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1.  The Yield of Serial Evaluation in At-Risk Family Members of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients 
Background
Incomplete penetrance and variable expressivity of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) complicate family screening.
Objectives
To determine the optimal approach to longitudinal follow-up regarding (1) screening interval and (2) testing strategy in at-risk relatives of ARVD/C patients.
Methods
We included 117 relatives (45% male, 33.3±16.3 years) from 64 families who were at risk of developing ARVD/C by virtue of their familial predisposition (72% mutation carriers [92% Plakophilin-2]; 28% first-degree relatives of a mutation-negative proband). Subjects were evaluated using ECG, Holter monitoring, signal-averaged ECG, and cardiac magnetic resonance (CMR). Disease progression was defined as the development of a new criterion by the 2010 Task Force criteria (TFC; not “Hamid criteria”) at last follow-up, which was absent at enrollment.
Results
At first evaluation, 43 (37%) subjects fulfilled ARVD/C diagnosis according to the 2010 TFC. Among the remaining 74 (63%) individuals, 11/37 (30%) subjects with complete reevaluation experienced disease progression during 4.1±2.3 years of follow-up. Electrical progression (n=10 [27%] including ECG 14%, Holter monitoring 11%, signal-averaged ECG 14%) was more frequently observed than structural progression (n=1 [3%] on CMR). All 5/37 (14%) patients with clinical ARVD/C diagnosis at last follow-up had an abnormal ECG or Holter monitor, and the only patient with an abnormal CMR already had an abnormal ECG at enrollment.
Conclusion
Over a mean follow-up of 4 years, our study showed that (1) almost one-third of at-risk relatives have electrical progression; (2) structural progression is rare; and (3) electrical abnormalities precede detectable structural changes. This information could be valuable in determining family screening protocols.
doi:10.1016/j.jacc.2014.04.044
PMCID: PMC4380221  PMID: 25034067
Cardiomyopathy; Progression; Electrocardiography; Magnetic Resonance Imaging; Screening
2.  Coronary Artery Plaque Volume and Obesity in Patients with Diabetes: The Factor-64 Study 
Radiology  2014;272(3):690-699.
The extent of coronary plaque in asymptomatic diabetic patients is related to body mass index and duration of diabetes.
Purpose
To determine the relationship between coronary plaque detected with coronary computed tomographic (CT) angiography and clinical parameters and cardiovascular risk factors in asymptomatic patients with diabetes.
Materials and Methods
All patients signed institutional review board–approved informed consent forms before enrollment. Two hundred twenty-four asymptomatic diabetic patients (121 men; mean patient age, 61.8 years; mean duration of diabetes, 10.4 years) underwent coronary CT angiography. Total coronary artery wall volume in all three vessels was measured by using semiautomated software. The coronary plaque volume index (PVI) was determined by dividing the wall volume by the coronary length. The relationship between the PVI and cardiovascular risk factors was determined with multivariable analysis.
Results
The mean PVI (±standard deviation) was 11.2 mm2 ± 2.7. The mean coronary artery calcium (CAC) score (determined with the Agatston method) was 382; 67% of total plaque was noncalcified. The PVI was related to age (standardized β = 0.32, P < .001), male sex (standardized β = 0.36, P < .001), body mass index (BMI) (standardized β = 0.26, P < .001), and duration of diabetes (standardized β = 0.14, P = .03). A greater percentage of soft plaque was present in younger individuals with a shorter disease duration (P = .02). The soft plaque percentage was directly related to BMI (P = .002). Patients with discrepancies between CAC score and PVI rank quartiles had a higher percentage of soft and fibrous plaque (18.7% ± 3.3 vs 17.4% ± 3.5 [P = .008] and 52.2% ± 7.2 vs 47.2% ± 8.8 [P < .0001], respectively).
Conclusion
In asymptomatic diabetic patients, BMI was the primary modifiable risk factor that was associated with total and soft coronary plaque as assessed with coronary CT angiography.
