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.
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.
myocardial fat; proton spectroscopy; fat fraction
Dietary phosphorus consumption has risen steadily in the United States. Oral phosphorus loading alters key regulatory hormones and impairs vascular endothelial function which may lead to an increase in left ventricular mass (LVM). We investigated the association of dietary phosphorus with LVM in 4,494 participants from the Multi-Ethnic Study of Atherosclerosis, a community-based study of individuals free of known cardiovascular disease. The intake of dietary phosphorus was estimated using a 120-item food frequency questionnaire and the LVM was measured using magnetic resonance imaging. Regression models were used to determine associations of estimated dietary phosphorus with LVM and left ventricular hypertrophy (LVH). Mean estimated dietary phosphorus intake was 1,167 mg/day in men and 1,017 mg/day in women. After adjustment for demographics, dietary sodium, total calories, lifestyle factors, comorbidities, and established LVH risk factors, each quintile increase in the estimated dietary phosphate intake was associated with an estimated 1.1 gram greater LVM. The highest gender-specific dietary phosphorus quintile was associated with an estimated 6.1 gram greater LVM compared to the lowest quintile. Higher dietary phosphorus intake was associated with greater odds of LVH among women, but not men. These associations require confirmation in other studies.
Phosphorus; phosphate; diet; consumption; left ventricular mass; left ventricular hypertrophy
The pulmonary vasculature is an important site of renin-angiotensin metabolism. While angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (collectively AIABs) have a role in left ventricular (LV) disease, the impact of AIABs on right ventricular (RV) function is unknown. AIAB use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were obtained via cardiac magnetic resonance imaging. The relationship between AIAB use and RV measures was assessed using multivariable linear regression, stratified by race/ethnicity, and adjusted for multiple covariates. AIAB use was associated with lower RV mass (-0.7 g, 95% confidence interval [CI] -1.3 to -0.1, P=0.03) in African Americans (N=1012) after adjustment for multiple covariates including LV mass. Among Caucasians (N=1591), AIAB use was associated with larger RV end-diastolic volume (3.7 mL, 95% CI 0.7-6.8, P=0.02) after adjustment for LV volume. No significant associations were seen between AIAB use and other RV measures or in Hispanic or Chinese American participants. AIAB use was associated with RV morphology in a race-specific and LV-independent manner, suggesting the renin-angiotensin system may play a unique role in RV structure and function. The use of AIABs in those with RV dysfunction warrants further study.
angiotensin-converting enzyme inhibitor; angiotensin II receptor blockers; right ventricle; epidemiology; renin-angiotensin system
Current smoking is associated with type 2 diabetes mellitus and impaired glucose tolerance but its association with the metabolic syndrome (metS), particularly with sufficiently sampled African American representation, has not been clearly established.
To assess whether a) metS is associated with smoking; b) any increased risk of metS among smokers is independent of body mass index (BMI) compared with non-smokers; c) smoking status is differentially associated with the metS and its components across different ethnic groups.
Cross sectional analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) a community population-based sample free of cardiovascular disease.
Current smokers (N = 769) had higher risk of metS (odds ratio [OR, 95% confidence interval]: 1.4, 1.1-1.7) versus never (reference, N = 2981) and former smokers (1.0, 0.8-1.1, N = 2163) and for metS components: high waist circumference (WC) (OR:1.9, 1.2-2.1), low high density lipoprotein cholesterol (HDL-C) (1.5, 1.3-1.8), elevated plasma triglycerides (TG) (OR:1.4, 1.2-1.7) as well as high C-reactive protein (CRP, an inflammatory marker) concentration (OR: 1.6,1.3-2.0) compared to never and former smokers after adjustment for BMI. A smoking status by ethnicity interaction occurred such that African American current and former smokers had greater likelihood of low HDL-C than White counterparts.
This study found that smoking is associated with the metS and despite the lower BMI of current smokers the prevalence of low HDL-C, elevated TG and CRP is higher among them than among non-smokers. African Americans generally have higher HDL-C than Whites but smoking wipes out this advantage.
