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1.  Beyond Coronary Stenosis: Coronary Computed Tomographic Angiography for the Assessment of Atherosclerotic Plaque Burden 
Coronary computed tomographic angiography (CCTA) is emerging as a key non-invasive method for assessing cardiovascular risk by measurement of coronary stenosis and coronary artery calcium (CAC). New advancements in CCTA technology have led to the ability to directly identify and quantify the so-called “vulnerable” plaques that have features of positive remodeling and low density components. In addition, CCTA presents a new opportunity for noninvasive measurement of total coronary plaque burden that has not previously been available. The use of CCTA needs also to be balanced by its risks and, in particular, the associated radiation exposure. We review current uses of CCTA, CCTA’s ability to measure plaque quantity and characteristics, and new developments in risk stratification and CCTA technology. CCTA represents a quickly developing field that will play a growing role in the non-invasive management of cardiovascular disease.
PMCID: PMC3601491  PMID: 23524381
Coronary Computed Tomographic Angiography; CT; Atherosclerosis; Plaque; Non-Calcified; Acute Coronary Syndrome; Vulnerable Plaque; Spotty Calcification; Coronary Artery Calcium; Reconstruction
2.  Left Ventricular Global Function Index By Magnetic Resonance Imaging- A Novel Marker for Assessment of Cardiac Performance for the Prediction Of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis 
Hypertension  2013;61(4):770-778.
LV function is generally assessed independent of structural remodeling and vice versa. The purpose of this study was to evaluate a novel LV global function index (LVGFI) that integrates LV structure with global function and to assess its predictive value for cardiovascular (CV) events throughout adult life in a multi-ethnic population of men and women without history of cardiovascular diseases at baseline. A total of 5004 participants in the Multi-Ethnic Study of Atherosclerosis underwent a cardiac magnetic resonance (CMR) study and were followed up for a median of 7.2 years. The LVGFI by CMR was defined by the ratio of stroke volume divided by LV total volume defined as the sum of mean LV cavity and myocardial volumes. Cox proportional hazard models were constructed to predict the end points of heart failure (HF), hard CV events and a combined endpoint of all CV events after adjustment for established risk factors, calcium score and biomarkers. A total of 579 (11.6%) incident events were observed during the follow-up period. In adjusted models, the end points of HF, hard CV events and all events were all significantly associated with LVGFI (HF, hazard ratio [HR]= 0.64, p<0.0001; hard CV events, HR=0.79, p=0.007; all events, HR=0.79, p<0.0001). LVGFI had a significant independent predictive value in the multivariable models for all CV event categories. The LVGFI was a powerful predictor of incident heart failure, hard CV events and a composite endpoint including all events in this multiethnic cohort.
PMCID: PMC3691067  PMID: 23424238
left ventricle; ejection fraction; heart failure; LV mass; LV global function index
3.  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
4.  The Relationship between Measures of Obesity and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis 
Obesity (Silver Spring, Md.)  2013;21(9):1915-1922.
To evaluate the strength of association of body mass index (BMI) and waist circumference (WC) with incident heart failure (HF), exploring our associations by ethnicity and age.
Design and Methods
We included 6,809 participants, aged 45–84 years, without clinical cardiovascular disease (2000–2002), from the Multi-Ethnic Study of Atherosclerosis. Cox-Proportional hazards models were used to examine associations of BMI and WC with incident HF. The predictive abilities of BMI and WC were compared using receiver operating characteristic curves.
Over a median follow-up of 7.6 years, there were 176 cases. BMI and WC were associated with incident HF in men [1.33 (1.10–1.61) and 1.38 (1.18–1.62) respectively] and women [1.70 (1.33–2.17) and 1.64 (1.29–2.08) respectively]. These associations became non-significant after adjusting for obesity-related conditions (hypertension, dysglycemia, hypercholesterolemia, left ventricular hypertrophy, kidney disease and inflammation). The associations of BMI and WC did not vary significantly by ethnicity or age-group, but were inverse in Hispanic men. The area under the curve for BMI and WC was 0.749 and 0.750, respectively, in men and 0.782 and 0.777, respectively, in women.
