LV circumferential strain (EccSAX ) and worst for RV longitudinal strain (EllRV) as determined by 95% confidence intervals of the difference. Conclusions CMR-FT reliably detects quantitative wall motion and strain derived from SSFP cine imaging that corresponds to inotropic stimulation. The current implementation may need improvement to reduce observer-induced variance. Within a given CMR lab; this novel technique holds promise of easy and fast quantification of wall mechanics and strain.

Background: Recently, a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scarce, we aimed to assess the diagnostic and prognostic implications of LACI in a large AMI patient cohort., Methods: In total, 1046 patients following AMI were included. After primary percutaneous coronary intervention CMR imaging and subsequent functional analyses were performed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular (LV) end-diastolic volume. Major adverse cardiac events (MACE) including death, reinfarction or heart failure within 12 months after the index event were defined as primary clinical endpoint., Results: LACI was significantly higher in patients with MACE compared to those without MACE (p < 0.001). Youden Index identified an optimal LACI cut-off at 34.7% to classify patients at high-risk (p < 0.001 on log-rank testing). Greater LACI was associated with MACE on univariate regression modeling (HR 8.1, 95% CI 3.4-14.9, p < 0.001) and after adjusting for baseline confounders and LV ejection fraction (LVEF) on multivariate regression analyses (HR 3.1 95% CI 1.0-9, p = 0.049). Furthermore, LACI assessment enabled further risk stratification in high-risk patients with impaired LV systolic function (LVEF ≤ 35%; p < 0.001 on log-rank testing)., Conclusion: Atrial-ventricular interaction using CMR-derived LACI is a superior measure of outcome beyond LVEF especially in high-risk patients following AMI. Trial registration ClinicalTrials.gov, NCT00712101 and NCT01612312., (© 2023. The Author(s).)

Background: Myocardial deformation analyses using cardiovascular magnetic resonance (CMR) feature tracking (CMR-FT) have incremental value in the assessment of cardiac function beyond volumetric analyses. Since guidelines do not recommend specific imaging parameters, we aimed to define optimal spatial and temporal resolutions for CMR cine images to enable reliable post-processing., Methods: Intra- and inter-observer reproducibility was assessed in 12 healthy subjects and 9 heart failure (HF) patients. Cine images were acquired with different temporal (20, 30, 40 and 50 frames/cardiac cycle) and spatial resolutions (high in-plane 1.5 × 1.5 mm through-plane 5 mm, standard 1.8 × 1.8 x 8mm and low 3.0 × 3.0 x 10mm). CMR-FT comprised left ventricular (LV) global and segmental longitudinal/circumferential strain (GLS/GCS) and associated systolic strain rates (SR), and right ventricular (RV) GLS., Results: Temporal but not spatial resolution did impact absolute strain and SR. Maximum absolute changes between lowest and highest temporal resolution were as follows: 1.8% and 0.3%/s for LV GLS and SR, 2.5% and 0.6%/s for GCS and SR as well as 1.4% for RV GLS. Changes of strain values occurred comparing 20 and 30 frames/cardiac cycle including LV and RV GLS and GCS (p < 0.001-0.046). In contrast, SR values (LV GLS/GCS SR) changed significantly comparing all successive temporal resolutions (p < 0.001-0.013). LV strain and SR reproducibility was not affected by either temporal or spatial resolution, whilst RV strain variability decreased with augmentation of temporal resolution., Conclusion: Temporal but not spatial resolution significantly affects strain and SR in CMR-FT deformation analyses. Strain analyses require lower temporal resolution and 30 frames/cardiac cycle offer consistent strain assessments, whilst SR measurements gain from further increases in temporal resolution.

