Absence of DNA double-strand breaks in human peripheral blood mononuclear cells after 3 Tesla magnetic resonance imaging assessed by γH2AX flow cytometry.

OBJECTIVES: Magnetic resonance imaging (MRI) is regarded as a non-harming and non-invasive imaging modality with high tissue contrast and almost no side effects. Compared to other cross-sectional imaging modalities, MRI does not use ionising radiation. Recently, however, strong magnetic fields as applied in clinical MRI scanners have been suspected to induce DNA double-strand breaks in human lymphocytes. METHODS: In this study we investigated the impact of 3-T cardiac MRI examinations on the induction of DNA double-strand breaks in peripheral mononuclear cells by γH2AX staining and flow cytometry analysis. The study cohort consisted of 73 healthy non-smoking volunteers with 36 volunteers undergoing CMRI and 37 controls without intervention. Differences between the two cohorts were analysed by a mixed linear model with repeated measures. RESULTS: Both cohorts showed a significant increase in the γH2AX signal from baseline to post-procedure of 6.7 % (SD 7.18 %) and 7.8 % (SD 6.61 %), respectively. However, the difference between the two groups was not significant. CONCLUSION: Based on our study, γH2AX flow cytometry shows no evidence that 3-T MRI examinations as used in cardiac scans impair DNA integrity in peripheral mononuclear cells. KEY POINTS: • No evidence for DNA double-strand breaks after cardiac MRI. • Prospective study underlines safe use of MRI with regard to DNA damage. • Controlled trial involving both genders investigating DNA DSBs after 3-T MRI.

Early pneumonia and timing of antibiotic therapy in patients after nontraumatic out-of-hospital cardiac arrest.

BACKGROUND: While early pneumonia is common in patients after out-of-hospital cardiac arrest (OHCA), little is known about the impact of pneumonia and the optimal timing of antibiotic therapy after OHCA. METHODS: We conducted a 5-year retrospective cohort study, including patients who suffered from OHCA and were treated with therapeutic hypothermia. ICU treatment was strictly standardized with defined treatment goals and procedures. Medical records, chest radiographic images and microbiological findings were reviewed. RESULTS: Within the study period, 442 patients were admitted to our medical ICU after successfully resuscitated cardiac arrest. Of those, 174 patients fulfilled all inclusion and no exclusion criteria and were included into final analysis. Pneumonia within the first week could be confirmed in 39 patients (22.4%) and was confirmed or probable in 100 patients (57.5%), without a difference between survivors and non-survivors (37.8% vs. 23.1% confirmed pneumonia, p = 0.125). In patients with confirmed pneumonia a tracheotomy was performed more frequently (28.2 vs. 12.6%, p = 0.026) compared to patients without confirmed pneumonia. Importantly, patients with confirmed pneumonia had a longer ICU- (14.0 [8.5-20.0] vs. 8.0 [5.0-14.0] days, p < 0.001) and hospital stay (23.0 [11.5-29.0] vs. 15.0 [6.5-25.0] days, p = 0.016). A positive end expiratory pressure (PEEP) > =10.5 mbar on day 1 of the hospital stay was identified as early predictor of confirmed pneumonia (odds ratio 2.898, p = 0.006). No other reliable predictor could be identified. Median time to antibiotic therapy was 8.7 [5.4-22.8] hours, without a difference between patients with or without confirmed pneumonia (p = 0.381) and without a difference between survivors and non-survivors (p = 0.264). Patients receiving antibiotics within 12 hours after admission had a shorter ICU- (8.0 [4.0-14.0] vs. 10.5 [6.0-16.0] vs. 13.5 [8.0-20.0] days, p = 0.004) and hospital-stay (14.0 [6.0-25.0] vs. 16.5 [11.0-27.0] vs. 21.0 [17.0-28.0] days, p = 0.007) compared to patients receiving antibiotics after 12 to 36 or more than 36 hours, respectively. CONCLUSIONS: Early pneumonia may extend length of ICU- and hospital-stay after OHCA and its occurrence is difficult to predict. A delayed initiation of antibiotic therapy in OHCA patients may increase the duration of the ICU- and hospital-stay.

Non-invasive estimation of pulmonary outflow tract obstruction: A comparative study of cardiovascular phase contrast magnetic resonance and Doppler echocardiography versus cardiac catheterization.

