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1.  The association between cardiovascular risk and cardiovascular magnetic resonance measures of fibrosis: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Risk scores for cardiovascular disease (CVD) are in common use to integrate multiple cardiovascular risk factors in order to identify individuals at greatest risk for disease. The purpose of this study was to determine if individuals at greater cardiovascular risk have T1 mapping indices by cardiovascular magnetic resonance (CMR) indicative of greater myocardial fibrosis.
Methods
CVD risk scores for 1208 subjects (men, 50.8%) ages 55–94 years old were evaluated in the Multiethnic Study of Atherosclerosis (MESA) at six centers. T1 times were determined at 1.5Tesla before and after gadolinium administration (0.15 mmol/kg) using a modified Look-Locker pulse sequence. The relationship between CMR measures (native T1, 12 and 25 minute post-gadolinium T1, partition coefficient and extracellular volume fraction) and 14 established different cardiovascular risk scores were determined using regression analysis. Bootstrapping analysis with analysis of variance was used to compare different CMR measures. CVD risk scores were significantly different for men and women (p < 0.001).
Results
25 minute post gadolinium T1 time showed more statistically significant associations with risk scores (10/14 scores, 71%) compared to other CMR indices (e.g. native T1 (7/14 scores, 50%) and partition coefficient (7/14, 50%) in men. Risk scores, particularly the new 2013 AHA/ASCVD risk score, did not correlate with any CMR fibrosis index.
Conclusions
Men with greater CVD risk had greater CMR indices of myocardial fibrosis. T1 times at greater delay time (25 minutes) showed better agreement with commonly used risk score indices compared to ECV and native T1 time.
Clinical trial registration
http://www.mesa-nhlbi.org/, NCT00005487.
doi:10.1186/s12968-015-0121-5
PMCID: PMC4326517
Myocardium; Cardiovascular magnetic resonance; Risk factors
2.  Relation of Left Ventricular Mass at Age 23 to 35 years to Global Left Ventricular Systolic Function 20 Years Later (From the Coronary Artery Risk Development in Young Adults Study) 
The American journal of cardiology  2013;113(2):377-383.
Left ventricular (LV) mass and LV ejection fraction (EF) are major independent predictors of future cardiovascular disease. The association of LV mass with future LVEF in younger populations has not been studied. We investigated the relation of LV mass index (LVMI) at age 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA is a longitudinal study that enrolled young adults in 1985–1986. We included participants with echocardiographic examinations at both years-5 and -25. LVMI and LVEF were assessed using M-mode echocardiography at year-5 and using both M-mode and 2-dimensional images at year-25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters both cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year-25 was 62%. Although there was no cross-sectional correlation between LVMI and LVEF at year-5, there was a small, but statistically significant negative correlation between LVMI at year-5 and LVEF 20 years later (r = −0.10, p < 0.0001); this inverse association persisted for LVMI in the multivariable model. High LVMI was an independent predictor of systolic dysfunction (LVEF < 50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, we have shown that LVMI in young adulthood in association with chronic risk exposure impacts systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought.
doi:10.1016/j.amjcard.2013.08.052
PMCID: PMC3901209  PMID: 24176073
left ventricular mass; left ventricular ejection fraction; echocardiography; left ventricular remodeling
3.  Left ventricular mass and hypertrophy by echocardiography and cardiac magnetic resonance: The Multi-Ethnic Study of Atherosclerosis 
Echocardiography (Mount Kisco, N.Y.)  2013;31(1):10.1111/echo.12303.
BACKGROUND
Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk.
METHODS
MESA enrolled 880 participants in Baltimore City; 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height1.7, height2.7, or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson’s correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities.
RESULTS
LVM by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, p < 0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76.
CONCLUSIONS
Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.
doi:10.1111/echo.12303
PMCID: PMC3830716  PMID: 23930739
Left ventricular mass; left ventricular hypertrophy; echocardiography; image quality
5.  Mapping Soil Surface Macropores Using Infrared Thermography: An Exploratory Laboratory Study 
The Scientific World Journal  2014;2014:845460.
