Wu, Katherine C. | Gerstenblith, Gary | Guallar, Eliseo | Marine, Joseph E. | Dalal, Darshan | Cheng, Alan | Marbán, Eduardo | Lima, João A.C. | Tomaselli, Gordon F. | Weiss, Robert G.
Background
Annually, ~80,000 Americans receive guideline-based primary prevention implantable cardioverter defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on LVEF, which lacks sensitivity and specificity. Because scar-related, myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance (CMR) identification of myocardial heterogeneity improves risk stratification through: (1) its association with adverse cardiac events independent of clinical factors and biomarker levels; and (2) its ability to identify particularly high- and low-risk subgroups.
Methods and Results
In 235 ischemic and nonischemic patients with LVEF≤35%, undergoing clinically-indicated primary prevention ICD, gadolinium-enhanced CMR was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone-GZ) and dense core scar. Serum high sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary endpoint was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 patients (19%) at 3.6 year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ and core were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (p<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7%/year event rate) while those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1%/year, p<0.001.
Conclusions
In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk of adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00181233.
doi:10.1161/CIRCIMAGING.111.968024
PMCID: PMC3330427
PMID: 22267750
implantable cardioverter-defibrillator; myocardial delayed enhancement; cardiovascular magnetic resonance imaging; cardiomyopathy; ventricular arrhythmia
Background
The association of right ventricular (RV) structure and function with symptoms in individuals without cardiopulmonary disease is unknown. We hypothesized that greater RV mass and RV end-diastolic volume (RVEDV), smaller RV stroke volume (RVSV), and lower RV ejection fraction (RVEF) measured by cardiac magnetic resonance imaging (MRI) in participants free of clinical cardiovascular disease at baseline would be associated with a greater risk of self-reported dyspnea.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRIs on participants without clinical cardiovascular disease between 2000 and 2002. We excluded subjects who reported “prevalent” dyspnea at the first assessment (24 months). The presence of dyspnea was assessed at 24 months, 42 months, and 60 months from baseline. Cox proportional hazards models were used to examine the relationship between RV measures and incident dyspnea.
Results
In the final study sample (N = 2763), there were significant interactions between RV measures and sex in terms of the risk of dyspnea (p<0.05). Among men (N = 1453), lower RV mass (p = 0.003), smaller RVEDV (p<0.001), smaller RV end-systolic volume (RVESV) (p = 0.03) and decreased RVSV (p<0.001) were associated with an increased risk of developing dyspnea after adjusting for covariates. Associations remained after adjusting for left ventricular function and lung function. However, there were no significant associations between RV measures and the risk of dyspnea in women.
Conclusions
Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.
doi:10.1371/journal.pone.0056826
PMCID: PMC3574101
PMID: 23457622
Nacif, Marcelo Souto | Turkbey, Evrim B. | Gai, Neville | Nazarian, Saman | Geest, Rob J. van der | Noureldin, Radwa A | Sibley, Christopher T | Ugander, Martin | Liu, Songtao | Arai, Andrew E. | Lima, João A. C. | Bluemke, David A
PURPOSE
To evaluate the relationship between “Look-Locker” (LL) and modified Look-Locker Inversion recovery (MOLLI) approaches for T1 mapping of the myocardium.
MATERIALS AND METHODS
168 myocardial T1 maps using MOLLI and 165 maps using LL were obtained in human subjects at 1.5 Tesla. The T1 values of the myocardium were calculated before and at five time points after gadolinium administration. All time and heart rate normalizations were done. The T1 values obtained were compared to determine the absolute and bias agreement.
RESULTS
The pre-contrast global T1 values were similar when measured by the LL and by MOLLI technique (mean 1004.9 ms +/- 120.3 vs. 1034.1 ms +/- 53.1, respectively, p = 0.26). Post-contrast myocardial T1 time from LL was significantly longer than MOLLI from 5 to 25 minutes (mean difference, LL - MOLLI was +61.8 +/- 46.4 ms, p < 0.001). No significant differences in T1 values were noted between long and short axis measurements for either MOLLI or LL.
CONCLUSION
Post-contrast LL and MOLLI showed very good agreement, although LL vaules are higher than MOLLI. Pre-contrast T1 values showed good agreement, however LL has greater limits of agreement. Short and long axis planes can reliably assess T1 values.
doi:10.1002/jmri.22753
PMCID: PMC3221792
PMID: 21954119
Magnetic resonance imaging; diffuse myocardium fibrosis; T1 mapping
Objective
The aim of this study was to use multi-detector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.
