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1.  Prognostic implication of right ventricular involvement in peripartum cardiomyopathy: a cardiovascular magnetic resonance study 
Esc Heart Failure  2015;2(4):139-149.
Peripartum cardiomyopathy (PPCM) is a major cause of acute heart failure in the peripartum period and considered potentially life threatening. While many aspects of its clinical profiles have been frequently reported, functional analysis, in particular of the right ventricle, and tissue characterization by cardiovascular magnetic resonance (CMR) imaging have been only sporadically described. The aim of the present study was to analyse pathological alterations and their prognostic relevance found in CMR imaging of patients newly diagnosed with PPCM.
Methods and results
In this multicenter study 34 patients with confirmed PPCM underwent CMR imaging at the time of diagnosis and at 5 ± 1 months follow‐up. Cine imaging of PPCM patients showed moderate to severe reduction of systolic left ventricular (LV) function (mean LVEF: 29.7 ± 12.8%). In 35% of the patients right ventricular (RV) systolic function was also reduced with a mean RVEF of 42.9 ± 13.9%. Dilatation of the LV was observed in 91% (mean LV‐EDV/BSA 128.5 ± 32.1 mL/m2), and dilatation of the RV was present in 24% (mean RV‐EDV/BSA 87.4 ± 18.5 mL/m2) of the patients. Focal non‐ischemic late gadolinium enhancement (LGE) was visible in 71%, and regional wall motion abnormalities were evident in 88% of the patients. LGE and wall motion abnormalities were predominantly located in the anteroseptal and basal to midventricular segments. RV dysfunction at baseline was associated with reduced probability of full cardiac recovery at 5 ± 1 months follow‐up.
Besides LV systolic dysfunction, RV dysfunction and dilatation are observed in about one third of PPCM patients at the time of diagnosis. RV dysfunction is associated with unfavourable outcome. A distinct pattern of LV wall motion abnormalities and myocardial scar is evident in most PPCM patients. The present study may help to establish a set of CMR criteria suitable for diagnosis in patients with suspected PPCM and may add further knowledge to the pathology of the disease.
PMCID: PMC5054874  PMID: 27774259
Peripartum cardiomyopathy; Multiparametric cardiovascular magnetic resonance imaging; Right ventricular involvement
2.  Assessment of Pentalogy of Cantrell using 3D Multidetector Computed Tomography 
Radiology Case Reports  2016;4(1):273.
A 7-month-old white female with Pentalogy of Cantrell was imaged using 64 slice multidetector computed tomography (MDCT) with 3D mapping to better determine the extent of cardiac, thoracic, and abdominal malformations. Complimentary to ultrasound, the use of 3D 64 slice MDCT can facilitate effective diagnosis and treatment planning in cases of Pentalogy of Cantrell.
PMCID: PMC5106532  PMID: 27843529
MDCT, multidetector computed tomography
3.  Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study 
Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease.
Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema.
Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output.
Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers.
Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.
PMCID: PMC4595687  PMID: 26067761
pulmonary microvascular blood flow (PMBF); gadolinium-enhanced MRI; chronic obstructive pulmonary disease (COPD); lung emphysema; small airway disease
4.  Cannulation strategies for percutaneous extracorporeal membrane oxygenation in adults 
Extracorporeal membrane oxygenation (ECMO) has revolutionized treatment of severe isolated or combined failure of lung and heart. Due to remarkable technical development the frequency of use is growing fast, with increasing adoption by interventional cardiologists independent of cardiac surgery. Nevertheless, ECMO support harbors substantial risk such as bleeding, thromboembolic events and infection. Percutaneous ECMO circuits usually comprise cannulation of two large vessels (‘dual’ cannulation), either veno-venous for respiratory and veno-arterial for circulatory support. Recently experienced centers apply more advanced strategies by cannulation of three large vessels (‘triple’ cannulation), resulting in veno-veno-arterial or veno-arterio-venous cannulation. While the former intends to improve drainage and unloading, the latter represents a very potent method to provide circulatory and respiratory support at the same time. As such triple cannulation expands the field of application at the expense of increased complexity of ECMO systems. Here, we review percutaneous dual and triple cannulation strategies for different clinical scenarios of the critically ill. As there is no unifying terminology to date, we propose a nomenclature which uses “A” and all following letters for supplying cannulas and all letters before “A” for draining cannulas. This general and unequivocal code covers both dual and triple ECMO cannulation strategies (VV, VA, VVA, VAV). Notwithstanding the technical evolution, current knowledge of ECMO support is mainly based on observational experience and mostly retrospective studies. Prospective controlled trials are urgently needed to generate evidence on safety and efficacy of ECMO support in different clinical settings.
