Publications by authors named "Harjit Chahal"

23 Publications

  • Page 1 of 1

Resting Heart Rate, Short-Term Heart Rate Variability and Incident Atrial Fibrillation (from the Multi-Ethnic Study of Atherosclerosis (MESA)).

Am J Cardiol 2019 12 6;124(11):1684-1689. Epub 2019 Sep 6.

Division of Cardiology, Section for Cardiac Electrophysiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Evidence suggests an association between autonomical nervous system (ANS) function and atrial fibrillation (AF) development. We sought to examine the association of baseline resting heart rate (RHR) and short-term heart rate variability (HRV) as surrogates of (ANS) with incident AF in individuals without previous cardiovascular disease. A total of 6,261 participants of the Multi-Ethnic Study of Atherosclerosis who were free of AF and diagnosed cardiovascular disease were enrolled. Three standard 10-second, 12-lead electrocardiograms (ECG) were used to measure RHR, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Cox proportional hazards models adjusted for demographics, atrioventricular nodal agents, and known cardiovascular risk factors were used to examine the association of baseline RHR, and log transformed SDNN and RMSDD with incident AF. Over a mean follow-up of 11.3 ± 3.7 years, 754 (12%) participants developed AF. Spline curve analysis revealed a nonlinear association between RHR, HRV, and incident AF. In fully adjusted models higher (but not lower) baseline RHR (RHR >76 beats/min) was associated with incident AF (hazard ratio 1.48 95% confidence interval 1.18 to 1.86). Additionally, lower values of RMSDD and SDNN and higher values of RMSDD were independently associated with incident AF. In conclusion, cardiac ANS dysregulation indicated as higher RHR and lower HRV is associated with incident AF independent of known cardiovascular risk factors.
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http://dx.doi.org/10.1016/j.amjcard.2019.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939867PMC
December 2019

Prognostic implications of QRS dispersion for major adverse cardiovascular events in asymptomatic women and men: the Multi-Ethnic Study of Atherosclerosis.

J Interv Card Electrophysiol 2019 Oct 3;56(1):45-53. Epub 2019 Sep 3.

Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background: QRS dispersion measured as the difference between maximal and minimal QRS duration in the standard 12-lead electrocardiogram has been shown to be associated with increased mortality in heart failure (HF) patients and increased arrhythmic events in patients with cardiomyopathy.

Aims: This study sought to examine the prognostic association between baseline QRS dispersion and future cardiovascular events in individuals without known prior cardiovascular disease.

Methods: The association of QRS dispersion with cardiovascular events was examined in 6510 MESA (Multi-Ethnic Study of Atherosclerosis) participants. Participants with bundle branch block were excluded. Study participants were divided into two groups based on the 95th percentile of QRS dispersion (QRS dispersion < 34 ms [group I] and QRS dispersion ≥ 34 ms [group II]). Cox proportional hazard models adjusting for demographic and clinical risk factors were used to examine the association of QRS dispersion with incident cardiovascular events (major adverse cardiovascular events [MACE]) and mortality. Analysis was repeated by forcing Framingham risk factors.

Results: Mean age was 62 ± 10 years in group I and 63 ± 10 years in group II (P = 0.02). QRS dispersion ≥ 34 ms was associated significantly with MACE (HR 1.30; 95% CI 1.04-1.62) and mortality (HR 1.33; 95% CI 1.03-1.73) after adjustment for cardiovascular risk factors and potential cofounders. Similar results were seen for mortality after adjustment for Framingham risk factors.

Conclusion: QRS dispersion ≥ 34 ms predicts cardiovascular events and mortality.
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http://dx.doi.org/10.1007/s10840-019-00614-yDOI Listing
October 2019

Healthy aging of the left ventricle in relationship to cardiovascular risk factors: The Multi-Ethnic Study of Atherosclerosis (MESA).

PLoS One 2017 22;12(6):e0179947. Epub 2017 Jun 22.

Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.

Background: Understanding the relationship of cardiovascular structure and function to age is confounded by the high prevalence of traditional risk factors in the United States. The purpose of the study is to compare left ventricular (LV) and aortic structural, and functional parameters in individuals with and without traditional risk factors in a population-based cohort.