© RSNA, 2014
Clinical trial registration no. NCT00488033
Online supplemental material is available for this article.
doi:10.1148/radiol.14140611
PMCID: PMC4263628  PMID: 24754493
3.  Left atrial structure and functional quantitation using cardiovascular magnetic resonance and multimodality tissue tracking: validation and reproducibility assessment 
Background
Left atrium (LA) strain, volume and function are important markers of cardiovascular disease and myocardial impairment. We aimed to assess the accuracy of LA biplane volume and function measured by Multimodality Tissue Tracking (MTT). Also we assessed the inter-study reproducibility for cardiovascular magnetic resonance (CMR) derived LA volume and function parameters.
Methods
Thirty subjects (mean age: 71.3 ± 8.7, 87 % male) including twenty subjects with cardiovascular events and ten healthy subjects, with CMR were evaluated in the Multi-Ethnic Study of Atherosclerosis (MESA). LA volumes were computed by the modified biplane method from 2- and 4-chamber projections and the Simpson’s method from short-axis slices using both methods - manual and semi-automated delineation using MTT. LA total, active and passive ejection fractions were calculated. Pearson’s correlation and Bland-Altman analysis were used to compare the measurements. In a second sample of 25 subjects (age: 65.7 ± 7.1, 72 % males) inter study, intra and inter reader reliability analysis was performed. The intra-class correlation coefficient (ICC) was evaluated.
Results
Left atrial MTT structural and functional parameters were not different from manual delineation, yet image analysis was only half as time consuming on average with MTT. Maximal volume MTT was not different between the Simpson’s and Biplane methods, functional parameters, however were different. MTT allowed us to measure multiple LA parameters with good-excellent (ICC; 0.88– 0.98, p < 0.001) intra-and inter reader reproducibility and fair-good (ICC; 0.44–0.82, p < 0.05–0.001) inter study reproducibility.
Conclusions
MTT derived LA biplane volume and function is accurate and reproducible and is suited for use in longitudinal studies.
doi:10.1186/s12968-015-0152-y
PMCID: PMC4487838  PMID: 26126732
Left atrial function; Tissue tracking; Left atrial strain; Reproducibility; Cardiovascular magnetic resonance
4.  Age at Menopause and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis 
Menopause (New York, N.Y.)  2014;21(6):585-591.
Objective
To evaluate associations of early menopause (menopause occurring before 45 years of age) and age at menopause with incident heart failure (HF) in post-menopausal women. We also explored associations of early, and age at menopause with left ventricular (LV) measures of structure and function in post-menopausal women.
Methods
We included 2947 post-menopausal women, aged 45-84 years, without known cardiovascular disease (2000-2002), from the Multi-Ethnic study of Atherosclerosis. Cox-Proportional hazards models were used to examine associations of early, and age at menopause with incident HF. In 2123 post-menopausal women in whom cardiac magnetic resonance imaging was obtained at baseline, we explored associations of early, and age at menopause with LV measures using multivariable linear regression.
Results
Over a median follow-up of 8.5 years, we observed 71 HF events. There were no significant interactions with ethnicity for incident HF (Pinteraction>0.05). In adjusted analysis, early menopause was associated with increased risk of incident HF [1.66 (1.01-2.73)], while each year increase in age at menopause was associated with decreased risk of incident HF [0.96 (0.94-0.99)]. We observed significant interactions between early menopause and ethnicity for LV mass to volume ratio (LVMVR), Pinteraction=0.02. In Chinese-American women, early menopause was associated with higher LVMVR (+0.11, p=0.0002), while each year increase in age at menopause was associated with lower LVMVR (−0.004, p=0.04) at baseline.
Conclusion
An older menopausal age is independently associated with decreased risk of incident HF. Concentric LV remodelling, indicated by a higher LVMVR was present in Chinese-American women with early menopause at baseline.
doi:10.1097/GME.0000000000000138
PMCID: PMC4031284  PMID: 24423934
Menopause; Heart failure; Estrogen
5.  Association of CMR-Measured LA Function With Heart Failure Development 
JACC. Cardiovascular imaging  2014;7(6):570-579.
OBJECTIVES
The goal of this study was to assess the association between left atrial (LA) volume and function measured with feature-tracking cardiac magnetic resonance (CMR) and development of heart failure (HF) in asymptomatic individuals.
