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1.  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.
PMCID: PMC3958856  PMID: 24518681
colitis; polysaccharides; mushroom; anti-inflammatory; Caripia montagnei
2.  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.
PMCID: PMC3886376  PMID: 24455276
3.  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.
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).
RV hypertrophy was associated with the risk of heart failure or death in a multi-ethnic population free of clinical cardiovascular disease at baseline.
PMCID: PMC3532921  PMID: 22932258
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension; survival
4.  Assessment of Cardiac Involvement in Myotonic Muscular Dystrophy by T1 Mapping on Magnetic Resonance Imaging 
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.
Our aim was to define functional and post-contrast myocardial T1 time cardiac magnetic resonance (CMR) characteristics in myotonic muscular dystrophy (DM) patients.
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.
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.
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.
PMCID: PMC3459147  PMID: 22710483
Myotonic muscular dystrophy; MRI; T1 mapping; ventricular function
6.  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.
PMCID: PMC3476721  PMID: 22033762
Magnetic resonance imaging; ECG; Trigger
7.  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.
PMCID: PMC3501209  PMID: 22897998
LVM; LVH; cardiovascular events; cardiac magnetic resonance; echocardiography
8.  Normal left ventricular myocardial thickness for middle aged and older subjects with SSFP cardiac MR: The Multi-Ethnic Study of Atherosclerosis 
Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac MR (CMR) and to assess variation with image acquisition plane, demographics and LV function.
Methods and Results
End-diastolic LVMT was measured on CMR steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9mm and 6.3±1.1mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men were 7mm/9mm (long axis) and 7mm/8mm (short axis). Mean LVMT was positively associated with weight (0.02mm/kg, p=0.01) and body-surface-area (1.1mm/m2, p<0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower LV end-diastolic volume (0.01mm/ml, p<0.01), a lower LV end-systolic volume (−0.01mm/ml, p=0.01) and lower LV stroke volume (−0.01mm/ml, p<0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images.
Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.
PMCID: PMC3412148  PMID: 22705587
magnetic resonance imaging; myocardial thickness; normal values
9.  Association of number of live births with left ventricular structure and function. The Multi-Ethnic Study of Atherosclerosis (MESA) 
American heart journal  2012;163(3):470-476.
Pregnancy is associated with marked maternal cardiovascular/hemodynamic changes. A greater number of pregnancies may be associated with long-term subclinical changes in left ventricular (LV) remodeling.
Among 2,234 white, black, Hispanic, and Chinese women (mean age 62 years) in the MESA, we used linear regression to relate live births and cardiac magnetic resonance imaging LV measures. Covariates included age, ethnicity, height, income, education, birth country, smoking, menopause, and oral contraceptive duration. Models were additionally adjusted for potential mediators: systolic blood pressure, antihypertensive use, total/high-density lipoprotein cholesterol, triglycerides, diabetes, and body mass index. We performed sensitivity analyses excluding 763 women in the lowest socioeconomic group: annual income <$25,000 and lower high school level of education.
With each live birth, LV mass increased 1.26 g; LV end-diastolic volume, 0.74 mL; and LV end-systolic volume, 0.45 mL; LV ejection fraction decreased 0.18% (P trend <0.05). Changes were most notable for the category of women with ≥5 pregnancies. Upon adjustment for potential biologic mediators, live births remained positively associated with LV mass and end-systolic volume. Live births remained significantly associated with LV end-systolic, end-diastolic volumes, and LV mass (P trend ≤0.02) after excluding women in the lowest socioeconomic group.
Number of live births is associated with key LV structural and functional measures in middle to older ages, even after adjustment for sociodemographic factors and cardiovascular disease risk factors. Hemodynamic changes during pregnancy may be associated with cardiac structure/function beyond childbearing years.
PMCID: PMC3656723  PMID: 22424019
10.  Trabeculated (Non-Compacted) and Compact Myocardium in Adults: The Multi-Ethnic Study of Atherosclerosis 
A high degree of non-compacted (trabeculated) myocardium in relationship to compact myocardium (T/M ratio >2.3) has been associated with a diagnosis of left ventricular non-compaction (LVNC). The purpose of this study was to determine the normal range of the T/M ratio in a large population-based study and to examine the relationship to demographic and clinical parameters.