The association between obesity and incident HF is largely mediated by obesity-related conditions. BMI and WC have similar predictive abilities for incident HF.
PMCID: PMC3664654  PMID: 23441088
Obesity; heart failure; body mass index and waist circumference
5.  Associations among Lung Function, Arterial Elasticity and Circulating Endothelial and Inflammation Markers: the Multi-Ethnic Study of Atherosclerosis 
Hypertension  2013;61(2):542-548.
A parallel physiologic pathway for elastic changes is hypothesized for declines in arterial elasticity and lung function. Endothelial dysfunction and inflammation could potentially decrease elasticity of both vasculature and lung tissue. We examined biomarkers, large (LAE) and small (SAE) arterial elasticity, and forced vital capacity (FVC) in a period cross-sectional design in the Multi-Ethnic Study of Atherosclerosis, which recruited 1,823 women and 1,803 men, age range 45–84 years, black, white, Hispanic, and Chinese, free of clinically recognized CVD. Radial artery tonometric pulse waveform registration was performed and LAE and SAE were derived from diastole. Spirometric data and markers of endothelial dysfunction and inflammation (soluble intracellular adhesion molecule-1, fibrinogen, hs-C-reactive protein, and interleukin-6) were obtained. Mean LAE was 13.7 ± 5.5 ml/mmHgx10 and SAE was 4.6 ± 2.6 ml/mmHgx100. Mean FVC was 3,192 ± 956.0 mL and FEV1 was 2,386 ± 734.5 mL. FVC was about 40 ± 5 mL higher per SD of SAE, stronger in men than women. The association was slightly weaker with LAE, with no sex interaction. After regression adjustment for demographic, anthropometric, and cardiovascular risk factors, the biomarkers tended to be related to reduced SAE and FVC, particularly in men. These biomarker associations suggest important CVD risk alterations that occur concurrently with lower arterial elasticity and lung function. The observed positive association of SAE with FVC and with FEV1 in middle-aged to older free-living people is consistent with the hypothesis of parallel physiologic pathways for elastic changes in the vasculature and in lung parenchymal tissue.
PMCID: PMC3586233  PMID: 23283358
arterial stiffness; endothelial markers; inflammatory markers; large and small artery elasticity; lung function; MESA Study
6.  Genome-Wide Association Study of Cardiac Structure and Systolic Function in African Americans: The Candidate Gene Association Resource (CARe) Study 
Using data from four community-based cohorts of African Americans (AA), we tested the association between genome-wide markers (SNPs) and cardiac phenotypes in the Candidate-gene Association REsource (CARe) study.
Methods and Results
Among 6,765 AA, we related age, sex, height and weight-adjusted residuals for nine cardiac phenotypes (assessed by echocardiogram or MRI) to 2.5 million SNPs genotyped using Genome-Wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within cohort genome-wide association analysis was conducted followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0 ×10−07). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested look-ups in one consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (p=1.43 × 10−07) for left ventricular mass (LVM); rs7213314 in WIPI1 (p=1.68 × 10−07) for LV internal diastolic diameter (LVIDD); rs1571099 in PPAPDC1A (p= 2.57 × 10−08) for interventricular septal wall thickness (IVST); and rs9530176 in KLF5 (p=4.02 × 10−07) for ejection fraction (EF). Associated variants were enriched in three signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry were confirmed in look-ups in EchoGEN.
In the largest GWAS of cardiac structure and function to date in AA, we identified 4 genetic loci related to LVM, IVST, LVIDD and EF that reached genome-wide significance. Replication results suggest that these loci may represent unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes.
