Adipokines and the Right Ventricle: The MESA-RV Study.

ObjectiveObesity is associated with changes in both right (RV) and left (LV) ventricular morphology, but the biological basis of this finding is not well established. We examined whether adipokine levels were associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.MethodsWe examined relationships of leptin, resistin, TNF-α, and adiponectin with RV morphology and function (from cardiac MRI) in participants (n = 1,267) free of clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of each adipokine with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF).ResultsHigher leptin levels were associated with significantly lower levels of RV mass, RVEDV, RVESV and stroke volume, but not RVEF, after adjustment for age, gender, race, height and weight. These associations were somewhat attenuated but still significant after adjustment for traditional risk factors and covariates, and were completely attenuated when correcting for the respective LV measures. There were no significant interactions of age, gender, or race/ethnicity on the relationship between the four adipokines and RV structure or function.ConclusionsLeptin levels are associated with favorable RV morphology in a multi-ethnic population free of cardiovascular disease, however these associations may be explained by a yet to be understood bi-ventricular process as this association was no longer present after adjustment for LV values. These findings complement the associations previously shown between adipokines and LV structure and function in both healthy and diseased patients. The mechanisms linking adipokines to healthy cardiovascular function require further investigation

Myocardial tissue tagging with cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) is currently the gold standard for assessing both global and regional myocardial function. New tools for quantifying regional function have been recently developed to characterize early myocardial dysfunction in order to improve the identification and management of individuals at risk for heart failure. Of particular interest is CMR myocardial tagging, a non-invasive technique for assessing regional function that provides a detailed and comprehensive examination of intra-myocardial motion and deformation. Given the current advances in gradient technology, image reconstruction techniques, and data analysis algorithms, CMR myocardial tagging has become the reference modality for evaluating multidimensional strain evolution in the human heart. This review presents an in depth discussion on the current clinical applications of CMR myocardial tagging and the increasingly important role of this technique for assessing subclinical myocardial dysfunction in the setting of a wide variety of myocardial disease processes

Progression of Coronary Artery Calcium and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

BackgroundAlthough the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi-Ethnic Study of Atherosclerosis.Methods and resultsThe Multi-Ethnic Study of Atherosclerosis is a population-based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi-Ethnic Study of Atherosclerosis participants who had baseline and follow-up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2 years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow-up of 9.6 (interquartile range: 8.8-10.6) years, 182 participants developed incident HF. CAC progression of 10 units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease (P=0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (β=0.16; P=0.03) and LV end systolic volume (β=0.12; P=0.006) after excluding participants with any coronary heart disease.ConclusionsCAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow-up exam independent of overt coronary heart disease

Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons.

Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart failure in human immunodeficiency virus (HIV)-coinfected persons is unknown. The objective was to characterize cardiac function and morphology in HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on antiretroviral therapy without known cardiovascular disease or diabetes mellitus underwent cardiac magnetic resonance imaging and spectroscopy for measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these, 10 had untreated HCV coinfection and eight had HIV monoinfection. Global systolic and diastolic function in the cohort were normal, and median myocardial fat content was 0.48% (interquartile range 0.35-1.54). Left ventricular (LV) mass index and LV mass/volume ratio were significantly greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected group. In the HIV-monoinfected group, there was more myocardial fibrosis as measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected patients in cardiac structure and morphology. Larger studies are needed to examine whether HIV and HCV independently contribute to mechanisms of heart failure

Cardiovascular magnetic resonance characterization of peri-infarct zone remodeling following myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Clinical studies implementing late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) studies suggest that the peri-infarct zone (PIZ) contains a mixture of viable and non-viable myocytes, and is associated with greater susceptibility to ventricular tachycardia induction and adverse cardiac outcomes. However, CMR data assessing the temporal formation and functional remodeling characteristics of this complex region are limited. We intended to characterize early temporal changes in scar morphology and regional function in the PIZ.</p> <p>Methods and results</p> <p>CMR studies were performed at six time points up to 90 days after induction of myocardial infarction (MI) in eight minipigs with reperfused, anterior-septal infarcts. Custom signal density threshold algorithms, based on the remote myocardium, were applied to define the infarct core and PIZ region for each time point. After the initial post-MI edema subsided, the PIZ decreased by 54% from day 10 to day 90 (<it>p </it>= 0.04). The size of infarct scar expanded by 14% and thinned by 56% from day 3 to 12 weeks (<it>p </it>= 0.004 and <it>p </it>< 0.001, respectively). LVEDV increased from 34.7. ± 2.2 ml to 47.8 ± 3.0 ml (day3 and week12, respectively; p < 0.001). At 30 days post-MI, regional circumferential strain was increased between the infarct scar and the PIZ (-2.1 ± 0.6 and -6.8 ± 0.9, respectively;* <it>p </it>< 0.05).</p> <p>Conclusions</p> <p>The PIZ is dynamic and decreases in mass following reperfused MI. Tensile forces in the PIZ undergo changes following MI. Remodeling characteristics of the PIZ may provide mechanistic insights into the development of life-threatening arrhythmias and sudden cardiac death post-MI.</p