Methods and Results
The thickness of trabeculation and the compact myocardium were measured in eight LV regions on long axis cardiac magnetic resonance (CMR) steady-state free precession cine images in 1000 participants (551 women; 68.1±8.9 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Of 323 participants without cardiac disease or hypertension and with all regions evaluable 140 (43%) had a T/M ratio >2.3 in at least one region; in 20/323 (6%), T/M>2.3 was present in more than two regions. Multivariable linear regression model revealed no association of age, gender, ethnicity, height and weight with maximum T/M ratio in participants without cardiac disease or hypertension (p>0.05). In the entire cohort (n=1000) LVEF (β=−0.02/%; p=0.015), LVEDV (β=0.01/ml; p=<0.0001) and LVESV (β=0.01/ml; p<0.001) were associated with maximum T/M ratio in adjusted models while there was no association with hypertension or myocardial infarction (p>0.05). At the apical level T/M ratios were significantly lower when obtained on short- compared to long-axis images (p=0.017).
A ratio of trabeculated to compact myocardium of more than 2.3 is common in a large population based cohort. These results suggest reevaluation of the current CMR criteria for LVNC may be necessary.
PMCID: PMC3399115  PMID: 22499849
cardiovascular magnetic resonance imaging; cardiomyopathy; non-compaction; trabeculation
11.  Combined Cardiac MRI and C-Reactive Protein Levels Identify a Cohort at Low Risk for Defibrillator Firings and Death 
Annually, ~80,000 Americans receive guideline-based primary prevention implantable cardioverter defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on LVEF, which lacks sensitivity and specificity. Because scar-related, myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance (CMR) identification of myocardial heterogeneity improves risk stratification through: (1) its association with adverse cardiac events independent of clinical factors and biomarker levels; and (2) its ability to identify particularly high- and low-risk subgroups.
Methods and Results
In 235 ischemic and nonischemic patients with LVEF≤35%, undergoing clinically-indicated primary prevention ICD, gadolinium-enhanced CMR was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone-GZ) and dense core scar. Serum high sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary endpoint was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 patients (19%) at 3.6 year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ and core were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (p<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7%/year event rate) while those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1%/year, p<0.001.
In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk of adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool.
Clinical Trial Registration
URL: Unique identifier: NCT00181233.
PMCID: PMC3330427  PMID: 22267750
implantable cardioverter-defibrillator; myocardial delayed enhancement; cardiovascular magnetic resonance imaging; cardiomyopathy; ventricular arrhythmia
12.  Right Ventricular Morphology and the Onset of Dyspnea: The MESA-Right Ventricle Study 
PLoS ONE  2013;8(2):e56826.
The association of right ventricular (RV) structure and function with symptoms in individuals without cardiopulmonary disease is unknown. We hypothesized that greater RV mass and RV end-diastolic volume (RVEDV), smaller RV stroke volume (RVSV), and lower RV ejection fraction (RVEF) measured by cardiac magnetic resonance imaging (MRI) in participants free of clinical cardiovascular disease at baseline would be associated with a greater risk of self-reported dyspnea.
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRIs on participants without clinical cardiovascular disease between 2000 and 2002. We excluded subjects who reported “prevalent” dyspnea at the first assessment (24 months). The presence of dyspnea was assessed at 24 months, 42 months, and 60 months from baseline. Cox proportional hazards models were used to examine the relationship between RV measures and incident dyspnea.
In the final study sample (N = 2763), there were significant interactions between RV measures and sex in terms of the risk of dyspnea (p<0.05). Among men (N = 1453), lower RV mass (p = 0.003), smaller RVEDV (p<0.001), smaller RV end-systolic volume (RVESV) (p = 0.03) and decreased RVSV (p<0.001) were associated with an increased risk of developing dyspnea after adjusting for covariates. Associations remained after adjusting for left ventricular function and lung function. However, there were no significant associations between RV measures and the risk of dyspnea in women.
Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.
PMCID: PMC3574101  PMID: 23457622
13.  Myocardial T1 Mapping with MRI: comparison of Look-Locker and MOLLI sequences 
To evaluate the relationship between “Look-Locker” (LL) and modified Look-Locker Inversion recovery (MOLLI) approaches for T1 mapping of the myocardium.
168 myocardial T1 maps using MOLLI and 165 maps using LL were obtained in human subjects at 1.5 Tesla. The T1 values of the myocardium were calculated before and at five time points after gadolinium administration. All time and heart rate normalizations were done. The T1 values obtained were compared to determine the absolute and bias agreement.