AIM: To compare estimated pressure gradients from routine follow-up cardiovascular phase-contrast magnetic resonance (PC-MR) with those from Doppler echocardiography and invasive catheterization in patients with congenital heart disease (CHD) and pulmonary outflow tract obstruction. METHODS: In 75 patients with pulmonary outflow tract obstruction maximal and mean PC-MR gradients were compared to maximal and mean Doppler gradients. Additionally, in a subgroup of 31 patients maximal and mean PC-MR and Doppler pressure gradients were compared to catheter peak-to-peak pressure gradients (PPG). RESULTS: Maximal and mean PC-MR gradients underestimated pulmonary outflow tract obstruction as compared to Doppler (max gradient: bias = + 8.4 mm Hg (+ 47.6%), r = 0.89, p < 0.001; mean gradient: + 4.3 mm Hg (+ 49.0%), r = 0.88, p < 0.001). However, in comparison to catheter PPG, maximal PC-MR gradients (bias = + 1.8 mm Hg (+ 8.8%), r = 0.90, p = 0.14) and mean Doppler gradients (bias = - 2.3 mm Hg (- 11.2%), r = 0.87, p = 0.17) revealed best agreement. Mean PC-MR gradients underestimated (bias = - 7.7 mm Hg (- 55.6%), r = 0.90, p < 0.001) while maximal Doppler gradients systematically overestimated catheter PPG (bias = + 13.9 mm Hg (+ 56.5%), r = 0.88, p < 0.001). CONCLUSIONS: Estimated maximal PC-MR pressure gradients from routine CHD follow-up agree well with invasively assessed peak-to-peak pressure gradients. Estimated maximal Doppler pressure gradients tend to overestimate, while Doppler mean gradients agree better with catheter PPG. Therefore, our data provide reasonable arguments to either apply maximal PC-MR gradients or mean Doppler gradients to non-invasively evaluate the severity of pulmonary outflow tract obstruction in the follow-up of CHD.

Peak flow velocities in the ascending aorta-real-time phase-contrast magnetic resonance imaging vs. cine magnetic resonance imaging and echocardiography.

This prospective study of eight healthy volunteers evaluates peak flow velocities (PFV) in the ascending aorta using real-time phase-contrast magnetic resonance imaging (MRI) in comparison to cine phase-contrast MRI and echocardiography. Flow measurements by echocardiography and cine phase-contrast MRI with breath-holding were performed according to clinical standards. Real-time phase-contrast MRI at 40 ms temporal resolution and 1.3 mm in-plane resolution was based on highly undersampled radial fast low-angle shot (FLASH) sequences with image reconstruction by regularized nonlinear inversion (NLINV). Evaluations focused on the determination of PFV. Linear regressions and Bland-Altman plots were used for comparisons of methods. When averaged across subjects, real-time phase-contrast MRI resulted in PFV of 120±20 cm s(-1) (mean ± SD) in comparison to 122±16 cm s(-1) for cine MRI and 124±20 cm s(-1) for echocardiography. The maximum deviations between real-time phase-contrast MRI and echocardiography ranged from -20 to +14 cm s(-1) (cine MRI: -10 to +12 cm s(-1)). Thus, in general, real-time phase-contrast MRI of cardiac outflow revealed quantitative agreement with cine MRI and echocardiography. The advantages of real-time MRI are measurements during free breathing and access to individual cardiac cycles.

Right Atrial Volume is Increased in Corrected Tetralogy of Fallot and Correlates with the Incidence of Supraventricular Arrhythmia: A CMR Study.

The aim of this study was to evaluate right atrial (RA) volume in corrected Tetralogy of Fallot (cTOF) and assess its correlation with the occurrence of supraventricular (SV) arrhythmia. Cardiac magnetic resonance imaging (CMR) and 24-h Holter were performed in n = 67 consecutive cTOF patients (age 30 ± 11.3 years). The CMR protocol included standard HASTE, SSFP cine, and blood flow measurements. Correlations between arrhythmia in ECG, heart volume, and functional parameters were investigated by negative binominal regression. Patients' characteristics (mean ± SD) included mean RA volume of 49 ± 19 ml/m(2) (HASTE sequence), mean right ventricular (RV) end-diastolic volume of 98 ± 27 ml/m(2), mean pulmonary valve regurgitation fraction (PR) of 21 ± 19 %, BMI of 25 kg/m(2), and heart rate of 75/min. Twenty-eight out of 67 patients experienced SV arrhythmia including SV couplets or bigeminus or longer non-sustained SV tachycardia (SVT) episodes. RA volume index was identified as an independent risk factor for different degrees of SV arrhythmia (SV couplets/bigeminus p < 0.001, SVT p < 0.001). Further risk factors for SV arrhythmia were male gender (p = 0.023) and decreased left ventricular (LV) ejection fraction (EF) (LV EF p < 0.001). RA volume is increased in adult patients with cTOF with larger RA volumes relating to higher incidence of SV arrhythmia. SV arrhythmia also appeared more often in male patients and those with decreased LV EF. Risk stratification according to these parameters could help to optimize early prevention and adjusted individual therapy to improve patient outcome and quality of life.