PMCID: PMC3591479  PMID: 23275298
echocardiography; ethnic; genome-wide association studies; Left atrium genetics; left ventricular mass genetics
7.  Modified Look-Locker T1 Evaluation Using Bloch Simulations: Human and Phantom Validation 
Modified Look-Locker imaging is frequently used for T1 mapping of the myocardium. However, the specific effect of various MRI parameters (e.g., encoding scheme, modifications of flip angle, heart rate, T2, and inversion times) on the accuracy of T1 measurement has not been studied through Bloch simulations. In this work, modified Look-Locker imaging was characterized through a numerical solution for Bloch equations. MRI sequence parameters that may affect T1 accuracy were systematically varied in the simulation. For validation, phantoms were constructed with various T2 and T1 times and compared with Bloch equation simulations. Human volunteers were also evaluated with various pulse sequences parameters to assess the validity of the numerical simulations. There was close agreement between simulated T1 times and T1 times measured in phantoms and volunteers. Lower T2 times (i.e., <30 ms) resulted in errors greater than 5% for T1 determination. Increasing maximum inversion time value improved T1 accuracy particularly for precontrast myocardial T1. Balanced steady-state free precession k space centric encoding improved accuracy for short T1 times (post gadolinium), but linear encoding provided improved accuracy for precontrast T1 values. Lower flip angles are preferred if the signal-to-noise ratio is sufficiently high. Bloch simulations for modified Look-Locker imaging provide an accurate method to comprehensively quantify the effect of pulse sequence parameters on T1 accuracy. As an alternative to otherwise lengthy phantom studies or human studies, such simulations may be useful to optimize the modified Look-Locker imaging sequence and compare differences in T1-derived measurements from different scanners or institutions.
PMCID: PMC3826815  PMID: 22457268
MOLLI; T1 mapping; Bloch simulation
8.  Association Between Cardiovascular Autonomic Neuropathy and Left Ventricular Dysfunction 
The goal of these studies was to determine the association between cardiovascular autonomic neuropathy (CAN) and indices of left ventricle (LV) structure and function in patients with type 1 diabetes (T1DM) in the DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) study.
The pathophysiology of LV dysfunction in T1DM remains unclear, especially when the LV ejection fraction (EF) is preserved. Whether CAN is associated with LV dysfunction is unclear.
Indices of LV structure and function were obtained by cardiac magnetic resonance imaging (CMRI). CAN was assessed by cardiovascular reflex testing (R-R response to paced breathing, Valsalva ratio, and blood pressure response to standing). Analyses were performed in 966 DCCT/EDIC participants with valid CMRI and CAN data (mean age 51 years, 52% men, mean diabetes duration 29 years, and mean glycosylated hemoglobin 7.9%).
Systolic function (EF, end-systolic and end-diastolic volumes, stroke volumes) was not different in 371 subjects with CAN compared with 595 subjects without CAN. In multiple-adjusted analyses, participants with either abnormal R-R variation or a composite of abnormal R-R variation, abnormal Valsalva ratio, and postural blood pressure changes had significantly higher LV mass, mass-to-volume-ratio, and cardiac output compared with those with normal tests (p < 0.0001 for all). After further adjustment for traditional cardiovascular risk factors, subjects with abnormal R-R variation had higher LV mass and cardiac output compared with those with a normal R-R variation (p < 0.05).
In this large cohort of patients with T1DM, CAN is associated with increased LV mass and concentric remodeling as assessed by CMRI independent of age, sex, and other factors. (Diabetes Control and Complications Trial [DCCT];NCT00360815) (Epidemiology of Diabetes Interventions and Complications [EDIC]; NCT00360893)
PMCID: PMC3616477  PMID: 23265339
cardiovascular autonomic neuropathy; left ventricle hypertrophy; myocardial dysfunction; type 1 diabetes
9.  Von Willebrand Factor and the Right Ventricle (The MESA-Right Ventricle Study) 
The American journal of cardiology  2012;110(12):1846-1851.