The pre-contrast global T1 values were similar when measured by the LL and by MOLLI technique (mean 1004.9 ms +/- 120.3 vs. 1034.1 ms +/- 53.1, respectively, p = 0.26). Post-contrast myocardial T1 time from LL was significantly longer than MOLLI from 5 to 25 minutes (mean difference, LL - MOLLI was +61.8 +/- 46.4 ms, p < 0.001). No significant differences in T1 values were noted between long and short axis measurements for either MOLLI or LL.
Post-contrast LL and MOLLI showed very good agreement, although LL vaules are higher than MOLLI. Pre-contrast T1 values showed good agreement, however LL has greater limits of agreement. Short and long axis planes can reliably assess T1 values.
PMCID: PMC3221792  PMID: 21954119
Magnetic resonance imaging; diffuse myocardium fibrosis; T1 mapping
14.  Multi-Detector Computed Tomography for the Evaluation of Myocardial Cell Therapy in Heart Failure:_A Comparison with Cardiac Magnetic Resonance Imaging 
JACC. Cardiovascular imaging  2011;4(12):1284-1293.
The aim of this study was to use multi-detector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.
Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical setting. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).
Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n=9) or 200 million mesenchymal stem cells (MSCs, n=13), twelve weeks after myocardial infarction (MI). Cardiac MRI and MDCT acquisitions were performed prior to randomization 12 weeks after MI induction and at the study endpoint 24 week post-MI. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV-volumes and LVEF. Delayed enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.
MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3±1.2% to 10.3±1.5% of LV-mass (p=0.005) while infarct size increased in non-treated animals (from 13.8±1.3% to 16.5±1.5%; p=0.02) (Placebo vs MSC; p=0.003). Both observers had excellent agreement for infarct size (r=0.96; p<0.001). LVEF increased from 32.6±2.2% to 36.9±2.7% in MSC treated animals (p=0.03) and decreased in placebo animals (from 33.3±1.4 to 29.1±1.5%; p=0.01; at week 24: placebo vs MSC p=0.02). Infarct size, end-diastolic LV volume and LVEF assessed by MDCT compared favorably with MRI acquisitions (r=0.70; r=0.82; r=0.902; respectively, p<0.001).
This study demonstrates that cardiac MDCT can be used to evaluate infarct size, LV-volumes, and LVEF after intramyocardial delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies. (word count 299)
PMCID: PMC3245738  PMID: 22172785
MDCT; MRI; Delayed Contrast Enhancement; Göttingen Minipig; Mesenchymal Stem Cell; Myocardial Infarction; Heart failure
15.  Characterization of Peri-Infarct Zone Heterogeneity by Contrast Enhanced Multi-detector Computed Tomography: Comparison with Magnetic Resonance Imaging 
We examined whether MDCT improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to MRI.
The PIZ as characterized by delayed enhanced (de) MRI identifies patients susceptible to ventricular arrhythmias and predicts outcome after myocardial infarction (MI).
Fifteen mini-pigs underwent coronary artery occlusion followed by reperfusion. MDCT and MRI were performed on the same day approximately 6 months after MI induction followed by animal sacrifice and ex-vivo MRI (n=5). Signal density threshold algorithms were applied to MRI and MDCT data sets reconstructed at various slice thicknesses (1–8mm) to define the PIZ and quantify partial volume effects.
De-MDCT reconstructed at 8mm slice thickness demonstrated excellent correlation of infarct size with post mortem pathology (r2=0.97; p<0.0001) and MRI (r2=0.92; p<0.0001). De-MDCT and de-MRI were able to detect a PIZ in all animals, which correlates to a mixture of viable and non-viable myocytes at the PIZ by histology. The ex-vivo de-MRI PIZ volume decreased with slice thickness from 0.9±0.2cc at 8mm to 0.2±0.1cc at 1mm (p=0.01). PIZ volume/mass by de-MDCT increased with decreasing slice thickness due to declining partial volume averaging in the PIZ, but was susceptible to increased image noise.
De-MDCT provides a more detailed assessment of the PIZ in chronic MI and is less susceptible to partial volume effects than MRI. This increased resolution best reflects the extent of tissue mixture by histopathology and has the potential to further enhance the ability to define the substrate of malignant arrhythmia in ischemic heart disease non-invasively.