PMCID: PMC4805695  PMID: 26608160
Cardiogenic shock; Heart failure; ECMO; Extracorporeal circulation; Mechanical circulatory support
5.  Calcific Tendinosis: A Potential Mimicker of Malignancy on PET 
Radiology Case Reports  2015;1(2):38-41.
We report a case of a 53 year old female with breast cancer and elevated glucose activity at the left greater trochanter on PET imaging. Further imaging with CT and MRI showed that this focus of increased FDG activity on PET was calcific tendinosis of the gluteus medius tendon, which mimicked metastatic disease in this patient.
PMCID: PMC4891466  PMID: 27298678
PET, positron emission tomography; MDP, methylene diphosphonate; FDG, fluorodeoxyglucose; SUV, standardized uptake value; CT, computed tomography; MRI, magnetic resonance imaging
6.  Quantification of Pathologic Air Trapping in Lung Transplant Patients Using CT Density Mapping: Comparison with Other CT Air Trapping Measures 
PLoS ONE  2015;10(10):e0139102.
To determine whether density mapping (DM) is more accurate for detection and quantification of pathologic air trapping (pAT) in patients after lung transplantation compared to other CT air trapping measures. One-hundred forty-seven lung and heart-lung transplant recipients underwent CT-examinations at functional residual capacity (FRC) and total lung capacity (TLC) and PFT six months after lung transplantation. Quantification of air trapping was performed with the threshold-based method in expiration (EXP), density mapping (DM) and the expiratory to inspiratory ratio of the mean lung density (E/I-ratio MLD). A non-rigid registration of inspiration-expiration CT-data with a following voxel-to-voxel mapping was carried out for DM. Systematic variation of attenuation ranges was performed for EXP and DM and correlated with the ratio of residual volume to total lung capacity (RV/TLC) by Spearman rank correlation test. AT was considered pathologic if RV/TLC was above the 95th percentile of the predicted upper limit of normal values. Receiver operating characteristic (ROC) analysis was performed. The optimal attenuation range for the EXP method was from -790 HU to -950 HU (EXP-790 to -950HU) (r = 0.524, p<0.001) to detect air trapping. Within the segmented lung parenchyma, AT was best defined as voxel difference less than 80 HU between expiration and registered inspiration using the DM method. DM correlated best with RV/TLC (r = 0.663, p<0.001). DM and E/I-ratio MLD showed a larger AUC (0.78; 95% CI 0.69–0.86; 0.76, 95% CI 0.67–0.85) than EXP -790 HU to -950 HU (0.71, 95% CI 0.63–0.78). DM and E/I-ratio MLD showed better correlation with RV/TLC and are more suited quantitative CT-methods to detect pAT in lung transplant patients than the EXP-790HU to -950HU.
PMCID: PMC4592198  PMID: 26430890
7.  Bidimensional measurements of right ventricular function for prediction of survival in patients with pulmonary hypertension: comparison of reproducibility and time of analysis with volumetric cardiac magnetic resonance imaging analysis 
Pulmonary Circulation  2015;5(3):527-537.