Situs inversus totalis with congenitally corrected transposition of the great arteries: insights from cardiac MRI.

INTRODUCTION: Situs inversus totalis with congenitally corrected transposition of the great arteries represents a relatively rare congenital condition. CASE DESCRIPTION: The current report describes the case of a 56 year old patient with an atrio-ventricular and ventricular-arterial discordance of the heart chambers without surgical correction, incidentally detected during hepatocellular carcinoma evaluation. The systemic venous blood arrived via the right atrium and a mitral valve in the morphologically left but pulmonary arterial ventricle that gave rise to a pulmonary trunk. The pulmonary venous blood passed the left atrium and the tricuspid valve into a morphologically right but systemic ventricle that gave rise to the aorta. DISCUSSION AND EVALUATION: The switched anatomy was incidentally detected on echocardiography. The patient was referred to cardiac magnetic resonance imaging (CMR) including flow measurements, volumetry and late enhancement. CMR results showed a mildly impaired function and the switched anatomy. During a follow-up period of 2 years the patient was suffering from only mild heart failure and dyspnea. CONCLUSIONS: Heart failure symptoms and arrhythmias can appear with increasing age in patients with congenitally corrected transposition. Early CMR allows accurate diagnosis and timely introduction of adequate therapy thereby avoiding disease progression.

Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism.

Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.

Quantification of left ventricular torsion and diastolic recoil using cardiovascular magnetic resonance myocardial feature tracking.

OBJECTIVES: Cardiovascular magnetic resonance feature tracking (CMR-FT) offers quantification of myocardial deformation from routine cine images. However, data using CMR-FT to quantify left ventricular (LV) torsion and diastolic recoil are not yet available. We therefore sought to evaluate the feasibility and reproducibility of CMR-FT to quantify LV torsion and peak recoil rate using an optimal anatomical approach. METHODS: Short-axis cine stacks were acquired at rest and during dobutamine stimulation (10 and 20 µg · kg(-1) · min(-1)) in 10 healthy volunteers. Rotational displacement was analysed for all slices. A complete 3D-LV rotational model was developed using linear interpolation between adjacent slices. Torsion was defined as the difference between apical and basal rotation, divided by slice distance. Depending on the distance between the most apical (defined as 0% LV distance) and basal (defined as 100% LV distance) slices, four different models for the calculation of torsion were examined: Model-1 (25-75%), Model-2 (0-100%), Model-3 (25-100%) and Model-4 (0-75%). Analysis included subendocardial, subepicardial and global torsion and recoil rate (mean of subendocardial and subepicardial values). RESULTS: Quantification of torsion and recoil rate was feasible in all subjects. There was no significant difference between the different models at rest. However, only Model-1 (25-75%) discriminated between rest and stress (Global Torsion: 2.7 ± 1.5° cm(-1), 3.6 ± 2.0° cm(-1), 5.1 ± 2.2° cm(-1), p<0.01; Global Recoil Rate: -30.1 ± 11.1° cm(-1) s(-1),-46.9 ± 15.0° cm(-1) s(-1),-68.9 ± 32.3° cm(-1) s(-1), p<0.01; for rest, 10 and 20 µg · kg(-)1 · min(-1) of dobutamine, respectively). Reproducibility was sufficient for all parameters as determined by Bland-Altman analysis, intraclass correlation coefficients and coefficient of variation. CONCLUSIONS: CMR-FT based derivation of myocardial torsion and recoil rate is feasible and reproducible at rest and with dobutamine stress. Using an optimal anatomical approach measuring rotation at 25% and 75% apical and basal LV locations allows effective quantification of torsion and recoil dynamics. Application of these new measures of deformation by CMR-FT should next be explored in disease states.

Comparison of end-diastolic versus end-systolic cardiac-computed tomography reconstruction interval in patient's prior to pulmonary vein isolation.