PMCID: PMC3381611  PMID: 19406346
MDCT; delayed enhancement; peri-infarct zone; MRI
16.  T1 Mapping of the Gadolinium-Enhanced Myocardium: Adjustment for Factors Affecting Interpatient Comparison 
Quantitative T1 mapping of delayed gadolinium-enhanced cardiac magnetic resonance imaging has shown promise in identifying diffuse myocardial fibrosis. Despite careful control of magnetic resonance imaging parameters, comparison of T1 times between different patients may be problematic because of patient specific factors such as gadolinium dose, differing glomerular filtration rates, and patient specific delay times. In this work, a model driven approach to account for variations between patients to allow for comparison of T1 data is provided. Kinetic model parameter values were derived from healthy volunteer time-contrast curves. Correction values for the factors described above were used to normalize T1 values to a matched state. Examples of pre- and postcorrected values for a pool of normal subjects and in a patient cohort of type 1 diabetic patients shows tighter clustering and improved discrimination of disease state.
PMCID: PMC3092826  PMID: 21500267
T1 mapping; myocardial fibrosis; patient T1 comparison; GFR; delayed enhancement
17.  Sex and Race Differences in Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
Circulation  2011;123(22):2542-2551.
Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease, however determinants of RV anatomy have not been well-studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants. RV volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived using an allometric approach. The study sample (N = 4123) was 61.5 ± 10.1 years old and 47.5% male. Older age was associated with lower RV mass (~5% lower mass per decade) with larger age-related decrements in men than in women (p for interaction < 0.05). Older age was also associated with higher RV ejection fraction (RVEF), an association which differed between races/ethnicities (p for interaction ≤ 0.01). Overall, men had greater RV mass (~8%) and larger RV volumes than women, but had lower RVEF (4% in absolute terms) (p < 0.001). African Americans had lower RV mass than Caucasians (p ≤ 0.002), whereas Hispanics had higher RV mass (p ≤ 0.02). Using the derived normative equations, 7.3% (95%CI, 6.5–8.1%) met criteria for RV hypertrophy and 5.9% (95%CI, 5.2–6.6%) had RV dysfunction.
In conclusion, age, sex, and race are associated with significant differences in RV mass, RV volumes and RVEF, potentially explaining distinct responses of the RV to cardiopulmonary disease.
PMCID: PMC3111939  PMID: 21646505
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension
18.  Articles with short titles describing the results are cited more often 
Clinics  2012;67(5):509-513.
The aim of this study was to evaluate some features of article titles from open access journals and to assess the possible impact of these titles on predicting the number of article views and citations.
Research articles (n = 423, published in October 2008) from all Public Library of Science (PLoS) journals and from 12 Biomed Central (BMC) journals were evaluated. Publication metrics (views and citations) were analyzed in December 2011. The titles were classified according to their contents, namely methods-describing titles and results-describing titles. The number of title characters, title typology, the use of a question mark, reference to a specific geographical region, and the use of a colon or a hyphen separating different ideas within a sentence were analyzed to identify predictors of views and citations. A logistic regression model was used to identify independent title characteristics that could predict citation rates.
Short-titled articles had higher viewing and citation rates than those with longer titles. Titles containing a question mark, containing a reference to a specific geographical region, and that used a colon or a hyphen were associated with a lower number of citations. Articles with results-describing titles were cited more often than those with methods-describing titles. After multivariate analysis, only a low number of characters and title typology remained as predictors of the number of citations.
Some features of article titles can help predict the number of article views and citation counts. Short titles presenting results or conclusions were independently associated with higher citation counts. The findings presented here could be used by authors, reviewers, and editors to maximize the impact of articles in the scientific community.
PMCID: PMC3351256  PMID: 22666797
Articles; Citations; Visualization; Titles
19.  Cardiovascular magnetic resonance characterization of peri-infarct zone remodeling following myocardial infarction 
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.
Methods and results
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 (p = 0.04). The size of infarct scar expanded by 14% and thinned by 56% from day 3 to 12 weeks (p = 0.004 and p < 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;* p < 0.05).
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.
PMCID: PMC3352163  PMID: 22510220
Cardiovascular magnetic resonance imaging; Myocardial infarction; Late gadolinium enhancement; Peri-infarct zone; Myocardial strain
20.  Alcohol and coronary artery calcium prevalence, incidence and progression: results from the Multi-Ethnic Study of Atherosclerosis (MESA) 
Alcohol use has been consistently found to have a J-shaped association with coronary heart disease, with moderate drinkers exhibiting a decreased risk compared to both heavy drinkers and non-drinkers. However, studies of the association between alcohol use and subclinical coronary artery disease have conflicted.