Multi-Ethnic Study of Atherosclerosis (MESA) ClinicalTrials.gov Identifier: NCT00005487
Metabolic syndrome; Smoking; Ethnic groups; Body mass index
SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit+ cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). Here, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.
Methods and Results
A total of 33 patients (20 CSC-treated and 13 controls) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 ± 1.6% to 35.1 ± 2.4 % [P=0.004, n=8] and 41.2 ± 4.5 % [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 ± 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 ± 3.5 g [-30.2%] at 12 months [P=0.039, n=6],). LV non-viable mass decreased even more (-11.9 ± 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 ± 3.9 g [-58.6%] at 12 months [P=0.013]), while LV viable mass increased (+11.6 ± 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 ± 11.0 g at 12 months [P=0.035]).
Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue, which persist at least 1 year and are consistent with cardiac regeneration.
Clinical Trial Registration
This study is registered with clinicaltrials.gov, trial number NCT00474461.
Coronary artery bypass; heart failure; infarction; magnetic resonance imaging; stem cells; regeneration
The determination of the underlying etiology of symptoms suggestive of obstructive coronary artery disease (CAD, ≥50% stenosis in a major coronary artery) is a common clinical challenge in both primary care and cardiology clinics. Usual care in low to medium risk patients often involves a family history, risk factor assessment, and then stress testing with or without non-invasive imaging. If positive, this is often followed by invasive coronary angiography (ICA). Despite extensive adoption of this usual care paradigm, more than 60% of patients referred for angiography do not have obstructive CAD. In order to robustly identify those symptomatic patients without obstructive CAD, who can avoid subsequent cardiac testing and look elsewhere for the cause of their symptoms, a recently described whole blood gene expression score (GES: Corus® CAD, CardioDx, Inc., Palo Alto, CA) has been developed and validated in two multi-center trials. This paper reviews the published literature and assessments by independent parties regarding the analytical and clinical validity as well as the clinical utility of the Corus® CAD test.
Even among asymptomatic people at low risk (<10%) by Framingham Risk Score (FRS), high coronary artery calcium (CAC) scores signify higher predicted risk of coronary heart disease (CHD) events. We sought to determine non-invasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3046 participants from MESA at low 10-year predicted risk (FRS <10%) for CHD events. Multivariable logistic regression was used to assess the association of novel markers with presence of any CAC (CAC >0) and advanced CAC (CAC ≥ 300). CAC >0 and CAC ≥ 300 were present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen and sICAM were each associated with CAC presence (P ≤ 0.02); and C-reactive protein, D-dimer and carotid intima-media thickness (CIMT) with advanced CAC (P ≤ 0.03). The base model combining traditional risk factors had excellent discrimination for advanced CAC (C-statistic, 0.808). Addition of the 2 best-fit models combining biomarkers plus/minus CIMT improved the c-statistics to 0.822 and 0.820, respectively. All 3 models calibrated well, but were similar in estimating individual risk probabilities for advanced CAC (prevalence = 9.97%, 10.63% and 10.10% in the highest quartiles of predicted probabilities versus 0.26%, 0.26% and 0.26% in the lowest quartiles, respectively). In conclusion, in low risk individuals, traditional risk factors alone predicted advanced CAC with high discrimination and calibration. Biomarker combinations +/− CIMT were also significantly associated with advanced CAC, but improvement in prediction and estimation of clinical risk were modest compared to traditional risk factors alone.
coronary calcium; biomarkers; novel markers; low-risk; risk factors
Coronary MDCT angiography has been shown to be an accurate noninvasive tool for the diagnosis of obstructive coronary artery disease (CAD). Its sensitivity and negative predictive value for diagnosing percentage of stenosis are unsurpassed compared with those of other noninvasive testing methods. However, in its current form, it provides no information regarding the physiologic impact of CAD and is a poor predictor of myocardial ischemia. CORE320 is a multicenter multinational diagnostic study with the primary objective to evaluate the diagnostic accuracy of 320-MDCT for detecting coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected CAD compared with the reference standard of conventional coronary angiography and SPECT myocardial perfusion imaging.