Background: Sex-specific outcome data following myocardial infarction (MI) are inconclusive with some evidence suggesting association of female sex and increased major adverse cardiac events (MACE). Since mechanistic principles remain elusive, we aimed to quantify the underlying phenotype using cardiovascular magnetic resonance (CMR) quantitative deformation imaging and tissue characterisation., Methods: In total, 795 ST-elevation MI patients underwent post-interventional CMR imaging. Feature-tracking (CMR-FT) was performed in a blinded core-laboratory. Left ventricular function was quantified using ejection fraction (LVEF) and global longitudinal/circumferential/radial strains (GLS/GCS/GRS). Left atrial function was assessed by reservoir (εs), conduit (εe) and booster-pump strains (εa). Tissue characterisation included infarct size, microvascular obstruction and area at risk. Primary endpoint was the occurrence of MACE within 1 year., Results: Female sex was associated with increased MACE (HR 1.96, 95% CI 1.13-3.42, p = 0.017) but not independently of baseline confounders (p = 0.526) with women being older, more often diabetic and hypertensive (p < 0.001) and of higher Killip-class (p = 0.010). Tissue characterisation was similar between sexes. Women showed impaired atrial (εs p = 0.011, εe p < 0.001) but increased systolic ventricular mechanics (GLS p = 0.001, LVEF p = 0.048). While atrial and ventricular function predicted MACE in men only LV GLS and GCS were associated with MACE in women irrespective of confounders (GLS p = 0.036, GCS p = 0.04)., Conclusion: In men ventricular systolic contractility is impaired and volume assessments precisely stratify elevated risks. In contrast, women experience reduced atrial but increased ventricular systolic strain. This may reflect ventricular diastolic failure with systolic compensation, which is independently associated with MACE adding incremental value to sex-specific prognosis evaluation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study sought to investigate the potential of the noninvasive albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR) for detection of coronary plaques that can cause acute coronary syndromes (ACS)., Background: ACS are frequently caused by rupture or erosion of coronary plaques that initially do not cause hemodynamically significant stenosis and are therefore not detected by invasive x-ray coronary angiography (XCA)., Methods: A total of 25 patients with ACS or symptoms of stable coronary artery disease underwent GE-CMR, clinically indicated XCA, and optical coherence tomography (OCT) within 24 h. GE-CMR was performed approximately 24 h following a 1-time application of gadofosveset-trisodium. Contrast-to-noise ratio (CNR) was quantified within coronary segments in comparison with blood signal., Results: A total of 207 coronary segments were analyzed on GE-CMR. Segments containing a culprit lesion in ACS patients (n = 11) showed significant higher signal enhancement (CNR) following gadofosveset-trisodium application than segments without culprit lesions (n = 196; 6.1 [3.9 to 16.5] vs. 2.1 [0.5 to 3.5]; p < 0.001). GE-CMR was able to correctly identify culprit coronary lesions in 9 of 11 segments (sensitivity 82%) and correctly excluded culprit coronary lesions in 162 of 195 segments (specificity 83%). Additionally, segmented areas of thin-cap fibroatheroma (n = 22) as seen on OCT demonstrated significantly higher CNR than segments without coronary plaque or segments containing early atherosclerotic lesions (n = 185; 9.2 [3.3 to 13.7] vs. 2.1 [0.5 to 3.4]; p = 0.001)., Conclusions: In this study, we demonstrated for the first time the noninvasive detection of culprit coronary lesions and thin-cap fibroatheroma of the coronary arteries in vivo by using GE-CMR. This method may represent a novel approach for noninvasive cardiovascular risk prediction., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Continued uptake of modified low-density lipoproteins (LDL) by the scavenger receptor, CD68, of activated macrophages is a crucial process in the development of atherosclerotic plaques and leads to the formation of foam cells. Eight-weeks-old male Apolipoprotein E-deficient (ApoE(-/-)) mice (n = 6) were fed a high-fat diet for 12 weeks. C57BL/6J wildtype (WT) mice served as controls (n = 6). Positron emission tomography (PET) with an acquisition time of 1800 s (NanoPET/CT scanner; Mediso, Hungary & Bioscan, USA) was carried out 24h after intravenous tail vein administration of 50 µl (64)Cu-CD68-Fc (~20-30 µg labeled protein/mouse containing approximately 10-12 MBq (64)Cu-CD68-Fc per mouse). Three days after PET/CT, all mice received an intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-binding contrast agent to assess plaque burden and vessel wall remodeling. Two hours after injection, mice were imaged in a 3T clinical MR scanner (Philips Healthcare, Best, NL) using a dedicated single loop surface coil (23 mm). Enhanced (64)Cu-CD68-Fc uptake was found in the aortic arches of ApoE(-/-) compared to WT mice (ApoE(-/-) mice:10.5 ± 1.5 Bq/cm(3) vs. WT mice: 2.1 ± 0.3 Bq/cm(3); P = 0.002). Higher gadolinium-based elastin-binding contrast agent uptake was also detected in the aortic arch of ApoE(-/-) compared to WT mice using R(1) maps (R(1) = 1.47 ± 0.06 s(-1) vs. 0.92 ± 0.05 s(-1); P <0.001). Radiolabeled scavenger receptor ((64)Cu-CD68-Fc) may help to target foam cell rich plaques with high content of oxidized LDL. This novel imaging biomarker tool may have potential to identify unstable plaques and for risk stratification., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Cardiac inflammation has been suggested to play a critical role in the pathogenesis of inflammatory cardiomyopathy as well as in progressive heart failure (HF). CXC motif ligand 16 (CXCL16) is a recently discovered chemokine produced by several inflammatory cells and representing an important pathogenic mediator in the development of HF. The present study evaluates the diagnostic and prognostic relevance of CXCL16 expression in endomyocardial biopsies of consecutive patients with congestive HF., Methods and Results: 174 patients (age 54.4±14.6 years) with congestive HF undergoing endomyocardial biopsy for diagnostic reasons were prospectively enrolled. Biopsies were analyzed using established histopathological and immunohistological criteria together with CXCL16 staining. CXCL16 was significantly enhanced in patients with inflammatory cardiomyopathy (78/127, 61.4%) as compared to patients with non-inflammatory cardiomyopathy (17/47, 36.2%, p=0.003). During a mean follow-up of 27.5 months, 20 patients (11.5%) reached the primary endpoint (death of all causes). Of all clinical (age, gender, NYHA functional class, systolic pulmonary artery pressure, left ventricular ejection fraction), laboratory (brain natriuretic peptide) and immunohistological (CXCL16) parameters tested, CXCL16 was the only independent predictor of death (hazard ratio 5.4; 95% confidence interval 1.2 to 24.0; p=0.027). Subgroup analysis revealed CXCL16 as a predictor of death in both patients with inflammatory and with non-inflammatory cardiomyopathy., Conclusion: According to the present observations CXCL16 is enhanced in inflammatory cardiomyopathy and turned out as an independent predictor of death in patients with HF undergoing endomyocardial biopsy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Identification of new risk markers in aortic valve stenosis (AS) is of great interest. Here, we hypothesized that the presence of severe autonomic failure (SAF) is an important prognostic marker in both, symptomatic patients undergoing invasive treatment for severe AS, and in asymptomatic patients with severe AS who were primarily treated conservatively., Methods: We prospectively enrolled 300 patients with severe AS (aortic valve area<1.0 cm2 or mean aortic gradient>40 mmHg) in sinus rhythm. All patients underwent a 24-h Holter recording for assessment of heart rate turbulence (HRT) and deceleration capacity (DC). Patients with both, abnormal DC and HRT were considered to suffer from SAF., Results: The first hypothesis was tested in 216 symptomatic patients who underwent successful aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). During follow-up of 2 years, 29 of these patients died. SAF was the strongest independent predictor of mortality (hazard ratio 5.6, 95% confidence interval 2.6-12.0; p<0.001) with 2-year mortality rates of 50.0% and 10.7% in SAF-positive and SAF-negative patients, respectively (p<0.001). The second hypothesis was tested in 71 patients, who were asymptomatic at study entry and for whom a primarily conservative treatment strategy was proposed. During follow-up, 10 of these patients died. SAF also predicted death in asymptomatic patients with 2-year mortality rates of 52.4% and 8.7% in SAF-positive and SAF-negative patients, respectively (p=0.010)., Conclusions: SAF is a strong and independent predictor of mortality in symptomatic and asymptomatic patients with severe AS., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Cardiovascular Magnetic Resonance (CMR) myocardial perfusion imaging has the potential to evolve into a method allowing full quantification of myocardial blood flow (MBF) in clinical routine. Multiple quantification pathways have been proposed. However at present it remains unclear which algorithm is the most accurate. An isolated perfused, magnetic resonance (MR) compatible pig heart model allows very accurate titration of MBF and in combination with high-resolution assessment of fluorescently-labeled microspheres represents a near optimal platform for validation. We sought to investigate which algorithm is most suited to quantify myocardial perfusion by CMR at 1.5 and 3 Tesla using state of the art CMR perfusion techniques and quantification algorithms., Methods: First-pass perfusion CMR was performed in an MR compatible blood perfused pig heart model. We acquired perfusion images at physiological flow ("rest"), reduced flow ("ischaemia") and during adenosine-induced hyperaemia ("hyperaemia") as well as during coronary occlusion. Perfusion CMR was performed at 1.5 Tesla (n = 4 animals) and at 3 Tesla (n = 4 animals). Fluorescently-labeled microspheres and externally controlled coronary blood flow served as reference standards for comparison of different quantification strategies, namely Fermi function deconvolution (Fermi), autoregressive moving average modelling (ARMA), exponential basis deconvolution (Exponential) and B-spline basis deconvolution (B-spline)., Results: All CMR derived MBF estimates significantly correlated with microsphere results. The best correlation was achieved with Fermi function deconvolution both at 1.5 Tesla (r = 0.93, p < 0.001) and at 3 Tesla (r = 0.9, p < 0.001). Fermi correlated significantly better with the microspheres than all other methods at 3 Tesla (p < 0.002). B-spline performed worse than Fermi and Exponential at 1.5 Tesla and showed the weakest correlation to microspheres (r = 0.74, p < 0.001). All other comparisons were not significant. At 3 Tesla exponential deconvolution performed worst (r = 0.49, p < 0.001)., Conclusions: CMR derived quantitative blood flow estimates correlate with true myocardial blood flow in a controlled animal model. Amongst the different techniques, Fermi function deconvolution was the most accurate technique at both field strengths. Perfusion CMR based on Fermi function deconvolution may therefore emerge as a useful clinical tool providing accurate quantitative blood flow assessment.