Macropores and water flow in soils and substrates are complex and are related to topics like preferential flow, nonequilibrium flow, and dual-continuum. Hence, the quantification of the number of macropores and the determination of their geometry are expected to provide a better understanding on the effects of pores on the soil's physical and hydraulic properties. This exploratory study aimed at evaluating the potential of using infrared thermography for mapping macroporosity at the soil surface and estimating the number and size of such macropores. The presented technique was applied to a small scale study (laboratory soil flume).
doi:10.1155/2014/845460
PMCID: PMC4211149  PMID: 25371915
6.  The Association Between Physical Activity and Both Incident Coronary Artery Calcification and Ankle Brachial Index Progression: The Multi-Ethnic Study of Atherosclerosis 
Atherosclerosis  2013;230(2):278-283.
Objective
Both coronary artery calcification (CAC) and the ankle brachial index (ABI) are measures of subclinical atherosclerotic disease. The influence of physical activity on the longitudinal change in these measures remains unclear. To assess this we examined the association between these measures and self-reported physical activity in the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods
At baseline, the MESA participants were free of clinically evident cardiovascular disease. We included all participants with an ABI between 0.90 and 1.40 (n=5656). Predictor variables were based on self-reported measures with physical activity being assessed using the Typical Week Physical Activity Survey from which metabolic equivalent-minutes/week of activity were calculated. We focused on physical activity intensity, intentional exercise, sedentary behavior, and conditioning. Incident peripheral artery disease (PAD) was defined as the progression of ABI to values below 0.90 (given the baseline range of 0.90 to 1.40). Incident CAC was defined as a CAC score >0 Agatston units upon follow up with a baseline score of 0 Agatston units.
Results
Mean age was 61 years, 53% were female, and mean body mass index was 28 kg/m2. After adjusting for traditional cardiovascular risk factors and socioeconomic factors, intentional exercise was protective for incident peripheral artery disease (Relative Risk (RR)= 0.85, 95% Confidence Interval (CI): 0.74 to 0.98). After adjusting for traditional cardiovascular risk factors and socioeconomic factors, there was a significant association between vigorous PA and incident CAC (RR=0.97, 95% CI: 0.94 to 1.00). There was also a significant association between sedentary behavior and increased amount of CAC among participants with CAC at baseline (Δlog(Agatston Units +25)=0.027, 95% CI 0.002, 0.052).
Conclusions
These data suggest that there is an association between physical activity/sedentary behavior and the progression of two different measures of subclinical atherosclerotic disease.
doi:10.1016/j.atherosclerosis.2013.07.045
PMCID: PMC4085097  PMID: 24075757
Ankle Brachial Index; Coronary Artery Calcification; Physical Activity; Epidemiology; Prospective Cohort Study
7.  Evaluation of Age-Related Interstitial Myocardial Fibrosis With Cardiac Magnetic Resonance Contrast-Enhanced T1 Mapping in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Journal of the American College of Cardiology  2013;62(14):10.1016/j.jacc.2013.05.078.
Objectives
This study sought to determine the relationship of cardiovascular magnetic resonance (CMR) measures of tissue composition to age in the Multi-Ethnic Study of Atherosclerosis (MESA).
Background
Animal and human studies have demonstrated increased collagen deposition in senescent hearts. New CMR indices of tissue composition by using T1 mapping are sensitive to the presence of myocardial fibrosis.
Methods
A total of 1,231 study participants (51% women; age range 54 to 93 years) of the MESA cohort were evaluated with T1 mapping by using 1.5-T CMR scanners. None of the participants had focal scar on delayed enhancement CMR. Single-slice T1 mapping was performed at the midventricular level before and at 12- and 25-min delay after administration of gadolinium contrast by using a modified Look-Locker inversion recovery sequence. The partition coefficient was determined by the slope of the linear relationship of (1/T1myo vs. 1/T1blood). The extracellular volume fraction (ECV) was derived accounting for the hematocrit level. Multivariable regression analyses were performed, adjusting for traditional risk factors and left ventricular structure.
Results
Women had significantly greater partition coefficient, ECV, and precontrast T1 than men, as well as lower post-contrast T1 values (all p < 0.05). In general, linear regression analyses demonstrated that greater partition coefficient, pre-contrast T1 values, and ECV were associated with older age in men (multivariate regression coefficients = 0.01; 5.9 ms; and 1.04% per 10 years’ change; all p < 0.05). ECV was also significantly associated with age in women after multivariable adjustments.
Conclusions
CMR parameters that have been associated with myocardial fibrosis were related to older age in the MESA study. Women had higher ECV than men but less ECV change over time.
doi:10.1016/j.jacc.2013.05.078
PMCID: PMC3807823  PMID: 23871886
aging; magnetic resonance imaging; myocardial fibrosis; T1 mapping
8.  Mannosylated lipoarabinomannan in serum as a biomarker candidate for subclinical bovine tuberculosis 
BMC Research Notes  2014;7(1):559.