Elevation in plasma activity of von Willebrand Factor (vWF) reflects endothelial dysfunction and predicts death in pulmonary arterial hypertension (PAH). Higher vWF activity is also associated with lower right ventricular (RV) ejection fraction in PAH. Little is known about the relationship between vWF and RV structure and function in adults without cardiovascular disease. In the current investigation, we included 1,976 participants with MRI assessment of RV structure and function and measurement of vWF activity from the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to estimate the associations between vWF activity and measures of RV structure and function after adjusting for demographics, anthropometrics, smoking, diabetes mellitus, hypertension and the corresponding left ventricular (LV) parameter. The average vWF activity was 140.7 ± 57.2%. Elevated vWF activity was independently associated with lower RV mass, RV end-diastolic volume and RV stroke volume in models with and without adjustment for the corresponding LV parameter (all p < 0.05). There was no association observed between vWF activity and RV ejection fraction. In conclusion, higher vWF activity is associated with lower RV mass, RV end-diastolic volume and RV stroke volume. These associations are independent of common cardiovascular risk factors and LV morphologic changes.
PMCID: PMC3696516  PMID: 22995970
Cardiovascular Imaging; Biomarkers; Pulmonary Hypertension; Right Ventricle
10.  A new twist on an old idea: a two‐dimensional speckle tracking assessment of cyclosporine as a therapeutic alternative for heart failure with preserved ejection fraction 
Physiological Reports  2013;1(7):e00174.
We recently reported that mitochondrial dysfunction, characterized by increased mitochondrial permeability transition (MPT), was present in a translational swine model of heart failure with preserved ejection fraction (HFpEF). Cyclophilin D is a key component of the MPT pore, therefore, the purpose of this study was to test the efficacy of a novel cyclosporine (CsA) dosing scheme as a therapeutic alternative for HFpEF. Computed tomography (CT), two‐dimensional speckle tracking two‐dimensional speckle tracking (2DST), and invasive hemodynamics were used to evaluate cardiac function. CT imaging showed 14 weeks of CsA treatment caused eccentric myocardial remodeling (contrasting concentric remodeling in untreated HF animals) and elevated systemic pressures. 2DST detected left ventricular (LV) mechanics associated with systolic and diastolic dysfunction prior to the onset of significantly increased LV end diastolic pressure including: (1) decreased systolic apical rotation rate, longitudinal displacement, and longitudinal/radial/circumferential strain; (2) decreased early diastolic untwisting and longitudinal strain rate; and (3) increased late diastolic radial/circumferential mitral strain rate. LV mechanics associated with systolic and diastolic impairment was enhanced to a greater extent than seen in untreated HF animals following CsA treatment. In conclusion, CsA treatment accelerated the development of heart failure, including dilatory LV remodeling and impaired systolic and diastolic mechanics. Although our findings do not support CsA as a viable therapy for HFpEF, 2DST was effective in differentiating between progressive gradations of developing HF and detecting diastolic impairment prior to the development of overt diastolic dysfunction.
We recently reported that mitochondrial dysfunction, characterized by increased mitochondrial permeability transition (MPT), was present in a translational swine model of heart failure with preserved ejection fraction (HFpEF). Cyclophilin D is a key component of the MPT pore, therefore, the purpose of this study was to test the efficacy of a novel cyclosporine (CsA) dosing scheme as a therapeutic alternative for HFpEF. CsA treatment accelerated the development of heart failure, including dilatory LV remodeling and impaired systolic and diastolic mechanics. Although our findings do not support CsA as a viable therapy for HFpEF, 2DST was effective in differentiating between progressive gradations of developing HF and detecting diastolic impairment prior to the development of overt diastolic dysfunction.
PMCID: PMC3970750
2D speckle tracking; CT; cyclosporine; diastolic heart failure; HFpEF
11.  Myocardial Structural Associations with Local Electrograms: A Study of Post-Infarct Ventricular Tachycardia Pathophysiology and Magnetic Resonance Based Non-Invasive Mapping 
The association of scar on late-gadolinium enhancement cardiac magnetic resonance (LGE-CMR) with local electrograms on electroanatomic mapping (EAM) has been investigated. We aimed to quantify these associations to gain insights regarding LGE-CMR image characteristics of tissues and critical sites that support post-infarct ventricular tachycardia (VT).