We tested the hypothesis that bidimensional measurements of right ventricular (RV) function obtained by cardiac magnetic resonance imaging (CMR) in patients with pulmonary arterial hypertension (PAH) are faster than volumetric measures and highly reproducible, with comparable ability to predict patient survival. CMR-derived tricuspid annular plane systolic excursion (TAPSE), RV fractional shortening (RVFS), RV fractional area change (RVFAC), standard functional and volumetric measures, and ventricular mass index (VMI) were compared with right heart catheterization data. CMR analysis time was recorded. Receiver operating characteristic curves, Kaplan-Meier, Cox proportional hazard (CPH), and Bland-Altman test were used for analysis. Forty-nine subjects with PAH and 18 control subjects were included. TAPSE, RVFS, RVFAC, RV ejection fraction, and VMI correlated significantly with pulmonary vascular resistance and mean pulmonary artery pressure (all P < 0.05). Patients were followed up for a mean (± standard deviation) of 2.5 ± 1.6 years. Kaplan-Meier curves showed that death was strongly associated with TAPSE <18 mm, RVFS <16.7%, and RVFAC <18.8%. In CPH models with TAPSE as dichotomized at 18 mm, TAPSE was significantly associated with risk of death in both unadjusted and adjusted models (hazard ratio, 4.8; 95% confidence interval, 2.0–11.3; P = 0.005 for TAPSE <18 mm). There was high intra- and interobserver agreement. Bidimensional measurements were faster (1.5 ± 0.3 min) than volumetric measures (25 ± 6 min). In conclusion, TAPSE, RVFS, and RVFAC measures are efficient measures of RV function by CMR that demonstrate significant correlation with invasive measures of PAH severity. In patients with PAH, TAPSE, RVFS, and RVFAC have high intra- and interobserver reproducibility and are more rapidly obtained than volumetric measures. TAPSE <18 mm by CMR was strongly and independently associated with survival in PAH.
PMCID: PMC4556504  PMID: 26401254
pulmonary arterial hypertension; tricuspid annular plane systolic excursion (TAPSE); cardiac MRI; survival
8.  Normal values for cardiovascular magnetic resonance in adults and children 
Morphological and functional parameters such as chamber size and function, aortic diameters and distensibility, flow and T1 and T2* relaxation time can be assessed and quantified by cardiovascular magnetic resonance (CMR). Knowledge of normal values for quantitative CMR is crucial to interpretation of results and to distinguish normal from disease. In this review, we present normal reference values for morphological and functional CMR parameters of the cardiovascular system based on the peer-reviewed literature and current CMR techniques and sequences.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-015-0111-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4403942  PMID: 25928314
Normal values; Reference values; Cardiovascular magnetic resonance
9.  “Cor pulmonale parvus” in chronic obstructive pulmonary disease (COPD) and emphysema. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study 
The classic cardiovascular complication of chronic obstructive pulmonary disease (COPD) is cor pulmonale, or enlargement of the right ventricle (RV). Most studies of cor pulmonale were conducted decades ago.
We aimed to examine RV changes in contemporary COPD and emphysema using cardiac magnetic resonance imaging (MRI).
We performed a case-control study nested predominantly in two general population studies of 310 participants with COPD and controls ages 50–79 years with ≥ 10 pack-years of smoking and who were free of clinical cardiovascular disease. RV volumes and mass were assessed using MRI. COPD and COPD severity were defined by standard spirometric criteria. Percent emphysema was defined as percent of lung regions <-950 Hounsfield units on full-lung computed tomography; emphysema subtypes were scored by radiologists. Results were adjusted for age, race/ethnicity, sex, height, weight, smoking status, pack-years, systemic hypertension and sleep apnea.
RV end-diastolic volume was reduced in COPD compared to controls (-7.8 mL, 95% CI: -15.0, -0.5 mL; p=0.04). Increasing severity of COPD was associated with smaller RV end-diastolic volume (p=0.004) and lower RV stroke volume (p<0.001). RV mass and ejection fraction were similar between the groups. Greater percent emphysema was also associated with smaller RV end-diastolic volume (p=0.005) and stroke volume (p<0.001), as was the presence of centrilobular and paraseptal emphysema.
RV volumes are lower without significant alterations in RV mass and ejection fraction in contemporary COPD (“cor pulmonale parvus”) and this reduction is related to greater percent emphysema on computed tomography.
PMCID: PMC4347835  PMID: 25440095
right ventricle; chronic obstructive pulmonary disease; pulmonary heart disease; pulmonary hypertension; heart failure
11.  Axial Black Blood Turbo Spin Echo Imaging of the Right Ventricle 
Black blood turbo spin echo (TSE) imaging of the right ventricle (RV) free wall is highly sensitive to cardiac motion, frequently resulting in non-diagnostic images. Temporal and spatial parameters of a black blood TSE pulse sequence were evaluated for visualization of the RV free wall. 74 patient studies were retrospectively evaluated for the effects of acquisition timing on image quality. Axial black blood TSE images were acquired on 10 healthy volunteers to assess the role of spatial misregistration on right ventricle visualization; increasing the double inversion recovery (DIR) slice thickness beyond 300% had no effect on image quality (p=0.2). 35 patient studies were prospectively evaluated with inversion times (TIs) corresponding to the mid-diastolic rest period and end-systole based on visual analysis of a four chamber cine. When TIs were chosen to be within the patients’ RV rest period, mean image quality score was significantly improved (2.3 vs. 1.86, p<0.001) and the number of clinically diagnostic images increased from 32% to 46%. Black blood TSE imaging of the RV free wall is highly sensitive to cardiac motion. Image quality can be improved by choosing TIs concordant with the rest period of the patient’s RV that may occur at mid-diastole or end-systole.