Background
Early and unambiguous detection of bovine tuberculosis (bTB), a significant disease of cattle worldwide, is necessary to control the spread of infection to other animals and humans. Current testing strategies are laborious, time consuming and heavily reliant on host responses that do not distinguish bTB from other mycobacteria. We report the presence of a pathogen signature, liparabinomannan (LAM), as a potential biomarker for bTB infection.
Findings
Fifty-five animals (uninfected [n = 33], bTb [n = 10] and exposed cases [n = 12]) from a well characterized bovine serum repository were screened for the presence of LAM using a commercially available ELISA. Analysis showed that LAM had a sensitivity of 100% and a specificity of 91.7% for bTB detection (bTB positive versus bTB exposed animals).
Conclusion
LAM detection easily separated bTB infected animals from bTB exposed and negative controls. We propose that pathogen related markers, such as LAM, should be included with current testing strategies as a battery diagnostic for bTB.
Electronic supplementary material
The online version of this article (doi:10.1186/1756-0500-7-559) contains supplementary material, which is available to authorized users.
doi:10.1186/1756-0500-7-559
PMCID: PMC4152573  PMID: 25146892
Bovine tuberculosis; Biomarker; Mycobacterium bovis; Cattle; Lipoarabinomannan; Diagnostics; Subclinical Infection; Serum
9.  Regional Left Ventricular Myocardial Dysfunction as a Predictor of Incident Cardiovascular Events 
Objectives
We sought to examine the prognostic value of subclinical left ventricular (LV) regional myocardial dysfunction (RMD) measured by magnetic resonance imaging (MRI) among asymptomatic individuals.
Background
LV RMD, defined as segmental impairment in systolic wall thickening, predicts adverse events in patients with established cardiovascular disease. MRI is highly accurate for detecting subtle RMD, of which the prognostic significance in a large multiethnic asymptomatic population is not known.
Methods
We used MRI to evaluate baseline regional LV myocardial function and prospectively followed a multiethnic (African American, Caucasian, Chinese, and Hispanic) population-based sample of 4,510 men and women without cardiovascular disease for a mean of 4.6 years. Regional myocardial dysfunction was defined as the presence of impaired systolic wall thickening (<10th percentile of segment-specific population distribution) in ≥2 contiguous LV segments within any given coronary artery territory.
Results
Baseline prevalence of RMD was 25.6%. Heart failure developed in 34 (1.0%) and 30 (2.6%) participants without and with RMD, respectively (p < 0.001). After adjustment for demographics and traditional risk factors, RMD remained independently associated with incident heart failure (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.56 to 4.39; p < 0.001). The relationship persisted after further adjustment for biomarkers of reported association with cardiovascular disease and indexes of global LV systolic dysfunction and hypertrophy (HR: 1.80; 95% CI: 1.02 to 3.20; p = 0.044). Similarly, RMD independently conferred an increased risk for hard coronary events (myocardial infarction or death from coronary heart disease; HR: 1.75; 95% CI: 1.06 to 2.89; p = 0.029), the composite of hard coronary events and stroke (HR: 1.72; 95% CI: 1.16 to 2.56; p = 0.005), and all atherosclerotic cardiovascular events (HR: 1.50; 95% CI: 1.09 to 2.07; p = 0.012).
Conclusions
Among an asymptomatic multiethnic American cohort, RMD is an independent predictor beyond traditional risk factors and global LV assessment for incident heart failure and atherosclerotic cardiovascular events. The clinical utility of early recognition of this subclinical phenotype deserves further investigation.
doi:10.1016/j.jacc.2010.10.060
PMCID: PMC4124734  PMID: 21511109
epidemiology; heart failure; magnetic resonance imaging; myocardial dysfunction; prognosis
10.  Prognostic Implications of Left Ventricular Dyssynchrony for Major Adverse Cardiovascular Events in Asymptomatic Women and Men: The Multi‐Ethnic Study of Atherosclerosis 
Background
Left ventricular (LV) dyssynchrony is related to adverse outcomes in systolic heart failure, but its prognostic importance in asymptomatic population is not known. Our objective was to assess the prognostic implications of LV mechanical dyssynchrony in a large multiethnic population before the occurrence of global LV dysfunction.