Background: To test alternative medicine approaches with a specifically designed Tibetan dietary and behavioral program in patients with established coronary artery disease (CAD) and manifest metabolic syndrome., Methods: This was a randomized, controlled, double-blinded, parallel group dietary and behavioral intervention study. Between December 2008 and November 2010, patients were randomly adjudicated either to evidence-based Western diet (usual care), or to Tibetan diet. We evaluated 524 patients undergoing coronary angiography. All patients were white Caucasian, presented with a body mass index (BMI) >25 kg/m(2), and had evidence of metabolic syndrome. The primary endpoint was change in body weight and BMI at 6 months follow-up. Secondary endpoints included blood pressure, heart rate, intima media thickness, lipids, fasting glucose, glycated hemoglobin, fibrinogen, C-reactive protein (CRP) at 6 months follow-up and change in body weight and BMI at 12 months., Results: Both groups of patients showed significantly reduced body weight and BMI compared to baseline (6 months, usual care weight change: -3.2 ± 3.0 kg; BMI change: -1.1 ± 1.0 kg/m(2); Tibetan diet weight change: -6.2 ± 4.4 kg/m(2); BMI change: -2.1 ± 1.5 kg/m(2)), but these changes were more pronounced in Tibetan diet compared to usual care (all, p<0.001). Beneficial effects on weight and BMI were maintained after 12 months of follow-up (p<0.0001). Levels of total and LDL cholesterols, fibrinogen and CRP were decreased in both groups, but more pronounced in Tibetan diet (Tibetan diet vs. usual care (total cholesterol): 176.2 ± 43.7 vs. 185.1 ± 47.8 mg/dL; p=0.024; LDL: 111.6 ± 37.8 vs. 119.4 ± 40.9 mg/dL; p=0.026; fibrinogen: 318.3 ± 90.4 vs. 334.1 ± 87.9 mg/dL; p=0.040; CRP: 1.2 ± 3.0 vs. 2.2 ± 4.5mg/dL; p=0.036)., Conclusions: Tibetan diet reduces body weight and BMI in patients with CAD and metabolic syndrome after 6 months significantly better than Western diet and may induce lipid-modifying and anti-inflammatory effects (ClinicalTrials.gov identifier: NCT00810992)., (© 2013.)

Background: Low dose dobutamine stress magnetic resonance imaging is valuable to assess viability in patients with ischemic cardiomyopathy. Analysis is usually qualitative with considerable operator dependency. The aim of the current study was to investigate the feasibility of cine images derived quantitative cardiac magnetic resonance (CMR) myocardial feature tracking (FT) strain parameters to assess viability in patients with ischemic cardiomyopathy., Methods: 15 consecutive patients with ischemic cardiomyopathy referred for viability assessment were studied at 3T at rest and during low dose dobutamine stress (5 and 10μg/kg/min of dobutamine). Subendocardial and subepicardial circumferential (Eccendo and Eccepi) and radial (Err) strains were assessed using steady state free precession (SSFP) cine images orientated in 3 short axis slices covering 16 myocardial segments., Results: Dysfunctional segments without scar (n=75) improved in all three strain parameters: Eccendo (Rest: -10.5±6.9; 5μg: -12.1±6.9; 10μg: -14.1±9.2; p<0.05), Eccepi (Rest: -7±4.8; 5μg: -8.2±5.5; 10μg: -9.1±5.9; p<0.05) and Err (Rest: 11.7±8.3; 5μg: 16±10.9; 10μg: 16.5±12.8; p<0.05). There was no response to dobutamine in dysfunctional segments with scar transmurality above 75% (n=6): Eccendo (Rest: -4.7±3.0; 5μg: -2.9±2.5; 10μg: -6.6±3.3; p=ns), Eccepi (Rest: -2.9±2.9; 5μg: -5.4±3.9; 10μg: -4.5±4.2; p=ns) and Err (Rest:9.5±5; 5μg:5.4±6.2; 10μg:4.9±3.3; p=ns). Circumferential strain (Eccendo, Eccepi) improved in all segments up to a transmurality of 75% (n=60; p<0.05). Err improved in segments <50% transmurality (n=45; p<0.05) and remained unchanged above 50% transmurality (n=21; p=ns)., Conclusions: CMR-FT is a novel technique, which detects quantitative wall motion derived from SSFP cine imaging at rest and with low dose dobutamine stress. CMR-FT holds promise of quantitative assessment of viability in patients with ischemic cardiomyopathy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to test the hypothesis that transmural perfusion gradients (TPG) on adenosine stress myocardial perfusion cardiac magnetic resonance (CMR) predict hemodynamically significant coronary artery disease (CAD) as defined by fractional flow reserve (FFR)., Background: Myocardial ischemia affects the subendocardial layers of the left ventricular myocardium earlier and more severely than the outer layers, and the identification of TPG should be