Methods And Results: 3015 study participants (48% men, age 55-94, mean 69.01±9.17 years) in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent cardiovascular magnetic resonance (CMR) imaging from 2010-2012. Absence of cardiovascular (CV) risk factors (no hypertension, diabetes or impaired fasting glucose, obesity, smoking or hypercholesterolemia) was infrequent, occurring in just 314 (10.4%, 38% men) of 3015 participants. In multivariable analyses adjusting for age, sex and race, individuals with CV risk factors had significantly larger LV mass index (by 17%) and lower LV contractibility (circumference strain, lower by 14%). Indexed LV volumes and stroke volume were inversely associated with age, but such relationships were not statistically significant in risk-free male subjects (p>0.05). Men with CV risk factors showed positive association of CMR T1 indices of myocardial fibrosis with age. Aortic function was similar in individuals with and without risk factors; age was associated with decline of aortic function in both CV and no CV risk factor groups.

Conclusion: Our results support that LV structure and function are better preserved in senescent hearts in the absence of traditional cardiovascular risk factors, and such protection is more prominent in men than in women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179947PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481019PMC
September 2017

Cardiac CT: present and future applications.

Heart 2016 Nov 13;102(22):1840-1850. Epub 2016 Sep 13.

Division of Cardiology, Montefiore Medical Center-Albert Einstein College of Medicine, Bronx, New York, USA.

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http://dx.doi.org/10.1136/heartjnl-2015-307481DOI Listing
November 2016

Aortocavitary fistula as a complication of infective endocarditis and subsequent complete heart block in a patient with severe anemia.

J Community Hosp Intern Med Perspect 2015 11;5(6):29446. Epub 2015 Dec 11.

Department of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.

Infective endocarditis has different presentations depending on the involvement of valvular and perivalvular structures, and it is associated with high morbidity and mortality. Aortocavitary fistula is a rare complication. We introduce the case of a 48-year-old female with native valve endocarditis, complicated by aortocavitary fistula to the right atrium, and consequently presented with syncope.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677595PMC
http://dx.doi.org/10.3402/jchimp.v5.29446DOI Listing
December 2015

Ability of Reduced Lung Function to Predict Development of Atrial Fibrillation in Persons Aged 45 to 84 Years (from the Multi-Ethnic Study of Atherosclerosis-Lung Study).

Am J Cardiol 2015 Jun 24;115(12):1700-4. Epub 2015 Mar 24.

Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois. Electronic address:

Atrial fibrillation (AF) occurs frequently in patients with chronic obstructive pulmonary disease. Epidemiologic studies have found inconsistent associations between lung function and AF, and none have studied pulmonary emphysema, which overlaps only partially with chronic obstructive pulmonary disease in the general population. The aim of this study was to assess the relation among lung function measured by spirometry, the percentage of emphysema-like lung on computed tomography, and incident AF. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study following 6,814 subjects free of clinical cardiovascular disease, including AF, at baseline. Spirometry was performed in a subset of 3,965 participants. Percentage emphysema was defined on baseline computed tomographic scans as lung regions <950 Hounsfield units. Incident AF was identified from hospital discharge diagnosis and Medicare claims data. Cox proportional hazards models were used to assess independent associations of lung volumes and percentage emphysema with AF. A total of 3,811 participants with valid spirometric results were included in this study. The mean age was 64.5 ± 9.8 years, and 49.4% were men. AF developed in 149 subjects (3.8%) over a mean follow-up period of 4.1 years after spirometry. Lower levels of forced expiratory volume at 1 second and forced vital capacity were associated with a higher risk for AF (hazard ratios 1.21 and 1.19 per 500 ml, respectively, p <0.001) after adjustment for demographic and cardiovascular risk factors. Percentage emphysema was not significantly related to AF. In conclusion, in a multiethnic community-based sample of subjects free of cardiovascular disease at baseline, functional airflow limitation was related to a higher risk for AF.
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http://dx.doi.org/10.1016/j.amjcard.2015.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450133PMC
June 2015

Transthyretin cardiac amyloidosis: an under-diagnosed cause of heart failure.

J Community Hosp Intern Med Perspect 2014 25;4(5):25500. Epub 2014 Nov 25.

Department of Cardiology, Medstar Union Memorial Hospital, Baltimore, MD, USA.

Introduction: Cardiac amyloidosis is the most common cause of infiltrative cardiomyopathy and is associated with a poor prognosis. Transthyretin cardiac amyloidosis, particularly the type caused by the mutation that replaces the amino acid valine with the amino acid isoleucine at position 122 (Val122Ile), is most common among African- Americans above 65 years of age. Evidence suggests that this mutation is an important, though under-diagnosed, cause of heart failure in this population.