Background
Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical setting. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).
Methods
Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n=9) or 200 million mesenchymal stem cells (MSCs, n=13), twelve weeks after myocardial infarction (MI). Cardiac MRI and MDCT acquisitions were performed prior to randomization 12 weeks after MI induction and at the study endpoint 24 week post-MI. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV-volumes and LVEF. Delayed enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.
Results
MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3±1.2% to 10.3±1.5% of LV-mass (p=0.005) while infarct size increased in non-treated animals (from 13.8±1.3% to 16.5±1.5%; p=0.02) (Placebo vs MSC; p=0.003). Both observers had excellent agreement for infarct size (r=0.96; p<0.001). LVEF increased from 32.6±2.2% to 36.9±2.7% in MSC treated animals (p=0.03) and decreased in placebo animals (from 33.3±1.4 to 29.1±1.5%; p=0.01; at week 24: placebo vs MSC p=0.02). Infarct size, end-diastolic LV volume and LVEF assessed by MDCT compared favorably with MRI acquisitions (r=0.70; r=0.82; r=0.902; respectively, p<0.001).
Conclusions
This study demonstrates that cardiac MDCT can be used to evaluate infarct size, LV-volumes, and LVEF after intramyocardial delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies. (word count 299)
doi:10.1016/j.jcmg.2011.09.013
PMCID: PMC3245738
PMID: 22172785
MDCT; MRI; Delayed Contrast Enhancement; Göttingen Minipig; Mesenchymal Stem Cell; Myocardial Infarction; Heart failure
Schuleri, Karl H. | Centola, Marco | George, Richard T. | Amado, Luciano C. | Evers, Kristine S. | Kitagawa, Kakuya | Vavere, Andrea L. | Evers, Robert | Hare, Joshua M. | Cox, Christopher | McVeigh, Elliot R. | Lima, João A.C. | Lardo, Albert C.
Objectives
We examined whether MDCT improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to MRI.
Background
The PIZ as characterized by delayed enhanced (de) MRI identifies patients susceptible to ventricular arrhythmias and predicts outcome after myocardial infarction (MI).
Methods
Fifteen mini-pigs underwent coronary artery occlusion followed by reperfusion. MDCT and MRI were performed on the same day approximately 6 months after MI induction followed by animal sacrifice and ex-vivo MRI (n=5). Signal density threshold algorithms were applied to MRI and MDCT data sets reconstructed at various slice thicknesses (1–8mm) to define the PIZ and quantify partial volume effects.
Results
De-MDCT reconstructed at 8mm slice thickness demonstrated excellent correlation of infarct size with post mortem pathology (r2=0.97; p<0.0001) and MRI (r2=0.92; p<0.0001). De-MDCT and de-MRI were able to detect a PIZ in all animals, which correlates to a mixture of viable and non-viable myocytes at the PIZ by histology. The ex-vivo de-MRI PIZ volume decreased with slice thickness from 0.9±0.2cc at 8mm to 0.2±0.1cc at 1mm (p=0.01). PIZ volume/mass by de-MDCT increased with decreasing slice thickness due to declining partial volume averaging in the PIZ, but was susceptible to increased image noise.
Conclusion
De-MDCT provides a more detailed assessment of the PIZ in chronic MI and is less susceptible to partial volume effects than MRI. This increased resolution best reflects the extent of tissue mixture by histopathology and has the potential to further enhance the ability to define the substrate of malignant arrhythmia in ischemic heart disease non-invasively.
doi:10.1016/j.jacc.2009.01.056
PMCID: PMC3381611
PMID: 19406346
MDCT; delayed enhancement; peri-infarct zone; MRI
Quantitative T1 mapping of delayed gadolinium-enhanced cardiac magnetic resonance imaging has shown promise in identifying diffuse myocardial fibrosis. Despite careful control of magnetic resonance imaging parameters, comparison of T1 times between different patients may be problematic because of patient specific factors such as gadolinium dose, differing glomerular filtration rates, and patient specific delay times. In this work, a model driven approach to account for variations between patients to allow for comparison of T1 data is provided. Kinetic model parameter values were derived from healthy volunteer time-contrast curves. Correction values for the factors described above were used to normalize T1 values to a matched state. Examples of pre- and postcorrected values for a pool of normal subjects and in a patient cohort of type 1 diabetic patients shows tighter clustering and improved discrimination of disease state.
doi:10.1002/mrm.22716
PMCID: PMC3092826
PMID: 21500267
T1 mapping; myocardial fibrosis; patient T1 comparison; GFR; delayed enhancement
Kawut, Steven M. | Lima, João A.C. | Barr, R. Graham | Chahal, Harjit | Jain, Aditya | Tandri, Harikrishna | Praestgaard, Amy | Bagiella, Emilia | Kizer, Jorge R. | Johnson, W. Craig | Kronmal, Richard A. | Bluemke, David A.