We aim to describe the CT acquisition, reconstruction, and analysis methods of the CORE320 study.
coronary atherosclerosis; coronary CT angiography; myocardial CT perfusion imaging; myocardial ischemia; SPECT
Rationale: Sex hormones have effects on the left ventricle, but hormonal influences on the right ventricle (RV) are unknown.
Objectives: We hypothesized that sex hormones would be associated with RV morphology in a large cohort free of cardiovascular disease.
Methods: Sex hormones were measured by immunoassay and RV ejection fraction (RVEF), stroke volume (RVSV), mass, end-diastolic volume, and end-systolic volume (RVESV) were measured by cardiac magnetic resonance imaging in 1,957 men and 1,738 postmenopausal women. The relationship between each hormone and RV parameter was assessed by multivariate linear regression.
Measurements and Main Results: Higher estradiol levels were associated with higher RVEF (β per 1 ln[nmol/L], 0.88; 95% confidence interval [CI], 0.32 to 1.43; P = 0.002) and lower RVESV (β per 1 ln[nmol/L], −0.87; 95% CI, −1.67 to −0.08; P = 0.03) in women using hormone therapy. In men, higher bioavailable testosterone levels were associated with higher RVSV (β per 1 ln[nmol/L], 1.97; 95% CI, 0.20 to 3.73; P = 0.03) and greater RV mass and volumes (P ≤ 0.01). Higher dehydroepiandrosterone levels were associated with higher RVSV (β per 1 ln[nmol/L], 1.37; 95% CI, 0.15 to 2.59; P = 0.03) and greater RV mass (β per 1 ln[nmol/L], 0.25; 95% CI, 0.00 to 0.49; P = 0.05) and volumes (P ≤ 0.001) in women.
Conclusions: Higher estradiol levels were associated with better RV systolic function in women using hormone therapy. Higher levels of androgens were associated with greater RV mass and volumes in both sexes.
sex; sex hormones; right ventricle
Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114).
SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex.
After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48–5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19–1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02–12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes.
SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study.
The purpose of this study was to assess predictors of MRI-identified septal delayed enhancement mass at the right ventricular (RV) insertion sites in relation to RV remodeling, altered regional mechanics, and pulmonary hemodynamics in patients with suspected pulmonary hypertension (PH).
SUBJECTS AND METHODS
Thirty-eight patients with suspected PH were evaluated with right heart catheterization and cardiac MRI. Ten age- and sex-matched healthy volunteers acted as controls for MRI comparison. Septal delayed enhancement mass was quantified at the RV insertions. Systolic septal eccentricity index, global RV function, and remodeling indexes were quantified with cine images. Peak systolic circumferential and longitudinal strain at the sites corresponding to delayed enhancement were measured with conventional tagging and fast strain-encoded MRI acquisition, respectively.
PH was diagnosed in 32 patients. Delayed enhancement was found in 31 of 32 patients with PH and in one of six patients in whom PH was suspected but proved absent (p = 0.001). No delayed enhancement was found in controls. Delayed enhancement mass correlated with pulmonary hemodynamics, reduced RV function, increased RV remodeling indexes, and reduced eccentricity index. Multiple linear regression analysis showed RV mass index was an independent predictor of total delayed enhancement mass (p = 0.017). Regional analysis showed delayed enhancement mass was associated with reduced longitudinal strain at the basal anterior septal insertion (r = 0.6, p < 0.01). Regression analysis showed that basal longitudinal strain remained an independent predictor of delayed enhancement mass at the basal anterior septal insertion (p = 0.02).
In PH, total delayed enhancement burden at the RV septal insertions is predicted by RV remodeling in response to increased afterload. Local fibrosis mass at the anterior septal insertion is associated with reduced regional longitudinal contractility at the base.
delayed enhancement; fast strain-encoded imaging; MRI; pulmonary hypertension; tagging
Motivation: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape and wall motion and characterize cardiac function among and within population groups.
