Cardiac paraganglioma: diagnostic work up and review of the literature.

Paraganglioma of the heart are potentially invasive, highly vascularized tumors for which complete resection may be curative. Derived from the cardiac wall in most instances, resectability can be assessed after integration of the data provided by MRI in T2 sequence, and coronarography. A fully documented case of a large cardiac pheochromocytoma of the left atrium and AV groove is reported and the pertinent literature on the subject is here presented.

Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2.

Nedd4-2 has been proposed to play a critical role in regulating epithelial Na+ channel (ENaC) activity. Biochemical and overexpression experiments suggest that Nedd4-2 binds to the PY motifs of ENaC subunits via its WW domains, ubiquitinates them, and decreases their expression on the apical membrane. Phosphorylation of Nedd4-2 (for example by Sgk1) may regulate its binding to ENaC, and thus ENaC ubiquitination. These results suggest that the interaction between Nedd4-2 and ENaC may play a crucial role in Na+ homeostasis and blood pressure (BP) regulation. To test these predictions in vivo, we generated Nedd4-2 null mice. The knockout mice had higher BP on a normal diet and a further increase in BP when on a high-salt diet. The hypertension was probably mediated by ENaC overactivity because 1) Nedd4-2 null mice had higher expression levels of all three ENaC subunits in kidney, but not of other Na+ transporters; 2) the downregulation of ENaC function in colon was impaired; and 3) NaCl-sensitive hypertension was substantially reduced in the presence of amiloride, a specific inhibitor of ENaC. Nedd4-2 null mice on a chronic high-salt diet showed cardiac hypertrophy and markedly depressed cardiac function. Overall, our results demonstrate that in vivo Nedd4-2 is a critical regulator of ENaC activity and BP. The absence of this gene is sufficient to produce salt-sensitive hypertension. This model provides an opportunity to further investigate mechanisms and consequences of this common disorder.

Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design.

BACKGROUND: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. METHODS/DESIGN: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. DISCUSSION: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. TRIAL REGISTRATION: The TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

Three-dimensional ordered-subset expectation maximization iterative protocol for evaluation of left ventricular volumes and function by quantitative gated SPECT: a dynamic phantom study.

The purposes of this study were to characterize the performance of a 3-dimensional (3D) ordered-subset expectation maximization (OSEM) algorithm in the quantification of left ventricular (LV) function with (99m)Tc-labeled agent gated SPECT (G-SPECT), the QGS program, and a beating-heart phantom and to optimize the reconstruction parameters for clinical applications. METHODS: A G-SPECT image of a dynamic heart phantom simulating the beating left ventricle was acquired. The exact volumes of the phantom were known and were as follows: end-diastolic volume (EDV) of 112 mL, end-systolic volume (ESV) of 37 mL, and stroke volume (SV) of 75 mL; these volumes produced an LV ejection fraction (LVEF) of 67%. Tomographic reconstructions were obtained after 10-20 iterations (I) with 4, 8, and 16 subsets (S) at full width at half maximum (FWHM) gaussian postprocessing filter cutoff values of 8-15 mm. The QGS program was used for quantitative measurements. RESULTS: Measured values ranged from 72 to 92 mL for EDV, from 18 to 32 mL for ESV, and from 54 to 63 mL for SV, and the calculated LVEF ranged from 65% to 76%. Overall, the combination of 10 I, 8 S, and a cutoff filter value of 10 mm produced the most accurate results. The plot of the measures with respect to the expectation maximization-equivalent iterations (I x S product) revealed a bell-shaped curve for the LV volumes and a reverse distribution for the LVEF, with the best results in the intermediate range. In particular, FWHM cutoff values exceeding 10 mm affected the estimation of the LV volumes. CONCLUSION: The QGS program is able to correctly calculate the LVEF when used in association with an optimized 3D OSEM algorithm (8 S, 10 I, and FWHM of 10 mm) but underestimates the LV volumes. However, various combinations of technical parameters, including a limited range of I and S (80-160 expectation maximization-equivalent iterations) and low cutoff values (< or =10 mm) for the gaussian postprocessing filter, produced results with similar accuracies and without clinically relevant differences in the LV volumes and the estimated LVEF.

Too cold may not be so cool: spontaneous hypothermia as a marker of poor outcome after cardiac arrest.

In a recent issue of Critical Care, den Hartog and colleagues show an association between spontaneous hypothermia, defined by an admission body temperature < 35°C, and poor outcome in patients with coma after cardiac arrest (CA) treated with therapeutic hypothermia (TH). Given that TH alters neurological prognostication, studies aiming to identify early markers of injury severity and outcome are welcome, since they may contribute overall to optimize the management of comatose CA patients. This study provides an important message to clinicians involved in post-resuscitation care and raises important questions that need to be taken into account in future studies.