BACKGROUND
Whether alterations of LA structure and function precede or follow HF development remains incompletely understood. We hypothesized that significant alterations of LA deformation and architecture precede the development of HF in the general population.
METHODS
In a case-control study nested in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA volume and function assessed using CMR feature-tracking were compared between 112 participants with incident HF (mean age 68.4 ± 8.2 years; 66% men) and 224 age- and sex-matched controls (mean age 67.7 ± 8.9 years; 66% men). Participants were followed up for 8 years. All individuals were in normal sinus rhythm at the time of imaging, without any significant valvular abnormalities and free of clinical cardiovascular diseases.
RESULTS
Individuals with incident HF had greater maximal and minimal LA volume indexes (LAVImin) than control subjects (40 ± 13 mm3/m2 vs. 33 ± 10 mm3/m2 [p <0.001] for maximal LA index and 25 ± 11 mm3/m2 vs. 17 ± 7 mm3/m2 [p <0.001] for LAVImin). The HF case subjects also had smaller global peak longitudinal atrial strain (PLAS) (25 ± 11% vs. 38 ± 16%; p <0.001) and lower LA emptying fraction (40 ± 11% vs. 48 ± 9%; p <0.001) at baseline. After adjustment for traditional cardiovascular risk factors, left ventricular mass, and N-terminal pro–B-type natriuretic peptide, global PLAS (odds ratio: 0.36 per SD [95% confidence interval: 0.22 to 0.60]) and LAVImin (odds ratio: 1.65 per SD [95% confidence interval: 1.04 to 2.63]) were independently associated with incident HF.
CONCLUSIONS
Deteriorations in LA structure and function preceded development of HF. Lower global PLAS and higher LAVImin, measured using CMR feature-tracking, were independent markers of incident HF in a multiethnic population of asymptomatic individuals.
doi:10.1016/j.jcmg.2014.01.016
PMCID: PMC4129378  PMID: 24813967
feature-tracking MRI; heart failure; left atrial function; left atrial strain
6.  Association of Electrocardiographic and Imaging Surrogates of Left Ventricular Hypertrophy with Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis 
Objectives
To examine the association between LVH, defined by cardiovascular magnetic resonance (CMR) and electrocardiography (ECG), with incident AF.
Background
Previous studies of the association between atrial fibrillation (AF) and left ventricular hypertrophy (LVH) were based primarily on echocardiographic measures of LVH.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) study enrolled 4942 participants free of clinically recognized cardiovascular disease. Incident AF was based on MESA ascertained hospital discharge ICD codes and Centers for Medicare and Medicaid Services (CMS) inpatient hospital claims. CMR-LVH was defined as left ventricular mass ≥ 95th percentile of the MESA population distribution. Eleven ECG-LVH criteria were assessed. The association of LVH with incident AF was evaluated using multivariable Cox proportional hazards models adjusted for CVD risk factors.
Results
During a median follow-up of 6.9 years, 214 incident AF events were documented. Participants with AF were more likely to be older, hypertensive, and overweight. The risk of AF was greater in participants with CMR-derived LVH [Hazard ratio (HR) 2.04, 95% CI 1.15-3.62]. AF was associated with ECG-derived LVH measure of Sokolow-Lyon voltage product after adjusting for CMR-LVH [HR=1.83 (1.06, 3.14), p= 0.02]. The associations with AF for CMR LVH and Sokolow-Lyon voltage product were attenuated when adjusted for CMR LA volumes.
Conclusion
In a multi-ethnic cohort of participants without clinically detected CVD, both CMR and ECG-derived LVH were associated with incident AF. ECG-LVH showed prognostic significance independent of CMR-LVH. The association was attenuated when adjusted for CMR LA volumes.
doi:10.1016/j.jacc.2014.01.066
PMCID: PMC4024364  PMID: 24657688
Atrial Fibrillation; Left Ventricular Hypertrophy; Cardiac MRI; ECG
7.  Physical Activity, Measures of Obesity, and Cardiometabolic Risk: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
The influence of higher physical activity on the relationship between adiposity and cardiometabolic risk is not completely understood.
