Myocardial injury in patients with acute ischemic stroke detected by cardiovascular magnetic resonance imaging.

BACKGROUND: Patients with acute ischemic stroke (AIS) are at high risk of adverse cardiovascular events. Until now, the burden of myocardial injury derived from cardiovascular magnetic resonance imaging (CMR) has not been established in this population. METHODS: Patients with AIS underwent CMR at 3 Tesla within 120 h after the index stroke as part of a prospective, single-center study. Patients with persistent atrial fibrillation were excluded. Morphology and function of both cardiac chambers and atria were assessed applying SSFP cine. Myocardial tissue differentiation was based on native and contrast-enhanced imaging including late gadolinium enhancement (LGE) after 0.15 mmol/kg gadobutrol for focal fibrosis and parametric T2- and T1-mapping for diffuse findings. To detect myocardial deformation global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain was measured applying feature tracking. Cardiac troponin was measured using a high-sensitivity assay (99th percentile upper reference limit 14 ng/L). T2 mapping values were compared with 20 healthy volunteers. RESULTS: CMR with contrast media was successfully performed in 92 of 115 patients (mean age 74 years, 40% female, known myocardial infarction 6%). Focal myocardial fibrosis (LGE) was detected in 31 of 92 patients (34%) of whom 23/31 (74%) showed an ischemic pattern. Patients with LGE were more likely to have diabetes, prior myocardial infarction, prior ischemic stroke, and to have elevated troponin levels compared to those without. Presence of LGE was accompanied by diffuse fibrosis (increased T1 native values) even in remote cardiac areas as well as reduced global radial, circumferential and longitudinal strain values. In 14/31 (45%) of all patients with LGE increased T2-mapping values were detectable. CONCLUSIONS: More than one-third of patients with AIS have evidence of focal myocardial fibrosis on CMR. Nearly half of these changes may have acute or subacute onset. These findings are accompanied by diffuse myocardial changes and reduced myocardial deformation. Further studies, ideally with serial CMR measurements during follow-up, are required to establish the impact of these findings on long-term prognosis after AIS.

Central venous catheter contamination rate in suspected sepsis patients: an observational clinical study.

BACKGROUND: More than 160,000 central-line-associated bloodstream infections (CLABSIs) are estimated for Europe each year, leading to about 25,000 deaths. AIM: To characterize the contamination of administration sets in suspected CLABSI cases in the intensive care unit (ICU). METHODS: In ICU patients (from February 2017 to February 2018) with suspected CLABSI, all sampled central venous catheters (CVCs) were examined in four segments (from CVC tip to connected tubing systems) for contamination. A risk factor analysis using binary logistic regression was performed. FINDINGS: Fifty-two consecutively sampled CVCs with 1004 elements were analysed with 45 elements being positive for at least one micro-organism (4.48%). There was a significant association with the duration of catheterization (P = 0.038, N = 50) with a daily increase of contamination risk by 11.5% (odds ratio: 1.115). The mean number of CVC manipulations was 40 within 72 h (standard deviation: 20.5), with no association with contamination risk (P = 0.381). The contamination risk of the CVC segments decreased from proximal to distal. Non-replaceable components of the CVC had a high risk (14 times higher; P = 0.01). A significant positive correlation was detected between positive tip cultures and microbial growth in the administration set (r(49) = 0.437; P = 0.001). CONCLUSION: Although only a minority of CLABSI-suspect patients had positive blood cultures, the contamination rate of CVCs and administration set was high, possibly indicating a relevant underreporting. The finding of identical species in adjacent segments underlines the role of upward or downward spread of micro-organisms within the tubes; therefore, aseptic tasks should be emphasized.

Guidelines for training in cardiovascular magnetic resonance (CMR).

These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

Regional cerebral oxygen saturation during cardiopulmonary resuscitation as a predictor of return of spontaneous circulation and favourable neurological outcome - A review of the current literature.