Methods and Results
A total of 1392 participants in the Multi‐Ethnic Study of Atherosclerosis (MESA; mean age: 64.7 years; 46% were women) with cardiac magnetic resonance imaging at baseline were followed for a median duration of 8.3 years. Harmonic phase imaging analysis was used to derive systolic circumferential strain. Greater standard deviation of time to peak systolic strain (SD‐TPS) indicates greater dyssynchrony. With SD‐TPS as a continuous variable, Cox proportional hazards analysis was used to assess hazards ratio after adjusting for demographics, cardiovascular risk factors, LV mass‐to‐volume ratio, and ejection fraction. Using the 75th percentile of SD‐TPS as a cutoff, Kaplan–Meier analysis was performed between 2 categorical groups for each gender. Higher values of dyssynchrony in women predicted major adverse cardiovascular events, defined as myocardial infarction, heart failure, stroke, and death (hazard ratio: 1.01 per 1‐ms increment in SD‐TPS, P=0.015), hard coronary events (hazard ratio: 1.05 per 1‐ms increment in SD‐TPS, P=0.026), and cerebrovascular events (hazard ratio: 1.03 per 1‐ms increment in SD‐TPS, P=0.013). In contrast, dyssynchrony in men was not predictive of events. Kaplan–Meier analyses in women revealed increased event occurrence in the higher dyssynchrony group, but this was not the case in men.
Conclusions
In an asymptomatic cohort, greater LV dyssynchrony determined by cardiac magnetic resonance imaging predicts adverse cardiovascular outcome in women but not in men.
Clinical Trial Registration
URL: http://clinicaltrials.gov. Unique identifier: NCT00005487.
doi:10.1161/JAHA.114.000975
PMCID: PMC4310386  PMID: 25092789
cardiac magnetic resonance imaging; cardiovascular events; left ventricular dyssynchrony; prognosis
11.  Double-lumen catheter in the right jugular vein induces two sub-endothelial abscesses in an unusual place, the transition between the superior vena cava and the right atrium: a case report 
Endocarditis is a type of infection that is common in internal medicine wards and in haemodialysis clinics. The location that is most affected are the heart valves. Herein, we report a case of an uncommon abscess, a sub-endothelial abscess between the transition of the superior vena cava and the right atrium. There were several emboli to the lung and foot, and the agent was related to Staphylococcus aureus and a double-lumen catheter. Usually, this type of abscess is located in valves, either the tricuspid valve if related to catheters or injection drug use or the mitral valve if related to other causes. An exhaustive review was made, but we found no information about the location of this abscess and the rarity of the event motivating the report of infection.
doi:10.1186/1755-7682-7-37
PMCID: PMC4125593  PMID: 25110520
Endocarditis; Central venous catheters; Renal dialysis; Hospitalisation
12.  In silico single strand melting curve: a new approach to identify nucleic acid polymorphisms in Totiviridae 
BMC Bioinformatics  2014;15(1):243.
Background
The PCR technique and its variations have been increasingly used in the clinical laboratory and recent advances in this field generated new higher resolution techniques based on nucleic acid denaturation dynamics. The principle of these new molecular tools is based on the comparison of melting profiles, after denaturation of a DNA double strand. Until now, the secondary structure of single-stranded nucleic acids has not been exploited to develop identification systems based on PCR. To test the potential of single-strand RNA denaturation as a new alternative to detect specific nucleic acid variations, sequences from viruses of the Totiviridae family were compared using a new in silico melting curve approach. This family comprises double-stranded RNA virus, with a genome constituted by two ORFs, ORF1 and ORF2, which encodes the capsid/RNA binding proteins and an RNA-dependent RNA polymerase (RdRp), respectively.
Results
A phylogenetic tree based on RdRp amino acid sequences was constructed, and eight monophyletic groups were defined. Alignments of RdRp RNA sequences from each group were screened to identify RNA regions with conserved secondary structure. One region in the second half of ORF2 was identified and individually modeled using the RNAfold tool. Afterwards, each DNA or RNA sequence was denatured in silico using the softwares MELTSIM and RNAheat that generate melting curves considering the denaturation of a double stranded DNA and single stranded RNA, respectively. The same groups identified in the RdRp phylogenetic tree were retrieved by a clustering analysis of the melting curves data obtained from RNAheat. Moreover, the same approach was used to successfully discriminate different variants of Trichomonas vaginalis virus, which was not possible by the visual comparison of the double stranded melting curves generated by MELTSIM.
