Thoracic Aortic Volume as a Predictor of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: It is unclear whether thoracic aortic volume (TAV) is useful for cardiovascular (CV) disease prognosis and risk assessment. PURPOSE: This study evaluated cross-sectional associations of TAV with CV risk factors, and longitudinal association with incident CV events in the multiethnic study of atherosclerosis. STUDY TYPE: Retrospective cohort analysis of prospective data. POPULATION: 1182 participants (69 ± 9 years, 54% female, 37% Caucasian, 18% Chinese, 31% African American, 14% Hispanic, 60% hypertensive, and 20% diabetic) without prior CV disease. FIELD STRENGTH AND SEQUENCES: Axial black-blood turbo spin echo or bright blood steady-state free precession images on 1.5T scanners. ASSESSMENT: TAV was calculated using Simpson's method from axial images, and included the ascending arch and descending segments. Traditional CV risk factors were assessed at the time of MRI. CV outcomes over a 9-year follow-up period were recorded and represented a composite of stroke, stroke death, coronary heart disease (CHD), CHD death, atherosclerotic death, and CVD death. STATISTICAL TESTS: Multivariable linear regression models adjusted for height and weight were used to determine the relationship (ß coefficient) between TAV and CV risk factors. Cox regression models assessed the association of TAV and incident CV events. A P-value of <0.05 was deemed statistically significant. RESULTS: Mean TAV was = 139 ± 41 mL. In multivariable regression, TAV was directly associated with age (ß = 1.6), male gender (ß = 23.9), systolic blood pressure (ß = 0.1), and hypertension medication use (ß = 7.9); and inversely associated with lipid medication use (ß = -5.3) and treated diabetes (ß = -8.9). Compared to Caucasians, Chinese Americans had higher TAV (ß = 11.4), while African Americans had lower TAV (ß = -7.0). Higher TAV was independently associated with incident CV events (HR: 1.057 per 10 mL). CONCLUSION: Greater TAV is associated with incident CV events, increased age, and hypertension in a large multiethnic population while treated diabetes and lipid medication use were associated with lower TAV. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Management of Biliary Stricture in Pediatric Liver Transplantation Patients: Long-Term Outcomes.

Postoperative biliary complications have been reported to occur in 10% to 33% of pediatric liver transplantation (LT) recipients. Percutaneous intervention has become the primary treatment method for these complications; however, the efficacy and outcomes of these patients have not been well studied. Institutional pediatric LT from 1998 to 2019 were retrospectively reviewed to determine the patients referred for percutaneous treatment of post-LT biliary strictures. Clinical parameters, percutaneous transhepatic cholangiograms (PTCs), biliary catheter placement, cholangioplasty, and long-term outcomes were analyzed. Of the 396 consecutive pediatric LT recipients during our study period, 50 (12.6%) were diagnosed with biliary strictures on PTC. LT biliary reconstructions were Roux-en-Y hepaticojejunostomy in 28 patients (56%), choledochojejunostomy in 11 patients (22%), and choledochocholedochostomy in 11 patients (22%). Median age at LT was 23.2 months (interquartile range [IQR], 10.9-90.6), and 14 patients (28%) developed hepatic artery thrombosis. A total of 44 patients (88%) were treated with internal/external biliary catheters, of whom 38 (76%) underwent balloon cholangioplasty. By 12 months, 84% of patients had complete stricture resolution and catheter removal. Median total duration of catheter drainage was 152 days (IQR, 76-308). A total of 8 patients required additional surgery (biliary reconstruction or repeat LT [re-LT]) or died with a drainage catheter in place from complications unrelated to PTC intervention. Among the 6 patients (12%) treated with unilateral external biliary drainage catheters, 2 had catheters removed for inadequate drainage but then had spontaneous biliary obstruction resolution, 1 underwent duct reconstruction, and 3 required long-term catheterization. Biliary strictures following pediatric LT can be successfully treated with internal/external biliary drainage catheters and cholangioplasty if the stricture can be crossed. However, patients with isolated strictured ducts may require long-term external catheter drainage until re-LT or percutaneous obliteration of isolated ducts.