PMCID: PMC4301616  PMID: 19165884
cardiac MRI; black blood; turbo spin echo; right ventricle
12.  Cardiac Mass and Function Decrease in Bronchiolitis Obliterans Syndrome after Lung Transplantation: Relationship to Physical Activity? 
PLoS ONE  2014;9(12):e114001.
There is a need to expand knowledge on cardio-pulmonary pathophysiology of bronchiolitis obliterans syndrome (BOS) following lung transplantation (LTx).
The purpose of this study was to assess MRI-derived biventricular cardiac mass and function parameters as well as flow hemodynamics in patients with and without BOS after LTx.
Using 1.5T cardiac MRI, measurements of myocardial structure and function as well as measurements of flow in the main pulmonary artery and ascending aorta were performed in 56 lung transplant patients. The patients were dichotomized into two gender matched groups of comparable age range: one with BOS (BOS stages 1–3) and one without BOS (BOS 0/0p).
Measurements and Main Results
Significantly lower biventricular cardiac mass, right and left ventricular end-diastolic volume, biventricular stroke volume, flow hemodynamics and significant higher heart rate but preserved cardiac output were observed in patients with BOS 1–3 compared to the BOS 0/0p group (p<0.05). In a stepwise logistic regression analysis global cardiac mass (p = 0.046) and days after LTx (p = 0.0001) remained independent parameters to predict BOS. In a second model an indicator for the physical fitness level - walking number of stairs - was added to the logistic regression model. In this second model, time after LTx (p = 0.005) and physical fitness (p = 0.01) remained independent predictors for BOS.
The observed changes in biventricular cardiac mass and function as well as changes in hemodynamic flow parameters in the pulmonary trunk and ascending aorta are likely attributed to the physical fitness level of patients after lung transplantation, which in turn is strongly related to lung function.
PMCID: PMC4257554  PMID: 25479016
13.  Endothelial Microparticles in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease Study 
Rationale: Basic research implicates alveolar endothelial cell apoptosis in the pathogenesis of chronic obstructive pulmonary disease (COPD) and emphysema. However, information on endothelial microparticles (EMPs) in mild COPD and emphysema is lacking.
Objectives: We hypothesized that levels of CD31+ EMPs phenotypic for endothelial cell apoptosis would be elevated in COPD and associated with percent emphysema on computed tomography (CT). Associations with pulmonary microvascular blood flow (PMBF), diffusing capacity, and hyperinflation were also examined.
Methods: The Multi-Ethnic Study of Atherosclerosis COPD Study recruited participants with COPD and control subjects age 50–79 years with greater than or equal to 10 pack-years without clinical cardiovascular disease. CD31+ EMPs were measured using flow cytometry in 180 participants who also underwent CTs and spirometry. CD62E+ EMPs phenotypic for endothelial cell activation were also measured. COPD was defined by standard criteria. Percent emphysema was defined as regions less than −950 Hounsfield units on full-lung scans. PMBF was assessed on gadolinium-enhanced magnetic resonance imaging. Hyperinflation was defined as residual volume/total lung capacity. Linear regression was used to adjust for potential confounding factors.
Measurements and Main Results: CD31+ EMPs were elevated in COPD compared with control subjects (P = 0.03) and were notably increased in mild COPD (P = 0.03). CD31+ EMPs were positively related to percent emphysema (P = 0.045) and were inversely associated with PMBF (P = 0.047) and diffusing capacity (P = 0.01). In contrast, CD62E+ EMPs were elevated in severe COPD (P = 0.003) and hyperinflation (P = 0.001).
Conclusions: CD31+ EMPs, suggestive of endothelial cell apoptosis, were elevated in mild COPD and emphysema. In contrast, CD62E+ EMPs indicative of endothelial activation were elevated in severe COPD and hyperinflation.