Background
Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease, however determinants of RV anatomy have not been well-studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants. RV volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived using an allometric approach. The study sample (N = 4123) was 61.5 ± 10.1 years old and 47.5% male. Older age was associated with lower RV mass (~5% lower mass per decade) with larger age-related decrements in men than in women (p for interaction < 0.05). Older age was also associated with higher RV ejection fraction (RVEF), an association which differed between races/ethnicities (p for interaction ≤ 0.01). Overall, men had greater RV mass (~8%) and larger RV volumes than women, but had lower RVEF (4% in absolute terms) (p < 0.001). African Americans had lower RV mass than Caucasians (p ≤ 0.002), whereas Hispanics had higher RV mass (p ≤ 0.02). Using the derived normative equations, 7.3% (95%CI, 6.5–8.1%) met criteria for RV hypertrophy and 5.9% (95%CI, 5.2–6.6%) had RV dysfunction.
Conclusions
In conclusion, age, sex, and race are associated with significant differences in RV mass, RV volumes and RVEF, potentially explaining distinct responses of the RV to cardiopulmonary disease.
doi:10.1161/CIRCULATIONAHA.110.985515
PMCID: PMC3111939
PMID: 21646505
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension
OBJECTIVE:
The aim of this study was to evaluate some features of article titles from open access journals and to assess the possible impact of these titles on predicting the number of article views and citations.
METHODS:
Research articles (n = 423, published in October 2008) from all Public Library of Science (PLoS) journals and from 12 Biomed Central (BMC) journals were evaluated. Publication metrics (views and citations) were analyzed in December 2011. The titles were classified according to their contents, namely methods-describing titles and results-describing titles. The number of title characters, title typology, the use of a question mark, reference to a specific geographical region, and the use of a colon or a hyphen separating different ideas within a sentence were analyzed to identify predictors of views and citations. A logistic regression model was used to identify independent title characteristics that could predict citation rates.
RESULTS:
Short-titled articles had higher viewing and citation rates than those with longer titles. Titles containing a question mark, containing a reference to a specific geographical region, and that used a colon or a hyphen were associated with a lower number of citations. Articles with results-describing titles were cited more often than those with methods-describing titles. After multivariate analysis, only a low number of characters and title typology remained as predictors of the number of citations.
CONCLUSIONS:
Some features of article titles can help predict the number of article views and citation counts. Short titles presenting results or conclusions were independently associated with higher citation counts. The findings presented here could be used by authors, reviewers, and editors to maximize the impact of articles in the scientific community.
doi:10.6061/clinics/2012(05)17
PMCID: PMC3351256
PMID: 22666797
Articles; Citations; Visualization; Titles
Background
Clinical studies implementing late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) studies suggest that the peri-infarct zone (PIZ) contains a mixture of viable and non-viable myocytes, and is associated with greater susceptibility to ventricular tachycardia induction and adverse cardiac outcomes. However, CMR data assessing the temporal formation and functional remodeling characteristics of this complex region are limited. We intended to characterize early temporal changes in scar morphology and regional function in the PIZ.
Methods and results
CMR studies were performed at six time points up to 90 days after induction of myocardial infarction (MI) in eight minipigs with reperfused, anterior-septal infarcts. Custom signal density threshold algorithms, based on the remote myocardium, were applied to define the infarct core and PIZ region for each time point. After the initial post-MI edema subsided, the PIZ decreased by 54% from day 10 to day 90 (p = 0.04). The size of infarct scar expanded by 14% and thinned by 56% from day 3 to 12 weeks (p = 0.004 and p < 0.001, respectively). LVEDV increased from 34.7. ± 2.2 ml to 47.8 ± 3.0 ml (day3 and week12, respectively; p < 0.001). At 30 days post-MI, regional circumferential strain was increased between the infarct scar and the PIZ (-2.1 ± 0.6 and -6.8 ± 0.9, respectively;* p < 0.05).