Results: Three main open-source software components were developed: (i) a database with web-interface; (ii) a modeling client for 3D + time visualization and parametric description of shape and motion; and (iii) open data formats for semantic characterization of models and annotations. The database was implemented using a three-tier architecture utilizing MySQL, JBoss and Dcm4chee, in compliance with the DICOM standard to provide compatibility with existing clinical networks and devices. Parts of Dcm4chee were extended to access image specific attributes as search parameters. To date, approximately 3000 de-identified cardiac imaging examinations are available in the database. All software components developed by the CAP are open source and are freely available under the Mozilla Public License Version 1.1 (http://www.mozilla.org/MPL/MPL-1.1.txt).
Supplementary information: Supplementary data are available at Bioinformatics online.
Although arrhythmogenic right ventricular dysplasia (ARVD) is characterized by predominantly right sided morphologic changes, genetic/histological and molecular changes are biventricular. Alterations in regional left ventricular (LV) strain in patients referred for suspicion of ARVD have not previously been determined.
Methods and Results
The study population included 21 patients with suspected ARVD who underwent evaluation with MRI including tagging. Eleven healthy volunteers served as controls. Global RV and LV function were studied by MRI and peak regional systolic circumferential strain (Ecc, %) was calculated by harmonic phase from tagged MRI based on a 16-segment model. Patients who met ARVD Task Force criteria were classified as definite ARVD, whereas patients with a positive family history who had one additional minor criterion and patients without a family history with at least 1 major or 2 minor criteria were classified as probable ARVD.
Of the 21 ARVD subjects, 11 had definite ARVD (63.6% males, mean age 41.2 ± 14.2 years) and, 10 had probable ARVD (30% males, 34.9 ± 12.1 years). Compared with controls (58.9 ± 6.2%), probable ARVD patients (53.6 ± 7.6%) had similar global RV ejection fraction (RVEF) (p> 0.05), but definite ARVD patients (45.2 ± 6.0%) had significantly reduced RVEF (p< 0.0001). Global LVEF was normal in all three groups (p>0.05). Compared to controls, mean LV circumferential strain (Ecc) was significantly reduced in 7/16 (44%) segments in definite ARVD, and 3/16 segments (19%) in probable ARVD (p< 0.05 for all).
There was a high prevalence of regional LV dysfunction in patients with definite ARVD, with less dysfunction in those with probable ARVD. Further, the extent of regional LV dysfunction appeared to parallel RV dysfunction, whereas global LV function was normal. Similar to the RV abnormalities, our findings suggest ARVD results in regional alterations of LV dysfunction prior to global abnormalities.
ARVD; LV involvement; tagging; regional strain
Proton MR spectroscopy (1H-MRS) has been used for in vivo quantification of intracellular triglycerides within the sarcolemma. The purpose of this study was to assess whether breath-hold dual-echo in- and out-of-phase MRI at 3.0 T can quantify the fat content of the myocardium. Biases, including T1,
T2∗, and noise, that confound the calculation of the fat fraction were carefully corrected. Thirty-four of 46 participants had both MRI and MRS data. The fat fractions from MRI showed a strong correlation with fat fractions from MRS (r = 0.78; P < 0.05). The mean myocardial fat fraction for all 34 subjects was 0.7 ± 0.5% (range: 0.11–3%) assessed with MRS and 1.04 ± 0.4% (range: 0.32–2.44%) assessed with in- and out-of-phase MRI (P < 0.05). Scanning times were less than 15 sec for Dixon imaging, plus an additional minute for the acquisition used for calculation, and 15-20 min for MRS. The average postprocessing time for MRS was 3 min and 5 min for MRI including
T2∗ measurement. We conclude that the dual echo method provides a rapid means to detect and quantifying myocardial fat content in vivo. Correction/adjustment for field inhomogeneity using three or more echoes seems crucial for the dual echo approach.
cardiac steatosis; Dixon; spectroscopy; magnetic resonance imaging; water-fat separation
Myocardial fat accumulation could occur in diseased hearts. The degree of heterogeneity is unknown because accurate assessment is difficult using conventional 1H-MRS techniques in a beating heart. The purpose of this study was to characterize the distribution of intramyocellular lipid content and to determine its association with disease characteristics. 1H-MRS was performed on formalin-fixed slices of human hearts at various circumferential locations (N=55). 29% of the hearts had the highest fat content measured in the septum, followed by posterior (27%), lateral (26%), and anterior (18%) wall. Age was significantly correlated with the mean fat percentages (r2=0.12, p=0.007). Those who died from cardiovascular disease demonstrated significantly higher and more heterogeneous fat distribution than those who did not (1.62±1.1% vs 0.59±0.4%, p=0.002). In summary, septal fat content is representative of mean fat percentage. Fat content increases with age; fat distribution may be heterogeneous when associated with cardiovascular disease.