Methods
Between 2000–2002, data were collected on 6795 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Self-reported intentional physical activity in the lowest quartile (0–105 MET-minutes/week) was categorized as inactive and the upper three quartiles (123–37,260 MET-minutes/week) as active. Associations of body mass index (BMI) and waist circumference categories, stratified by physical activity status (inactive or active) with cardiometabolic risk factors (dyslipidemia, hypertension, upper quartile of homeostasis model assessment of insulin resistance [HOMA-IR] for population, and impaired fasting glucose or diabetes) were assessed using logistic regression analysis adjusting for age, gender, race/ethnicity, and current smoking.
Results
Among obese participants, those who were physically active had reduced odds of insulin resistance (47% lower; P < .001) and impaired fasting glucose/diabetes (23% lower; P = .04). These associations were weaker for central obesity. However, among participants with a normal waist circumference, those who were inactive were 63% more likely to have insulin resistance (OR [95% CI] 1.63 [1.24–2.15]) compared with the active reference group.
Conclusions
Physical activity was inversely related to the cardiometabolic risk associated with obesity and central obesity.
doi:10.1123/jpah.2012-0326
PMCID: PMC4418627  PMID: 23676525
cardiovascular disease; diabetes; ethnicity; obesity
8.  Traffic-related Air Pollution and the Right Ventricle. The Multi-ethnic Study of Atherosclerosis 
Rationale: Right heart failure is a cause of morbidity and mortality in common and rare heart and lung diseases. Exposure to traffic-related air pollution is linked to left ventricular hypertrophy, heart failure, and death. Relationships between traffic-related air pollution and right ventricular (RV) structure and function have not been studied.
Objectives: To characterize the relationship between traffic-related air pollutants and RV structure and function.
Methods: We included men and women with magnetic resonance imaging assessment of RV structure and function and estimated residential outdoor nitrogen dioxide (NO2) concentrations from the Multi-ethnic Study of Atherosclerosis, a study of individuals free of clinical cardiovascular disease at baseline. Multivariable linear regression estimated associations between NO2 exposure (averaged over the year prior to magnetic resonance imaging) and measures of RV structure and function after adjusting for demographics, anthropometrics, smoking status, diabetes mellitus, and hypertension. Adjustment for corresponding left ventricular parameters, traffic-related noise, markers of inflammation, and lung disease were considered in separate models. Secondary analyses considered oxides of nitrogen (NOx) as the exposure.
Measurements and Main Results: The study sample included 3,896 participants. In fully adjusted models, higher NO2 was associated with greater RV mass and larger RV end-diastolic volume with or without further adjustment for corresponding left ventricular parameters, traffic-related noise, inflammatory markers, or lung disease (all P < 0.05). There was no association between NO2 and RV ejection fraction. Relationships between NOx and RV morphology were similar.
Conclusions: Higher levels of NO2 exposure were associated with greater RV mass and larger RV end-diastolic volume.
doi:10.1164/rccm.201312-2298OC
PMCID: PMC4098110  PMID: 24593877
air pollutants; pulmonary circulation; heart ventricles; pulmonary hypertension
9.  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.
doi:10.1186/s12968-015-0111-7
PMCID: PMC4403942  PMID: 25928314
Normal values; Reference values; Cardiovascular magnetic resonance
10.  Diastolic function assessed from tagged MRI predicts heart failure and atrial fibrillation over an 8-year follow-up period: the multi-ethnic study of atherosclerosis 
Objectives
The strain relaxation index (SRI), a novel diastolic functional parameter derived from tagged magnetic resonance imaging (MRI), is used to assess myocardial deformation during left ventricular relaxation. We investigated whether diastolic function indexed by SRI predicts heart failure (HF) and atrial fibrillation (AF) over an 8-year follow-up.
Methods
As a part of the multi-ethnic study of atherosclerosis, 1544 participants free of known cardiovascular disease (CVD) underwent tagged MRI in 2000–02. Harmonic phase analysis was used to compute circumferential strain. Standard parameters, early diastolic strain rate (EDSR) and the peak torsion recoil rate were calculated. An SRI was calculated as difference between post-systolic and systolic times of the strain peaks, divided by the EDSR peak. It was normalized by the total interval of relaxation. Over an 8-year follow-up period, we defined AF (n = 57) or HF (n = 36) as combined (n = 80) end-points. Cox regression assessed the ability of SRI to predict events adjusted for risk factors and markers of subclinical disease. Integrated discrimination index (IDI) and net reclassification index (NRI) of SRI, compared with conventional indices, were also assessed.
