Cross-frequency coupling in EEG revealed by adaptive oscillation tracking.

Introduction: Neuronal oscillations have been the focus of increasing interest in the neuroscientific community, in part because they have been considered as a possible integrating mechanism through which internal states can influence stimulus processing in a top-down way (Engel et al., 2001). Moreover, increasing evidence indicates that oscillations in different frequency bands interact with one other through coupling mechanisms (Jensen and Colgin, 2007). The existence and the importance of these cross-frequency couplings during various tasks have been verified by recent studies (Canolty et al., 2006; Lakatos et al., 2007). In this study, we measure the strength and directionality of two types of couplings - phase-amplitude couplings and phase-phase couplings - between various bands in EEG data recorded during an illusory contour experiment that were identified using a recently-proposed adaptive frequency tracking algorithm (Van Zaen et al., 2010). Methods: The data used in this study have been taken from a previously published study examining the spatiotemporal mechanisms of illusory contour processing (Murray et al., 2002). The EEG in the present study were from a subset of nine subjects. Each stimulus was composed of 'pac-man' inducers presented in two orientations: IC, when an illusory contour was present, and NC, when no contour could be detected. The signals recorded by the electrodes P2, P4, P6, PO4 and PO6 were averaged, and filtered into the following bands: 4-8Hz, 8-12Hz, 15-25Hz, 35-45Hz, 45-55Hz, 55-65Hz and 65-75Hz. An adaptive frequency tracking algorithm (Van Zaen et al., 2010) was then applied in each band in order to extract the main oscillation and estimate its frequency. This additional step ensures that clean phase information is obtained when taking the Hilbert transform. The frequency estimated by the tracker was averaged over sliding windows and then used to compare the two conditions. Two types of cross-frequency couplings were considered: phase-amplitude couplings and phase-phase couplings. Both types were measured with the phase locking value (PLV, Lachaux et al., 1999) over sliding windows. The phase-amplitude couplings were computed with the phase of the low frequency oscillation and the phase of the amplitude of the high frequency one. Different coupling coefficients were used when measuring phase-phase couplings in order to estimate different m:n synchronizations (4:3, 3:2, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 and 9:1) and to take into account the frequency differences across bands. Moreover, the direction of coupling was estimated with a directionality index (Bahraminasab et al., 2008). Finally, the two conditions IC and NC were compared with ANOVAs with 'subject' as a random effect and 'condition' as a fixed effect. Before computing the statistical tests, the PLV values were transformed into approximately normal variables (Penny et al., 2008). Results: When comparing the mean estimated frequency across conditions, a significant difference was found only in the 4-8Hz band, such that the frequency within this band was significantly higher for IC than NC stimuli starting at ~250ms post-stimulus onset (Fig. 1; solid line shows IC and dashed line NC). Significant differences in phase-amplitude couplings were obtained only when the 4-8 Hz band was taken as the low frequency band. Moreover, in all significant situations, the coupling strength is higher for the NC than IC condition. An example of significant difference between conditions is shown in Fig. 2 for the phase-amplitude coupling between the 4-8Hz and 55-65Hz bands (p-value in top panel and mean PLV values in the bottom panel). A decrease in coupling strength was observed shortly after stimulus onset for both conditions and was greater for the condition IC. This phenomenon was observed with all other frequency bands. The results obtained for the phase-phase couplings were more complex. As for the phase-amplitude couplings, all significant differences were obtained when the 4-8Hz band was considered as the low frequency band. The stimulus condition exhibiting the higher coupling strength depended on the ratio of the coupling coefficients. When this ratio was small, the IC condition exhibited the higher phase-phase coupling strength. When this ratio was large, the NC condition exhibited the higher coupling strength. Fig. 3 shows the phase-phase couplings between the 4-8Hz and 35-45Hz bands for the coupling coefficient 6:1, and the coupling strength was significantly higher for the IC than NC condition. By contrast, for the coupling coefficient 9:1 the NC condition gave the higher coupling strength (Fig. 4). Control analyses verified that it is not a consequence of the frequency difference between the two conditions in the 4-8Hz band. The directionality measures indicated a transfer of information from the low frequency components towards the high frequency ones. Conclusions: Adaptive tracking is a feasible method for EEG analyses, revealing information both about stimulus-related differences and coupling patterns across frequencies. Theta oscillations play a central role in illusory shape processing and more generally in visual processing. The presence vs. absence of illusory shapes was paralleled by faster theta oscillations. Phase-amplitude couplings were decreased more for IC than NC and might be due to a resetting mechanism. The complex patterns in phase-phase coupling between theta and beta/gamma suggest that the contribution of these oscillations to visual binding and stimulus processing are not as straightforward as conventionally held. Causality analyses further suggest that theta oscillations drive beta/gamma oscillations (see also Schroeder and Lakatos, 2009). The present findings highlight the need for applying more sophisticated signal analyses in order to establish a fuller understanding of the functional role of neural oscillations.

Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation.

In solid organ transplantation, ischemia/reperfusion (IR) injury during organ procurement, storage and reperfusion is an unavoidable detrimental event for the graft, as it amplifies graft inflammation and rejection. Intracellular mitogen-activated protein kinase (MAPK) signaling pathways regulate inflammation and cell survival during IR injury. The four best-characterized MAPK subfamilies are the c-Jun NH2-terminal kinase (JNK), extracellular signal- regulated kinase-1/2 (ERK1/2), p38 MAPK, and big MAPK-1 (BMK1/ERK5). Here, we review the role of MAPK activation during myocardial IR injury as it occurs during heart transplantation. Most of our current knowledge regarding MAPK activation and cardioprotection comes from studies of preconditioning and postconditioning in nontransplanted hearts. JNK and p38 MAPK activation contributes to myocardial IR injury after prolonged hypothermic storage. p38 MAPK inhibition improves cardiac function after cold storage, rewarming and reperfusion. Small-molecule p38 MAPK inhibitors have been tested clinically in patients with chronic inflammatory diseases, but not in transplanted patients, so far. Organ transplantation offers the opportunity of starting a preconditioning treatment before organ procurement or during cold storage, thus modulating early events in IR injury. Future studies will need to evaluate combined strategies including p38 MAPK and/or JNK inhibition, ERK1/2 activation, pre- or postconditioning protocols, new storage solutions, and gentle reperfusion.

Antibody-mediated status epilepticus: a retrospective multicenter survey.

Background: In recent years, an increasing number of auto-antibodies (AB) have been detected in the CSF and serum of patients with new onset epilepsy. Some of these patients develop convulsive or nonconvulsive status epilepticus (AB-SE), necessitating intensive medical care and administration of multiple antiepileptic and immunomodulatory treatments of uncertain effectiveness. Objectives: In this retrospective multicenter survey we aimed to determine the spectrum of gravity, the duration and the prognosis of the disorder. In addition, we sought to identify the antibodies associated with this condition, as well as determine whether there is a most effective treatment regime. Methods: 12 European Neurology University Clinics, with extensive experience in the treatment of SE patients, were sent a detailed questionnaire regarding symptoms and treatment of AB-SE patients. Seven centers responded positively, providing a total of 13 patients above the age of 16. Results: AB-SE affects mainly women (12/13, 92%) with a variable age at onset (17-69 years, median: 25 years). The duration of the disease is also variable (10 days to 12 years, median: 2 months). Only the 3 oldest patients died (55-69 years). Most patients were diagnosed with anti NMDAR encephalitis (8/13) and had oligoclonal bands in the CSF (9/13). No specific treatment regimen (antiepileptic, immunomodulatory) was found to be clearly superior. Most of the surviving 10 patients (77%) recovered completely or nearly so within 2 years of index poststatus. Conclusion: AB-SE is a severe but potentially reversible condition. Long duration does not seem to imply fatal outcome; however, age older than 50 years at time of onset appears to be a risk factor for death. There was no evidence for an optimal antiepileptic or immunomodulatory treatment. A prospective multicenter study is warranted in order to stratify the optimal treatment algorithm, determine clear risk factors of unfavorable outcome and long-term prognosis.

Numerical simulation of left ventricular assist device implantations: comparing the ascending and the descending aorta cannulations.

In this work we present numerical simulations of continuous flow left ventricle assist device implantation with the aim of comparing difference in flow rates and pressure patterns depending on the location of the anastomosis and the rotational speed of the device. Despite the fact that the descending aorta anastomosis approach is less invasive, since it does not require a sternotomy and a cardiopulmonary bypass, its benefits are still controversial. Moreover, the device rotational speed should be correctly chosen to avoid anomalous flow rates and pressure distribution in specific location of the cardiovascular tree. With the aim of assessing the differences between these two approaches and device rotational speed in terms of flow rate and pressure waveforms, we set up numerical simulations of network of one-dimensional models where we account for the presence of an outflow cannula anastomosed to different locations of the aorta. Then, we use the resulting network to compare the results of the two different cannulations for several stages of heart failure and different rotational speed of the device. The inflow boundary data for the heart and the cannulas are obtained from a lumped parameters model of the entire circulatory system with an assist device, which is validated with clinical data. The results show that ascending and descending aorta cannulations lead to similar waveforms and mean flow rate in all the considered cases. Moreover, regardless of the anastomosis region, the rotational speed of the device has an important impact on wave profiles; this effect is more pronounced at high RPM.