Case Presentation: A 74-year-old African American male with a diagnosis of non-ischemic cardiomyopathy for several years, presented with gradually worsening dyspnea on exertion and lower extremity edema. There is no known cardiac disease in his family. An echocardiogram was done showing a decrease in ejection fraction to 30% from 45% in the span of a year. An endomyocardial biopsy analysis identified transthyretin amyloid with the Val122Ile mutation, confirming the diagnosis of familial transthyretin cardiomyopathy.

Discussion: Systemic amyloidosis is a group of diseases caused by the deposition of an abnormally folded, insoluble protein that can accumulate in multiple organs causing progressive and irreversible dysfunction. The mutations that most commonly induce variant transthyretin cardiac amyloidosis are Val122Ile, Val30Met and Thr60Ala. The Val122Ile mutation has been found to be present in 3-4% of the African American/Caribbean population.

Conclusions: Familial amyloid cardiomyopathy is an uncommonly recognized cause of heart failure in the population, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. Patients that meet the high-risk profile criteria - male gender, age 65 years and older, heart failure symptoms, symmetric left ventricular (LV) hypertrophy, and moderately depressed LV function - should likely undergo additional testing for cardiac amyloidosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246150PMC
http://dx.doi.org/10.3402/jchimp.v4.25500DOI Listing
November 2014

Heart failure risk prediction in the Multi-Ethnic Study of Atherosclerosis.

Heart 2015 Jan 7;101(1):58-64. Epub 2014 Nov 7.

Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.

Objective: Heart failure (HF) is a leading cause of mortality especially in older populations. Early detection of high-risk individuals is imperative for primary prevention. The purpose of this study was to develop a HF risk model from a population without clinical cardiac disease.

Methods: The Multi-Ethnic Study of Atherosclerosis is a multicentre observational cohort study following 6814 subjects (mean age 62±10 years; 47% men) who were free of clinical cardiovascular disease at baseline. Median follow-up was 4.7 years. HF events developed in 176 participants. Cox proportional hazards models and regression coefficients were used to determine independent risk factors and generate a 5-year risk score for incident HF. Bootstrapping with bias correction was used for internal validation.

Results: Independent predictors for HF (HR, p value) were age (1.30 (1.10 to 1.50) per 10 years), male gender (2.27 (1.53 to 3.36)), current smoking (1.97 (1.15 to 3.36)), body mass index (1.40 (1.10 to 1.80) per 5 kg/m(2)), systolic blood pressure (1.10 (1.00 to 1.10) per 10 mm Hg), heart rate (1.30) (1.10 to 1.40) per 10 bpm), diabetes (2.27 (1.48 to 3.47)), N-terminal pro-B-type natriuretic peptide (NT proBNP) (2.48 (2.16 to 2.84) per unit log increment) and left ventricular mass index (1.40 (1.30 to 1.40) per 10 g/m(2)). A parsimonious model based on age, gender, body mass index, smoking status, systolic blood pressure, heart rate, diabetes and NT proBNP natriuretic peptide predicted incident HF risk with a c-statistic of 0.87.

Conclusions: A clinical algorithm based on risk factors readily available in the primary care setting can used to identify individuals with high likelihood of developing HF without pre-existing cardiac disease.
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http://dx.doi.org/10.1136/heartjnl-2014-305697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685458PMC
January 2015

Association of CMR-measured LA function with heart failure development: results from the MESA study.

JACC Cardiovasc Imaging 2014 Jun 7;7(6):570-9. Epub 2014 May 7.

Cardiology Division, Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland. Electronic address:

Objectives: The goal of this study was to assess the association between left atrial (LA) volume and function measured with feature-tracking cardiac magnetic resonance (CMR) and development of heart failure (HF) in asymptomatic individuals.

Background: Whether alterations of LA structure and function precede or follow HF development remains incompletely understood. We hypothesized that significant alterations of LA deformation and architecture precede the development of HF in the general population.

Methods: In a case-control study nested in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA volume and function assessed using CMR feature-tracking were compared between 112 participants with incident HF (mean age 68.4 ± 8.2 years; 66% men) and 224 age- and sex-matched controls (mean age 67.7 ± 8.9 years; 66% men). Participants were followed up for 8 years. All individuals were in normal sinus rhythm at the time of imaging, without any significant valvular abnormalities and free of clinical cardiovascular diseases.