Conclusion
In silico analysis indicate that ssRNA melting curves are more informative than dsDNA melting curves. Furthermore, conserved RNA structures may be determined from analysis of individuals that are phylogenetically related, and these regions may be used to support the reconstitution of their phylogenetic groups. These findings are a robust basis for the development of in vitro systems to ssRNA melting curves detection.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-243) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2105-15-243
PMCID: PMC4119202  PMID: 25030031
RNA secondary structure; Infectious Myonecrosis Virus; high resolution melting curve; Virus detection; IHHNV, WSSV, Trichomonas
13.  Aversive Prediction Error Signals in the Amygdala 
The Journal of Neuroscience  2014;34(27):9024-9033.
Prediction error signals are fundamental to learning. Here, in mice, we show that aversive prediction signals are found in the hemodynamic responses and theta oscillations recorded from the basolateral amygdala. During fear conditioning, amygdala responses evoked by footshock progressively decreased, whereas responses evoked by the auditory cue that predicted footshock concomitantly increased. Unexpected footshock evoked larger amygdala responses than expected footshock. The magnitude of the amygdala response to the footshock predicted behavioral responses the following day. The omission of expected footshock led to a decrease below baseline in the amygdala response suggesting a negative aversive prediction error signal. Thus, in mice, amygdala activity conforms to temporal difference models of aversive learning.
doi:10.1523/JNEUROSCI.4465-13.2014
PMCID: PMC4078079  PMID: 24990922
amygdala; fear; hemodynamic; prediction error; theta oscillations; tissue oxygen
14.  Examining the association between salivary cortisol levels and subclinical measures of atherosclerosis: the Multi-Ethnic Study of Atherosclerosis 
Psychoneuroendocrinology  2012;38(7):1036-1046.
Objective
To investigate the association between salivary cortisol and two markers of subclinical cardiovascular disease (CVD), coronary calcification (CAC), and ankle-brachial index (ABI).
Methods
Data from an ancillary study to the Multi-Ethnic Study of Atherosclerosis (MESA), the MESA Stress Study, were used to analyze associations of salivary cortisol data collected six times per day over three days with CAC and ABI. The authors used mixed models with repeat cortisol measures nested within persons to determine if specific features of the cortisol profile were associated with CAC and ABI.
Results
total of 464 participants were included in the CAC analysis and 610 in the ABI analysis. The mean age of participants was 65.6 years. A 1-unit increase in log coronary calcium was associated with a 1.77% flatter early decline in cortisol (95% CI: 0.23, 3.34) among men and women combined. Among women low ABI was associated with a steeper early decline (−13.95% CI:−25.58, −3.39) and a marginally statistically significant flatter late decline (1.39% CI: −0.009, 2.81). The cortisol area under the curve and wake to bedtime slope were not associated with subclinical CVD.
Conclusions
This study provides weak support for the link between cortisol and measures of subclinical atherosclerosis. We found an association between some features of the diurnal cortisol profile and coronary calcification and ABI but associations were not consistent across subclinical measures. There are methodological challenges in detecting associations of cortisol measures at a point in time with health outcomes that develop over a lifetime. Studies of short-term mechanisms linking stress to physiological processes related to the development of early atherosclerosis may be more informative.
doi:10.1016/j.psyneuen.2012.10.007
PMCID: PMC4020284  PMID: 23146655
salivary cortisol; ankle brachial index; coronary calcification; atherosclerosis; stress; cortisol awakening response; cortisol diurnal pattern; Multi-Ethnic Study of Atherosclerosis
15.  Pentraxin-3 and the right ventricle: the Multi-Ethnic Study of Atherosclerosis–Right Ventricle Study 
Pulmonary Circulation  2014;4(2):250-259.