Results
The hazard ratio for SRI remained significant for the combined HF and AF end-points as well as for HF alone after adjustment. For the combined end-point, IDI was 1.5% (P < 0.05) and NRI was 11.4% (P < 0.05) for SRI. Finally, SRI was more robust than all other existing cardiovascular magnetic resonance diastolic functional parameters.
Conclusion
SRI predicts HF and AF over an 8-year follow-up period in a large population free of known CVD, independent of established risk factors and markers of subclinical CVD.
doi:10.1093/ehjci/jet189
PMCID: PMC3976111  PMID: 24145457
Heart failure; Atrial; Fibrillation; Diastole; Magnetic resonance imaging
11.  Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: The Multi-Ethnic Study of Atherosclerosis 
OBJECTIVE
To investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction.
BACKGROUND
The association of resting heart rate to HF and LV function is not well described in an asymptomatic multi-ethnic population.
METHODS
Participants in the Multi-Ethnic Study of Atherosclerosis had resting heart rate measured at inclusion. Incident HF was registered (n=176) during follow-up (median 7 years) in those who underwent cardiac MRI (n=5000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume and mass in addition to resting heart rate.
RESULTS
Cox analysis demonstrated that for 1 bpm increase in resting heart rate there was a 4% greater adjusted relative risk for incident HF (Hazard Ratio: 1.04 (1.02, 1.06 (95% CI); P<0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even in analyses when all coronary heart disease events were excluded from the model.
CONCLUSION
Elevated resting heart rate is associated with increased risk for incident HF in asymptomatic participants in MESA. Higher heart rate is related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease.
doi:10.1016/j.jacc.2013.11.027
PMCID: PMC4037739  PMID: 24412444
resting heart rate; heart failure; coronary heart disease; left ventricular dysfunction; myocardial strain; cardiac MRI
12.  “Cor pulmonale parvus” in chronic obstructive pulmonary disease (COPD) and emphysema. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study 
Background
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.
Objective
We aimed to examine RV changes in contemporary COPD and emphysema using cardiac magnetic resonance imaging (MRI).
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.jacc.2014.07.991
PMCID: PMC4347835  PMID: 25440095
right ventricle; chronic obstructive pulmonary disease; pulmonary heart disease; pulmonary hypertension; heart failure
13.  Interstitial Fibrosis, Left Ventricular Remodeling and Myocardial Mechanical Behavior in a Population-Based Multi-ethnic Cohort: MESA Study 
Background
Tagged cardiac magnetic resonance (CMR) provides detailed information on regional myocardial function and mechanical behavior. T1 mapping by CMR allows non-invasive quantification of myocardial extracellular expansion (ECE) which has been related to interstitial fibrosis in previous clinical and sub-clinical studies. We assessed gender associated differences in the relation of ECE to LV remodeling and myocardial systolic and diastolic deformation in a large community based multi-ethnic population.
Methods and Results
Mid-ventricular mid-wall peak circumferential shortening and early diastolic strain rate (EDSR); LV torsion and torsional recoil rate were determined using CMR tagging. Mid ventricular short axis T1 maps were acquired in the same examination pre and post-contrast injection using Modified Look-Locker Inversion Recovery sequence (MOLLI). Multivariable linear regression (B= estimated regression coefficient) was used to adjust for risk factors and sub-clinical disease measures. Of 1230 participants, 114 participants had visible myocardial scar by late gadolinium enhancement. Participants without visible myocardial scar (n=1116) had no previous history of clinical events. In the latter group, multivariable linear regression demonstrated that lower post-contrast T1 times, reflecting greater ECE were associated with lower circumferential shortening (B=−0.1, p=0.0001), lower end diastolic volume index (LVEDVi) (B=0.6, p=0.0001) and lower LV end diastolic mass index (LVMi) (B=0.4, p=0.0001). In addition, lower post-contrast T1 times were associated with lower EDSR (B=0.01, p=0.03) in women only; and lower LV torsion (B=0.005, p=0.03) a lower LV ejection fraction (B=0.2, p=0.01) in men only.