INTRODUCTION: Regional cerebral oxygen saturation (rSO2) can be measured non-invasively even at no- or low-flow states. It thus allows assessment of brain oxygenation during CPR. Certain rSO2 values had been associated with return of spontaneous circulation (ROSC) and neurological outcome in the past. Clear-cut thresholds for the prediction of beneficial outcome, however, are still lacking. METHODS: We conducted a database search to extract all available investigations on rSO2 measurement during CPR. Mean, median, and ΔrSO2 values were either taken from the studies or calculated. Thresholds for the outcome "ROSC" and "neurological outcome" were sought. RESULTS: We retrieved 26 publications for the final review. The averaged mean rSO2 for patients achieving ROSC was 41 ±â€¯12% vs. 30 ±â€¯12% for non-ROSC (p = .009). ROSC was not observed when mean rSO2 remained <26%. In ROSC patients, ΔrSO2 was 22 ±â€¯16% vs. 7 ±â€¯10% in non-ROSC patients (p = .009). A rSO2 threshold of 36% predicted ROSC with a sensitivity of 67% and specificity of 69% while ΔrSO2 of 7% showed a sensitivity of 100% and a specificity of 86% (AUC = 0.733 and 0.893, respectively). Mean rSO2 of 47 ±â€¯11% was associated with favourable and 38 ±â€¯12% with poor neurological outcome. There was, however, a great overlap between groups due to scarce data. CONCLUSION: Higher rSO2 consistently correlated with increased rates of ROSC. The discriminatory power of rSO2 to prognosticate favourable neurological outcome remains unclear. Measuring rSO2 during CPR could potentially facilitate clinical decision-making.

Branched-chain amino acid catabolism rather than amino acids plasma concentrations is associated with diet-induced changes in insulin resistance in overweight to obese individuals.

BACKGROUND & AIMS: 3-Hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, which stimulates muscle fatty acid uptake, has been implicated in the pathogenesis of insulin resistance. We tested the hypothesis that circulating 3-HIB herald insulin resistance and that metabolic improvement with weight loss are related to changes in BCAAs and 3-HIB. METHODS AND RESULTS: We analyzed plasma and urine in 109 overweight to obese individuals before and after six months on hypocaloric diets reduced in either carbohydrates or fat. We calculated the homeostasis model assessment index (HOMA-IR) and whole body insulin sensitivity from oral glucose tolerance tests and measured intramyocellular fat by magnetic resonance spectroscopy. BCAAs and 3-HIB plasma concentrations were inversely related to insulin sensitivity but not to intramyocellular fat content at baseline. With 7.4 ± 4.5% weight loss mean BCAA and 3-HIB plasma concentrations did not change, irrespective of dietary macronutrient content. Individual changes in 3-HIB with 6-month diet but not BCAAs were correlated to the change in whole body insulin sensitivity and HOMA-IR independently of BMI changes. CONCLUSIONS: 3-HIB relates to insulin sensitivity but is not associated with intramyocellular fat content in overweight to obese individuals. Moreover, changes in 3-HIB rather than changes in BCAAs are associated with metabolic improvements with weight loss. Registration number for clinical trials: ClinicalTrials.gov Identifier: NCT00956566.

Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung.

Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response.

Branched-chain and aromatic amino acids, insulin resistance and liver specific ectopic fat storage in overweight to obese subjects.

BACKGROUND & AIMS: Amino acids may interfere with insulin action, particularly in obese individuals. We hypothesized that increased circulating branched-chain and aromatic amino acids herald insulin resistance and ectopic fat storage, particularly hepatic fat accumulation. METHODS AND RESULTS: We measured fasting branched-chain and aromatic amino acids (tryptophan, tyrosine, and phenylalanine) by mass spectrometry in 111 overweight to obese subjects. We applied abdominal magnetic resonance imaging and spectroscopy to assess adipose tissue distribution and ectopic fat storage, respectively. Plasma branched-chain amino acids concentrations were related to insulin sensitivity and intrahepatic fat independent from adiposity, age and gender, but not to abdominal adipose tissue or intramyocellular fat. CONCLUSIONS: In weight stable overweight and obese individuals, branched-chain amino acid concentrations are specifically associated with hepatic fat storage and insulin resistance.