Reproducibility and Changes in Vena Caval Blood Flow by Using 4D Flow MRI in Pulmonary Emphysema and Chronic Obstructive Pulmonary Disease (COPD): The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Substudy.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with hemodynamic changes in the pulmonary vasculature. However, cardiac effects are not fully understood and vary by phenotype of chronic lower respiratory disease.PurposeTo use four-dimensional (4D) flow MRI for comprehensive assessment of the right-sided cardiovascular system, assess its interrater and intraobserver reproducibility, and examine associations with venous return to the right heart in individuals with chronic COPD and emphysema.Materials and MethodsThe Multi-Ethnic Study of Atherosclerosis COPD substudy prospectively recruited participants who smoked and who had COPD and nested control participants from population-based samples. Electrocardiography and respiratory gated 4D flow 1.5-T MRI was performed at three sites with full volumetric coverage of the thoracic vessels in 2014-2017 with postbronchodilator spirometry and inspiratory chest CT to quantify percent emphysema. Net flow, peak velocity, retrograde flow, and retrograde fraction were measured on 14 analysis planes. Interrater reproducibility was assessed by two independent observers, and the principle of conservation of mass was employed to evaluate the internal consistency of flow measures. Partial correlation coefficients were adjusted for age, sex, race/ethnicity, height, weight, and smoking status.ResultsAmong 70 participants (29 participants with COPD [mean age, 73.5 years ± 8.1 {standard deviation}; 20 men] and 41 control participants [mean age, 71.0 years ± 6.1; 22 men]), the interrater reproducibility of the 4D flow MRI measures was good to excellent (intraclass correlation coefficient range, 0.73-0.98), as was the internal consistency. There were no statistically significant differences in venous flow parameters according to COPD severity (P > .05). Greater percent emphysema at CT was associated with greater regurgitant flow in the superior and inferior caval veins and tricuspid valve (adjusted r = 0.28-0.55; all P < .01), particularly in the superior vena cava.ConclusionFour-dimensional flow MRI had good-to-excellent observer variability and flow consistency. Percent emphysema at CT was associated with statistically significant differences in retrograde flow, greatest in the superior vena cava.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Choe in this issue.

Cardiovascular Event Prediction by Machine Learning: The Multi-Ethnic Study of Atherosclerosis.

RATIONALE: Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. OBJECTIVE: To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. METHODS AND RESULTS: We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). CONCLUSIONS: Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Carotid Artery Wall Thickness and Incident Cardiovascular Events: A Comparison between US and MRI in the Multi-Ethnic Study of Atherosclerosis (MESA).

Purpose To compare common carotid artery (CCA) wall thickness measured manually by using US and semiautomatically by using MRI, and to examine their associations with incident coronary heart disease and stroke. Materials and Methods This prospective study enrolled 698 participants without a history of clinical cardiovascular disease (CVD) from the Multi-Ethnic Study of Atherosclerosis (MESA) from July 2000 to December 2013 (mean age, 63 years; range, 45 to 84 years; same for men and women). All participants provided written informed consent. CCA wall thickness was measured with US as well as both noncontrast proton-density-weighted and intravenous gadolinium-enhanced MRI. Cox proportional hazards models were used to assess the associations between wall thickness measurements by using US and MRI with CVD outcomes. Results The adjusted hazard ratios for coronary heart disease, stroke, and CVD associated with per standard deviation increase in intima-media thickness were 1.10, 1.08, and 1.14, respectively. The corresponding associations for mean wall thickness measured with proton-density-weighted MRI were 1.32, 1.48, and 1.37, and for mean wall thickness measured with gadolinium-enhanced MRI were 1.27, 1.58, and 1.38. When included simultaneously in the same model, MRI wall thickness, but not intima-media thickness, remained associated with outcomes. Conclusion For individuals without known cardiovascular disease at baseline, wall thickness measurements by using MRI were more consistently associated with incident cardiovascular disease, particularly stroke, than were intima-media thickness by using US. © RSNA, 2018 Online supplemental material is available for this article.