PMCID: PMC3735242  PMID: 23600492
chronic obstructive pulmonary disease; emphysema; antigens, CD31; endothelium; pulmonary disease
14.  Quantitative and Semi-quantitative Measures of Regional Pulmonary Parenchymal Perfusion by Magnetic Resonance Imaging and their Relationships to Global Lung Perfusion and Lung Diffusing Capacity – The MESA COPD Study 
Investigative radiology  2013;48(4):223-230.
To evaluate quantitative and semi-quantitative measures of regional pulmonary parenchymal perfusion in patients with COPD in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO).
Materials and Methods
One hundred and forty three participants in the MESA COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion MRI at 1.5 T. Pulmonary blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semi-quantitative parameters for regional lung perfusion were calculated from signal-intensity time curves in the lung parenchyma. Intra- and inter-observer coefficients of variation (CV) and correlations between quantitative and semi-quantitative MRI parameters and with GLP and DLCO were determined.
Quantitative and semi-quantitative parameters of pulmonary parenchymal perfusion were reproducible with CVs for all <10%. Furthermore, these MRI parameters were correlated with GLP and DLCO and there was good agreement between PBF and GLP. Quantitative and semi-quantitative MRI parameters were closely correlated (e.g., r=0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements.
Regional pulmonary parenchymal perfusion can reliably be quantified from dynamic contrast-enhanced MRI. MRI-derived quantitative and semi-quantitative perfusion measures correlate with GLP and DLCO.
PMCID: PMC3952075  PMID: 23385398
Pulmonary perfusion; chronic obstructive pulmonary disease (COPD); dynamic contrast-enhanced MRI; quantitative perfusion maps; diffusing lung capacity
15.  Cardiac MRI evaluation of hypertrophic cardiomyopathy: Left ventricular outflow tract/aortic valve diameter ratio predicts severity of LVOT obstruction 
To evaluate if left ventricular outflow tract /aortic valve (LVOT/AO) diameter ratio measured by cardiac magnetic resonance (CMR) imaging is an accurate marker for LVOT obstruction in patients with hypertrophic cardiomyopathy (HCM) compared to Doppler echocardiography.
92 patients with hypertrophic cardiomyopathy were divided into 3 groups based on their resting echocardiographic LVOT pressure gradient (PG): <30mmHg at rest (non-obstructive, n=31), <30 mmHg at rest, >30mmHg after provocation (latent, n=29) and >30mmHg at rest (obstructive, n=32).The end-systolic dimension of the LVOT on 3-chamber steady state free precession (SSFP) CMR was divided by the end diastolic aortic valve diameter to calculate the LVOT/AO diameter ratio.
There were significant differences in the LVOT/AO diameter ratio among the 3 subgroups (non-obstructive 0.60±0.13, latent 0.41±0.16, obstructive 0.24±0.09, p<0.001). There was a strong linear inverse correlation between the LVOT/AO diameter ratio and the log of the LVOT pressure gradient (r=−0.84, p<0.001). For detection of a resting gradient >30mmHg, the LVOT/AO diameter ratio the area under the ROC curve was 0.91 (95% CI 0.85-0.97). For detection of a resting and/or provoked gradient >30mmHg, the LVOT/AO diameter ratio area under the ROC curve was 0.90 (95% CI 0.84-0.96).
The LVOT/AO diameter ratio is an accurate, reproducible, noninvasive and easy to use CMR marker to assess LVOT pressure gradients in patients with HCM.
PMCID: PMC3411926  PMID: 22549972
hypertrophic cardiomyopathy; left ventricular outflow tract; MRI
16.  Pulmonary Function is Associated with Distal Aortic Calcium, not Proximal Aortic Distensibility. MESA Lung Study 
COPD  2011;8(2):71-78.
Forced expiratory volume in one second strongly predicts mortality from cardiovascular disease. FEV1 has been associated with aortic stiffness a strong independent predictor of cardiovascular mortality. However, the anatomical site and possible mechanisms linking aortic stiffness and lung function are unknown. We therefore examined if FEV1 and CT percent emphysema were associated with calcification of the abdominal aorta or reduced distensibility of the proximal thoracic aorta.