sensitive and specific for the diagnosis of CAD. Previous studies have shown that high spatial resolution myocardial perfusion CMR allows quantitation of TPG between the subendocardium and the subepicardium., Methods: Sixty-seven patients (53 men, age 61 ± 9 years) underwent coronary angiography and high-resolution (1.2 × 1.2-mm in-plane) adenosine stress perfusion CMR at 3.0-T. TPG was calculated for 3 coronary territories. Visual analysis was performed to identify myocardial ischemia. FFR was measured in all vessels with ≥50% severity stenosis. FFR <0.8 was considered hemodynamically significant. In a training group of 30 patients, the optimal threshold of TPG to detect significant CAD was determined (Group 1). This threshold was then tested prospectively in the remaining 37 patients (Group 2)., Results: In Group 1, a 20% TPG provided the best diagnostic threshold on both per-segment and per-patient analysis. Applied to Group 2, this threshold yielded a sensitivity of 0.78, specificity of 0.94, and area under the curve of 0.86 for the detection of CAD in a per-segment analysis and of 0.89, 0.83, and 0.86 in a per-patient analysis, respectively. TPG had a similar diagnostic accuracy to visual assessment. Linear regression analysis showed a relationship between TPG and FFR values, with r = 0.63 (p < 0.001)., Conclusions: The quantitative analysis of transmural perfusion gradients on high-resolution myocardial perfusion CMR accurately predicts hemodynamically significant CAD as defined by FFR. A TPG diagnostic threshold of 20% is as accurate as visual assessment., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Acute coronary syndrome (ACS) along with myocardial ischemic injury are the leading causes for chest pain. Platelet surface expression of stromal-cell-derived factor-1 (SDF-1) is enhanced during ischemic events and may play an important role in trafficking hematopoietic progenitor cells for tissue regeneration and neovascularization. This study examined the platelet surface expression of SDF-1 in patients with chest pain., Methods: We consecutively evaluated 1000 patients, who were admitted to the emergency department with chest pain. Platelet surface expression of GPIb and SDF-1 was determined by two-color whole blood flow cytometry., Results: Patients with ACS showed significantly enhanced SDF-1 expression on admission compared to patients with other causes such as stable angina pectoris (SAP) and other origin of chest pain (CPO) (ACS vs. SAP/CPO (mean fluorescence intensity (MFI)± SD): 39.7 ± 26.3 vs. SAP: 37.6 ± 31.5;P=0.045; arterial hypertension: 27.3 ± 12.7;P=0.003; orthopedic disease: 22.1 ± 6.5;P=0.014; pulmonary embolism: 26.6 ± 19.1;P=0.003; Da Costa's syndrome: 22.1 ± 12.5;P=0.021; inflammatory cardiomyopathy: 19.8 ± 11.5;P=0.025). Logistic regression analysis showed that surface expression of platelet SDF-1 was significantly associated with ACS (P=0.026), however, the superiority of troponin-I in predicting ACS remains on a high level (P=0.001). Areas under the curve of receiver operating characteristic analysis revealed 0.718 (95% confidence interval (CI):0.680-0.757) using SDF-1, and 0.795 (95%CI:0.760-0.829) applying troponin-I baseline serum levels. Patients with enhanced SDF-1 levels (cutoff:MFI ≥ 27.7) had a 1.4-fold relative risk (95%CI:1.17-1.52) for ACS., Conclusions: Platelet SDF-1 surface expression was significantly enhanced in patients with ACS compared to SAP or CPO. Determination of platelet SDF-1 may be useful as an early additional biomarker for cardiovascular risk stratification., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: During inflammatory cardiomyopathy matrix metalloproteinases are crucially involved in cardiac remodeling. The aim of the present study was to investigate whether the "extracellular matrix metalloproteinase inducer" EMMPRIN (CD147) and its ligand Cyclophilin A (CyPA) are upregulated in inflammatory cardiomyopathy and may serve as diagnostic markers. Therefore, a series of 102 human endomyocardial biopsies were analyzed for the expression of EMMPRIN and CyPA and correlated with histological and immunohistological findings., Methods and Results: Endomyocardial biopsies were stained for EMMPRIN and CyPA in addition to standard histology (HE, Trichrom) and immunohistological stainings (MHC-II, CD68, CD3). 