Prognostication in comatose survivors of cardiac arrest: An advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

OBJECTIVES: To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS: GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS: Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron-specific enolase at 48-72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

Combined functional and viability cardiac MR imaging in a single breathhold

The combination of cardiac viability and functional information enhances the identification of different heart tissues in the setting of ischemic heart disease. A method has recently been proposed for obtaining black-blood delayed-enhancement (DE) viability images using the stimulated-echo acquisition mode (STEAM) MRI pulse sequence in a single short breathhold. The method was validated against conventional inversion-recovery (IR) DE images for identifying regions of myocardial infarction (MI). The method was based on the acquisition of three consecutive images of the same anatomical slice. One image has T(1)-weighted contrast in which infarction appears bright. The two other images are used to construct an anatomical image of the heart, which is combined with the first image to produce a black-blood viability image. However, using appropriate modulation and demodulation frequencies, the latter two images bear useful information about myocardial deformation that results in a cardiac strain-encoding (SENC) functional image. In this work, a method is proposed for obtaining three consecutive SENC images in a single acquisition that can be combined to produce a composite image of the heart, which shows both functional and viability information. The proposed technique reduces scan time by one-half, compared with separate acquisitions of functional and viability images, and alleviates misregistration problems caused by separate breathholds.

On some numerical aspects of an active strain model in cardiac mechanics

We are interested in the development, implementation and testing of an orthotropic model for cardiac contraction based on an active strain decomposition. Our model addresses the coupling of a transversely isotropic mechanical description at the cell level, with an orthotropic constitutive law for incompressible tissue at the macroscopic level. The main differences with the active stress model are addressed in detail, and a finite element discretization using Taylor-Hood and MINI elements is proposed and illustrated with numerical examples.

Cardiac raptor ablation impairs adaptive hypertrophy, alters metabolic gene expression, and causes heart failure in mice.

Background- Cardiac hypertrophy involves growth responses to a variety of stimuli triggered by increased workload. It is an independent risk factor for heart failure and sudden death. Mammalian target of rapamycin (mTOR) plays a key role in cellular growth responses by integrating growth factor and energy status signals. It is found in 2 structurally and functionally distinct multiprotein complexes called mTOR complex (mTORC) 1 and mTORC2. The role of each of these branches of mTOR signaling in the adult heart is currently unknown. Methods and Results- We generated mice with deficient myocardial mTORC1 activity by targeted ablation of raptor, which encodes an essential component of mTORC1, during adulthood. At 3 weeks after the deletion, atrial and brain natriuretic peptides and β-myosin heavy chain were strongly induced, multiple genes involved in the regulation of energy metabolism were altered, but cardiac function was normal. Function deteriorated rapidly afterward, resulting in dilated cardiomyopathy and high mortality within 6 weeks. Aortic banding-induced pathological overload resulted in severe dilated cardiomyopathy already at 1 week without a prior phase of adaptive hypertrophy. The mechanism involved a lack of adaptive cardiomyocyte growth via blunted protein synthesis capacity, as supported by reduced phosphorylation of ribosomal S6 kinase 1 and 4E-binding protein 1. In addition, reduced mitochondrial content, a shift in metabolic substrate use, and increased apoptosis and autophagy were observed. Conclusions- Our results demonstrate an essential function for mTORC1 in the heart under physiological and pathological conditions and are relevant for the understanding of disease states in which the insulin/insulin-like growth factor signaling axis is affected such as diabetes mellitus and heart failure or after cancer therapy.

A-kinase anchoring proteins: Molecular regulators of the cardiac stress response

In response to stress or injury the heart undergoes a pathological remodeling process, associated with hypertrophy, cardiomyocyte death and fibrosis, that ultimately causes cardiac dysfunction and heart failure. It has become increasingly clear that signaling events associated with these pathological cardiac remodeling events are regulated by scaffolding and anchoring proteins, which allow coordination of pathological signals in space and time. A-kinase anchoring proteins (AKAPs) constitute a family of functionally related proteins that organize multiprotein signaling complexes that tether the cAMP-dependent protein kinase (PKA) as well as other signaling enzymes to ensure integration and processing of multiple signaling pathways. This review will discuss the role of AKAPs in the cardiac response to stress. Particular emphasis will be given to the adaptative process associated with cardiac hypoxia as well as the remodeling events linked to cardiac hypertrophy and heart failure. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Regulation of glucose transporter expression in cardiac myocytes: p38 MAPK is a strong inducer of GLUT4.