Conclusions
The PIZ is dynamic and decreases in mass following reperfused MI. Tensile forces in the PIZ undergo changes following MI. Remodeling characteristics of the PIZ may provide mechanistic insights into the development of life-threatening arrhythmias and sudden cardiac death post-MI.
doi:10.1186/1532-429X-14-24
PMCID: PMC3352163
PMID: 22510220
Cardiovascular magnetic resonance imaging; Myocardial infarction; Late gadolinium enhancement; Peri-infarct zone; Myocardial strain
Background
Alcohol use has been consistently found to have a J-shaped association with coronary heart disease, with moderate drinkers exhibiting a decreased risk compared to both heavy drinkers and non-drinkers. However, studies of the association between alcohol use and subclinical coronary artery disease have conflicted.
Objective
To determine whether alcohol is associated with the presence, amount, or progression of coronary calcium over a 2- to 4-year period.
Design
MESA is a prospective community-based cohort study of subclinical cardiovascular disease in a multi-ethnic cohort. In 2000–2002, 6814 participants free of clinical cardiovascular disease were enrolled at 6 participating centers.
Results
There were 3766 (55.5%) current drinkers, 1635 (24.1%) former drinkers, and 1390 (20.5%) never drinkers included in the analysis. Although light to moderate alcohol consumption was associated with lower coronary heart disease risk, we found no evidence of a protective or J-shaped association of alcohol and coronary artery calcium (CAC). In fact there was evidence that heavy consumption of hard liquor was associated with greater CAC accumulation. Other alcoholic beverages were not associated with CAC prevalence, incidence or progression.
Conclusions
This is the first large study to evaluate the association of alcohol and coronary artery calcium in four racial/ethnic groups, and to evaluate progression of calcification. These results suggest that the cardiovascular benefits that may be derived from light to moderate alcohol consumption are not mediated through reduced CAC accumulation.
doi:10.3945/ajcn.2008.26420
PMCID: PMC3319440
PMID: 19064520
Gottlieb, Ilan | Miller, Julie M. | Arbab-Zadeh, Armin | Dewey, Marc | Clouse, Melvin E. | Sara, Leonardo | Niinuma, Hiroyuki | Bush, David E. | Paul, Narinder | Vavere, Andrea L. | Texter, John | Brinker, Jeffery | Lima, João A. C. | Rochitte, Carlos E.
Objectives
This study was designed to evaluate whether the absence of coronary calcium could rule out ≥50% coronary stenosis or the need for revascularization.
Background
The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients.
Methods
A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before.
Resutls
In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 ± 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of ≥50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 ≥50% stenosis. The overall sensitivity for CS = 0 to predict the absence of ≥50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with ≥50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium.
Conclusions
The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification.
doi:10.1016/j.jacc.2009.07.072
PMCID: PMC3294287
PMID: 20170786
coronary artery disease; calcium score; computed tomography; coronary angiography; coronary stenosis
Background
Racial/ethnic differences in the incidence and severity of heart failure (HF) are not well understood, but may be related to pre-existing variations in myocardial function.
Objective
To examine racial/ethnic differences in regional myocardial function among asymptomatic individuals free of known cardiovascular disease.
Design, setting and patients
The Multi-Ethnic Study of Atherosclerosis is a prospective, observational study of individuals without baseline cardiovascular disease, representing four major racial/ethnic groups. A total of 1099 study participants underwent cardiac MRI with tissue tagging; for each study, peak systolic strain (Ecc) and strain rate (SRs) were determined in four left ventricular (LV) regions.
Main outcome measures
Multiple linear regression was used to analyse the relationship between race/ethnicity and regional strain (Ecc and SRs) while adjusting for cardiovascular risk factors.
Results
Compared with other racial/ethnic groups, Chinese-Americans had the greatest magnitude of Ecc in a majority of LV regions (–19.60±3.78, p<0.05); Chinese-Americans also had the greatest absolute values for SRs in all regions, reflecting higher rate of systolic contraction (–2.01±0.76, p<0.05). Conversely, African-Americans had the lowest Ecc values (–17.50±4.00, p<0.05) in the majority of wall regions while Hispanics demonstrated the lowest rate of contractility in all wall regions (–1.44±0.50, p≤0.001) in comparison with the other racial/ethnic groups. These race-based differences remained significant in the majority of LV wall regions after adjusting for multiple variables, including hypertension and LV mass.