cardiac steatosis; magnetic resonance spectroscopy; heterogeneity; ex-vivo
Left ventricular remodeling during the development of heart failure is a strong predictor of cardiovascular mortality. However, methods to objectively quantify remodeling-associated shape changes are not routinely available but may be possible with new computational anatomy tools. In this study, we analyzed and compared multi-detector computed tomographic (MDCT) images of ventricular shape at endsystole (ES) and end-diastole (ED) to determine whether regional structural characteristics could be identified and, as a proof of principle, whether differences in hearts of patients with anterior myocardial infarction (MI) and ischemic cardiomyopathy (ICM) could be distinguished from those with global nonischemic cardiomyopathy (NICM). MDCT images of hearts from 11 patients (5 with ICM) with ejection fractions (EF) > 35% were analyzed. An average ventricular shape model (template) was constructed for each cardiac phase by bringing heart shapes into correspondence using linear and nonlinear image matching algorithms. Next, transformation fields were computed between the template image and individual heart images in the population. Principal component analysis (PCA) method was used to quantify ventricular shape differences described by the transformation vector fields. Statistical analysis of PCA coefficients revealed significant ventricular shape differences at ED (p = 0.03) and ES (p = 0.03). For validation, a second set of 14 EF-matched patients (8 with ICM) were evaluated. The discrimination rule learned from the training data set was able to differentiate ICM from NICM patients (p = 0.008). Application of a novel shape analysis method to in vivo human cardiac images acquired on a clinical scanner is feasible and can quantify regional shape differences at end-systole in remodeled myopathic human myocardium. This approach may be useful in identifying differences in the remodeling process between ICM and NICM populations and possibly in differentiating the populations.
Cardiomyopathy; Imaging; Remodeling
To define age-related geometric changes of the aortic arch and determine their relationship to central aortic stiffness and left ventricular remodeling.
The proximal aorta has been shown to thicken, enlarge in diameter and lengthen with aging in humans. However, no systematic study has described age-related longitudinal and transversal remodeling of the aortic arch and their relationship with left ventricular mass and remodeling.
We studied 100 subjects (55 women, 45 men, average age: 46±16 years) free of overt cardiovascular disease using magnetic resonance imaging to determine aortic arch geometry (length, diameters, height, width and curvature), aortic arch function (local aortic distensibility and arch pulse wave velocity PWV) and left ventricular volumes and mass. Radial tonometry was used to calculate central blood pressure.
Aortic diameters and arch length increased significantly with age. The ascending aorta increased most with age leading to aortic arch widening and decreased curvature. These geometric changes of the aortic arch were significantly related to decreased ascending aortic distensibility, increased aortic arch PWV (p<0.001) and to increased central blood pressures (p<0.001). Increased ascending aortic diameter, lengthening and decreased curvature of the aortic arch (unfolding) were all significantly associated with increased LV mass and concentric remodeling independently of age, gender, body size and central blood pressure (p<0.01).
Age-related unfolding of the aortic arch is related to increased proximal aortic stiffness in individuals without cardiovascular disease and associated with increased LV mass and mass-to-volume ratio independent of age, body size, central pressure and cardiovascular risk factors.
magnetic resonance imaging; aortic geometry; aging; elasticity; left ventricular remodeling
We report relationships of cardiovascular disease (CVD) risk factors with myocardial structure, function and scar in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.