PURPOSE: Aim of the study was to investigate diagnostic accuracy of cardiac computed tomography angiography (CCTA) between left ventricular end-systolic (LVES) and left ventricular end-diastolic (LVED) cardiac phase for thrombus detection in patient's prior to pulmonary vein isolation (PVI). MATERIALS AND METHODS: 182 consecutive Patients with drug refractory AF scheduled for PVI (62.6% male, mean age 64.1 ± 10.2 years) underwent routine pre-procedural evaluation including transesophageal echocardiography (TEE) and CCTA for evaluation of left atrial (LA)/left atrial appendage (LAA) anatomy and thrombus formation. Qualitative and quantitative analysis (using aorta ascendens (AA)/LAA ratio) was performed. Measurements of the LA/LAA in LVES and LVED cardiac phase were obtained. RESULTS: End-systolic volumes (LA/LAA) measured in 30 patients without filling defects as control group and all 14 with filling defects of 182 patients were significantly larger (p < 0.01) than in end-diastolic phase. Qualitative analysis was inferior to quantitative analysis using LA/LAA ratio (<0.5; accuracy: 100%, 88%,100%, 99% vs 100%). 5 out of 182 patients (2.7%) showed thrombus formation of the LAA in CCTA confirmed by TEE and quantitative analysis. Intra/-interobserver variability was lower in end-systolic vs end-diastolic reconstruction interval. CONCLUSION: For evaluating CCTA datasets in patients prior PVI, the LVES reconstruction interval is recommended due to significantly larger LA/LAA volumes and lower intra/- interobserver variability's.

Giant bypass aneurysm, a cause of suspected cardiac mass.

INTRODUCTION: A 66-years old man suffering from coronary artery disease appeared without symptoms for routine follow-up in our clinic. CASE DESCRIPTION: The echocardiogram revealed a tumorous mass of the right atrium and right ventricle. In the past, coronary revascularization with venous grafts of the right coronary artery and circumflex artery as well as internal mammaria graft to the left anterior descending artery was performed 20 years before. The general clinicians presented the case to the surgeons and it was decided to perform cardiac MRI as a preoperative diagnostic modality. DISCUSSION AND EVALUATION: Following cardiac magnetic resonance imaging (MRI) showed a mass in the pericardium in the right atrioventricular groove with thrombotic material. Due to the MRI the patient underwent coronary angiography to confirm an aneurysm. CONCLUSIONS: The learning points from this case are that cardiac MRI is a very useful tool for further evaluation of suspected cardiac masses and should be performed for further characterization.

Persistent left superior vena cava detected after central venous catheter insertion.

INTRODUCTION: Persistent left superior vena cava is a rare case with an appearance of 0.3% to 0.5% of individuals in general population. Indication for jugular venous intervention could be different, such as implantable venous catheters for oncological therapy. The present report describes a case of a patient with a persistent left superior vena cava detected after central venous catheter (CVC) installation using computer-assisted tomography (CT). CASE DESCRIPTION: In a control chest X-ray the CVC was not in the right superior vena cava as expected to be. A following blood gas analysis revealed venous concentration. The consultation of additional CT diagnostics yielded a persistent left superior vena cava with an outlet to dilated coronary sinus. DISCUSSION AND EVALUATION: The patient was followed over 1 year with the underlying disease of chronic obstructive pulmonary disease. Cardiac insufficiency, sinus aneurysm and arryhtmias could appear with growing age in patients with persistence left superior vena cava, but most of them are asymptomatic. Knowing the venous anatomy is important for correct position and function of e.g. totally implantable venous catheters, central lines or pacemakers. CONCLUSION: The importance of early imaging diagnosis of this anatomical variation could optimize adequate therapy and finally improve living conditions. CT can help adapting correct therapy with correct diagnostics.

The total right/left-volume index: a new and simplified cardiac magnetic resonance measure to evaluate the severity of Ebstein anomaly of the tricuspid valve: a comparison with heart failure markers from various modalities.