Pulmonary artery stiffness in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) and particularly emphysema are characterized by stiffness of the aorta, due in part to accelerated elastin degradation in the lungs and aorta. Stiffness of the pulmonary arteries (PAs) may also be increased in COPD and emphysema, but data are lacking. We assessed PA stiffness using MRI in patients with COPD and related these measurements to COPD severity and percent emphysema. MATERIALS AND METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited 290 participants, age 50-79 years with 10 or more packyears and free of clinical cardiovascular disease. COPD severity were defined on postbronchodilator spirometry by ATS/ERS criteria. Percent emphysema was defined as the percentage of regions of the lung < -950 Hounsfield units on full-lung computed tomography (CT). PA stain was defined by the percent change in cross-sectional PA area between systole and diastole on MRI. Blood flow across the tricuspid and mitral valves was assessed by phase-contrast MRI for determination of the ventricular diastolic dysfunction (E/A ratio). RESULTS: PA strain was reduced in COPD compared with controls (P = 0.002) and was inversely correlated with COPD severity (P = 0.004). PA strain was inversely associated to percent emphysema (P = 0.01). PA strain was also markedly correlated with right ventricular diastolic dysfunction measured by E/A ratios in the fully adjusted mix models (P = 0.02). CONCLUSION: PA strain is reduced in COPD, related in part to percent emphysema on CT scan, which may have implications for pulmonary small vessel flow and right ventricular function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:262-271.

Comparison of Triple-Drug Transcatheter Arterial Chemoembolization (TACE) With Single-Drug TACE Using Doxorubicin-Eluting Beads: Long-Term Survival in 313 Patients.

OBJECTIVE: We compared survival outcomes in 313 patients with unresectable hepatocellular carcinoma (HCC) treated with two different transcatheter arterial chemoembolization (TACE) regimens: triple-drug TACE or single-drug TACE using drug-eluting beads. MATERIALS AND METHODS: In this retrospective study, patient selection criteria were uniform. The triple-drug group (n = 166) underwent TACE using ethiodized oil with doxorubicin, cisplatin, and mitomycin-C with a microsphere embolic. The single-drug group (n = 147) underwent TACE using doxorubicin-eluting beads. Group characteristics were classified and analyzed, and survival was calculated using standard statistical methods. All patients were followed until death. Those undergoing orthotopic liver transplant (OLT) were also followed. RESULTS: There were no significant differences between the two groups in terms of demographics, Child-Pugh class, or Okuda stage. With patients undergoing OLT censored (n = 73), the mean (± standard error) survival in the triple-drug group was 23.49 ± 2.38 months, and the median survival was 16.00 ± 1.51 months. Mean survival in the single-drug bead group was 28.16 ± 2.75 months, and the median survival was 15.00 ± 1.50 months (p = 0.168). With patients undergoing OLT censored, the mean and median survival for the total cohort were 26.25 ± 1.97 and 15.00 ± 1.08 months, respectively. In the entire cohort that did not undergo OLT, patients with Child-Pugh class A disease survived significantly longer than did patients with Child-Pugh class B disease. Elevated α-fetoprotein levels were associated with shorter survival, and patients undergoing TACE with drug-eluting beads had shorter hospital stays. Although a greater percentage annual survival was observed in patients undergoing drug-eluting bead TACE who had Child-Pugh class A, Okuda stage I, and Barcelona Clinic Liver Cancer classes A and B disease starting at 36 months, this suggested survival advantage did not reach statistical significance. CONCLUSION: We found no significant survival difference in patients with unresectable HCC treated with triple-drug TACE compared with single-drug TACE using doxorubicin-eluting beads.