[Hypertrophic and restrictive cardiomyopathy. Differentiation by imaging]. / Hypertrophe und restriktive Kardiomyopathie. Differenzierung mittels Bildgebung.

The differentiation between hypertrophic and restrictive cardiomyopathies is often challenging in the routine clinical setting. Advances in the field of multimodal imaging have improved the diagnostics of these diseases and understanding of the underlying pathophysiology. Each imaging method, such as echocardiography, cardiac magnetic resonance imaging (CMR), cardiac computed tomography (CT) and coronary angiography including cardiac catheterization for pressure measurements, is of significant value in clinical diagnostics and also regarding therapeutic approaches and prognostic implications. This review gives an overview of developments of the past few years, describes recent insights and puts these findings into a scientific context. Particularly CMR has added valuable information to current knowledge by its unique potential of contrast-enhanced tissue characterization. Another promising CMR tool, parametric mapping has appeared on the horizon and may further deepen our understanding of cardiac pathophysiology as well as offer new therapeutic options to patients.

4D flow magnetic resonance imaging in bicuspid aortic valve disease demonstrates altered distribution of aortic blood flow helicity.

PURPOSE: Changes in aortic geometry or presence of aortic valve (AoV) disease can result in substantially altered aortic hemodynamics. Dilatation of the ascending aorta or AoV abnormalities can result in an increase in helical flow. METHODS: 4D flow magnetic resonance imaging was used to test the feasibility of quantitative helicity analysis using equidistantly distributed 2D planes along the entire aorta. The evaluation of the method included three parts: (1) the quantification of helicity in 12 healthy subjects, (2) an evaluation of observer variability and test-retest reliability, and (3) the quantification of helical flow in 16 patients with congenitally altered bicuspid AoVs. RESULTS: Helicity quantification in healthy subjects revealed consistent directions of flow rotation along the entire aorta with high clockwise helicity in the aortic arch and an opposite rotation sense in the ascending and descending aorta. The results demonstrated good scan-rescan and inter- and intraobserver agreement of the helicity parameters. Helicity quantification in patients revealed a significant increase in absolute peak relative helicity during systole and a considerably greater heterogeneous distribution of mean helicity in the aorta. CONCLUSION: The method has the potential to serve as a reference distribution for comparisons of helical flow between healthy subjects and patients or between different patient groups.

[Cardiovascular ultrahigh field magnetic resonance imaging : challenges, technical solutions and opportunities]. / Ultrahochfeld-MR-Tomographie in der Kardiologie : Herausforderungen, Lösungen und Chancen.

CLINICAL/METHODICAL ISSUE: This involves high spatial resolution cardiac imaging with ultrahigh magnetic fields (7 T) and clinically acceptable image quality. STANDARD RADIOLOGICAL METHODS: Cardiovascular magnetic resonance imaging (MRI) at a field strength of 1.5 T using a spatial resolution of (2 × 2 × 6-8) mm(3). METHODICAL INNOVATIONS: Cardiac MRI at ultrahigh field strength makes use of multitransmit/receive radiofrequency (RF) technology and development of novel technology that utilizes the traits of ultrahigh field MRI. PERFORMANCE: Enhanced spatial resolution which is superior by a factor of 6-10 to what can be achieved by current clinical cardiac MRI. The relative spatial resolution (pixels per anatomical structure) comes close to what can be accomplished by current cardiac MRI in small rodents. ACHIEVEMENTS: Feasibility studies demonstrate the gain in spatial resolution at 7.0 T due to the sensitivity advantage inherent to ultrahigh magnetic fields. PRACTICAL RECOMMENDATIONS: Please stay tuned and please put further weight behind the solution of the remaining technical problems of cardiac MRI at 7.0 T.

[Cardiomyopathies and myocarditis]. / Kardiomyopathien und Myokarditis.