Cardiac rotation and relaxation after anterolateral myocardial infarction.

BACKGROUND: Both systolic and diastolic dysfunction have been observed in patients with anterolateral myocardial infarction. Diastolic dysfunction is related to disturbances in relaxation and diastolic filling. OBJECTIVE: To analyse cardiac rotation, regional shortening and diastolic relaxation in patients with anterolateral infarction. METHODS: Cardiac rotation and relaxation in controls and patients with chronic anterolateral infarction were assessed by myocardial tagging. Myocardial tagging is based on magnetic resonance imaging and allows us to label specific myocardial regions for imaging cardiac motion (rotation, translation and radial displacement). A rectangular grid was placed on the myocardium (basal, equatorial and apical short-axis plane) of each of 18 patients with chronic anterolateral infarction and 13 controls. Cardiac rotation, change in area and shortening of circumference were determined in each case. RESULTS: The left ventricle in controls performs a systolic wringing motion with a clockwise rotation at the base and a counterclockwise rotation at the apex when viewed from the apex. During relaxation a rotational motion in the opposite direction (namely untwisting) can be observed. In patients with anterolateral infarction, there is less systolic rotation at the apex and diastolic untwisting is delayed and prolonged in comparison with controls. In the presence of a left ventricular aneurysm (n = 4) apical rotation is completely lost. There is less shortening of circumference in infarcted and remote regions. CONCLUSIONS: The wringing motion of the myocardium might be an important mechanism involved in maintaining normal cardiac function with minimal expenditure of energy. This mechanism no longer operates in patients with left ventricular aneurysms and operates significantly less than normal in those with anterolateral hypokinaesia. Diastolic untwisting is significantly delayed and prolonged in patients with anterolateral infarction, which could explain the occurrence of diastolic dysfunction in these patients.

Adipose tissue integrity as a prerequisite for systemic energy balance: a critical role for peroxisome proliferator-activated receptor gamma.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is an essential regulator of adipocyte differentiation, maintenance, and survival. Deregulations of its functions are associated with metabolic diseases. We show here that deletion of one PPARgamma allele not only affected lipid storage but, more surprisingly, also the expression of genes involved in glucose uptake and utilization, the pentose phosphate pathway, fatty acid synthesis, lipolysis, and glycerol export as well as in IR/IGF-1 signaling. These deregulations led to reduced circulating adiponectin levels and an energy crisis in the WAT, reflected in a decrease to nearly half of its intracellular ATP content. In addition, there was a decrease in the metabolic rate and physical activity of the PPARgamma(+/-) mice, which was abolished by thiazolidinedione treatment, thereby linking regulation of the metabolic rate and physical activity to PPARgamma. It is likely that the PPARgamma(+/-) phenotype was due to the observed WAT dysfunction, since the gene expression profiles associated with metabolic pathways were not affected either in the liver or the skeletal muscle. These findings highlight novel roles of PPARgamma in the adipose tissue and underscore the multifaceted action of this receptor in the functional fine tuning of a tissue that is crucial for maintaining the organism in good health.

Lower thigh subcutaneous and higher visceral abdominal adipose tissue content both contribute to insulin resistance.

It is well known that visceral adipose tissue (VAT) is associated with insulin resistance (IR). Considerable debate remains concerning the potential positive effect of thigh subcutaneous adipose tissue (TSAT). Our objective was to observe whether VAT and TSAT are opposite, synergistic or additive for both peripheral and hepatic IR. Fifty-two volunteers (21 male/31 female) between 30 and 75 years old were recruited from the general population. All subjects were sedentary overweight or obese (mean BMI 33.0 ± 3.4 kg/m(2)). Insulin sensitivity was determined by a 4-h hyperinsulinemic-euglycemic clamp with stable isotope tracer dilution. Total body fat and lean body mass were determined by dual X-ray absorptiometry. Abdominal and mid-thigh adiposity was determined by computed tomography. VAT was negatively associated with peripheral insulin sensitivity, while TSAT, in contrast, was positively associated with peripheral insulin sensitivity. Subjects with a combination of low VAT and high TSAT had the highest insulin sensitivity, subjects with a combination of high VAT and low TSAT were the most insulin resistant. These associations remained significant after adjusting for age and gender. These data confirm that visceral excess abdominal adiposity is associated with IR across a range of middle-age to older men and women, and further suggest that higher thigh subcutaneous fat is favorably associated with better insulin sensitivity. This strongly suggests that these two distinct fat distribution phenotypes should both be considered in IR as important determinants of cardiometabolic risk.