Conclusions
Greater ECE is associated with reduced LVEDVi and LVMi in a large multi-ethnic population without history of previous cardiovascular events. In addition, greater ECE is associated with reduced circumferential shortening, lower EDSR, and a preserved ejection fraction in women; while in men, greater ECE is associated with greater LV dysfunction manifested as reduced circumferential shortening, reduced LV Torsion and reduced ejection fraction.
doi:10.1161/CIRCIMAGING.113.001073
PMCID: PMC3992469  PMID: 24550436
interstitial myocardial fibrosis; circumferential strain; LV torsion; T1 mapping; tagging
14.  The Effects of Applying Breast Compression in Dynamic Contrast Material–enhanced MR Imaging 
Radiology  2014;272(1):79-90.
Applying breast compression compromises the contrast enhancement of breast lesions and glandular tissue in an unpredictable manner, affecting the early contrast-enhanced phase more than the delayed phase.
Purpose
To evaluate the effects of breast compression on breast cancer masses, contrast material enhancement of glandular tissue, and quality of magnetic resonance (MR) images in the identification and characterization of breast lesions.
Materials and Methods
This was a HIPAA-compliant, institutional review board–approved retrospective study, with waiver of informed consent. Images from 300 MR imaging examinations in 149 women (mean age ± standard deviation, 51.5 years ± 10.9; age range, 22–76 years) were evaluated. The women underwent diagnostic MR imaging (no compression) and MR-guided biopsy (with compression) between June 2008 and February 2013. Breast compression was expressed as a percentage relative to the noncompressed breast. Percentage enhancement difference was calculated between noncompressed- and compressed-breast images obtained in early and delayed contrast-enhanced phases. Breast density, lesion type (mass vs non-masslike enhancement [NMLE]), lesion size, percentage compression, and kinetic curve type were evaluated. Linear regression, receiver operating characteristic (ROC) curve analysis, and κ test were performed.
Results
Mean percentage compression was 31.3% ± 9.2 (range, 5.8%–53.2%). Percentage enhancement was higher in noncompressed- versus compressed-breast studies in early (146% ± 66 vs 107% ± 42, respectively; P < .001) and delayed (158% ± 68 vs 107% ± 42, respectively; P = .1) phases. Among breast lesions, 12% (seven of 59) were significantly smaller when compressed, which led to underestimation of TNM classification (P < .001). Breast masses (n = 35) showed significantly higher early percentage enhancement (157% ± 71) than lesions with NMLE (n = 15, 120% ± 40; P = .02) and a percentage enhancement difference (47.5% ± 64 vs 17% ± 28, respectively; P = .023). Kinetic curve performance for identifying invasive cancer decreased after compression (area under ROC curve = 0.53 vs 0.71, respectively; P = .02). Breast compression resulted in complete loss of enhancement of nine of 210 lesions (4%).
Conclusion
Breast compression during biopsy affected breast lesion detection, lesion size, and dynamic contrast-enhanced MR imaging interpretation and performance. Limiting the application of breast compression is recommended, except when clinically necessary.
© RSNA, 2014
Online supplemental material is available for this article.
doi:10.1148/radiol.14131384
PMCID: PMC4263656  PMID: 24620911
15.  Late Systolic Central Hypertension as a Predictor of Incident Heart Failure: The Multi‐Ethnic Study of Atherosclerosis 
Background
Experimental studies demonstrate that high aortic pressure in late systole relative to early systole causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure.
Methods and Results
We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last one third of systole) to early (first two thirds of systole) pressure–time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 6124 adults. The late/early systolic PTI ratio (L/ESPTI) was assessed as a predictor of incident HF during median 8.5 years of follow‐up. The L/ESPTI was predictive of incident HF (hazard ratio per 1% increase=1.22; 95% CI=1.15 to 1.29; P<0.0001) even after adjustment for established risk factors for HF (HR=1.23; 95% CI=1.14 to 1.32: P<0.0001). In a multivariate model that included brachial systolic and diastolic blood pressure and other standard risk factors of HF, L/ESPTI was the modifiable factor associated with the greatest improvements in model performance. A high L/ESPTI (>58.38%) was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95% CI=0.86 to 2.23; P=0.18), whereas the HR associated with a high L/E was 2.31 (95% CI=1.52 to 3.49; P<0.0001).