In silico single strand melting curve: a new approach to identify nucleic acid polymorphisms in Totiviridae

CpG-island promoters of developmental genes are unmethylated. DNA methylation state of CpG islands overlapping and surrounding the promoter region of Pax3 (a) and Pax7 (b) genes in myogenic (MB, MT, MF) and non-myogenic samples (ESC). CpG islands are indicated in green and regions analysed by sodium bisulphite sequencing are shown in red. Each circle represents a CpG dinucleotide and its distance to the gene TSS is indicated below. The colour gradient represents the percentage of methylation indicated in the legend. Abbreviations: ESC, embryonic stem cell; MB, myoblast; MT, myotube; MF, myofiber; TSS, transcription start site. c. DNA methylation state of -5 kb distal regulatory region for MyoD was analysed by sodium bisulphite sequencing in ESC and myoblast samples, and represented as above. (PDF 171 kb

Cardiac CT and MRI guide surgery in impending left ventricular rupture after acute myocardial infarction

We report the case of a 67 year-old patient who presented with worsening chest pain and shortness of breath, four days post acute myocardial infarction. Contrast enhanced computed tomography of the chest ruled out a pulmonary embolus but revealed an unexpected small subepicardial aneurysm (SEA) in the lateral left ventricular wall which was confirmed on cardiac magnetic resonance imaging. Intraoperative palpation of the left lateral wall was guided by the cardiac MRI and CT findings and confirmed the presence of focally thinned and weakened myocardium, covered by epicardial fat. An aneurysmorrhaphy was subsequently performed in addition to coronary bypass surgery and a mitral valve repair. The patient was discharged home on post operative day eight in good condition and is feeling well 2 years after surgery

Repertoire, Genealogy and Genomic Organization of Cruzipain and Homologous Genes in Trypanosoma cruzi, T. cruzi-Like and Other Trypanosome Species

Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches

Spatial point analysis based on dengue surveys at household level in central Brazil

<p>Abstract</p> <p>Background</p> <p>Dengue virus (DENV) affects nonimunne human populations in tropical and subtropical regions. In the Americas, dengue has drastically increased in the last two decades and Brazil is considered one of the most affected countries. The high frequency of asymptomatic infection makes difficult to estimate prevalence of infection using registered cases and to locate high risk intra-urban area at population level. The goal of this spatial point analysis was to identify potential high-risk intra-urban areas of dengue, using data collected at household level from surveys.</p> <p>Methods</p> <p>Two household surveys took place in the city of Goiania (~1.1 million population), Central Brazil in the year 2001 and 2002. First survey screened 1,586 asymptomatic individuals older than 5 years of age. Second survey 2,906 asymptomatic volunteers, same age-groups, were selected by multistage sampling (census tracts; blocks; households) using available digital maps. Sera from participants were tested by dengue virus-specific IgM/IgG by EIA. A Generalized Additive Model (GAM) was used to detect the spatial varying risk over the region. Initially without any fixed covariates, to depict the overall risk map, followed by a model including the main covariates and the year, where the resulting maps show the risk associated with living place, controlled for the individual risk factors. This method has the advantage to generate smoothed risk factors maps, adjusted by socio-demographic covariates.</p> <p>Results</p> <p>The prevalence of antibody against dengue infection was 37.3% (95%CI [35.5–39.1]) in the year 2002; 7.8% increase in one-year interval. The spatial variation in risk of dengue infection significantly changed when comparing 2001 with 2002, (ORadjusted = 1.35; p < 0.001), while controlling for potential confounders using GAM model. Also increasing age and low education levels were associated with dengue infection.</p> <p>Conclusion</p> <p>This study showed spatial heterogeneity in the risk areas of dengue when using a spatial multivariate approach in a short time interval. Data from household surveys pointed out that low prevalence areas in 2001 surveys shifted to high-risk area in consecutive year. This mapping of dengue risks should give insights for control interventions in urban areas.</p