METHODS and RESULTS
Cardiac magnetic resonance (CMR) was obtained in 1017 patients with type 1 diabetes. Gadolinium CMR was also obtained in 741 patients. The mean age was 49 ± 7 years, 52% were men, and mean diabetes duration was 28± 5 years. Associations of CVD risk factors with CMR parameters were examined using linear and logistic regression models. History of macroalbuminuria was positively associated with LV mass (by +14.8 g) leading to a significantly higher LV mass/EDV ratio (by 8%). Mean hemoglobin A1c (HbA1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (−3.0 ml per unit mean HbA1c %) and stroke volume (−2.3 ml per unit mean HbA1c %) and positively related to elevated LV mass/EDV ratio (0.02 g/ml per unit). The overall prevalence of myocardial scar was 4.3% by CMR and 1.4% by clinical adjudication of myocardial infarction. Both mean HbA1c (Odds ratio (O.R.) 1.5 [1.0–2.2] per unit) and macroalbuminuria (OR 3.5 [1.2–9.9]) were significantly associated with myocardial scar as well as traditional CVD risk factors.
In addition to traditional CVD risk factors, elevated mean HbA1c and macroalbuminuria were significantly associated with alterations in LV structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function.
Myocardial function; myocardial scar; type 1 diabetes; delayed enhancement; CMR
The ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction.
Methods and Results
Ten dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm × 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1±7.2% versus 20.4±7.4%, mean difference 0.7%; chronic infarcts 4.15±1.93% versus 4.92±2.06%, mean difference −0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred ≈5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow.
The spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.
tomography; heart diseases; imaging; contrast media; myocardial infarction
The objective of this study was to investigate the impact of image acquisition settings and patients' characteristics on image quality and radiation dose for coronary angiography by 320-row computed tomography (CT). CORE320 is a prospective study to investigate the diagnostic performance of 320-detector CT for detecting coronary artery disease and associated myocardial ischemia. A run-in phase in 65 subjects was conducted to test the adequacy of the computed tomography angiography (CTA) acquisition protocol. Tube current, exposure window, and number of cardiac beats per acquisition were adjusted according to subjects' gender, heart rate, and body mass index (BMI). Main outcome measures were image quality, assessed by contrast/noise measurements and qualitatively on a 4-point scale, and radiation dose, estimated by the dose-length-product. Average heart rate at image acquisition was 55.0±7.3 bpm. Median Agatston calcium score was 27.0 (interquartile range 1–330). All scans were prospectively triggered. Single heart beat image acquisition was obtained in 61 of 65 studies (94%). Sixty-one studies (94%) and 437 of 455 arterial segments (96%) were of diagnostic image quality. Estimated radiation dose was significantly greater in obese (5.3±0.4 mSv) than normal weight (4.6±0.3 mSv) or overweight (4.7±0.3 mSv) subjects (P<0.001). BMI was the strongest factor influencing image quality (odds ratio=1.457, P=0.005). The CORE320 CTA image acquisition protocol achieved a good balance between image quality and radiation dose for a 320-detector CT system. However, image quality in obese subjects was reduced compared to normal weight subjects, possibly due to tube voltage/current restrictions mandated by the study protocol.
CT angiography; image acquisition; image quality; radiation dose; body mass index; contrast to noise ratio.
Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45–84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p = 0.008 and p = 0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p<0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p = 0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.
Inflammation; thrombosis; hypertension; pulmonary
Increasing evidence suggests that elevated plasma fibrinogen is associated with incident heart failure. However, the underlying pathophysiological mechanisms have not been well elucidated.
We examined the relationship between plasma fibrinogen level and peak systolic mid-wall circumferential strain(Ecc) at the base, mid-cavity and apex of the left ventricle measured by magnetic resonance imaging myocardial tagging in 1,096 participants without clinical cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis(MESA).
After adjustment for demographics, established risk factors and body-mass-index, elevated fibrinogen was independently associated with reductions in absolute Ecc indicative of impaired systolic function in all regions(all P=0.015). The relationships were consistently significant upon further adjustment for measures of atherosclerosis(all P≤0.024), and were modestly attenuated with regional heterogeneity after additional adjustment for other inflammatory biomarker and N-terminal pro-brain-natriuretic peptide. In this fully-adjusted model, every one-standard deviation(74mg/dL) increment in plasma fibrinogen was independently associated with a reduction in left ventricular absolute Ecc of 0.29%(95%CI=0.03%–0.59%, P=0.048) at the base, 0.22%(95%CI=0.006%–0.43%, P=0.044) at mid-cavity, 0.20%(95%CI=−0.035%–0.43%, P=0.097) at the apex, and 0.24%(95%CI=0.05–0.43, P=0.015) overall.