Conclusions
Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population.
doi:10.1161/JAHA.114.001335
PMCID: PMC4392425  PMID: 25736440
arterial hemodynamics; heart failure; late systolic load; left ventricular afterload
16.  Validity of the Surface Electrocardiogram Criteria for Right Ventricular Hypertrophy: The MESA - Right Ventricle Study 
Objectives
We aimed to assess the diagnostic properties of ECG criteria for RVH measured by cardiac magnetic resonance imaging (cMRI) in adults without clinical cardiovascular disease.
Background
Current electrocardiographic (ECG) criteria for right ventricular hypertrophy (RVH) were based on cadaveric dissection in small studies.
Methods
The Multi-Ethnic Study of Atherosclerosis performed cMRIs with complete right ventricle (RV) interpretation on 4,062 participants without clinical cardiovascular disease. Endocardial margins of the RV were manually contoured on diastolic and systolic images. The ECG screening criteria for RVH from the 2009 AHA Recommendations for Standardization and Interpretation of the ECG were examined in participants with and without left ventricular hypertrophy or reduced ejection fraction. RVH was defined using sex-specific normative equations based on age, height, and weight.
Results
The study sample with normal left ventricular morphology and function (n = 3,719) was 61.3 ± 10.0 years old, 53.5% female, 39.6% Caucasian, 25.5% African-American, 21.9% Hispanic, and 13.0% Asian. The mean BMI was 27.9 ± 5.0 kg/m2. Six percent had RVH which was generally mild. Traditional ECG criteria were specific (many > 95%) but had low sensitivity for RVH by cMRI. The positive predictive values were not sufficiently high as to be clinically useful (maximum 12%). The results did not differ based on age, sex, race, smoking status, or with including participants with abnormal LV mass or function. Classification and regression tree analysis revealed that no combination of ECG variables was better than the criteria used singly.
Conclusions
The recommended ECG screening criteria for RVH are not sufficiently sensitive or specific for screening for mild RVH in adults without clinical cardiovascular disease.
doi:10.1016/j.jacc.2013.08.1633
PMCID: PMC3944058  PMID: 24080107
Right Ventricular Hypertrophy; Magnetic Resonance Imaging; Electrocardiogram
17.  The Effects of Applying Breast Compression in Dynamic Contrast Material–enhanced MR Imaging1 
Radiology  2014;272(1):79-90.
Purpose
To evaluate the effects of breast compression on breast cancer masses, contrast material enhancement of glandular tissue, and quality of magnetic resonance (MR) images in the identification and characterization of breast lesions.
Materials and Methods
This was a HIPAA-compliant, institutional review board–approved retrospective study, with waiver of informed consent. Images from 300 MR imaging examinations in 149 women (mean age ± standard deviation, 51.5 years ± 10.9; age range, 22–76 years) were evaluated. The women underwent diagnostic MR imaging (no compression) and MR-guided biopsy (with compression) between June 2008 and February 2013. Breast compression was expressed as a percentage relative to the noncompressed breast. Percentage enhancement difference was calculated between noncompressed- and compressed-breast images obtained in early and delayed contrast-enhanced phases. Breast density, lesion type (mass vs non-masslike enhancement [NMLE]), lesion size, percentage compression, and kinetic curve type were evaluated. Linear regression, receiver operating characteristic (ROC) curve analysis, and κ test were performed.
Results
Mean percentage compression was 31.3% ± 9.2 (range, 5.8%–53.2%). Percentage enhancement was higher in noncompressed- versus compressed-breast studies in early (146% ± 66 vs 107% ± 42, respectively; P < .001) and delayed (158% ± 68 vs 107% ± 42, respectively; P = .1) phases. Among breast lesions, 12% (seven of 59) were significantly smaller when compressed, which led to underestimation of TNM classification (P < .001). Breast masses (n = 35) showed significantly higher early percentage enhancement (157% ± 71) than lesions with NMLE (n = 15, 120% ± 40; P = .02) and a percentage enhancement difference (47.5% ± 64 vs 17% ± 28, respectively; P = .023). Kinetic curve performance for identifying invasive cancer decreased after compression (area under ROC curve = 0.53 vs 0.71, respectively; P = .02). Breast compression resulted in complete loss of enhancement of nine of 210 lesions (4%).