Conclusions
Important race-based differences in regional LV systolic function in a large cohort of asymptomatic individuals have been demonstrated. Further research is needed to investigate the possible mechanisms related to the race/ethnicity-based variations found in this study.
doi:10.1136/hrt.2010.209452
PMCID: PMC3034784
PMID: 21258000
Miller, Julie M. | Dewey, Marc | Vavere, Andrea L. | Rochitte, Carlos E. | Niinuma, Hiroyuki | Arbab-Zadeh, Armin | Paul, Narinder | Hoe, John | de Roos, Albert | Yoshioka, Kunihiro | Lemos, Pedro A. | Bush, David E. | Lardo, Albert C. | Texter, John | Brinker, Jeffery | Cox, Christopher | Clouse, Melvin E. | Lima, João A. C.
Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its noninvasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective “CORE-64” trial (“Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors”). This multi-centre trialwas unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.
doi:10.1007/s00330-008-1203-7
PMCID: PMC3289939
PMID: 18998142
Computed tomography; Coronary vessels; Multi-centre study; Methods; Design
Aaron, Carrie P. | Tandri, Harikrishna | Barr, R. Graham | Johnson, W. Craig | Bagiella, Emilia | Chahal, Harjit | Jain, Aditya | Kizer, Jorge R. | Bertoni, Alain G. | Lima, João A. C. | Bluemke, David A. | Kawut, Steven M.
Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown.
Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent–minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity.
Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes.
Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications.
doi:10.1164/rccm.201003-0469OC
PMCID: PMC3056232
PMID: 20813888
exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging
Jain, Aditya | McClelland, Robyn L. | Polak, Joseph F. | Shea, Steven | Burke, Gregory L. | Bild, Diane E. | Watson, Karol E. | Budoff, Matthew J. | Liu, Kiang | Post, Wendy S. | Folsom, Aaron R. | Lima, João A.C. | Bluemke, David A.
Background
Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD.
Methods and Results
The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05).
Conclusions
There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.
doi:10.1161/CIRCIMAGING.110.959403
PMCID: PMC3037859
PMID: 21068189
imaging; cardiovascular diseases; sex
Arnett, Donna K | McClelland, Robyn L | Bank, Alan | Bluemke, David A | Cushman, Mary | Szalai, Alexander J | Jain, Nishank | Gomes, Antoinette S | Heckbert, Susan R | Hundley, W Gregory | Lima, João A
Purpose
Biomarkers of inflammation and hemostasis have been associated with left ventricular (LV) mass. We studied relationships of C-reactive protein (CRP), interleukin-6 (IL6), D-dimer, soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor 1 (PAI-1), soluble thrombomodulin (sTM), soluble tumor necrosis factor type 1 receptor (sTNFR1), von Willebrand factor (vWF), soluble E-selectin (sE-selectin), factor VIII, fibrinogen, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) with LV mass in an asymptomatic population. Multi-Ethnic Study of Atherosclerosis participants underwent magnetic resonance imaging to characterize LV mass; biomarkers were measured using standardized protocols (N = 763 to 4979). Adjusted models were used to associate each biomarker with LV mass while correcting for potential confounding.
Findings
LV mass was associated with many biomarkers after adjustment for demographic characteristics and traditional cardiovascular risk factors. Although the demographic and risk factor adjustments attenuated the association of CRP and IL6 with LV mass, further adjustment for weight changed regression coefficients from positive to negative for CRP and IL6 for LV mass. sTM, Factor VIII, and vWF were directly associated with LV mass in fully-adjusted models. For sTNFR1, sICAM-1, D-dimer, fibrinogen, and PAI-1, adjustment for risk factors and weight rendered associations with LV mass nonsignificant.
Conclusions
In this large cohort free of clinical cardiovascular disease, several hemostasis and inflammation markers were associated with LV mass. The unusual finding of a negative relationship of CRP and IL6 with LV mass only after adjustment for weight suggests that the effects of inflammation on LV mass are strongly influenced by obesity.
PMCID: PMC3243453
PMID: 22200000
Left ventricle; biomarker; hemostasis; inflammation
Anderson, Jennifer S. | Nettleton, Jennifer A. | Hundley, W. Gregory | Tsai, Michael Y. | Steffen, Lyn M. | Lemaitre, Rozenn N. | Siscovick, David | Lima, João | Prince, Martin R. | Herrington, David
Background. The association between plasma omega-6 fatty acids and cardiovascular disease (CVD) is unclear, and discrepancy remains concerning the cardiovascular benefit of the omega-3 fatty acid alpha-linolenic acid. Methods. Associations of plasma phospholipid fatty acid levels (arachidonic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid (DHA), and alpha-linolenic acid) with cardiac magnetic resonance imaging measures of left ventricular (LV) mass, LV volume, ejection fraction, stroke volume, and aortic distensibility were investigated in 1,274 adults. Results. Results of multivariate analysis showed no statistically significant associations of plasma omega-6 or omega-3 levels with cardiac magnetic resonance imaging measures. Stratification by gender revealed a positive association between DHA and LV mass in women (β = 1.89, P = 0.02; P interaction = 0.003) and a trend for a positive association between DHA and ejection fraction in men (β = 0.009, P = 0.05; P interaction = 0.03). Conclusion. Additional research is warranted to clarify the effects of plasma DHA on cardiac structure and function in women versus men.