Adverse Left Ventricular Remodeling and Age Assessed with Cardiac MR Imaging: The Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To evaluate age-related left ventricular (LV) remodeling during longitudinal observation of a large cohort of asymptomatic individuals who were free of clinical cardiovascular disease at baseline. MATERIALS AND METHODS: The applicable institutional review boards approved this study, and all participants gave informed consent. Cardiac magnetic resonance (MR) imaging was used to identify longitudinal changes in LV structure and function in 2935 participants who underwent baseline and follow-up cardiac MR imaging in the Multi-Ethnic Study of Atherosclerosis. Participants were free of clinical cardiovascular disease at baseline. Participants who experienced an incident coronary heart disease event were excluded. Data were analyzed with multivariable mixed-effects regression models in which the outcome was cardiac MR imaging measurement, and the covariates included follow-up time and cardiac risk factors. RESULTS: Participants were aged 54-94 years at follow-up, and 53% of the participants were women. Median time between baseline and follow-up cardiac MR imaging was 9.4 years. Over this period, LV mass increased in men and decreased slightly in women (8.0 and -1.6 g per decade, respectively; P < .001). In both men and women, LV end-diastolic volume decreased (-9.8 and -13.3 mL per decade, respectively; P < .001), stroke volume decreased (-8.8 and -8.6 mL per decade, respectively; P < .001), and mass-to-volume ratio increased (0.14 and 0.11 g/mL per decade, respectively; P < .001). Change in LV mass was positively associated with systolic blood pressure and body mass index and negatively associated with treated hypertension and high-density lipoprotein cholesterol level. In men, the longitudinal LV mass increase was in contrast to a cross-sectional pattern of LV mass decrease. CONCLUSION: As patients age, the LV responds differently in its mass and volume between men and women, although both men and women experience increased concentric LV remodeling with age. In men, the opposition of longitudinal and cross-sectional changes in LV mass highlights the importance of longitudinal study.

Reduced long axis strain is associated with heart failure and cardiovascular events in the multi-ethnic study of Atherosclerosis.

PURPOSE: To propose long axis strain (LAS), a novel index of global left ventricle (LV) function, as a sensitive and powerful predictor of hard cardiovascular events and heart failure in the Multi-Ethnic Study of Atherosclerosis (MESA). MATERIALS AND METHODS: Strain is an index of relative myocardial deformation, and enables normalization for differences in heart size. Measurement of strain conventionally requires dedicated software and protocols for image acquisition. LAS, however, can be analyzed using a caliper tool from conventional LV long axis magnetic resonance imaging (MRI) cine loops, reflecting the average myocardial contraction in the longitudinal direction. In all, 1651 participants (53% men) of the MESA study, without a history of myocardial infarction or heart failure, were assessed using conventional cine MR images. LV lengths were assessed at end-diastole (EDL ) and end-systole (ESL ), and LAS was calculated as 100*(EDL -ESL )/EDL . Participants were followed for 6.8 ± 1.8 years for a composite endpoint of congestive heart failure or hard cardiovascular events, and the predictive ability of LAS was tested, unadjusted and adjusted for established cardiovascular risk factors. RESULTS: A total of 114 events were observed. Mean LAS was 11.7 ± 2.5% and 10.0 ± 2.7% in participants without and with events, respectively (P < 0.001). Increased LAS reduced the hazard ratio to 0.75 for univariate, and 0.88 for multivariate assessments, respectively (both P < 0.001). CONCLUSION: Assessment of long axis LV deformation by LAS is feasible and reproducible. Moreover, LAS predicts hard cardiovascular events and congestive heart failure in a multi-ethnic population without overt cardiovascular disease at inclusion. J. Magn. Reson. Imaging 2016;44:178-185.

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.

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.

Pulmonary hyperinflation and left ventricular mass: the Multi-Ethnic Study of Atherosclerosis COPD Study.