39 (38.2%) biopsies met the immunohistological criteria of an inflammatory cardiomyopathy. EMMPRIN, which was predominantly expressed on cardiomyocytes, was slightly (but significantly) upregulated in non inflammatory cardiomyopathies compared to normal histopathological findings and highly upregulated in inflammatory cardiomyopathy compared to both non inflammatory cardiomyopathy and normal histopathology. In contrast, CyPA reveals no enhanced expression in non inflammatory cardiomyopathies and a highly enhanced expression in inflammatory cardiomyopathy, where it is closely associated with leucocytes infiltrates. We found a strong correlation between both EMMPRIN and CyPA with the expression of MHC-II molecules (correlation coefficient 0.475 and 0.527, p<0.05). Moreover, we found a correlation for both EMMPRIN and CyPA with CD68 (correlation coefficient 0.393 and 0.387, p<0.05) and CD3 (correlation coefficient 0.360 and 0.235, p<0.05)., Conclusion: EMMPRIN is enhanced in both inflammatory and non inflammatory cardiomyopathies and can serve as a marker of myocardial remodeling. CyPA may represent a novel and specific marker for cardiac inflammation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Direct comparison of CT and magnetic resonance (MR) perfusion techniques has been limited and in vivo assessment is affected by physiological variability, timing of image acquisition, and parameter selection., Objective: We precisely compared high-resolution k-t SENSE MR cardiac perfusion at 3 T with single-phase CT perfusion (CTP) under identical imaging conditions., Methods: We used a customized MR imaging and CT compatible dynamic myocardial perfusion phantom to represent the human circulation. CT perfusion studies were performed with a Philips iCT (256 slice) CT, with isotropic resolution of 0.6 mm(3). MR perfusion was performed with k-t SENSE acceleration at 3 T and spatial resolution of 1.2 × 1.2 × 10 mm. The image contrast between normal and underperfused myocardial compartments was quantified at various perfusion and photon energy settings. Noise estimates were based on published clinical data., Results: Contrast by CTP highly depends on photon energy and also timing of imaging within the myocardial perfusion upslope. For an identical myocardial perfusion deficit, the native image contrast-to-noise ratio (CNR) generated by CT and MR are similar. If slice averaging is used, the CNR of a perfusion deficit is expected to be greater for CTP than MR perfusion (MRP). Perfect timing during single time point CTP imaging is difficult to achieve, and CNR by CT decreases by 24%-31% two seconds from the optimal imaging time point. Although single-phase CT perfusion offers higher spatial resolution, MRP allows multiple time point sampling and quantitative analysis., Conclusion: The ability of CTP and current optimal MRP techniques to detect simulated myocardial perfusion deficits is similar., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Background: C-terminal portion of provasopressin (copeptin) has recently been discussed as a novel biomarker for the early rule-out of acute myocardial infarction (AMI). The aim is to investigate the prognostic value of copeptin with regard to mortality and morbidity in patients with symptomatic coronary artery disease (CAD)., Methods: We consecutively recruited a cath lab cohort of 2,700 patients (74.1% male; AMI, n=1316; stable angina pectoris, n=1384) presenting to the emergency department of a large primary care hospital. All patients received coronary angiography. Copeptin and other laboratory markers were sampled at the time of presentation or in the cath lab. Clinical outcomes were assessed by hospital chart analysis and telephone interviews. 2621 patients (97.1%) have been successfully followed-up at three months. The primary endpoint was a combined endpoint of rehospitalization for cardiovascular events, stroke, and all-cause death., Results: Using receiver operating characteristic curves, we calculated areas under the curve of 0.703 (95%confidence interval(CI):0.681-0.725) for the composite endpoint after three months (myocardial reinfarction, stroke, all-cause death;n=183), and 0.770 (95%CI:0.736-0.803) for all-cause death (n=76) for copeptin. A cutoff value of 21.6 pmol/L for the composite endpoint yielded a sensitivity of 56.3% and a specificity of 78.6%. The predictive performance of copeptin was independent of other clinical variables or cardiovascular risk factors, and superior to that of troponin I or other cardiac biomarkers (all:P<0.0001)., Conclusions: Copeptin may help in the prediction of major adverse cardiovascular events in patients with symptomatic CAD. Further