The Multi-Ethnic Study of Atherosclerosis (MESA) measured aortic calcification on cardiac and abdominal CT scans and proximal aortic distensibility using magnetic resonance among participants aged 45–84 years without clinical cardiovascular disease. Spirometry was measured following ATS/ERS guidelines and percent emphysema was measured in the lung fields of cardiac CT scans. Multivariate analyses adjusted for age, sex, race/ethnicity and cardiovascular risk factors.
Of 1,917 participants with aortic distensibility measures, 13% were current and 38% were former smokers. Eighteen percent had airflow limitation without asthma. FEV1 was associated with the extent of distal aortic calcification (0.76; 95%CI 0.60–0.97, p=0.02) but not proximal aortic calcification or proximal aortic distensibility (−0.04 mmHg−1; 95%CI −0.16–0.09 mmHg−1, p=0.60). Percent emphysema was associated with neither measure.
FEV1 was associated with severity of distal aortic calcification where it was present independently of smoking and other cardiovascular risk factors but not with distensibility or calcification of the proximal aorta.
PMCID: PMC3629728  PMID: 21495835
forced expiratory volume; pulmonary emphysema; aorta; calcification; compliance
17.  Semiquantified Noncalcified Coronary Plaque in Systemic Lupus Erythematosus 
The Journal of rheumatology  2012;39(12):2286-2293.
A major cause of morbidity and mortality in systemic lupus erythematosus (SLE) is accelerated coronary atherosclerosis. New technology (computed tomographic angiography) can measure noncalcified coronary plaque (NCP), which is more prone to rupture. We report on a study of semiquantified NCP in SLE.
Patients with SLE (n = 147) with no history of cardiovascular disease underwent 64-slice coronary multidetector computed tomography (MDCT). The MDCT scans were evaluated quantitatively by a radiologist, using dedicated software.
The group of 147 patients with SLE was 86% female, 70% white, 29% African American, and 3% other ethnicity. The mean age was 51 years. In our univariate analysis, the major traditional cardiovascular risk factors associated with noncalcified plaque were age (p = 0.007), obesity (p = 0.03; measured as body mass index), homocysteine (p = 0.05), and hypertension (p = 0.04). Anticardiolipin (p = 0.026; but not lupus anticoagulant) and anti-dsDNA (p = 0.03) were associated with higher noncalcified plaque. Prednisone and hydroxychloroquine therapy had no effect, but methotrexate (MTX) use was associated with higher noncalcified plaque (p = 0.0001). In the best multivariate model, age, current MTX use, and history of anti-dsDNA remained significant.
Our results suggest that serologic SLE (anti-dsDNA) and traditional cardiovascular risk factors contribute to semiquantified noncalcified plaque in SLE. The association with MTX is not understood, but should be replicated in larger studies and in multiple centers.
PMCID: PMC3605898  PMID: 23027889
18.  Glycemic Associations With Endothelial Function and Biomarkers Among 5 Ethnic Groups: The Multi‐Ethnic Study of Atherosclerosis and the Mediators of Atherosclerosis in South Asians Living in America Studies 
The association of prediabetic states with endothelial dysfunction measured by flow‐mediated dilation (FMD) or endothelial biomarker levels remains controversial. We examined data from 5 ethnic groups to determine the association between glucose categories and FMD or endothelial biomarkers. We determined whether these associations vary by ethnic group or body mass index.
Methods and Results
We used data from 3516 participants from 5 race/ethnic groups with brachial FMD, endothelial biomarkers, and glucose category (normal, impaired fasting glucose [IFG], and diabetes) measures. There were significant ethnic differences in FMD, biomarker levels, and the prevalence of IFG and diabetes. However, all 5 ethnic groups showed similar patterns of higher FMD for the IFG group compared with the normal glucose and diabetes groups, which was most significant among whites and Asian Indians. Associations between glucose categories and endothelial biomarkers were more uniform, with the IFG and diabetes groups having higher biomarker levels than the normal glucose group. These associations did not change with further adjustment for fasting insulin levels. Whites with normal BMI had higher FMD values with higher glucose levels, but those with BMI in the overweight or obese categories had the inverse association (P for interaction=0.01).
The discordance of IFG being associated with higher FMD but more abnormal endothelial biomarker levels is a novel finding. This higher FMD for the IFG group was most notable in whites of normal BMI. The higher FMD among those with impaired fasting glucose may reflect differences in insulin signaling pathways between the endothelium and skeletal muscle.