To determine whether alcohol is associated with the presence, amount, or progression of coronary calcium over a 2- to 4-year period.
MESA is a prospective community-based cohort study of subclinical cardiovascular disease in a multi-ethnic cohort. In 2000–2002, 6814 participants free of clinical cardiovascular disease were enrolled at 6 participating centers.
There were 3766 (55.5%) current drinkers, 1635 (24.1%) former drinkers, and 1390 (20.5%) never drinkers included in the analysis. Although light to moderate alcohol consumption was associated with lower coronary heart disease risk, we found no evidence of a protective or J-shaped association of alcohol and coronary artery calcium (CAC). In fact there was evidence that heavy consumption of hard liquor was associated with greater CAC accumulation. Other alcoholic beverages were not associated with CAC prevalence, incidence or progression.
This is the first large study to evaluate the association of alcohol and coronary artery calcium in four racial/ethnic groups, and to evaluate progression of calcification. These results suggest that the cardiovascular benefits that may be derived from light to moderate alcohol consumption are not mediated through reduced CAC accumulation.
PMCID: PMC3319440  PMID: 19064520
21.  The Absence of Coronary Calcification Does Not Exclude Obstructive Coronary Artery Disease or the Need for Revascularization in Patients Referred for Conventional Coronary Angiography 
This study was designed to evaluate whether the absence of coronary calcium could rule out ≥50% coronary stenosis or the need for revascularization.
The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients.
A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before.
In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 ± 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of ≥50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 ≥50% stenosis. The overall sensitivity for CS = 0 to predict the absence of ≥50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with ≥50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium.
The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification.
PMCID: PMC3294287  PMID: 20170786
coronary artery disease; calcium score; computed tomography; coronary angiography; coronary stenosis
22.  Racial and ethnic differences in subclinical myocardial function: the Multi-Ethnic Study of Atherosclerosis 
Heart (British Cardiac Society)  2011;97(5):405-410.
Racial/ethnic differences in the incidence and severity of heart failure (HF) are not well understood, but may be related to pre-existing variations in myocardial function.
To examine racial/ethnic differences in regional myocardial function among asymptomatic individuals free of known cardiovascular disease.
Design, setting and patients
The Multi-Ethnic Study of Atherosclerosis is a prospective, observational study of individuals without baseline cardiovascular disease, representing four major racial/ethnic groups. A total of 1099 study participants underwent cardiac MRI with tissue tagging; for each study, peak systolic strain (Ecc) and strain rate (SRs) were determined in four left ventricular (LV) regions.
Main outcome measures
Multiple linear regression was used to analyse the relationship between race/ethnicity and regional strain (Ecc and SRs) while adjusting for cardiovascular risk factors.
Compared with other racial/ethnic groups, Chinese-Americans had the greatest magnitude of Ecc in a majority of LV regions (–19.60±3.78, p<0.05); Chinese-Americans also had the greatest absolute values for SRs in all regions, reflecting higher rate of systolic contraction (–2.01±0.76, p<0.05). Conversely, African-Americans had the lowest Ecc values (–17.50±4.00, p<0.05) in the majority of wall regions while Hispanics demonstrated the lowest rate of contractility in all wall regions (–1.44±0.50, p≤0.001) in comparison with the other racial/ethnic groups. These race-based differences remained significant in the majority of LV wall regions after adjusting for multiple variables, including hypertension and LV mass.
Important race-based differences in regional LV systolic function in a large cohort of asymptomatic individuals have been demonstrated. Further research is needed to investigate the possible mechanisms related to the race/ethnicity-based variations found in this study.
PMCID: PMC3034784  PMID: 21258000
23.  Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64 
European Radiology  2008;19(4):816-828.
Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its noninvasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective “CORE-64” trial (“Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors”). This multi-centre trialwas unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.
PMCID: PMC3289939  PMID: 18998142
Computed tomography; Coronary vessels; Multi-centre study; Methods; Design
24.  Physical Activity and Right Ventricular Structure and Function 
Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown.
Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent–minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity.
Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes.
Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications.
PMCID: PMC3056232  PMID: 20813888
exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging
25.  Cardiovascular Imaging for Assessing Cardiovascular Risk in Asymptomatic Men Versus Women 
Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD.
Methods and Results
The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05).
There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.
PMCID: PMC3037859  PMID: 21068189
imaging; cardiovascular diseases; sex

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