CLINICAL ISSUE: Cardiomyopathies and myocarditis are frequently challenging in clinical practice regarding differentiation, risk stratification and treatment strategy. There are various disease entities which often affect young or middle-aged adults and the course is variable from asymptomatic and irrelevant for prognosis to sudden cardiac death or severe heart failure even at an early age. Making the right diagnosis is therefore fundamental to correctly identify affected patients and to initiate treatment steps in time. STANDARD TREATMENT: Whereas causal treatment options exist for some forms of cardiomyopathy, the majority of patients receives standard heart failure and device therapy but others require lifelong careful monitoring. DIAGNOSTIC WORK-UP: The diagnosis of cardiomyopathy is mainly based on the cardiac phenotype; therefore, non-invasive imaging is very important. Cardiovascular magnetic resonance has become the gold standard to assess cardiomyopathy as it combines functional information (e.g. wall motion) with myocardial tissue analysis (e.g. fibrosis and edema) and in some cases it can replace invasive endomyocardial biopsies. PERFORMANCE: The importance of cardiovascular magnetic resonance to assess cardiomyopathy is based on several aspects: accurate analysis of cardiac dimensions and function, non-invasive tissue analysis to make the diagnosis (e.g. myocarditis), estimation of prognosis by non-invasive tissue analysis, high reproducibility for accurate follow-up examinations, potential for technical improvements (e.g. quantification of extracellular volume fraction by T1 mapping). ACHIEVEMENTS: In all types of cardiomyopathy, cardiovascular magnetic resonance has a major impact on the differential diagnosis, risk stratification and treatment. In some entities the appropriate clinical use is already confirmed by evidence (e.g. myocarditis) and in others there are first encouraging results that indicate the future potential (e.g. risk stratification in hypertrophic cardiomyopathy). PRACTICAL RECOMMENDATIONS: Cardiovascular magnetic resonance has evolved as the gold standard to assess cardiomyopathy as it provides both functional and morphological information. It is recommended to use this technique in a comprehensive approach to achieve complete work-up of affected patients.

Determinants of exercise-induced fat oxidation in obese women and men.

Endurance training at an intensity eliciting maximal fat oxidation may have a beneficial effect on body weight and glucose metabolism in obese patients. However, the exercise intensity at which maximal fat oxidation occurs and the factors limiting fat oxidation are not well studied in this population. Obese, otherwise healthy men (n=38) and women (n=91) performed an incremental exercise test up to exhaustion on a cycle ergometer. Substrate oxidation was estimated using indirect calorimetry. Magnetic resonance tomography and spectroscopy were conducted to assess body fat distribution and intramyocellular fat content. We determined the exercise intensity at which maximal body fat oxidation occurs and assessed whether body composition, body fat distribution, intramyocellular fat content, or oxidative capacity predict exercise-induced fat oxidation. Maximal exercise-induced fat oxidation was 0.30+/-0.02 g/min in men and 0.23+/-0.01 g/min in women (p<0.05). Exercise intensity at the maximum fat oxidation was 42+/-2.2% VO (2 max) in men and 43+/-1.7% VO (2 max) in women. With multivariate analysis, exercise-induced fat oxidation was related to fat-free mass, percent fat mass, and oxidative capacity, but not to absolute fat mass, visceral fat, or intramyocellular fat content. We conclude that in obese subjects the capacity to oxidize fat during exercise appears to be limited by skeletal muscle mass and oxidative capacity rather than the availability of visceral or intramyocellular fat.

Improvement of fractional flow reserve and collateral flow by treatment with external counterpulsation (Art.Net.-2 Trial).