doi:10.1155/2011/315134
PMCID: PMC3159987
PMID: 21869927
Background
Increased arterial stiffness could represent an intermediate subclinical outcome in the mechanistic pathway underlying associations between average long-term pollution exposure and cardiovascular events.
Objective
We hypothesized that 20 years of exposure to particulate matter (PM) ≤ 2.5 and 10 μm in aerodynamic diameter (PM2.5 and PM10, respectively) would be positively associated with arterial stiffness in 3,996 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were seen at six U.S. study sites.
Methods
We assigned pollution exposure during two decades preceding a clinical exam (2000–2002) using observed PM10 from monitors nearest participants’ residences and PM10 and PM2.5 imputed from a space-time model. We examined three log-transformed arterial stiffness outcome measures: Young’s modulus (YM) from carotid artery ultrasound and large (C1) and small (C2) artery vessel compliance from the radial artery pulse wave. All associations are expressed per 10 μg/m3 increment in PM and were adjusted for weather, age, sex, race, glucose, triglycerides, diabetes, waist:hip ratio, seated mean arterial pressure, smoking status, pack-years, cigarettes per day, environmental tobacco smoke, and physical activity. C1 and C2 models were further adjusted for heart rate, weight, and height.
Results
Long-term average particle exposure was not associated with greater arterial stiffness measured by YM, C1, or C2, and the few associations observed were not robust across metrics and adjustment schemes.
Conclusions
Long-term particle mass exposure did not appear to be associated with greater arterial stiffness in this study sample.
doi:10.1289/ehp.0901524
PMCID: PMC3114821
PMID: 21245016
air pollution; arterial stiffness; environmental air pollutants; epidemiology
Background
Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for LV mass measurement. Ethnicity is believed to affect ECG performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity.
Methods and Results
Data were analyzed from 4967 participants (48% males, mean age 62 ± 10 years; 39% Caucasian, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 yearsfor incident CVD. Thirteen traditional ECG-LVH criteria were assessed and showed overall and ethnicity-specific low sensitivity (10–26%) and high specificity (88–99%) in diagnosing MRI-defined LVH. 10 out of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared to Caucasians (p=0.02–0.001). The sum of amplitudes of S wave in V1, S wave in V2 and R wave in V5 (a MESA specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared to prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (ROC area=0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product and Framingham-adjusted Cornell voltage predicted increased CVD risk (p<0.05).
Conclusions
ECG has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared to other ethnic groups.
doi:10.1016/j.ahj.2009.12.035
PMCID: PMC2856691
PMID: 20362725
Giles, Jon T. | Malayeri, Ashkan A. | Fernandes, Veronica | Post, Wendy | Blumenthal, Roger S. | Bluemke, David | Vogel-Claussen, Jens | Szklo, Moyses | Petri, Michelle | Gelber, Allan C. | Brumback, Lyndia | Lima, João | Bathon, Joan M.
Background
Heart failure is a major contributor to cardiovascular morbidity and mortality in rheumatoid arthritis. However, little is known about myocardial structure and function in this population.
Methods
Using cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with rheumatoid arthritis enrolled in ESCAPE RA, a cohort study of subclinical cardiovascular disease in rheumatoid arthritis, and compared with controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.
Results
Myocardial measures were compared between 75 rheumatoid arthritis patients and 225 matched controls. After adjustment, mean left-ventricular mass was 26 grams lower for the RA group compared to controls (p<0.001), an 18% difference. After similar adjustment, mean left-ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the rheumatoid arthritis group vs. controls. Mean left-ventricular end-systolic and end-diastolic volumes did not differ by rheumatoid arthritis status. Within the rheumatoid arthritis group, higher levels of anti-CCP antibodies and current use of biologics, but not other disease activity or severity measures, were associated with significantly lower adjusted mean left-ventricular mass, end-diastolic volume, and stroke volume, but not ejection fraction. The combined associations of anti-CCP antibody level and biologic use on myocardial measures were additive, without evidence of interaction.