Pentraxin-3 (PTX3) is a protein mediator of innate immunity that is elevated in the setting of left heart disease and pulmonary arterial hypertension. The relationship between PTX3 and right ventricular (RV) structure and function is not known. We included men and women with magnetic resonance imaging assessment of RV structure and function and measurement of PTX3 from the Multi-Ethnic Study of Atherosclerosis, a study of individuals free of clinical cardiovascular disease. Multivariable linear regression estimated associations between PTX3 protein levels and RV measures after adjusting for demographic characteristics, anthropometrics, smoking status, diabetes mellitus, hypertension, and corresponding left ventricular (LV) parameters. Instrumental variable analysis exploiting Mendelian randomization was attempted using two-stage least squares regression. The study sample included 1,779 participants with available PTX3 levels, RV measures, and all covariables. Mean PTX3 level was 2.1 ng/mL. Higher PTX3 was independently associated with greater RV mass and larger RV end-diastolic volume with and without adjustment for the corresponding LV parameters or C-reactive protein (all P < .05). There was no association between PTX3 and RV ejection fraction or stroke volume. Single-nucleotide polymorphisms were not associated with PTX3 protein levels or RV measures after accounting for race. Instrumental variable analysis could not be reliably performed. Higher PTX3 protein levels were associated with greater RV mass and larger RV end-diastolic volume. These associations were independent of common cardiovascular risk factors and LV morphologic changes. Inflammation is associated with differences in the pulmonary circulation-RV axis in adults without clinical cardiovascular disease.
doi:10.1086/675988
PMCID: PMC4070771  PMID: 25006444
pulmonary hypertension; heart failure; inflammation; right ventricle; Mendelian randomization
16.  Pulmonary Hyperinflation and Left Ventricular Mass 
Circulation  2013;127(14):1503-1511e6.
Background
Left ventricular (LV) mass is an important predictor of heart failure and cardiovascular mortality, yet determinants of LV mass are incompletely understood. Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) may contribute to changes in intrathoracic pressure that increase LV wall stress. We therefore hypothesized that residual lung volume in COPD would be associated with greater LV mass.
Methods and results
The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50–79 years who were free of clinical cardiovascular disease. LV mass was measured by cardiac magnetic resonance. Pulmonary function testing was performed according to guidelines. Regression models were used to adjust for age, sex, body size, blood pressure and other cardiac risk factors.
Among 119 MESA COPD Study participants, mean age was 69±6 years, 55% were male and 65% had COPD, mostly of mild or moderate severity. Mean LV mass was 128±34 grams. Residual lung volume was independently associated with greater LV mass (7.2 grams per standard deviation increase in residual volume; 95% CI 2.2 to 12; P=0.004), and was similar in magnitude to that of systolic blood pressure (7.6 grams per standard deviation increase in systolic blood pressure, 95% CI 4.3 to 11 grams; p<0.001). Similar results were observed for LV mass to end-diastolic volume ratio (p=0.02) and with hyperinflation measured as residual volume to total lung capacity ratio (P=0.009).
Conclusions
Pulmonary hyperinflation, as measured by residual lung volume or residual lung volume to total lung capacity ratio, is associated with greater LV mass.
doi:10.1161/CIRCULATIONAHA.113.001653
PMCID: PMC4018203  PMID: 23493320
Left ventricular mass; hyperinflation; chronic obstructive pulmonary disease
17.  Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis 
Arquivos Brasileiros de Cardiologia  2014;102(4):327-335.
Background
Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (εCC) and longitudinal strain (εLL), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders.
Objective
We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE.
Methods
We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components.
Results
Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower εCC and lower εLL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative εCC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative εLL after adjustment for ethnicity, LVEF, and creatinine.
Conclusion
Left ventricular εCC and εLL, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.
doi:10.5935/abc.20140040
PMCID: PMC4028951  PMID: 24844874
Atherosclerosis; Metabolic X Syndrome; Diabetes Mellitus / mortality; Ventricular Dysfunction / physiopathology; Ethnic Group
18.  Effect of Glucans from Caripia montagnei Mushroom on TNBS-Induced Colitis 
In this study, we evaluated the effect of different doses of polysaccharides extracted from Caripia montagnei mushroom at different intervals of treatment on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The FT-IR analysis and NMR showed that the polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed the reduction of colonic lesions in all groups treated with the glucans. Such glucans significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that the glucans from C. montagnei acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01) and myeloperoxidase (p < 0.001), a result confirmed by the reduction of cellular infiltration observed microscopically. The increase of catalase activity possibly indicates a protective effect of these glucans on colonic tissue, confirming their anti-inflammatory potential.
doi:10.3390/ijms15022368
PMCID: PMC3958856  PMID: 24518681
colitis; polysaccharides; mushroom; anti-inflammatory; Caripia montagnei
19.  Prediction of Sentinel Node Status and Clinical Outcome in a Melanoma Centre 
Journal of Skin Cancer  2013;2013:904701.