studies should substantiate the findings and support the suggested cutoff value of the present study., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the possible association of plasma levels of stromal cell-derived factor-1 (SDF-1; CXCL12) with clinical presentation of symptomatic coronary artery disease (CAD) and with cardiovascular risk factors., Methods: A cath lab cohort of 492 consecutive patients with symptomatic CAD were recruited. Blood for plasma-SDF-1 determination was taken at the time of heart catheterization before percutaneous coronary intervention., Results: Plasma-SDF-1 was significantly decreased in ST-elevation myocardial infarction (STEMI) compared to stable angina pectoris (SAP) or to non-ST-elevation myocardial infarction (NSTEMI) (SAP vs. NSTEMI vs. STEMI: [pg/ml]: mean ± SD: 2110 ± 562 vs. 2127 ± 467 vs. 1834 ± 377; P < 0.001) independent of cardiovascular therapy. A weak correlation was observed between cholesterol levels and plasma SDF-1 in the whole study population. Left ventricular function and diabetes mellitus associated with plasma SDF-1 levels in patients with NSTEMI, while among STEMI patients, those with hyperlipidemia presented with even further decreased SDF-1 levels., Conclusion: Plasma SDF-1 is significantly decreased in patients with STEMI, a fact which may reflect the importance of SDF-1 regulation in patients with acute myocardial infarction., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics.We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR., Methods: 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; Tomtec; Germany). Right ventricular (RV) and left ventricular (LV) longitudinal strain (EllRV and EllLV) and LV long-axis radial strain (ErrLAX) were derived from a 4-chamber view at rest. LV short-axis circumferential strain (EccSAX) and ErrSAX; LV ejection fraction (EF) and volumes were analyzed at rest and during dobutamine stress (10 and 20 μg · kg⁻¹· min⁻¹)., Results: In all volunteers strain parameters could be derived from the SSFP images at rest and stress. EccSAX values showed significantly increased contraction with DSMR (rest: -24.1 ± 6.7; 10 μg: -32.7 ± 11.4; 20 μg: -39.2 ± 15.2; p < 0.05). ErrSAX increased significantly with dobutamine (rest: 19.6 ± 14.6; 10 μg: 31.8 ± 20.9; 20 μg: 42.4 ± 25.5; p < 0.05). In parallel with these changes; EF increased significantly with dobutamine (rest: 56.9 ± 4.4%; 10 μg: 70.7 ± 8.1; 20 μg: 76.8 ± 4.6; p < 0.05). Observer variability was best for LV circumferential strain (EccSAX ) and worst for RV longitudinal strain (EllRV) as determined by 95% confidence intervals of the difference., Conclusions: CMR-FT reliably detects quantitative wall motion and strain derived from SSFP cine imaging that corresponds to inotropic stimulation. The current implementation may need improvement to reduce observer-induced variance. Within a given CMR lab; this novel technique holds promise of easy and fast quantification of wall mechanics and strain.

Background: The purpose of the study was to test whether an elevated surface expression of platelet collagen receptor glycoprotein VI (GPVI) is an appropriate marker for the diagnosis of the acute coronary syndrome (ACS), especially when the electrocardiogram (ECG) is ambiguous., Methods: Between 2007 to 2008, we consecutively evaluated 378 patients with ACS and ambiguous ECG on hospital admission. In all patients, GPVI surface expression was determined by flow cytometry. In addition, the myocardial necrosis markers troponin-I (Tn-I) and creatine kinase-MB (CKMB) were measured., Results: We found that in patients with ACS and unclear ECG in whom GPVI levels (mean fluorescence intensity (MFI) ≥ 18.6) were elevated, the relative risk for ACS was 2.6-fold enhanced. Binary logistic regression analysis revealed that an elevated platelet GPVI level is indicating an ACS independent of biomarkers of myocardial necrosis including Tn-I, creatine kinase (CK), CKMB (GPVI: p=0.011; Tn-I: p=0.180; CKMB: p=0.250; CK: p=0.127). Patients with evident T-wave inversion and/or ST-depression showed a strong association between ACS and GPVI expression., Conclusions: Platelet GPVI surface expression is enhanced in patients with ACS with unclear ECG findings and is strongly associated with myocardial ischemia. Additional to the classical markers of myocardial necrosis Tn-I and CK, GPVI is an early biomarker for the diagnosis of ACS, especially when the ECG is ambiguous., (Copyright © 2009 Elsevier B.V. All rights reserved.)