BACKGROUND: Arteriogenesis (collateral artery growth) is nature's most efficient rescue mechanism to overcome the fatal consequences of arterial occlusion or stenosis. The goal of this trial was to investigate the effect of external counterpulsation (ECP) on coronary collateral artery growth. MATERIALS AND METHODS: A total of 23 patients (age 61 +/- 2.5 years) with stable coronary artery disease and at least one haemodynamic significant stenosis eligible for percutaneous coronary intervention were prospectively recruited into the two study groups in a 2 : 1 manner (ECP : control). One group (ECP group, n = 16) underwent 35 1-h sessions of ECP in 7 weeks. In the control group (n = 7), the natural course of collateral circulation over 7 weeks was evaluated. All patients underwent a cardiac catheterization at baseline and after 7 weeks, with invasive measurements of the pressure-derived collateral flow index (CFIp, primary endpoint) and fractional flow reserve (FFR). RESULTS: In the ECP group, the CFIp (from 0.08 +/- 0.01 to 0.15 +/- 0.02; P < 0.001) and FFR (from 0.68 +/- 0.03 to 0.79 +/- 0.03; P = 0.001) improved significantly, while in the control group no change was observed. Only the ECP group showed a reduction of the Canadian Cardiovascular Society (CCS, P = 0.008) and New York Heart Association (NYHA, P < 0.001) classification. CONCLUSION: In this study, we provide direct functional evidence for the stimulation of coronary arteriogenesis via ECP in patients with stable coronary artery disease. These data might open a novel noninvasive and preventive treatment avenue for patients with non-acute vascular stenotic disease.

Mechanical gluteal soft tissue material parameter validation under complex tissue loading.

BACKGROUND: Finite element (FE) simulations of mechanical tissue loading help provide insight into internal tissue stress and strain distribution. Thus, better understanding of pressure sore aetiology and pressure sore prophylaxis can be acquired. Indispensable in the simulation process is adequate mechanical description of interacting soft tissue and body support materials. Sufficient verification of employed material parameters is required. METHOD OF APPROACH: Gluteal soft tissue material parameters, previously derived from experimental tissue indentation of a geometrically limited buttock sub-domain are shown to be suitable in simulating complex deformation of the entire buttocks. In the context of parameter verification, defined tissue loading via a soft foam material specimen was performed. Making use of magnetic resonance imaging (MRI), the scenario was scanned to gain tissue displacement information. Anatomical surface data was reconstructed and an FE-model of the experimental situation was generated and simulated. MR-image information was compared with simulation results. RESULTS: Deformation of gluteal skin/fat and passive muscle tissue and support material under loading was in good agreement with the corresponding MR-image data. Visual accordance was found for deformed skin boundary as well as for internal fat-muscle tissue boundaries by superimposing experimental and numerical output. In addition, section surface boundaries of the MR-images and the FE-model of skin/fat and muscle at the deformed state were discretized and sufficient sample points were provided. A correlation factor of R2= 0.998 for skin/fat deformation was derived, comparing simulation with MRI output. CONCLUSION: Reliability of employed tissue material parameters for use in realistic loading scenarios at finite strains including complex tissue and bone anatomy, non-linear tissue support material, multiple tissue types and contact interactions is shown.

Myocardial tissue characterization in systemic lupus erythematosus: value of a comprehensive cardiovascular magnetic resonance approach.

Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disorder mainly affecting women and is associated with high cardiovascular morbidity and mortality. We tested the utility of a comprehensive cardiovascular magnetic resonance approach to assess myocardial involvement and to determine its relation to disease activity in SLE patients. We studied 20 SLE patients (19 females, 35+/-10 years) and 13 healthy volunteers (nine females, 28+/-11 years). Classification followed the criteria of the American College of Rheumatology and assessment of SLE activity was based on the European Consensus Lupus Activity Measurement index. Cardiovascular magnetic resonance (CMR) was performed on a 1.5T scanner and included the following sequences: steady-state free precession, T2-weighted, early and late T1-weighted after gadolinium-DTPA injection. Ejection fraction was not significantly different between groups (controls: 63+/-6, inactive SLE: 67+/-7, active SLE 64+/-8; P=0.003 for all groups). In contrast, relative T2 ratio (myocardium to skeletal muscle) was significantly higher in active SLE than in the other groups (controls: 1.7+/-0.3, inactive: 1.8+/-0.2, active: 2.1+/-0.2; P=0.003). Similarly, early enhancement ratio was significantly higher in active SLE (controls: 2.4+/-1.4, inactive: 2.8+/-1.1, active: 4.5+/-2.0, P=0.39). Both relative T2 and early enhancement ratios significantly correlated with disease activity. Intramural foci of late enhancement were observed in three of eight patients (all with active SLE). Of the five patients with no late enhancement, only one had active disease. An imaging approach combining T2-weighted, early and late enhancement imaging is a useful tool to assess possible myocardial involvement in SLE. CMR parameters of global myocardial involvement correlate well with disease activity, but not with usual clinical signs as summarized in a cardiac score.