Methods and Results
LGE-CMR was performed in 23 patients with ischemic cardiomyopathy before VT ablation. Left ventricular wall thickness and post-infarct scar thickness were measured in each of 20 sectors per LGE-CMR short-axis plane. EAM points were retrospectively registered to the corresponding LGE-CMR images. Multivariable regression analysis, clustered by patient, revealed significant associations between left ventricular wall thickness, post infarct scar thickness, and intramural scar location on LGE-CMR, and local endocardial electrogram bipolar/unipolar voltage, duration, and deflections on EAM. Antero-posterior and septal/lateral scar localization was also associated with bipolar and unipolar voltage. Anti-arrhythmic drug use was associated with electrogram duration. Critical sites of post-infarct VT were associated with >25% scar transmurality and slow conduction sites with >40 msec stimulus-QRS time were associated with >75% scar transmurality.
Critical sites for maintenance of post-infarct VT are confined to areas with >25% scar transmurality. Our data provides insights into the structural substrates for delayed conduction and VT, and may reduce procedural time devoted to substrate mapping, overcome limitations of invasive mapping due to sampling density, and enhance magnetic resonance based ablation by feature extraction from complex images.
PMCID: PMC3581804  PMID: 23149263
ischemic heart disease; magnetic resonance imaging; mapping; ventricular tachycardia; late gadolinium enhancement
12.  Age, Gender and Hypertension-Related Remodeling Influences Left Ventricular Torsion Assessed by Tagged Cardiac Magnetic Resonance in Asymptomatic Individuals: The Multi-Ethnic Study of Atherosclerosis 
Circulation  2012;126(21):2481-2490.
The aim of the present study was to evaluate how torsion is influenced by left ventricular (LV) remodeling associated with age, gender and hypertension in a large community-based population.
Methods and Results
Myocardial shortening and torsion were assessed by tagged cardiac magnetic resonance (CMR) in 1478 participants without clinically apparent cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Torsion was defined as the difference between apical and basal rotation, divided by slice distance. In multivariable linear regression models, older age was associated with lower stroke volume (−3.6 ml/decade, p<0.001) and higher LV mass –to-volume ratio (0.03 g/ml/decade, p<0.001) along with lower circumferential shortening (−0.17%/decade, p<0.05). Torsion, however, was greater at older ages (0.14 °/decade, p<0.001) and in women (0.37°/cm vs. men, p<0.001). Hypertensive participants had higher LV mass and LV mass –to-volume ratio (15.5g and 0.07 g/ml, respectively, p<0.001 for both). Circumferential shortening was lower in hypertensive (−0.42%, p<0.01), whereas torsion was higher after adjustment for age and gender (0.17°/cm, p<0.05).
Older age is associated with lower LV volumes and greater relative wall thickness, and accompanied by lower circumferential myocardial shortening, whereas torsion is greater with older age. Hypertensive individuals have greater LV volumes and relative wall thickness and lower circumferential shortening. Torsion, however, is greater in hypertension independent of age and gender. Torsion may therefore represent a compensatory mechanism to maintain an adequate stroke volume and cardiac output in the face of progressively reduced LV volumes and myocardial shortening associated with hypertension and aging.
PMCID: PMC3558706  PMID: 23147172
Torsion; Hypertension; Age; remodeling; Cardiac Magnetic Resonance
13.  Relationship between Carotid Intima-Media Thickness and Left Ventricular Mass in Type 1 Diabetes: results from the Epidemiology of Diabetes Interventions and Complications (EDIC) Study 
The American journal of cardiology  2012;110(10):1534-1540.
Type 1 diabetes mellitus is associated with early atherosclerosis and enhanced cardiovascular mortality. The relationship between carotid IMT (cIMT), a marker of subclinical atherosclerosis and left ventricular (LV) mass, an independent predictor of cardiovascular morbidity has not been previously studied in type 1 diabetics.
The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter observational study designed to follow up the Diabetes Control and Complications Trial (DCCT) cohort. LV mass was measured with cardiac MRI at EDIC year 15 and common cIMT was assessed using B-mode ultrasound at EDIC year 12. Multivariable linear regression models were used to assess the relationship between cIMT at year 12 and LV mass at year 15.