Vaccine potentials of an intrinsically unstructured fragment derived from the blood stage-associated Plasmodium falciparum protein PFF0165c.

We have identified new malaria vaccine candidates through the combination of bioinformatics prediction of stable protein domains in the Plasmodium falciparum genome, chemical synthesis of polypeptides, in vitro biological functional assays, and association of an antigen-specific antibody response with protection against clinical malaria. Within the predicted open reading frame of P. falciparum hypothetical protein PFF0165c, several segments with low hydrophobic amino acid content, which are likely to be intrinsically unstructured, were identified. The synthetic peptide corresponding to one such segment (P27A) was well recognized by sera and peripheral blood mononuclear cells of adults living in different regions where malaria is endemic. High antibody titers were induced in different strains of mice and in rabbits immunized with the polypeptide formulated with different adjuvants. These antibodies recognized native epitopes in P. falciparum-infected erythrocytes, formed distinct bands in Western blots, and were inhibitory in an in vitro antibody-dependent cellular inhibition parasite-growth assay. The immunological properties of P27A, together with its low polymorphism and association with clinical protection from malaria in humans, warrant its further development as a malaria vaccine candidate.

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

Co- and posttranslational modification of the alpha(1B)-adrenergic receptor: effects on receptor expression and function.

We have characterized the maturation, co- and posttranslational modifications, and functional properties of the alpha(1B)-adrenergic receptor (AR) expressed in different mammalian cells transfected using conventional approaches or the Semliki Forest virus system. We found that the alpha(1B)-AR undergoes N-linked glycosylation as demonstrated by its sensitivity to endoglycosidases and by the effect of tunicamycin on receptor maturation. Pulse-chase labeling experiments in BHK-21 cells demonstrate that the alpha(1B)-AR is synthesized as a 70 kDa core glycosylated precursor that is converted to the 90 kDa mature form of the receptor with a half-time of approximately 2 h. N-Linked glycosylation of the alpha(1B)-AR occurs at four asparagines on the N-terminus of the receptor. Mutations of the N-linked glycosylation sites did not have a significant effect on receptor function or expression. Surprisingly, receptor mutants lacking N-linked glycosylation migrated as heterogeneous bands in SDS-PAGE. Our findings demonstrate that N-linked glycosylation and phosphorylation, but not palmitoylation or O-linked glycosylation, contribute to the structural heterogeneity of the alpha(1B)-AR as it is observed in SDS-PAGE. The modifications found are similar in the different mammalian expression systems explored. Our findings indicate that the Semliki Forest virus system can provide large amounts of functional and fully glycosylated alpha(1B)-AR protein suitable for biochemical and structural studies. The results of this study contribute to elucidate the basic steps involved in the processing of G protein-coupled receptors as well as to optimize strategies for their overexpression.

Inhibitory Receptors Beyond T Cell Exhaustion.

Inhibitory receptors (iRs) are frequently associated with "T cell exhaustion". However, the expression of iRs is also dependent on T cell differentiation and activation. Therapeutic blockade of various iRs, also referred to as "checkpoint blockade", is showing -unprecedented results in the treatment of cancer patients. Consequently, the clinical potential in this field is broad, calling for increased research efforts and rapid refinements in the understanding of iR function. In this review, we provide an overview on the significance of iR expression for the interpretation of T cell functionality. We summarize how iRs have been strongly associated with "T cell exhaustion" and illustrate the parallel evidence on the importance of T cell differentiation and activation for the expression of iRs. The differentiation subsets of CD8 T cells (naïve, effector, and memory cells) show broad and inherent differences in iR expression, while activation leads to strong upregulation of iRs. Therefore, changes in iR expression during an immune response are often concomitant with T cell differentiation and activation. Sustained expression of iRs in chronic infection and in the tumor microenvironment likely reflects a specialized T cell differentiation. In these situations of prolonged antigen exposure and chronic inflammation, T cells are "downtuned" in order to limit tissue damage. Furthermore, we review the novel "checkpoint blockade" treatments and the potential of iRs as biomarkers. Finally, we provide recommendations for the immune monitoring of patients to interpret iR expression data combined with parameters of activation and differentiation of T cells.