BACKGROUND: The classification of clinical severity of Ebstein anomaly still remains a challenge. The aim of this study was to focus on the interaction of the pathologically altered right heart with the anatomically-supposedly-normal left heart and to derive from cardiac magnetic resonance (CMR) a simple imaging measure for the clinical severity of Ebstein anomaly. METHODS AND RESULTS: Twenty-five patients at a mean age of 26±14 years with unrepaired Ebstein anomaly were examined in a prospective study. Disease severity was classified using CMR volumes and functional measurements in comparison with heart failure markers from clinical data, ECG, laboratory and cardiopulmonary exercise testing, and echocardiography. All examinations were completed within 24 hours. A total right/left-volume index was defined from end-diastolic volume measurements in CMR: total right/left-volume index=(RA+aRV+fRV)/(LA+LV). Mean total right/left-volume index was 2.6±1.7 (normal values: 1.1±0.1). This new total right/left-volume index correlated with almost all clinically used biomarkers of heart failure: brain natriuretic peptide (r=0.691; P=0.0003), QRS (r=0.432; P=0.039), peak oxygen consumption/kg (r=-0.479; P=0.024), ventilatory response to carbon dioxide production at anaerobic threshold (r=0.426; P=0.048), the severity of tricuspid regurgitation (r=0.692; P=0.009), tricuspid valve offset (r=0.583; P=0.004), and tricuspid annular plane systolic excursion (r=0.554; P=0.006). Previously described severity indices ([RA+aRV]/[fRV+LA+LV]) and fRV/LV end-diastolic volume corresponded only to some parameters. CONCLUSIONS: In patients with Ebstein anomaly, the easily acquired index of right-sided to left-sided heart volumes from CMR correlated well with established heart failure markers. Our data suggest that the total right/left-volume index should be used as a new and simplified CMR measure, allowing more accurate assessment of disease severity than previously described scoring systems.

Binge drinking induces whole-body insulin resistance by impairing hypothalamic insulin action.

Individuals with a history of binge drinking have an increased risk of developing the metabolic syndrome and type 2 diabetes. Whether binge drinking impairs glucose homeostasis and insulin action is unknown. To test this, we treated Sprague-Dawley rats daily with alcohol (3 g/kg) for three consecutive days to simulate human binge drinking and found that these rats developed and exhibited insulin resistance even after blood alcohol concentrations had become undetectable. The animals were resistant to insulin for up to 54 hours after the last dose of ethanol, chiefly a result of impaired hepatic and adipose tissue insulin action. Because insulin regulates hepatic glucose production and white adipose tissue lipolysis, in part through signaling in the central nervous system, we tested whether binge drinking impaired brain control of nutrient partitioning. Rats that had consumed alcohol exhibited impaired hypothalamic insulin action, defined as the ability of insulin infused into the mediobasal hypothalamus to suppress hepatic glucose production and white adipose tissue lipolysis. Insulin signaling in the hypothalamus, as assessed by insulin receptor and AKT phosphorylation, decreased after binge drinking. Quantitative polymerase chain reaction showed increased hypothalamic inflammation and expression of protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling. Intracerebroventricular infusion of CPT-157633, a small-molecule inhibitor of PTP1B, prevented binge drinking-induced glucose intolerance. These results show that, in rats, binge drinking induces systemic insulin resistance by impairing hypothalamic insulin action and that this effect can be prevented by inhibition of brain PTP1B.

H(2)O(2)-mediated modulation of cytosolic signaling and organelle function in rat hippocampus.

Reactive oxygen species (ROS) released from (dys-)functioning mitochondria contribute to normal and pathophysiological cellular signaling by modulating cytosolic redox state and redox-sensitive proteins. To identify putative redox targets involved in such signaling, we exposed hippocampal neurons to hydrogen peroxide (H(2)O(2)). Redox-sensitive dyes indicated that externally applied H(2)O(2) may oxidize intracellular targets in cell cultures and acute tissue slices. In cultured neurons, H(2)O(2) (EC(50) 118 microM) induced an intracellular Ca(2+) rise which could still be evoked upon Ca(2+) withdrawal and mitochondrial uncoupling. It was, however, antagonized by thapsigargin, dantrolene, 2-aminoethoxydiphenyl borate, and high levels of ryanodine, which identifies the endoplasmic reticulum (ER) as the intracellular Ca(2+) store involved. Intracellular accumulation of endogenously generated H(2)O(2)-provoked by inhibiting glutathione peroxidase-also released Ca(2+) from the ER, as did extracellular generation of superoxide. Phospholipase C (PLC)-mediated metabotropic signaling was depressed in the presence of H(2)O(2), but cytosolic cyclic adenosine-5'-monophosphate (cAMP) levels were not affected. H(2)O(2) (0.2-5 mM) moderately depolarized mitochondria, halted their intracellular trafficking in a Ca(2+)- and cAMP-independent manner, and directly oxidized cellular nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH(2)). In part, the mitochondrial depolarization reflects uptake of Ca(2+) previously released from the ER. We conclude that H(2)O(2) releases Ca(2+) from the ER via both ryanodine and inositol trisphosphate receptors. Mitochondrial function is not markedly impaired even by millimolar concentrations of H(2)O(2). Such modulation of Ca(2+) signaling and organelle interaction by ROS affects the efficacy of PLC-mediated metabotropic signaling and may contribute to the adjustment of neuronal function to redox conditions and metabolic supply.