Conclusions
These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and non-modifiable factors may contribute to lower levels of left-ventricular mass and volume.
doi:10.1002/art.27349
PMCID: PMC3008503
PMID: 20131277
myocardial dysfunction; heart failure; inflammation; cardiac imaging
Methods to index left ventricular (LV) mass, measured by cardiovascular magnetic resonance (CMR), for body size have not been investigated. The purposes of this study were to develop allometric indices for LV mass measured by CMR and compare estimates of the prevalence and predictive value of LV hypertrophy defined by a new allometric height-weight index, LV mass/body surface area (BSA), height indices (a new allometric height index; and previously derived indices from echocardiographic measurements: LV mass/height2, LV mass/height2.7), and non-indexed LV mass. 5,004 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with CMR measurements of LV mass and no clinical cardiovascular disease at baseline were followed for a median of 4.1 years. The new indices and limits for hypertrophy (95th percentile) were derived from 822 normal-weight, normotensive, non-diabetic MESA participants. 107 events (coronary heart disease or stroke) were observed. The estimated prevalence of hypertrophy at baseline and hazard ratio for event associated with hypertrophy were 8% and 2.4 with the new allometric height-weight index, 11% and 2.2 with LV mass/BSA, 23–24% and 2.0–2.1 with height indices, and 20% and 1.7 with non-indexed LV mass. A statistically significant difference was detected between the hazard ratios based on the new height-weight index and non-indexed LV mass. The prevalence of hypertrophy is higher for indices that do not account for weight. The predictive value of hypertrophy is significantly better with the new allometric height-weight index than with non-indexed LV mass and may be better than indices without weight.
doi:10.1007/s10554-010-9584-5
PMCID: PMC3037862
PMID: 20107905
Cardiovascular risk; Hypertension; Hypertrophy; LV mass index; Magnetic resonance imaging; Obesity
Chamaecrista belongs to subtribe Cassiinae (Caesalpinioideae), and it comprises over 330 species, divided into six sections. The section Xerocalyx has been subjected to a profound taxonomic shuffling over the years. Therefore, we conducted a phylogenetic analysis using a cpDNA trnE-trnT intergenic spacer and nrDNA ITS/5.8S sequences from Cassiinae taxa, in an attempt to elucidate the relationships within this section from Chamaecrista. The tree topology was congruent between the two data sets studied in which the monophyly of the genus Chamaecrista was strongly supported. Our analyses reinforce that new sectional boundaries must be defined in the Chamaecrista genus, especially the inclusion of sections Caliciopsis and Xerocalyx in sect. Chamaecrista, considered here paraphyletic. The section Xerocalyx was strongly supported as monophyletic; however, the current data did not show C. ramosa (microphyllous) and C. desvauxii (macrophyllous) and their respective varieties in distinct clades, suggesting that speciation events are still ongoing in these specimens.
doi:10.1590/S1415-47572011000200014
PMCID: PMC3115318
PMID: 21734825
phylogeny; ITS/5.8S; Chamaecrista; Xerocalyx; trnE-trnT intergenic spacer
OBJECTIVES
The purpose of this study was to evaluate the relationship of left ventricular (LV) remodeling assessed by cardiac magnetic resonance to various measures of obesity in a large population-based study.
BACKGROUND
Obesity is a well-known risk factor for cardiovascular disease, yet its relationship with LV size and function is poorly understood.
METHODS
A total of 5,098 participants (age 45 to 84 years; 48% men) in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cardiovascular disease underwent cardiac magnetic resonance to assess LV size and function as well as measures of obesity, including body mass index, waist-to-hip ratio and waist circumference, and cardiovascular risk factors. Fat mass (FM) was estimated based on height-weight models derived from bioelectrical impedance studies. The associations of obesity measures with LV size and function were evaluated using linear spline regression models for body mass index and multivariable regression models for other measures of obesity; they were displayed graphically using generalized additive models.
RESULTS
LV mass and end-diastolic volume were positively associated with measures of obesity in both sexes after adjustment for risk factors (e.g., 5.7-g and 6.9-g increase in LV mass per 10-kg increase in FM in women and men, respectively [p < 0.001]). LV mass-to-volume ratio was positively associated with increased body mass index, waist-to-hip ratio, waist circumference, and estimated FM (e.g., 0.02-g/ml and 0.06-g/ml increase in mass-to-volume ratio per 10-kg increase in FM in women and men, respectively [p < 0.001]). The increased mass-to-volume ratio was due to a greater increase in LV mass relative to LV end-diastolic volume. All associations were stronger for men than for women. Ejection fraction showed no significant association with measures of obesity.