BACKGROUND: Left ventricular (LV) mass is an important predictor of heart failure and cardiovascular mortality, yet determinants of LV mass are incompletely understood. Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) may contribute to changes in intrathoracic pressure that increase LV wall stress. We therefore hypothesized that residual lung volume in COPD would be associated with greater LV mass. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers 50 to 79 years of age who were free of clinical cardiovascular disease. LV mass was measured by cardiac magnetic resonance. Pulmonary function testing was performed according to guidelines. Regression models were used to adjust for age, sex, body size, blood pressure, and other cardiac risk factors. Among 119 MESA COPD Study participants, the mean age was 69±6 years, 55% were male, and 65% had COPD, mostly of mild or moderate severity. Mean LV mass was 128±34 g. Residual lung volume was independently associated with greater LV mass (7.2 g per 1-SD increase in residual volume; 95% confidence interval, 2.2-12; P=0.004) and was similar in magnitude to that of systolic blood pressure (7.6 g per 1-SD increase in systolic blood pressure; 95% confidence interval, 4.3-11; P<0.001). Similar results were observed for the ratio of LV mass to end-diastolic volume (P=0.02) and with hyperinflation measured as residual volume to total lung capacity ratio (P=0.009). CONCLUSIONS: Pulmonary hyperinflation, as measured by residual lung volume or residual lung volume to total lung capacity ratio, is associated with greater LV mass.

Carotid artery plaque morphology and composition in relation to incident cardiovascular events: the Multi-Ethnic Study of Atherosclerosis (MESA).

PURPOSE: To determine if carotid plaque morphology and composition with magnetic resonance (MR) imaging can be used to identify asymptomatic subjects at risk for cardiovascular events. MATERIALS AND METHODS: Institutional review boards at each site approved the study, and all sites were Health Insurance Portability and Accountability Act (HIPAA) compliant. A total of 946 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated with MR imaging and ultrasonography (US). MR imaging was used to define carotid plaque composition and remodeling index (wall area divided by the sum of wall area and lumen area), while US was used to assess carotid wall thickness. Incident cardiovascular events, including myocardial infarction, resuscitated cardiac arrest, angina, stroke, and death, were ascertained for an average of 5.5 years. Multivariable Cox proportional hazards models, C statistics, and net reclassification improvement (NRI) for event prediction were determined. RESULTS: Cardiovascular events occurred in 59 (6%) of participants. Carotid IMT as well as MR imaging remodeling index, lipid core, and calcium in the internal carotid artery were significant predictors of events in univariate analysis (P < .001 for all). For traditional risk factors, the C statistic for event prediction was 0.696. For MR imaging remodeling index and lipid core, the C statistic was 0.734 and the NRI was 7.4% and 15.8% for participants with and those without cardiovascular events, respectively (P = .02). The NRI for US IMT in addition to traditional risk factors was not significant. CONCLUSION: The identification of vulnerable plaque characteristics with MR imaging aids in cardiovascular disease prediction and improves the reclassification of baseline cardiovascular risk.

Determinants and normal values of ascending aortic diameter by age, gender, and race/ethnicity in the Multi-Ethnic Study of Atherosclerosis (MESA).

PURPOSE: To determine the normal size and wall thickness of the ascending thoracic aorta (AA) and its relationship with cardiovascular risk factors in a large population-based study. MATERIALS AND METHODS: The mean AA luminal diameter was measured in 3573 Multi-Ethnic Study of Atherosclerosis (MESA) participants (age: 45-84 years), using gradient echo phase contrast cine MRI. Multiple linear regression models were used to evaluate the associations between risk factors and AA diameter. The median and upper normal limit (95th percentile) was defined in a "healthy" subgroup as well as AA wall thickness. RESULTS: The upper limits of body surface area indexed AA luminal diameter for age categories of 45-54, 55-64, 65-74, and 75-84 years are 21, 22, 22, and 28 mm/m(2) in women and 20, 21, 22, 23 mm/m(2) in men, respectively. The mean AA wall thickness was 2.8 mm. Age, gender, and body surface area were major determinants of AA luminal diameter (∼+1 mm/10 years; ∼+1.9 mm in men than women; ∼+1 mm/ 0.23 m(2) ; P < 0.001). The AA diameter in hypertensive subjects was +0.9 mm larger than in normotensives (P < 0.001). CONCLUSION: AA diameter increases gradually with aging for both genders among all race/ethnicities. The normal value of AA diameter is provided.

Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis.

AIMS: Left ventricular (LV) circumferential strain (Ecc) is a sensitive index of regional myocardial function. Currently, no studies have assessed its prognostic value in general population. We sought to investigate whether Ecc has a prognostic value for predicting incident heart failure (HF) and other major cardiovascular events in asymptomatic individuals without a history of previous cardiovascular diseases. METHODS AND RESULTS: We, prospectively, assessed incident HF and atherosclerotic events during a 5.5 ± 1.3-year period in 1768 asymptomatic individuals aged 45-84 (mean age 65 years; 47% female) who underwent tagged magnetic resonance imaging for strain determination. During the follow-up period, 39 (2.2%) participants experienced incident HF and 108 (6.1%) participants had atherosclerotic cardiovascular events. Average of peak Ecc of 12-LV segments (Ecc-global) and mid-slice (Ecc-mid) was -17.0 ± 2.4 and -17.5 ± 2.7%, respectively. Participants with average absolute Ecc-mid lower than -16.9% had a higher cumulative hazard of incident HF (log-rank test, P = 0.001). In cox regression analysis, Ecc-mid predicted incident HF independent of age, diabetes status, hypertension, interim myocardial infarction, LV mass index, and LV ejection fraction (hazard ratio 1.15 per 1%, 95% CI: 1.01-1.31, P = 0.03). This relationship remained significant after adjustment for LV-end-systolic wall stress into covariates. In addition, by adding Ecc-mid to risk factors, LV ejection fraction, and the LV mass index, both the global χ(2) value (76.6 vs. 82.4, P = 0.04) and category-less net-reclassification index (P = 0.01, SE = 0.18, z = 2.53) were augmented for predicting HF. Circumferential strain was also significantly related to the composite atherosclerotic cardiovascular events, but its relationship was attenuated after introducing the LV mass index. CONCLUSION: Circumferential shortening provides robust, independent, and incremental predictive value for incident HF in asymptomatic subjects without any history of previous clinical cardiovascular disease. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Age, sex, and hypertension-related remodeling influences left ventricular torsion assessed by tagged cardiac magnetic resonance in asymptomatic individuals: the multi-ethnic study of atherosclerosis.

BACKGROUND: The aim of the present study was to evaluate how torsion is influenced by left ventricular (LV) remodeling associated with age, sex, and hypertension in a large community-based population. METHODS AND RESULTS: Myocardial shortening and torsion were assessed by tagged cardiac magnetic resonance 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 per decade; P<0.001) and higher LV mass-to-volume ratio (0.03 g/mL per decade; P<0.001), along with lower circumferential shortening (-0.17% per decade; P<0.05). Torsion, however, was greater at older ages (0.14° per decade; P<0.001) and in women (0.37°/cm versus men; P<0.001). Hypertensive participants had higher LV mass and LV mass-to-volume ratio (15.5 g 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 sex (0.17°/cm; P<0.05). CONCLUSIONS: Older age is associated with lower LV volumes and greater relative wall thickness and is 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 independently of age and sex. Torsion may therefore represent a compensatory mechanism to maintain an adequate stroke volume and cardiac output in the face of the progressively reduced LV volumes and myocardial shortening associated with hypertension and aging.

High-sensitivity C-reactive protein as an independent predictor of progressive myocardial functional deterioration: the multiethnic study of atherosclerosis.

BACKGROUND: Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging 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. METHODS: Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc. RESULTS: 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, ∆Ecc change per 1 mg/L CRP change, 95% CI 0.036-0.126, P < .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 < .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events (B = 0.098, 0.049-0.147, P < .001, model 3). CONCLUSION: 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.

Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: a pilot study.

BACKGROUND: Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE. METHODS: 30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab. RESULTS: Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE. CONCLUSIONS: IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation at week 14. TRIAL REGISTRATION: ClinicalTrials.gov NCT00049322.