OBJECTIVE: In vivo differentiation of cardiac myocytes is associated with downregulation of the glucose transporter isoform GLUT1 and upregulation of the isoform GLUT4. Adult rat cardiomyocytes in primary culture undergo spontaneous dedifferentiation, followed by spreading and partial redifferentiation, which can be influenced by growth factors. We used this model to study the signaling mechanisms modifying the expression of GLUT4 in cardiac myocytes. RESULTS: Adult rat cardiomyocytes in primary culture exhibited spontaneous upregulation of GLUT1 and downregulation of GLUT4, suggesting resumption of a fetal program of GLUT gene expression. Treatment with IGF-1 and, to a minor extent, FGF-2 resulted in restored expression of GLUT4 protein and mRNA. Activation of p38 MAPK mediated the increased expression of GLUT4 in response to IGF-1. Transient transfection experiments in neonatal cardiac myocytes confirmed that p38 MAPK could activate the glut4 promoter. Electrophoretic mobility shift assay in adult rat cardiomyocytes and transient transfection experiments in neonatal cardiac myocytes indicated that MEF2 was the main transcription factor transducing the effect of p38 MAPK activation on the glut4 promoter. CONCLUSION: Spontaneous dedifferentiation of adult rat cardiomyocytes in vitro is associated with downregulation of GLUT4, which can be reversed by treatment with IGF-1. The effect of IGF-1 is mediated by the p38 MAPK/MEF2 axis, which is a strong inducer of GLUT4 expression.

Cardiac and neurologic outcome of cardiac rhabdomyoma considerations for prenatal counseling

Abstract : Cardíac rhabdomyomas are benign cardiac tumors with few cardiac complications but with a known association to tuberous sclerosis that affects the neurologic outcome of the patients. Thís study analyses the long-term cardiac and neurological outcome of patients with cardiac rhabdomyomas in order to allow comprehensive prenatal counseling. qll prenatal and postnatal cases with echocardiographic diagnosis of cardiac rhabdomyomas encountered from August 1982 -September 2007 have been recorded. Independent factors, such às the number and the location of the tumors, have been analyzed for association with a diagnosis of tuberous sclerosis, in order to predict the cardiac and neurologic outcome of the patients. Cardiac complications include arrhythmias, outflow tract obstruction, secondary cardiogenic shock. Arrhythmias are the most often encountered problems during the neonatal period. Supraventricular tachycardia is the commonest rhythm disturbance identified. However, no specific dimension or location of the cardiac rhabdomyomas may predict the rhythm disturbances. The importance of the diagnosis of tuberous sclerosis in patients presenting with cardiac rhabdomyomas is exemplified by the neurodevelopmental complications showing 80% of cases with epilepsy and 63% of cases with a delayed development. The presence of multiple cardiac tumors in patients suggests a higher risk to be affected by tuberous sclerosis, compared to patients with a single tumor. Cardiac rhabdomyomas generally regress aftér birth and after the perinatal period cardiac-related problems are rare, but tuberous sclerosis and the associated neurodevelopmental complications dominate the clinical picture and should form an important aspect of the prenatal counseling of parents. Résumé : Les rhabdomyomes cardiaques sont des tumeurs cardiaques bénignes avec toutefois des complications. cardiaques possibles et surtout avec une association pour la sclérose tubéreuse de Bourneville qui détermine le pronostic neurologique. Cette étude présente une analyse du suivi cardiologique. et neurologique à long terme d'enfants avec un diagnostic de rhabdomyomes cardiaques dans le but de mieux informer les parents lors de la consultation anténatale. L'ensemble des cas de rhabdomyomes cardiaques diagnostiqués au moyen de l'échocardiographie pendant la période anténatale ainsi que postnatale a été répertorié d'août 1982 à septembre 2007. Des facteurs indépendants, tels que le nombre et la localisation des tumeurs, ont été analysés pour leur association avec le diagnostic de la sclérose tubéreuse de Bourneville, afin de prédire le pronostic cardiaque et neurologique de ces patients. Les complications cardiaques retrouvées sont les arythmies, les obstructions des voies d'éjection ventriculaire et le choc cardiogène secondaire. Les arythmies sont les problèmes les plus fréquemment rencontrés pendant la période néonatale.. La tachycardie supraventriculaire est le trouble de rythme le plus souvent identifié. Néanmoins, il n'y a pas de dimension ou de localisation.- spécifique d'un rhabdomyome cardiaque qui pourrait prédire ces troubles du rythme. L'importance de l'association au diagnostic de la sclérose tubéreuse de Bourneville chez les patients atteints de rhabdomyomes est démontrée à travers les complications du développement neurologique avec une attéinte épileptique dans 80% des cas ainsi qu'un retard de développement dans 63% des cas. La présence de multiples tumeurs cardiaques chez un patient suggère un risque accru d'être atteint de la sclérose tubéreuse de Bourneville comparé à un patient atteint d'une tumeur unique. Les rhabdomyomes cardiaques régressent après la naissance et après la période périnatale les complications cardiaques deviennent rares. Toutefois, l'association à la sclérose tubéreuse de Bourneville domine le tableau clinique avec des complications au niveau du développement neurologique et formé donc un aspect important lors de la consultation anténatale.