CONCLUSIONS
Obesity was associated with concentric LV remodeling without change in ejection fraction in a large, multiethnic cohort study.
doi:10.1016/j.jcmg.2009.10.012
PMCID: PMC3037096
PMID: 20223423
cardiac magnetic resonance; cardiac morphology; epidemiology; left ventricular function; obesity
Background
The relationship between incident congestive heart failure (CHF) and ethnicity as well as racial/ethnic differences in the mechanisms leading to CHF have not been demonstrated in a multiracial, population-based study. Our objective was to evaluate the relationship between race/ethnicity and incident CHF.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a cohort study of 6814 participants of 4 ethnicities: white (38.5%), African American (27.8%), Hispanic (21.9%), and Chinese American (11.8%). Participants with a history of cardiovascular disease at baseline were excluded. Cox proportional hazards models were used for data analysis.
Results
During a median follow-up of 4.0 years, 79 participants developed CHF (incidence rate: 3.1 per 1000 person-years). African Americans had the highest incidence rate of CHF, followed by Hispanic, white, and Chinese American participants (incidence rates: 4.6, 3.5, 2.4, and 1.0 per 1000 person-years, respectively). Although risk of developing CHF was higher among African American compared with white participants (hazard ratio, 1.8; 95% confidence interval, 1.1-3.1), adding hypertension and/or diabetes mellitus to models including ethnicity eliminated statistical ethnic differences in incident CHF. Moreover, African Americans had the highest proportion of incident CHF not preceded by clinical myocardial infarction (75%) compared with other ethnic groups (P = .06).
Conclusions
The higher risk of incident CHF among African Americans was related to differences in the prevalence of hypertension and diabetes mellitus as well as socioeconomic status. The mechanisms of CHF also differed by ethnicity; interim myocardial infarction had the least influence among African Americans, and left ventricular mass increase had the greatest effect among Hispanic and white participants.
doi:10.1001/archinte.168.19.2138
PMCID: PMC3038918
PMID: 18955644
Objective
Coronary artery wall magnetic resonance imaging (MRI) has been developed to assess coronary lumen diameter and wall thickness. The purpose of this study was to evaluate the physiological parameters that affect the measures of coronary wall thickness using black-blood MRI pulse sequences.
Methods
Eighty-seven participants (38 men and 49 women) of the Multi-Ethnic Study of Atherosclerosis were enrolled in the coronary artery wall MRI study. Cine 4-chamber imaging was used to determine the coronary artery rest period. Free-breathing whole-heart magnetic resonance angiography with motion adaptor navigator was performed to localize the coronary arteries in 64 participants. Cross-sectional free-breathing black-blood images were acquired using electrocardiogram-gated, turbo spin echo sequence. Imaging parameters were as follows: repetition time = 2 R-R intervals, time to echo = 33 milliseconds, echo train length = 13, bandwidth = 305 Hz/pixel, matrix = 416 × 416, field of view = 420 × 420 mm, and slice thickness = 4 to 5 mm.
Results
Imaging was completed in 215 (92%) of 234 coronary segments; 9 participants had incomplete scans. Mean age was 62.6 ± 8.4 years (range, 45–81 years). Mean body mass index was 29.2 ± 5.9 kg/m2. A higher proportion of images with quality of “good” was seen in the right coronary artery (40.5%) compared to the left main and left anterior descending coronary arteries (31.9% and 26.4%, respectively). There was a very good agreement between observers in the image quality scores (κ = 0.79, P < 0.001). Lower heart rate, male sex, and longer coronary rest period were associated with higher image quality score (P < 0.05). Signal-to-noise ratio was higher in participants with Agatston calcium score of more than 10 in the right coronary and left main arteries (48.5 vs 69.7, P = 0.001; and 53.4 vs 61.6, P = 0.032, respectively).
Conclusion
Improved depiction of the coronary artery wall with MRI is related to coronary rest period and atherosclerotic plaque burden as measured by calcium score and inversely related to heart rate. Because longer coronary artery rest periods are associated with improved image quality both for angiography with MRI and coronary artery wall imaging, heart rate–lowering methods in association with these techniques appear to be a logical application.
doi:10.1097/RCT.0b013e3181648606
PMCID: PMC3037090
PMID: 19188777
coronary; magnetic resonance imaging; image quality; MRI; cardiac