PMCID: PMC3603246  PMID: 23525433
biomarkers; diabetes; endothelium; ethnicity; insulin resistance
20.  Increased Right Ventricular Septomarginal Trabeculation Mass is a Novel Marker for Pulmonary Hypertension: Comparison with Ventricular Mass Index and Right Ventricular Mass 
Investigative Radiology  2011;46(9):567-575.
To prospectively evaluate the cardiac magnetic resonance (MR) imaging-derived measurement of right ventricular (RV) septomarginal trabeculation (SMT) mass as a noninvasive marker for pulmonary hypertension (PH), compared to the ventricular mass index (VMI= RV mass/left ventricular mass) and RV mass.
Materials and Methods
Forty-nine patients (60 years ±12; 35 female) with suspected PH underwent cardiac MR and right heart catheterization (RHC) on the same day. Eighteen normal volunteers were also included. The performance of SMT mass, VMI and RV mass measurement, with regard to PH detection, was analyzed using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to assess the association between SMT mass, RV mass, VMI, and PH.
The area under the ROC curve for SMT mass/BSA, VMI and RV mass/BSA in diagnosing the presence or absence of PH was 0.88, 0.87 and 0.73 respectively. In multivariable models, both SMT mass/body surface area (BSA) (p=0.005, odds ratio 8.6) and VMI (p=0. 012, odds ratio 1.1) were found to be significant, independent predictors of PH.
Compared to RHC measurement, SMT mass and VMI are reproducible and non-invasive MR imaging markers for the diagnosis of PH.
PMCID: PMC3330237  PMID: 21577127
cardiac MRI; pulmonary hypertension; ventricular mass index; right ventricular septomarginal trabeculation
21.  In Hypertrophic Cardiomyopathy Reduction of Relative Resting Myocardial Blood Flow Is Related to Late Enhancement, T2-Signal and LV Wall Thickness 
PLoS ONE  2012;7(7):e41974.
To quantify resting myocardial blood flow (MBF) in the left ventricular (LV) wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE), T2-signal abnormalities (dark and bright signal), LV outflow tract obstruction and age.
Materials and Methods
Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2 bright signal), LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher’s exact test.
804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001), extent of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001), T2 dark signal (p<0.001) and age (p = 0.032) correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (p = 0.901). Multiple linear regression analysis revealed that LGE (p<0.001), edema (p = 0.026) and T2 dark signal (p = 0.019) were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion.
In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of disease.
PMCID: PMC3408401  PMID: 22860042
23.  Myocardial Delayed Enhancement in Pulmonary Hypertension: Pulmonary Hemodynamics, Right Ventricular Function, and Remodeling 
The purpose of this study was to assess predictors of MRI-identified septal delayed enhancement mass at the right ventricular (RV) insertion sites in relation to RV remodeling, altered regional mechanics, and pulmonary hemodynamics in patients with suspected pulmonary hypertension (PH).
Thirty-eight patients with suspected PH were evaluated with right heart catheterization and cardiac MRI. Ten age- and sex-matched healthy volunteers acted as controls for MRI comparison. Septal delayed enhancement mass was quantified at the RV insertions. Systolic septal eccentricity index, global RV function, and remodeling indexes were quantified with cine images. Peak systolic circumferential and longitudinal strain at the sites corresponding to delayed enhancement were measured with conventional tagging and fast strain-encoded MRI acquisition, respectively.
PH was diagnosed in 32 patients. Delayed enhancement was found in 31 of 32 patients with PH and in one of six patients in whom PH was suspected but proved absent (p = 0.001). No delayed enhancement was found in controls. Delayed enhancement mass correlated with pulmonary hemodynamics, reduced RV function, increased RV remodeling indexes, and reduced eccentricity index. Multiple linear regression analysis showed RV mass index was an independent predictor of total delayed enhancement mass (p = 0.017). Regional analysis showed delayed enhancement mass was associated with reduced longitudinal strain at the basal anterior septal insertion (r = 0.6, p < 0.01). Regression analysis showed that basal longitudinal strain remained an independent predictor of delayed enhancement mass at the basal anterior septal insertion (p = 0.02).
In PH, total delayed enhancement burden at the RV septal insertions is predicted by RV remodeling in response to increased afterload. Local fibrosis mass at the anterior septal insertion is associated with reduced regional longitudinal contractility at the base.