Validation of rotational thromboelastometry during cardiopulmonary bypass : a prospective, observational in-vivo study

Le ROTEM est un test de coagulation réalisable au près du malade qui permet d'objectiver la coagulopathie, de distinguer la contribution des différents éléments du système de coagulation et de cibler les produits procoagulants comme le plasma frais congelé (PFC), les plaquettes, le fibrinogène et les facteurs de coagulation purifiés ou les antifibrinolytiques. 3 des tests disponibles pour le ROTEM sont: EXTEM, INTEM, HEPTEM. Le premier test est stable sous hautes doses d'héparine alors que le deuxième est très sensible à sa présence. Dans le dernier test on rajoute de l'héparinase pour mettre en évidence l'éventuel effet résiduel de l'héparine en le comparant à l'INTEM. Idéalement, le ROTEM devrait être effectué avant la fin du bypass cardiopulmonaire (CEC), donc sous anticoagulation maximale pas héparine, afin de pouvoir administrer des produits pro¬coagulants dans les délais les plus brefs et ainsi limiter au maximum les pertes sanguines. En effet la commande et la préparation de certains produits procoagulants peut prendre plus d'une heure. Le but de cette étude est de valider l'utilisation du ROTEM en présence de hautes concentrations d'héparine. Il s'agit d'une étude observationnelle prospective sur 20 patients opérés électivement de pontages aorto-coronariens sous CEC. Méthode : l'analyse ROTEM a été réalisée avant l'administration d'héparine (TO), 10 minutes après l'administration d'héparine (Tl), à la fin de la CEC (T2) et 10 minutes après la neutralisation de l'anticoagulation avec la protamine (T3). L'état.d'héparinisation a été évalué par l'activité anti-Xa à T1,T2,T3. Résultats : Comparé à TO, la phase de polymérisation de la cascade de coagulation et l'interaction fibrine-plaquettes sont significativement détériorées par rapport à Tl pour les canaux EXTEM et HEPTEM. A T2 l'analyse EXTEM et INTEM sont comparables à celles de EXTEM et HEPTEM à T3. Conclusion: les hautes doses d'héparine utilisées induisent une coagulopathie qui reste stable durant toute la durée de la CEC et qui persiste même après la neutralisation de l'anticoagulation. Les mesures EXTEM et HEPTEM sont donc valides en présence de hautes concentrations d'héparine et peuvent être réalisés pendant la CEC avant l'administration de protamine.

Validation of rotational thromboelastometry during cardiopulmonary bypass: A prospective, observational in-vivo study.

BACKGROUND: Rotational thromboelastometry (ROTEM) is a whole blood point-of-test used to assess the patient's coagulation status. Three of the available ROTEM tests are EXTEM, INTEM and HEPTEM. In the latter, heparinase added to the INTEM reagent inactivates heparin to reveal residual heparin effect. Performing ROTEM analysis during cardiopulmonary bypass (CPB) might allow the anaesthesiologist to anticipate the need for blood products. OBJECTIVE: The goal of this study was to validate ROTEM analysis in the presence of very high heparin concentrations during CPB. DESIGN: Prospective, observational trial. SETTING: Single University Hospital. PARTICIPANTS: Twenty patients undergoing coronary artery bypass grafting. MAIN OUTCOME MEASURE: ROTEM analysis was performed before heparin administration (T0), 10 min after heparin (T1), at the end of CPB (T2) and 10 min after protamine (T3). The following tests were performed: EXTEM, INTEM, and HEPTEM. Heparin concentrations were measured at T1 and at the end of bypass (T2). RESULTS: At T1, EXTEM differed from baseline for coagulation time: +26.7 s (18.4 to 34.9, P < 0.0001), α: -3° (1.0 to 5.4, P = 0.006) and A10: -4.4 mm (2.3 to 6.5, P = 0.0004). INTEM at T0 was different from HEPTEM at T1 for coagulation time: + 47 s (34.3 to 59.6, P >0.0001), A10: -2.3 mm (0.5 to 4.0, P = 0.01) and α -2° (1.0 to 3.0; P = 0.0007). At T2, all parameters in EXTEM and HEPTEM related to fibrin-platelet interaction deteriorated significantly compared to T1. At T3, EXTEM and INTEM were comparable to EXTEM and HEPTEM at T2. CONCLUSION: HEPTEM and EXTEM measurements are valid in the presence of very high heparin concentrations and can be performed before protamine administration in patients undergoing cardiac surgery with CPB. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01455454.

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. METHODS: In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. RESULTS: Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. CONCLUSIONS: Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.