Results: Individuals with incident HF had greater maximal and minimal LA volume indexes (LAVImin) than control subjects (40 ± 13 mm(3)/m(2) vs. 33 ± 10 mm(3)/m(2) [p <0.001] for maximal LA index and 25 ± 11 mm(3)/m(2) vs. 17 ± 7 mm(3)/m(2) [p <0.001] for LAVImin). The HF case subjects also had smaller global peak longitudinal atrial strain (PLAS) (25 ± 11% vs. 38 ± 16%; p <0.001) and lower LA emptying fraction (40 ± 11% vs. 48 ± 9%; p <0.001) at baseline. After adjustment for traditional cardiovascular risk factors, left ventricular mass, and N-terminal pro-B-type natriuretic peptide, global PLAS (odds ratio: 0.36 per SD [95% confidence interval: 0.22 to 0.60]) and LAVImin (odds ratio: 1.65 per SD [95% confidence interval: 1.04 to 2.63]) were independently associated with incident HF.

Conclusions: Deteriorations in LA structure and function preceded development of HF. Lower global PLAS and higher LAVImin, measured using CMR feature-tracking, were independent markers of incident HF in a multiethnic population of asymptomatic individuals.
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http://dx.doi.org/10.1016/j.jcmg.2014.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129378PMC
June 2014

Complete esophageal obstruction following endoscopic variceal band ligation.

J Community Hosp Intern Med Perspect 2013 17;3(1). Epub 2013 Apr 17.

Department of Medicine, Medstar Union Memorial Hospital, Baltimore, MD, USA.

Variceal hemorrhage is a potential complication of portal hypertension. Besides medical management, endoscopic variceal band ligation (EVBL) has emerged as a promising prophylactic tool proving to be superior to sclerotherapy. EBVL is a simple procedure associated with minor complications and short recovery time. In this report, we present a case of a rare complication of complete esophageal obstruction following an EVBL procedure. Given the high numbers of such procedures performed, it is imperative that internists and specialists be aware of this unusual complication.
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http://dx.doi.org/10.3402/jchimp.v3i1.20043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716036PMC
July 2013

Percent emphysema and right ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis-Lung and Multi-Ethnic Study of Atherosclerosis-Right Ventricle Studies.

Chest 2013 Jul;144(1):136-144

Penn Cardiovascular Institute, Department of Medicine and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Background: Severe COPD can lead to cor pulmonale and emphysema and is associated with impaired left ventricular (LV) filling. We evaluated whether emphysema and airflow obstruction would be associated with changes in right ventricular (RV) structure and function and whether these associations would differ by smoking status.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI on 5,098 participants without clinical cardiovascular disease aged 45 to 84 years. RV and emphysema measures were available for 4,188 participants. Percent emphysema was defined as the percentage of voxels below -910 Hounsfield units in the lung windows on cardiac CT scans. Generalized additive models were used to control for confounders and adjust for respective LV parameters.

Results: Participants consisted of 13% current smokers, 36% former smokers, and 52% never smokers. Percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, cardiac output, and mass prior to adjustment for LV measures. After adjustment for LV end-diastolic volume, greater percent emphysema was associated with greater RV end-diastolic volume (+1.5 mL, P=.03) among current smokers, smaller RV end-diastolic volume (-0.8 mL, P=.02) among former smokers, and similar changes among never smokers.

Conclusions: Percent emphysema was associated with smaller RV volumes and lower mass. The relationship of emphysema to cardiac function is complex but likely involves increased pulmonary vascular resistance, predominantly with reduced cardiac output, pulmonary hyperinflation, and accelerated cardiopulmonary aging.
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http://dx.doi.org/10.1378/chest.12-1779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704233PMC
July 2013

The renin-angiotensin system and right ventricular structure and function: The MESA-Right Ventricle Study.

Pulm Circ 2012 Jul;2(3):379-86

Department of Medicine, and Health Services Policy & Practice, Alpert Medical School of Brown University, Providence, Rhode Island, USA.

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.
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http://dx.doi.org/10.4103/2045-8932.101657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487307PMC
July 2012

Right ventricular structure is associated with the risk of heart failure and cardiovascular death: the Multi-Ethnic Study of Atherosclerosis (MESA)--right ventricle study.