PMCID: PMC3034131  PMID: 21178051
delayed enhancement; fast strain-encoded imaging; MRI; pulmonary hypertension; tagging
24.  Bisphosphonate use and the Prevalence of Valvular and Vascular Calcification in Women: The Multi-Ethnic Study of Atherosclerosis 
To determine whether nitrogen-containing bisphosphonate (NCBP) therapy is associated with the prevalence of cardiovascular calcification.
Cardiovascular calcification correlates with atherosclerotic disease burden. Experimental data suggest that NCBP may limit cardiovascular calcification, which has implications for disease prevention.
The relationship of NCBP use to the prevalence of aortic valve, aortic valve ring, mitral annulus, thoracic aorta, and coronary artery calcification (AVC, AVRC, MAC, TAC, and CAC, respectively) detected by computed tomography was assessed in 3,636 women within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling.
Analyses were age-stratified because of a significant interaction between age and NCBP use (interaction p-values: AVC p<0.0001; AVRC p<0.0001; MAC p=0.002; TAC p<0.0001; CAC p=0.046). After adjusting for age, body mass index, demographics, diabetes, smoking, blood pressure, cholesterol levels, and statin, hormone replacement, and renin-angiotensin inhibitor therapy, NCBP use was associated with a lower prevalence of cardiovascular calcification in women ≥65 years old (prevalence ratio [95% confidence interval]: AVC 0.68 [0.41, 1.13]; AVRC 0.65 [0.51, 0.84]; MAC 0.54 [0.33, 0.93]; TAC 0.69 [0.54, 0.88]; CAC 0.89 [0.78, 1.02]), whereas calcification was more prevalent in NCBP users among the 2,181 women <65 years old (AVC 4.00 [2.33, 6.89]; AVRC 1.92 [1.42, 2.61]; MAC 2.35 [1.12, 4.84]; TAC 2.17 [1.49, 3.15]; CAC 1.23 [0.97, 1.57]).
Among women in the diverse MESA cohort, NCBPs were associated with decreased prevalence of cardiovascular calcification in older subjects, but more prevalent cardiovascular calcification in younger ones. Further study is warranted to clarify these age-dependent NCBP effects.
PMCID: PMC3004769  PMID: 21070928
bisphosphonate; calcification; coronary artery; valve; vascular
25.  Fibrinogen and Left Ventricular Myocardial Systolic Function: The Multi-Ethnic Study of Atherosclerosis 
American heart journal  2010;160(3):479-486.
Increasing evidence suggests that elevated plasma fibrinogen is associated with incident heart failure. However, the underlying pathophysiological mechanisms have not been well elucidated.
We examined the relationship between plasma fibrinogen level and peak systolic mid-wall circumferential strain(Ecc) at the base, mid-cavity and apex of the left ventricle measured by magnetic resonance imaging myocardial tagging in 1,096 participants without clinical cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis(MESA).
After adjustment for demographics, established risk factors and body-mass-index, elevated fibrinogen was independently associated with reductions in absolute Ecc indicative of impaired systolic function in all regions(all P=0.015). The relationships were consistently significant upon further adjustment for measures of atherosclerosis(all P≤0.024), and were modestly attenuated with regional heterogeneity after additional adjustment for other inflammatory biomarker and N-terminal pro-brain-natriuretic peptide. In this fully-adjusted model, every one-standard deviation(74mg/dL) increment in plasma fibrinogen was independently associated with a reduction in left ventricular absolute Ecc of 0.29%(95%CI=0.03%–0.59%, P=0.048) at the base, 0.22%(95%CI=0.006%–0.43%, P=0.044) at mid-cavity, 0.20%(95%CI=−0.035%–0.43%, P=0.097) at the apex, and 0.24%(95%CI=0.05–0.43, P=0.015) overall.
Among asymptomatic individuals without clinical cardiovascular disease, elevated fibrinogen is independently associated with impaired myocardial systolic function. These findings support roles of inflammation, procoagulation and hyperviscosity underlying hyperfibrinogenemia in the pathogenesis of incipient myocardial dysfunction.
PMCID: PMC2937158  PMID: 20826256
epidemiology; heart failure; myocardial function; fibrinogen; hyperviscosity; hypercoagulability; magnetic resonance imaging

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