A total of 889 participants had both cardiac MRI and cIMT measures available for these analyses. At EDIC year 15, the mean age of the participants was 49 (±7) years; mean diabetes duration was 28 (±5) years and 52% were males. Spearman correlation coefficient (r) between LV mass and cIMT was 0.33 (p<0.0001). After adjusting for basic covariates (machine, reader, age and gender), a significant association between LV mass and cIMT (estimate 2.0 g/m2 per 0.1 mm cIMT increment, p < 0.0001) was observed. This association was diminished by the addition of systolic blood pressure in particular 1.15 g/m2 per 0.1 mm cIMT increment, p<0.0001) and to a lessor extent other cardiovascular disease (CVD) risk factors. The relationship observed between LV mass and cIMT was stronger (HOW MUCH) in patients with shorter diabetes duration.
In a well characterized population with type 1 diabetes, cIMT was an independent predictor of higher LV mass. These findings suggest a common pathway, possibly mediated by blood pressure dependent mechanisms, for vascular and myocardial structural change in T1DM.
PMCID: PMC3488435  PMID: 22884107
14.  MR Proton Spectroscopy for Myocardial Lipid Deposition Quantification: a Quantitative Comparison between 1.5-T and 3-T 
To evaluate the 3-T magnetic resonance spectroscopy (MRS) derived myocardial fat-signal fractions in comparison to those from 1.5-T MRS.
Material and Methods
We conducted phantom, ex-vivo and in-vivo myocardial specimen evaluations at both 1.5-T and 3-T using 1H-MRS. A phantom with nine fat-water emulsions was constructed to assess the accuracy of the spectroscopy measurements. Ex-vivo spectroscopy data were acquired in 70 segments from 21 autopsy heart slices. In-vivo spectroscopy data were acquired in the inter-ventricular septum from 22 human volunteers.
Phantom experiments demonstrated that 1.5-T and 3-T measurements were highly correlated with the reference values (r= 0.78, p =<0.05). The ex-vivo and in-vivo experiments demonstrated an increase in signal-to-noise ratio (SNR) of 45 ± 73 % and 76 ± 72 % at 3-T compared to 1.5-T (p<0.05). The mean fat-signal fraction was similar at 3-T and 1.5-T (1.11±1.18 vs. 1.00±1.09, respectively, p=NS) in ex-vivo studies but were significantly different in the in-vivo studies (2.47±1.46 vs. 1.56±1.34, p<0.05). The fat-signal fractions from 3-T and 1.5-T correlated fairly well in all experiments.
3-T MRS has significantly greater SNR and could potentially be more accurate as compared to 1.5-T for quantification of myocardial fat fraction in in-vivo studies.
PMCID: PMC3482140  PMID: 22826193
myocardial fat; proton spectroscopy; fat fraction
15.  Association of QRS duration with left ventricular structure and function and risk of heart failure in middle-aged and older adults: the Multi-Ethnic Study of Atherosclerosis (MESA) 
European Journal of Heart Failure  2012;14(11):1285-1292.
Prolonged QRS duration (QRSd) on the electrocardiogram (ECG) has been associated with cardiac structural and functional abnormalities by echocardiography and an increased risk of heart failure (HF). Data are sparse on these relationships in middle-aged and elderly individuals free of baseline cardiovascular disease with respect to cardiac magnetic resonance imaging (MRI). We sought to determine whether QRSd is associated with incident HF and measures of cardiac structure and function by cardiac MRI.
Methods and results
We analysed baseline ECGs in the Multi-Ethnic Study of Atherosclerosis (MESA) to determine whether QRSd >100 ms was associated with incident HF. We adjusted for demographic and clinical risk factors, as well as MRI measures of left ventricular (LV) structure and function. Among 4591 eligible participants (51% women; 39% white; mean age 61 years), 75 developed incident HF over a mean follow-up of 7.1 years. QRSd >100 ms was significantly associated with MRI measures of cardiac structure and function, as well as incident HF, even after adjustment for demographic covariates [hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.29–3.42; P = 0.003] and clinical risk factors (HR 1.86, 95% CI 1.14–3.03; P = 0.01). With further adjustment for individual LV structural measures, findings were attenuated to non-significance. Separate adjustment for LV functional measures yielded only mild attenuation.