Background: There is cumulative evidence that the degree of inflammation correlates with prognosis after percutaneous coronary interventions (PCI). Additionally, there is a cross-link between platelet activation and inflammatory pathways. The aim of the present analysis was to evaluate the association of inflammatory markers and effects of dual antiplatelet therapy on platelet function and outcome in patients undergoing PCI., Methods and Results: In a pilot study, 157 patients with symptomatic coronary artery disease (CAD) undergoing PCI were consecutively evaluated. Platelet response to clopidogrel and acetylsalicylic acid was assessed using whole blood multiple electrode aggregometry (MEA). Baseline levels of IL-6, RANTES and MCP-1 were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Levels of IL-6, RANTES, and CRP correlated well with ADP and arachidonic acid (AA)-induced MEA. In a second step, a retrospective analysis of a cohort of 903 PCI-patients was performed to evaluate the association of on-treatment residual platelet aggregation (RPA) and baseline CRP levels on the incidence of myocardial infarction (MI), death and stent thrombosis (ST). Patients suffering a subsequent event had a significantly higher level of baseline CRP and higher RPA compared to patients without events. After multivariate adjustment high baseline CRP and high RPA were independent predictors for combined major events and ST after PCI., Conclusion: To our knowledge this is the first study linking inflammation, antiplatelet drug responsiveness and outcome in a large CAD-patient cohort. The results suggest a relevant interaction of these parameters and encourage multimodal therapeutic approaches to treat cardiovascular risk after PCI., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Upon coincubation with platelets, CD34(+) progenitor cells have the potential to differentiate into foam cells, and thereby may promote the progression of atherosclerosis. The exact mechanism of MMP-regulation during the cellular differentiation process to foam cells is still unclear. Thus, we investigated the role of EMMPRIN (CD147) and its ligand cyclophilin A (CyPA) during foam cell formation originating from both monocytes/macrophages and CD34(+) progenitor cells., Methods and Results: Differentiation of CD34(+) progenitor to foam cells was analyzed in a coculture model of progenitor cells and platelets. While CD34(+) cells did not express EMMPRIN or MT1-MMP, mature foam cells strongly expressed EMMPRIN, which was associated with MT1-MMP expression as well as MMP-9. Gene silencing of EMMPRIN by siRNA during the cell differentiation process hindered not only the upregulation of MMPs (MT1-MMP, MMP-9), but also the secretion of the cytokine M-CSF. During the differentiation process CyPA was substantially released into the supernatant. The presence of the CyPA inhibitor NIM811 significantly reduced MMP-9 secretion during the differentiation process. Similar results were obtained using the classical pathway of foam cell formation by coincubating human macrophages with AcLDL. Additionally, the presence of soluble EMMPRIN ligands (CyPA, recombinant EMMPRIN) further enhanced MMP-9 secretion by mature foam cells. Consistently, CyPA and EMMPRIN were found in atherosclerotic plaques of ApoE-deficient mice by immunohistochemistry., Conclusion: EMMPRIN is upregulated during the differentiation process from CD34(+) progenitor cells to foam cells, whereas its ligand, CyPA, is released. The CyPA/EMMPRIN activation pathway may play a relevant role in promoting the vulnerability of atherosclerotic plaques.

Objective: Cytokines have an important role in both the initiation and perpetuation of viral myocarditis. Because a causative therapy of myocarditis is not yet well established and immunomodulation is a promising approach, the influence of interleukin (IL)-15, a proinflammatory cytokine, on the course of experimental myocarditis in Coxsackievirus B3 (CVB3)-infected mice was examined., Methods: Hearts from CVB3-infected (n=14), sham-infected (n=14) and CVB3-infected BALB/c mice treated with IL-15 (n=6) or a competitive IL-15 fusion protein (n=6) were analyzed for hemodynamic function, cellular infiltrates and myocardial collagen content., Results: Induction of myocarditis was associated with significant loss of body and heart weight, decreased left ventricular function, and increased collagen content and cellular infiltrates in the myocardium. Treatment of infected animals with IL-15 resulted in normalization of body and heart weight, and significantly improved systolic and diastolic left ventricular function, comparable with that of uninfected animals. This was paralleled by a significant reduction of myocardial collagen content to levels observed in animals without disease and by markedly reduced cellular infiltration of lymphocytes and macrophages in the myocardium. Inhibition of intrinsic IL-15 with IL-15 fusion protein tended to aggravate the disease., Conclusions: Treatment with IL-15 has a positive effect on CVB3- induced murine myocarditis and seems to be a promising approach to modifying clinical course, hemodynamics and histopathology of virus-induced myocarditis. Further studies are needed to identify the underlying mechanisms.

A 67-year-old woman who presented with acute chest pain is reported. Three days before admission, she suffered from a flu-like infection. Coronary angiography showed no coronary stenosis. Ventriculography showed moderately reduced left ventricular function characterized by the so-called 'apical ballooning'. Endomyocardial biopsies and polymerase chain reaction analysis of the plasma revealed an acute infection with human herpesvirus 6 subtype A. Histological and immunohistochemical analyses revealed myocarditis with areas of interstitial macrophages and fibrosis. The present case report links, for the first time, myocarditis with a human herpesvirus 6 subtype A infection and the appearance of apical ballooning.