Circulation 2012 Oct 29;126(14):1681-8. Epub 2012 Aug 29.

Penn Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia,

Background: Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline.

Methods And Results: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on 5098 participants between 2000 and 2002 with follow-up for incident heart failure and cardiovascular death ("death") until January 2008. RV volumes and mass were available for 4204 participants. The study sample (n=4144) was 61.4±10.1 years old and 47.6% male. The presence of RV hypertrophy (increased RV mass) was associated with more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio, 2.52; 95% confidence interval, 1.55-4.10; P<0.001) and a doubling (or more) of risk with left ventricular mass at the mean value or lower (P for interaction=0.05).

Conclusions: RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.112.095216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532921PMC
October 2012

Relation between carotid intima-media thickness and left ventricular mass in type 1 diabetes mellitus (from the Epidemiology of Diabetes Interventions and Complications [EDIC] Study).

Am J Cardiol 2012 Nov 9;110(10):1534-40. Epub 2012 Aug 9.

Department of Radiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Type 1 diabetes mellitus (DM) is associated with early atherosclerosis and increased cardiovascular mortality. The relation between carotid intima-media thickness (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 DM. 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 magnetic resonance imaging 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 relation between cIMT at year 12 and LV mass at year 15. In total 889 participants had cardiac magnetic resonance imaging and cIMT measurements available for these analyses. At EDIC year 15, mean age of the participants was 49 ± 7 years, mean DM duration was 28 ± 5 years, and 52% were men. 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/m(2) per 0.1-mm cIMT increment, p <0.0001) was observed. This association was decreased by the addition of systolic blood pressure, in particular 1.15 g/m(2) per 0.1-mm cIMT increment (p <0.0001), and to a lesser extent other cardiovascular disease risk factors. Furthermore, the relation observed between LV mass and cIMT was stronger in patients with shorter duration of DM. In conclusion, cIMT was an independent predictor of larger LV mass in a well-characterized population with type 1 DM.
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http://dx.doi.org/10.1016/j.amjcard.2012.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488435PMC
November 2012

Brachial artery diameter and the right ventricle: the Multi-Ethnic Study of Atherosclerosis-right ventricle study.

Chest 2012 Dec;142(6):1399-1405

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address:

Background: Endothelial dysfunction is associated with left ventricular morphology and long-term cardiovascular outcomes. The purpose of this study was to assess the relationship between both baseline brachial artery diameter and peripheral endothelial function (assessed by brachial artery ultrasonography) and right ventricular (RV) mass, RV end-diastolic volume (RVEDV), and RV ejection fraction (RVEF).

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI and brachial artery ultrasonography on participants without clinical cardiovascular disease. Baseline brachial artery diameter and flow-mediated dilation were assessed.

Results: The mean age was 60.9 years, and 49.4% of subjects were men (n = 2,425). In adjusted models, larger brachial artery diameter was strongly associated with greater RV mass (β = 0.55 g, P < .001), larger RVEDV (β = 3.99 mL, P < .001), and decreased RVEF (β = -0.46%, P = .03). These relationships persisted after further adjustment for the respective left ventricular parameters. Flow-mediated dilation was not associated with RV mass or RVEF and was only weakly associated with RVEDV.

Conclusions: Brachial artery diameter is associated with greater RV mass and RVEDV, as well as lower RVEF. Changes in the systemic arterial circulation may have pathophysiologic links to pulmonary vascular dysfunction or abnormalities in RV perfusion.
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http://dx.doi.org/10.1378/chest.12-0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515023PMC
December 2012

Obesity and right ventricular structure and function: the MESA-Right Ventricle Study.

Chest 2012 Feb 25;141(2):388-395. Epub 2011 Aug 25.

Penn Cardiovascular Institute, Department of Medicine, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address:

Background: The relationship between obesity and right ventricular (RV) morphology is not well studied. We aimed to determine the association between obesity and RV structure and function in a large multiethnic population-based cohort.

Methods: The MESA-Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were divided into three categories based on BMI: lean ( ≤ 24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese ( ≥ 30 kg/m(2)).

Results: The study sample included 4,127 participants. After adjustment for demographics, height, education, and cardiovascular risk factors, overweight and obese participants had greater RV mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and 18% greater, respectively), larger RV stroke volume (7% and 16% greater, respectively), and lower RV ejection fraction ( ≥ 1% lower) than lean participants (all P < .001). These findings persisted after adjusting for the respective left ventricular (LV) parameters.