Background. Sentinel lymph node biopsy (SLNB) is a standard procedure for patients with localized cutaneous melanoma. The National Comprehensive Cancer Network (NCCN) Melanoma Panel has reinforced the status of the sentinel lymph node (SLN) as an important prognostic factor for melanoma survival. We sought to identify predictive factors associated with a positive SLNB and overall survival in our population. Methods. We performed a retrospective chart review of 221 patients who have done a successful SLNB for melanoma between 2004 and 2010 at our department. Univariate and multivariate analyses were done. Results. The SLNB was positive in 48 patients (21.7%). Univariate analysis showed that male gender, increasing Breslow thickness, tumor type, and absence of tumor-infiltrating lymphocytes were significantly associated with a positive SLNB. Multivariate analysis confirmed that Breslow thickness and the absence of tumor-infiltrating lymphocytes are independently predictive of SLN metastasis. The 5-year survival rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients. Breslow thickness and the SLN status independently predict overall survival. Conclusions. The risk factors for a positive SLNB are consistent with those found in the previous literature. In addition, the SLN status is a major determinant of survival, which highlights its importance in melanoma management.
doi:10.1155/2013/904701
PMCID: PMC3886376  PMID: 24455276
20.  Right Ventricular Structure is Associated with the Risk of Heart Failure and Cardiovascular Death: The MESA-Right Ventricle Study 
Circulation  2012;126(14):1681-1688.
Background
Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure (HF) or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants between 2000–2002 with follow-up for incident heart failure and cardiovascular death (“death”) until January 2008. RV volumes and mass were available for 4204 participants. The study sample (N = 4,144) was 61.4 ± 10.1 years old and 47.6 % male. The presence of RV hypertrophy (increased RV mass) was associated with a more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (HR = 2.52, 95%CI 1.55–4.10, p < 0.001) and a doubling of risk (or more) with left ventricular mass at the mean value or lower (p for interaction = 0.05).
Conclusions
RV hypertrophy was associated with the risk of heart failure or death in a multi-ethnic population free of clinical cardiovascular disease at baseline.
doi:10.1161/CIRCULATIONAHA.112.095216
PMCID: PMC3532921  PMID: 22932258
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension; survival
21.  Assessment of Cardiac Involvement in Myotonic Muscular Dystrophy by T1 Mapping on Magnetic Resonance Imaging 
Background
Patients with DM are at risk for atrioventricular block and left ventricular (LV) dysfunction. Non-invasive detection of diffuse myocardial fibrosis may improve disease management in this population.
Objective
Our aim was to define functional and post-contrast myocardial T1 time cardiac magnetic resonance (CMR) characteristics in myotonic muscular dystrophy (DM) patients.
Methods
Thirty-three DM patients (24 with type 1 and 9 with type 2) and 13 healthy volunteers underwent CMR for assessment of LV indices and evaluation of diffuse myocardial fibrosis by T1 mapping. The association of myocardial T1 time to ECG abnormalities and LV indices were examined among DM patients.
Results
DM patients had lower end-diastolic volume index (68.9 vs. 60.3 ml/m2, p=0.045), cardiac index (2.7 vs. 2.33 L/min/m2, p=0.005) and shorter myocardial T1time (394.5 vs. 441.4 ms, p<0.0001), compared to control subjects. Among DM patients, there was a positive association between higher T1 time and LV mass index (2.2 ms longer per gm/m2, p=0.006), LV end-diastolic volume index (1.3 ms longer per ml/m2, p=0.026), filtered QRS duration (1.2 ms longer per unit, p=0.005) and low-amplitude (<40mcV) late-potential duration (0.9 ms longer per unit, p=0.01). Using multivariate random effects regression, each 10 ms increase in myocardial T1 time of type 1 DM patients was independently associated with 1.3 ms increase in longitudinal PR and QRS intervals during follow-up.