In middle-aged and older adults without cardiovascular disease, a QRSd >100 ms was significantly associated with incident HF. After adjustment for LV structural measures, the association was attenuated to non-significance, suggesting that prolonged QRSd is potentially a useful marker of LV structure that may predispose to HF risk.
PMCID: PMC3530347  PMID: 22791081
Electrocardiogram; Heart failure; Magnetic resonance imaging; QRS duration
16.  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
17.  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
18.  Atlas-based analysis of cardiac shape and function: correction of regional shape bias due to imaging protocol for population studies 
Cardiovascular imaging studies generate a wealth of data which is typically used only for individual study endpoints. By pooling data from multiple sources, quantitative comparisons can be made of regional wall motion abnormalities between different cohorts, enabling reuse of valuable data. Atlas-based analysis provides precise quantification of shape and motion differences between disease groups and normal subjects. However, subtle shape differences may arise due to differences in imaging protocol between studies.
A mathematical model describing regional wall motion and shape was used to establish a coordinate system registered to the cardiac anatomy. The atlas was applied to data contributed to the Cardiac Atlas Project from two independent studies which used different imaging protocols: steady state free precession (SSFP) and gradient recalled echo (GRE) cardiovascular magnetic resonance (CMR). Shape bias due to imaging protocol was corrected using an atlas-based transformation which was generated from a set of 46 volunteers who were imaged with both protocols.
Shape bias between GRE and SSFP was regionally variable, and was effectively removed using the atlas-based transformation. Global mass and volume bias was also corrected by this method. Regional shape differences between cohorts were more statistically significant after removing regional artifacts due to imaging protocol bias.
Bias arising from imaging protocol can be both global and regional in nature, and is effectively corrected using an atlas-based transformation, enabling direct comparison of regional wall motion abnormalities between cohorts acquired in separate studies.
PMCID: PMC3848808  PMID: 24033990
Cardiovascular magnetic resonance; Atlas; Bias correction
19.  Hypertrophic cardiomyopathy: refining the lens of cardiac magnetic resonance to evaluate late gadolinium enhancement 
PMCID: PMC3432242  PMID: 22935465
Hypertrophic cardiomyopathy; Cardiac Magnetic resonance; Late gadolinium enhancement; myocardial fibrosis
20.  Partition coefficients for gadolinium chelates in the normal myocardium: Comparison of Gadopentetate dimeglumine and Gadobenate dimeglumine 
To evaluate the influence of contrast agents with different relaxivity on the partition coefficient (λ) and timing of equilibration by using a Modified Look-Locker Inversion Recovery (MOLLI) sequence in cardiac MRI.
Materials and Methods
MOLLI was acquired in 20 healthy subjects (1.5T) at mid-ventricular short axis pre contrast and 5, 10, 20, 25, and 30 min after administration of a bolus of 0.15mmol/kg Gadobenate dimeglumine (Gd-BOPTA) (n=10) or Gadopentetate dimeglumine (Gd-DTPA) (n=10). T1 times were measured in myocardium and blood pool. λ was approximated by ΔR1myocardium /ΔR1blood. Values for Gd-BOPTA and Gd-DTPA were compared. Inter-observer agreement was evaluated (intraclass correlation coefficient [ICC]).
T1 times of myocardium and blood pool (p<0.001) and λ (0.42±0.03 and 0.47±0.04, respectively, p<0.001; excluding 5 min for Gd-BOPTA) were significantly lower for Gd-BOPTA than Gd-DTPA. λ(Gd-DTPA) showed no significant variation between 5 and 30min. λ(Gd-BOPTA) values were significantly lower at 5min compared to other times (0.38 vs. 0.42; p<0.05). Inter-observer agreement for λ values was excellent with Gd-BOPTA (ICC=0.818) and good for Gd-DTPA (ICC=0.631).
λ(Gd-BOPTA) values are significantly lower compared to λ(Gd-DTPA) at the same administered dose. Using Gd-BOPTA, the equilibrium between myocardium and blood pool is not achieved at 5min post contrast.