Conclusion
Breast compression during biopsy affected breast lesion detection, lesion size, and dynamic contrast-enhanced MR imaging interpretation and performance. Limiting the application of breast compression is recommended, except when clinically necessary.
doi:10.1148/radiol.14131384
PMCID: PMC4263656  PMID: 24620911
18.  A Prospective Evaluation of a Protocol for Magnetic Resonance Imaging of Patients With Implanted Cardiac Devices 
Annals of internal medicine  2011;155(7):415-424.
Background
Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns.
Objective
To define the safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in patients with implanted cardiac devices.
Design
Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896)
Setting
One center in the United States (94% of examinations) and one in Israel.
Patients
438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies.
Intervention
Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachy-arrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist.
Measurements
Activation or inhibition of pacing, symptoms, and device variables.
Results
In 3 patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV [interquartile range {IQR}, −0.7 to 0 V]) and atrial and right and left ventricular lead impedances (median change, −2 Ω[IQR, −13 to 0 Ω], −4 Ω [IQR, −16 to 0 Ω], and −11 Ω [IQR, −40 to 0 Ω], respectively) were reduced immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, [IQR, −1.1 to 0.3 mV]), decreased RV lead impedance (median, −3 Ω, [IQR, −29 to 15 Ω]), increased RV capture threshold (median, 0 V, IQR, [0 to 0.2 Ω]), and decreased battery voltage (median, −0.01 V, IQR, −0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming.
Limitations
Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed.
Conclusion
With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential.
Primary Funding Source
National Institutes of Health.
doi:10.7326/0003-4819-155-7-201110040-00004
PMCID: PMC4337840  PMID: 21969340
19.  The association between cardiovascular risk and cardiovascular magnetic resonance measures of fibrosis: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Risk scores for cardiovascular disease (CVD) are in common use to integrate multiple cardiovascular risk factors in order to identify individuals at greatest risk for disease. The purpose of this study was to determine if individuals at greater cardiovascular risk have T1 mapping indices by cardiovascular magnetic resonance (CMR) indicative of greater myocardial fibrosis.
Methods
CVD risk scores for 1208 subjects (men, 50.8%) ages 55–94 years old were evaluated in the Multiethnic Study of Atherosclerosis (MESA) at six centers. T1 times were determined at 1.5Tesla before and after gadolinium administration (0.15 mmol/kg) using a modified Look-Locker pulse sequence. The relationship between CMR measures (native T1, 12 and 25 minute post-gadolinium T1, partition coefficient and extracellular volume fraction) and 14 established different cardiovascular risk scores were determined using regression analysis. Bootstrapping analysis with analysis of variance was used to compare different CMR measures. CVD risk scores were significantly different for men and women (p < 0.001).
Results
25 minute post gadolinium T1 time showed more statistically significant associations with risk scores (10/14 scores, 71%) compared to other CMR indices (e.g. native T1 (7/14 scores, 50%) and partition coefficient (7/14, 50%) in men. Risk scores, particularly the new 2013 AHA/ASCVD risk score, did not correlate with any CMR fibrosis index.
Conclusions
Men with greater CVD risk had greater CMR indices of myocardial fibrosis. T1 times at greater delay time (25 minutes) showed better agreement with commonly used risk score indices compared to ECV and native T1 time.
Clinical trial registration
http://www.mesa-nhlbi.org/, NCT00005487.
doi:10.1186/s12968-015-0121-5
PMCID: PMC4326517  PMID: 25827220
Myocardium; Cardiovascular magnetic resonance; Risk factors
25.  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.
doi:10.1002/mrm.21864
PMCID: PMC4301616  PMID: 19165884
cardiac MRI; black blood; turbo spin echo; right ventricle

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