Conclusions: Overweight and obesity were independently associated with differences in RV morphology even after adjustment for the respective LV measure. This association could be explained by increased RV afterload, increased blood volume, hormonal effects, or direct obesity-related myocardial effects.
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http://dx.doi.org/10.1378/chest.11-0172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277293PMC
February 2012

Sex and race differences in right ventricular structure and function: the multi-ethnic study of atherosclerosis-right ventricle study.

Circulation 2011 Jun;123(22):2542-51

Penn Cardiovascular Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.

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: In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac magnetic resonance imaging was performed on 5098 participants. Right ventricular volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived with an allometric approach. The study sample (n=4123) was 61.5±10.1 years of age and 47.5% men. Older age was associated with lower RV mass (≈5% lower mass per decade), with larger age-related decrements in men than in women (P<0.05 for interaction). Older age was also associated with higher RV ejection fraction, an association that differed between races/ethnicities (P≤0.01 for interaction). Overall, men had greater RV mass (≈8%) and larger RV volumes than women, but had lower RV ejection fraction (4% in absolute terms; P<0.001). Blacks had lower RV mass than whites (P≤0.002), whereas Hispanics had higher RV mass (P≤0.02). When the derived normative equations were used, 7.3% (95% confidence interval, 6.5 to 8.1) met the criteria for RV hypertrophy, and 5.9% (95% confidence interval, 5.2 to 6.6) had RV dysfunction.

Conclusion: Age, sex, and race are associated with significant differences in RV mass, RV volumes, and RV ejection fraction, potentially explaining distinct responses of the RV to cardiopulmonary disease.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.110.985515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111939PMC
June 2011

Age at surgery significantly impacts the amount of orbital relapse following hypertelorbitism correction: a 30-year longitudinal study.

Plast Reconstr Surg 2011 Apr;127(4):1620-1630

Campinas, Brazil; and Los Angeles, Calif. From the Institute of Plastic and Craniofacial Surgery, Brazilian Society of Research and Assistance to Craniofacial Rehabilitation Hospital (SOBRAPAR), and the Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California, Los Angeles Medical Center.

Background: The aim of this study was to identify variables that affect orbital relapse after hypertelorbitism correction.

Methods: The authors retrospectively reviewed the medical records of patients who underwent hypertelorbitism correction at a single institution between 1975 and 2005. Bony interorbital distance was measured postoperatively and at long-term follow-up. Orbital relapse was defined as the difference between bony interorbital distance measurements at these time points. Patients were stratified into groups based on age at primary surgical correction (early, <8 years; late, ≥ 8 years), the severity of the initial deformity (moderate, bony interorbital distance ≤ 40 mm; severe, bony interorbital distance >40 mm), and the type of surgical technique used (facial bipartition versus box osteotomy). Differences in relapse between the stratified groups were analyzed using paired t tests.

Results: A total of 22 patients met inclusion criteria for this study. Patients who underwent surgery before 8 years of age had a significantly higher degree of orbital relapse compared with older patients (5.9 mm versus 1.8 mm; p = 0.0142). There was no significant difference in orbital relapse based on the severity of the deformity or the operative technique used.

Conclusions: Surgical correction of hypertelorbitism in patients younger than 8 years leads to a significantly higher rate of bony interorbital distance relapse compared with patients who undergo surgery at an older age. Neither the initial degree of severity nor the type of surgical technique correlates with relapse. The authors therefore recommend that in the absence of urgent factors necessitating early intervention, hypertelorbitism correction should be performed after 8 years of age.
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http://dx.doi.org/10.1097/PRS.0b013e31820a6472DOI Listing
April 2011

Regional left ventricular systolic function and the right ventricle: the multi-ethnic study of atherosclerosis right ventricle study.

Chest 2011 Aug 17;140(2):310-316. Epub 2011 Feb 17.

Department of Medicine, University of Pennsylvania School of Medicine Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine Philadelphia, PA; Penn Cardiovascular Institute, University of Pennsylvania School of Medicine Philadelphia, PA. Electronic address:

Background: Dysfunction of the interventricular septum has been implicated in right ventricular (RV) failure. However, little is known about the relationship between ventricular septal and RV function in patients without clinical cardiovascular disease. We hypothesized that better septal function would be associated with higher RV ejection fraction and lower RV mass and volume by cardiac MRI.

Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac MRI was performed on community-based participants without clinical cardiovascular disease. Images were analyzed by the harmonic phase method to measure peak circumferential systolic midventricular strain for each wall (anterior, lateral, inferior, and septal). Multivariable linear regression and generalized additive models were used to assess the relationship between septal strain and RV morphology.

Results: There were 917 participants (45.7% women) with a mean age of 65.7 years. Better septal function was associated with higher RV ejection fraction in a nonlinear fashion after adjustment for all covariates (P = .03). There appeared to be a threshold effect for the contribution of septal strain to RV systolic function, with an almost linear decrement in RV ejection fraction with septal strain from -18% to -10%. Septal function was not related to RV mass or volume.

Conclusions: Interventricular septal function was linked to RV systolic function independent of other left ventricular regions, even in individuals without clinical cardiovascular disease. This finding confirms animal and human research suggesting the importance of septal function to the right ventricle and implies that changes in septal function could herald RV dysfunction.

Trial Registry: ClinicalTrials.gov; No.: NCT00005487; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1378/chest.10-1750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148792PMC
August 2011

Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are associated with right ventricular structure and function: the MESA-RV Study.

Biomarkers 2010 Dec 5;15(8):731-8. Epub 2010 Oct 5.

Penn Cardiovascular Institute, Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

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.
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http://dx.doi.org/10.3109/1354750X.2010.516455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045574PMC
December 2010

Physical activity and right ventricular structure and function. The MESA-Right Ventricle Study.

Am J Respir Crit Care Med 2011 Feb 2;183(3):396-404. Epub 2010 Sep 2.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.1164/rccm.201003-0469OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056232PMC
February 2011

Relation of cardiovascular risk factors to right ventricular structure and function as determined by magnetic resonance imaging (results from the multi-ethnic study of atherosclerosis).

Am J Cardiol 2010 Jul 13;106(1):110-6. Epub 2010 May 13.

Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The effect of cardiovascular risk factors on the left ventricle is well known but their effect on right ventricle has not been studied using advanced imaging techniques. The purpose of the present study was to determine the relation between the cardiovascular risk factors and right ventricular (RV) structure and function and its interaction with the left ventricle. Cardiac magnetic resonance images from 4,204 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis were analyzed. Multivariate linear regression models were used to study the cross-sectional association between individual RV parameters and risk factors. All RV parameters, except for ejection fraction, decreased with age (p <0.0001). The RV mass was positively associated with systolic blood pressure (+0.4 g, p <0.0001) and high-density lipoprotein cholesterol (+0.2 g, p <0.0001). It was inversely related with diastolic blood pressure (-0.3 g, p <0.0001) and total cholesterol (-0.2 g, p <0.01). The RV end-diastolic volume was positively associated with systolic blood pressure (+1.6 ml, p <0.01) and high-density lipoprotein cholesterol (+1.8 ml, p <0.0001). It was inversely related with diastolic blood pressure (-2.2 ml, p <0.01), total cholesterol (-1.4 ml, p <0.0001), current smoking (-2.7 ml, p <0.05), and diabetes mellitus (-3.1 ml, p <0.01). The RV ejection fraction was positively associated with systolic blood pressure (+1.0%, p <0.0001), high-density lipoprotein 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 high-density lipoprotein cholesterol, are associated with subclinical changes in the RV mass and volume.
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http://dx.doi.org/10.1016/j.amjcard.2010.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901248PMC
July 2010

Diagnostic and prognostic utility of electrocardiography for left ventricular hypertrophy defined by magnetic resonance imaging in relationship to ethnicity: the Multi-Ethnic Study of Atherosclerosis (MESA).

Am Heart J 2010 Apr;159(4):652-8

Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Left ventricular mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for left ventricular mass measurement. Ethnicity is believed to affect electrocardiographic (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: Data were analyzed from 4,967 participants (48% men, mean age 62 +/- 10 years; 39% white, 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 years for incident CVD.

Results: 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. Ten of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared with whites (P = .02-.001). The sum of amplitudes of S wave in V(1), S wave in V(2), and R wave in V(5) (a MESA-specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared with prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (receiver operating characteristic 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 < .05).

Conclusions: Electrocardiography 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 with other ethnic groups.
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http://dx.doi.org/10.1016/j.ahj.2009.12.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856691PMC
April 2010