PMCID: PMC3396792  PMID: 22488770
T1 mapping; Modified Look-Locker Inversion Recovery; partition coefficient; Gadopentetate dimeglumine; Gadobenate dimeglumine
21.  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
22.  A Framework of Whole Heart Extracellular Volume Fraction Estimation for Low Dose Cardiac CT Images 
Cardiac CT (CCT) is widely available and has been validated for detection of focal myocardial scar using delayed enhancement technique. CCT however has not been previously evaluated for quantification of diffuse myocardial fibrosis. In our investigation, we sought to evaluate the potential of low dose CCT for the measurement of myocardial whole heart extracellular volume (ECV) fraction. ECV is altered in conditions of increased myocardial fibrosis. A framework consisting of three main steps was proposed for CCT whole heart ECV estimation. First, a shape constrained graph cut (GC) method was proposed for myocardium and blood pool segmentation on post-contrast image. Second, the symmetric Demons deformable registration method was applied to register pre-contrast to post-contrast images. So the correspondences between the voxels from pre-contrast to post-contrast images were established. Finally, the whole heart ECV value was computed. The proposed method was tested on 20 clinical low dose CCT datasets with pre-contrast and post-contrast images. The preliminary results demonstrated the feasibility and efficiency of the proposed method.
PMCID: PMC3491075  PMID: 22711778
Cardiac CT; Myocardium Segmentation; Registration; Extracellular Volume Fraction
23.  High Sensitivity C-Reactive Protein as an Independent Predictor of Progressive Myocardial Functional Deterioration: The Multi-Ethnic Study of Atherosclerosis 
American heart journal  2012;164(2):251-258.
Systemic inflammation has been linked to the development of heart failure in population studies including MESA (Multi-Ethnic Study of Atherosclerosis) but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal MRI follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure.
Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac MRI both at baseline and at five-year follow-up were analyzed. Left ventricular (LV) midwall and mid-slice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Ecc change was calculated as the difference between baseline and follow-up Ecc.
During the follow-up period, participants (n=785) with elevated CRP experienced a decrease in strain, independent of age, gender and ethnicity (B=0.081; ΔEcc change per 1mg/L CRP change, 95% CI 0.036–0.126, p<0.001, Model 1), and additionally beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication and glomerular filtration rate (B=0.099, 0.052–0.145, p<0.001, Model 2). The relationship remained statistically significant after further adjustment for LV mass, coronary calcium score and interim clinical coronary events (B=0.098, 0.049–0.147, p<0.001, Model 3).
Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease.
PMCID: PMC3417227  PMID: 22877812
inflammation; myocardial function; magnetic resonance imaging
24.  Associations of Left Ventricular Hypertrophy with Prevalent and Incident Valve Calcification: The Multi-Ethnic Study of Atherosclerosis 
JACC. Cardiovascular imaging  2012;5(8):781-788.
We aim to evaluate the relationship between percent of predicted left ventricular mass (%PredLVM) and valve calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).
Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood.
MESA is a longitudinal cohort study of men and women aged 45-84 years without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling.
Prevalent AVC was observed in 630 and MAC in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, gender, body mass index, ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (OR=1.18 per SD increase in %PredLVM [95%CI 1.08 – 1.30]; p=0.0004) and MAC (OR=1.18 [95%CI 1.06 – 1.32]; p=0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95%CI 0.15 – 0.38]; p<0.0001) and MAC (risk difference = 0.20 [95%CI 0.03 – 0.37]; p=0.02). During follow-up (mean 2.4±0.9 years), 153 subjects (4%) developed AVC and 198 (5%) MAC. %PredLVM was associated with incident AVC (OR=1.24 [95%CI 1.04 – 1.47]; p=0.02) and MAC (OR=1.18 [1.01-1.40]; p=0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification.
Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders.
PMCID: PMC3426868  PMID: 22897991
aortic valve; calcification; left ventricular mass; mitral valve annulus
25.  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

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