Conclusion
DM is associated with structural alterations on CMR. Post-contrast myocardial T1 time was shorter in DM patients than controls likely reflecting the presence of diffuse myocardial fibrosis.
doi:10.1016/j.hrthm.2012.06.032
PMCID: PMC3459147  PMID: 22710483
Myotonic muscular dystrophy; MRI; T1 mapping; ventricular function
23.  Cardiac magnetic resonance imaging and its electrocardiographs (ECG): tips and tricks 
All cardiac magnetic resonance (CMR) techniques aim to create still depictions of a dynamic and ever-adapting organ. Most CMR methods rely on cardiac gating to capture information during fleeting periods of relative cardiac quiescence, at end diastole or end systole, or to acquire partial images throughout the cardiac cycle and average these signals over several heart beats. Since the inception of clinical CMR in the early 1980s, priority has been given to improving methods for image gating. The aim of this work is to provide a basic understanding of the ECG acquisition, demonstrate common ECG-related artifacts and to provide practical methods for overcoming these issues. Meticulous ECG preparation is essential for optimal CMR acquisition and these techniques must be adaptable to the individual patient.
doi:10.1007/s10554-011-9957-4
PMCID: PMC3476721  PMID: 22033762
Magnetic resonance imaging; ECG; Trigger
24.  LVM Assessed by Echocardiography and Cardiac Magnetic Resonance, Cardiovascular Outcomes, and Medical Practice 
JACC. Cardiovascular imaging  2012;5(8):837-848.
We investigate three important areas related to the clinical use of LVM (LVM): accuracy of assessments by echocardiography and cardiac magnetic resonance (CMR), the ability to predict cardiovascular outcomes, and the comparative value of different indexing methods. The recommended formula for echocardiographic estimation of LVM uses linear measurements and is based on the assumption of the left ventricle as a prolate ellipsoid of revolution. CMR permits a modeling of the left ventricle free of cardiac geometric assumptions or acoustic window dependency, showing better accuracy and reproducibility. However, echocardiography has lower cost, easier availability, and better tolerability. From the Medline database, 26 longitudinal echocardiographic studies and 5 CMR studies, investigating LVM or LV hypertrophy as predictors of death or major cardiovascular outcomes, were identified. LVM and LV hypertrophy were reliable cardiovascular risk predictors using both modalities. However, no study directly compared the methods for the ability to predict events, agreement in hypertrophy classification, or performance in cardiovascular risk reclassification. Indexing LVM to BSA was the earliest normalization process used, but it seems to underestimate the prevalence of hypertrophy in obese and overweight subjects. Dividing LVM by height to 1.7 or 2.7 as allometric powers are the most promising normalization methods in terms of practicality and usefulness from a clinical ans scientific standpoints for scaling myocardial mass to body size. The measurement of LVM, calculation of LVMi, and classification for LVH should be standardized by scientific societies across measurement techniques and adopted by clinicians in risk stratification and therapeutic decision.
doi:10.1016/j.jcmg.2012.06.003
PMCID: PMC3501209  PMID: 22897998
LVM; LVH; cardiovascular events; cardiac magnetic resonance; echocardiography
25.  Pulmonary Artery Pressure, Gender, Menopause, and Pregnancy in Schistosomiasis-Associated Pulmonary Hypertension 
Arquivos brasileiros de cardiologia  2013;101(2):154-159.
Background
Schistosomiasis-associated pulmonary arterial hypertension (SPAH) is a major concern worldwide. However, the role of gender specific contributing factors in SPAH is unknown.
Objective
We investigated how systolic pulmonary artery pressure (SPAP) values and the presence of severe SPAP relate to gender, menopausal status, and pregnancy history in SPAH patients.
Methods
Seventy-nine patients diagnosed with SPAH from 2000 to 2009 were assessed and 66 were enrolled in the study. Information about age, menopausal status, pregnancy, echocardiography-derived SPAP, and invasive mean pulmonary artery pressure (mPAP) was collected from medical records. The relation between values of SPAP and mPAP and their agreement for severe disease were assessed. Regression models assessed the association of gender, menopausal status, and pregnancy history with SPAP values and the presence of severe SPAP.
Results
Moderate correlation and good agreement for severe disease were found between mPAP and SPAP. Mean SPAP values were similar for men and women. A trend toward higher values of SPAP was found for non-menopausal women compared to men. Higher SPAP values were found for menopausal compared to non-menopausal women; the values were non-significant after adjustment for age. Pregnancy history had no association with SPAP. Menopause and positive pregnancy had no association with severe SPAP.
Conclusion
In SPAH patients, neither gender, nor menopausal status, nor pregnancy history showed independent correlation with SPAP values assessed by echocardiography.
doi:10.5935/abc.20130130
PMCID: PMC3998155  PMID: 23821406
Hypertension, Pulmonary; Schistosomiasis; Pregnancy; Menopause; Echocardiography, Doppler

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