Analysis of mechanical interaction between human gluteal soft tissue and body supports.

Pressure sores are the most common complication associated with patient immobilization. They develop through sustained localized tissue strain and stress, primarily caused by body supports. Modifying support design can reduce the risk and extent of pressure sore development with computational simulations helping to provide insight into tissue stress-strain distribution. Appropriate material parameters for human soft tissue and support material, as well as precise anatomical modelling, are indispensable in this process. A finite element (FE) model of the human gluteal region based on magnetic resonance imaging (MRI) data has been developed. In vivo human gluteal skin/fat and muscle long-term material parameters as well as open-cell polyurethane foam support long-term material parameters have been characterised. The Ogden form for slightly compressible materials was employed to describe human gluteal soft tissue behaviour. Altering support geometries and support materials, effects on human gluteal soft tissue could be quantified. FE-analysis indicated maximal tissue stress at the muscle-bone interface, not at the skin. Shear strain maxima were found in the muscle layer near the fat-muscle interface. Maximum compressive stress magnitude at the sacral bone depended strongly on the behaviour of the pelvic diaphragm musculature. We hypothesize that the compliance of the muscles forming the pelvic diaphragm govern the relative motion of the buttock tissue to the adjacent bone structure under compression, thus influencing tissue stress magnitudes.

A method for a mechanical characterisation of human gluteal tissue.

The most common complication associated with immobilization is pressure sores caused by sustained localized tissue strain and stress. Computational simulations have provided insight into tissue stress-strain distribution, subject to loading conditions. In the simulation process, adequate soft tissue material parameters are indispensable. An in vivo procedure to characterise material parameters of human gluteal skin/fat and muscle tissue has been developed. It employs a magnetic resonance imaging (MRI) device together with an MRI compatible loading device. Using the derived data as constraints in an iterative optimization process the inverse finite element (FE) method was applied. FE-models were built and the material constants describing skin/fat and muscle tissue were parameterized and optimized. Separate parameter sets for human gluteal skin/fat and muscle were established. The long-term shear modulus for human gluteal skin/fat was G_{infinity, S/F}= 1182 Pa and for muscle G_{infinity, M} = 1025 Pa. The Ogden form for slightly compressible materials was chosen to define passive human gluteal soft tissue material behaviour. To verify the approach, the human skin/fat-muscle tissue compound was simulated using the derived material parameter sets and the simulation result was compared to empirical values. A correlation factor of R;{2} = 0.997 was achieved.

Biochemical and bioimaging markers for risk assessment and diagnosis in major cardiovascular diseases: a road to integration of complementary diagnostic tools.

This report from the first International Course on Integrated Biomarkers, Biochemical and Bioimaging Endpoints in Cardiovascular Diagnosis, Prevention, Therapy and Drug Development provides the basis for optimizing diagnostic, prognostic and therapeutic information in four areas of cardiovascular medicine: primary prevention of cardiovascular diseases, acute coronary syndromes, heart failure and stroke. Risk stratification and treatment strategies can be refined and enhanced through integration of bioimaging and biochemical markers to characterize sub-clinical and clinical atherosclerosis. For the integrative approach to be useful, each of the biomarkers must be validated and cost-effective. Clinical decision is the primary level of integration and is based on clinical evaluation and the use of a combination of bioimaging and biochemical markers. The decision to initiate preventive or therapeutic intervention must take into account the factors affecting the levels of expression of the biomarker and the potential input the biomarker has on metabolic processes or modulation of other biomarkers. The optimal approach to intervention must take into consideration the risk-benefit and cost-effectiveness ratios.