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.

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.

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.

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.

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.

Nuclear magnetic resonance for the assessment of the effects of alcohol septal ablation in hypertrophic cardiomyopathy.

Alcohol ablation of the interventricular septum is a well-established method of treatment in hypertrophic obstructive cardiomyopathy (HOCM). The extent of ablation-induced iatrogenic infarction is usually assessed by the use of echocardiography. The role of nuclear magnetic resonance (NMR) in this setting has not yet been well established. In this report we describe five patients with HOCM who underwent alcohol septal ablation and subsequent NMR evaluation. The usefulness of NMR in these patients is discussed and comparison with echocardiographic results is presented.

Magnetic resonance planimetry of the vena contracta as a new approach to assessment of stenotic heart valves: an in vitro study.

Exact determination of the orifice area in stenotic valve disease is essential to guide therapy. With the standard imaging methods, the orifice area has to be calculated by empirically-derived formulas, which may be susceptible to changes in hemodynamic status, leading to wrong therapeutic decisions. We tested the ability of magnetic resonance imaging (MRI) to quantify the orifice area by planimetry of the proximal vena contracta (PVC) in an idealized, constant-flow model in a 1.0-T tomograph (Siemens Magnetom Expert). There was a close correlation of the PVC area in MRI and the true orifice area (r2 = 0.985), and agreement of the methods as measured by the Bland-Altman test was significant with a low systematic error of -0.02 cm2. We conclude that MRI planimetry of the PVC in stenotic valves in a constant-flow model may be used to reliably measure the orifice area.

Subclinical cardiotoxic effects of anthracyclines as assessed by magnetic resonance imaging-a pilot study.

BACKGROUND: Anthracyclines are potent chemotherapeutics burdened by their cardiotoxicity. So far no marker to detect early cardiac damage exists. We tested the ability of magnetic resonance imaging (MRI) to show early changes in myocardial signal and cardiac function after anthracycline therapy. METHODS: Twenty-two patients with normal cardiac function were investigated by MRI before and 3 and 28 days after anthracycline chemotherapy. Contrast enhanced fast spin echo images were obtained to characterize myocardial enhancement. Left ventricular ejection fraction was measured by MRI in contiguous short-axis planes. RESULTS: All patients remained clinically stable. Ejection fraction decreased from 67.8% +/- 1.4% to 58.9% +/- 1.9% after 28 days (P < .05). The relative myocardial contrast enhancement increased from 3.8 +/- 0.4 to 6.9 +/- 1.1 (P < .01). An increase of the enhancement of >5 on day 3 compared with baseline predicted a significant loss of ejection fraction at 28 days (67.5% +/- 2.8% to 51.4% +/- 5.6%, mean difference 16.1% +/- 6.6%; P < .05), whereas an increase of +5 was not associated with a significant loss of ejection fraction (67.6% +/- 1.7% to 62.5% +/- 1.4%, mean difference 4.1% +/- 2.6%; P not significant). CONCLUSIONS: MRI detects early changes in myocardial contrast and slightly deteriorating cardiac function in patients receiving anthracyclines. Larger patient cohorts and longer follow-up are needed to evaluate MRI as a predictor for anthracycline cardiotoxicity.

Measurement of left ventricular dimensions and function in patients with dilated cardiomyopathy.

Studies on medical therapy in heart failure are focused on changes of left ventricular (LV) dimensions and function. These changes may be small, requiring a large study group. We measured LV parameters (LV volumes, LV ejection fraction (LV-EF), and left ventricular mass (LVM)) with two-dimensional echocardiography (2D-echo) and magnetic resonance imaging (MRI) in 50 patients. Based on the difference between the measurements, we determined the variance of the results and calculated the sample sizes needed to detect changes of baseline values. For the calculated and measured parameters we found significant differences between the two techniques: LV-EF and LVM were higher in 2D-echo, and LV dimensions were comparable. The sample size to detect relevant changes from baseline with MRI was significantly (P < 0.01) smaller than in 2D-echo. We conclude that MRI is superior in clinical studies on left ventricular dimensional and functional changes, since measurements are more reproducible and the required sample size is substantially smaller, thereby reducing costs.