Among asymptomatic individuals without clinical cardiovascular disease, elevated fibrinogen is independently associated with impaired myocardial systolic function. These findings support roles of inflammation, procoagulation and hyperviscosity underlying hyperfibrinogenemia in the pathogenesis of incipient myocardial dysfunction.
epidemiology; heart failure; myocardial function; fibrinogen; hyperviscosity; hypercoagulability; magnetic resonance imaging
The impact of cardiovascular risk factors on the left ventricle is well known but their impact on right ventricle has not been studied using advanced imaging techniques. The purpose of this study was to determine the relation between cardiovascular risk factors and right ventricular (RV) structure and function and its interaction with the left ventricle. Cardiac magnetic resonance images were analyzed in 4204 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression models were used to study the cross sectional association between individual RV parameters and risk factors. All RV parameters except ejection fraction decreased with age (p<0.0001). RV mass was positively associated with systolic blood pressure (+0.4g, p<0.0001) and high density lipoprotein (HDL) cholesterol (+0.2g, p<0.0001); inversely with diastolic blood pressure (−0.3g, p<0.0001) and total cholesterol (−0.2g, p<0.01). RV end diastolic volume was positively associated with systolic blood pressure (+1.6ml, p<0.01) and HDL cholesterol (+1.8ml, p<0.0001); and inversely with diastolic blood pressure (−2.2 ml, p<0.0001), total cholesterol (−1.4ml, p<0.0001), current smoking (−2.7ml, p<0.05) and diabetes mellitus (−3.1ml, p<0.01). RV ejection fraction was positively related with systolic blood pressure (+1.0%, p<0.0001), HDL cholesterol (+0.4%, p<0.0001) and inversely with diastolic blood pressure (−0.7%, p<0.0001). In conclusion, the mass and volumes of the right ventricle decrease with age. Cardiovascular risk factors, especially blood pressure and HDL cholesterol are associated with subclinical changes in RV mass and volumes.
We sought to examine the relationship between circulating interleukin-6 (IL-6) level and regional left-ventricular (LV) function among apparently healthy individuals free of cardiovascular disease.
Methods and results
Using magnetic resonance myocardial tagging, we determined peak systolic circumferential strain (Ecc) as a measure of regional systolic function in 894 asymptomatic participants in the Multi-Ethnic Study of Atherosclerosis. Ecc was analysed by harmonic phase imaging separately in the LV anterior wall, septum, lateral wall, and inferior wall. Global Ecc was calculated as the average of Ecc in all myocardial segments. We performed multivariable linear regression to evaluate the independent associations between log IL-6 and Ecc, after adjusting for demographic features, cardiovascular risk factors, and markers of subclinical atherosclerosis. The inverse relationships between IL-6 and absolute Ecc were similar in both genders. In multivariable analysis, higher IL-6 level was independently associated with reduced systolic function (less negative Ecc) in the septum [regression coefficient = 1.03 per unit higher log IL-6, 95% confidence interval (CI) 0.26–1.79, P = 0.008] and inferior wall (regression coefficient = 1.65, 95% CI 0.74–2.56, P < 0.001), but not in the anterior wall (P = 0.27) or lateral wall (P = 0.52). Overall, there was an independent inverse association between IL-6 and global Ecc (regression coefficient = 0.94, 95% CI 0.37–1.51, P = 0.001). Compared with C-reactive protein, higher IL-6 level demonstrates a stronger independent association with reduced regional systolic function.
In asymptomatic men and women without documented cardiovascular disease, there is a strong, independent, inverse relationship between IL-6 and regional LV systolic function. These findings suggest that IL-6 may underlie the pathogenetic link between inflammation, LV dysfunction and incipient heart failure. The observed variable relationships between IL-6 and systolic function across different LV regions warrant further investigations.
Heart failure; Myocardial contraction; Interleukin-6; Magnetic resonance imaging