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1.  Applications of regenerative medicine in organ transplantation 
A worldwide shortage of organs for clinical implantation establishes the need to bring forward and test new technologies that will help in solving the problem. The concepts of regenerative medicine hold the potential for augmenting organ function or repairing damaged organ or allowing regeneration of deteriorated organs and tissue. Researchers are exploring possible regenerative medicine applications in organ transplantation so that coming together of the two fields can benefit each other. The present review discusses the strategies that are being implemented to regenerate or bio-engineer human organs for clinical purposes. It also highlights the limitations of the regenerative medicine that needs to be addressed to explore full potential of the field. A web-based research on MEDLINE was done using keywords “regenerative medicine,” “tissue-engineering,” “bio-engineered organs,” “decellularized scaffold” and “three-dimensional printing.” This review screened about 170 articles to get the desired knowledge update.
PMCID: PMC4517320
Bioartificial organs; regeneration; regenerative medicine; tissue-engineering
2.  Orofacial tuberculosis: Clinical manifestations, diagnosis and management 
Orofacial tuberculosis (TB) is an uncommon form of extrapulmonary TB and is nonspecific in its clinical presentation. It can be misdiagnosed especially when oral lesions are present before systemic symptoms become apparent. Doctors especially attending dentist who generally is the first among clinicians to come across such pathological entity should be aware of the orofacial lesions of TB and consider them in the differential diagnosis of suspicious oral lesions to ensure early diagnosis of TB and its treatment. In this review, we have discussed in detail the clinical presentation of various forms of orofacial TB, diagnosis, and management of patients. Also, an update is provided about recent anti-TB drug development.
PMCID: PMC4535091  PMID: 26288770
Dentist; diagnosis; mycobacterium; oral tuberculosis; tuberculosis
3.  Association of Electrocardiographic and Imaging Surrogates of Left Ventricular Hypertrophy with Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis 
To examine the association between LVH, defined by cardiovascular magnetic resonance (CMR) and electrocardiography (ECG), with incident AF.
Previous studies of the association between atrial fibrillation (AF) and left ventricular hypertrophy (LVH) were based primarily on echocardiographic measures of LVH.
The Multi-Ethnic Study of Atherosclerosis (MESA) study enrolled 4942 participants free of clinically recognized cardiovascular disease. Incident AF was based on MESA ascertained hospital discharge ICD codes and Centers for Medicare and Medicaid Services (CMS) inpatient hospital claims. CMR-LVH was defined as left ventricular mass ≥ 95th percentile of the MESA population distribution. Eleven ECG-LVH criteria were assessed. The association of LVH with incident AF was evaluated using multivariable Cox proportional hazards models adjusted for CVD risk factors.
During a median follow-up of 6.9 years, 214 incident AF events were documented. Participants with AF were more likely to be older, hypertensive, and overweight. The risk of AF was greater in participants with CMR-derived LVH [Hazard ratio (HR) 2.04, 95% CI 1.15-3.62]. AF was associated with ECG-derived LVH measure of Sokolow-Lyon voltage product after adjusting for CMR-LVH [HR=1.83 (1.06, 3.14), p= 0.02]. The associations with AF for CMR LVH and Sokolow-Lyon voltage product were attenuated when adjusted for CMR LA volumes.
In a multi-ethnic cohort of participants without clinically detected CVD, both CMR and ECG-derived LVH were associated with incident AF. ECG-LVH showed prognostic significance independent of CMR-LVH. The association was attenuated when adjusted for CMR LA volumes.
PMCID: PMC4024364  PMID: 24657688
Atrial Fibrillation; Left Ventricular Hypertrophy; Cardiac MRI; ECG
4.  A comparative study of visual and auditory reaction times on the basis of gender and physical activity levels of medical first year students 
Reaction time (RT) is a measure of the response to a stimulus. RT plays a very important role in our lives as its practical implications may be of great consequences. Factors that can affect the average human RT include age, sex, left or right hand, central versus peripheral vision, practice, fatigue, fasting, breathing cycle, personality types, exercise, and intelligence of the subject.
The aim was to compare visual RTs (VRTs) and auditory RTs (ARTs) on the basis of gender and physical activity levels of medical 1st year students.
Materials and Methods:
The present cross-sectional study was conducted on 120 healthy medical students in age group of 18–20 years. RT for target stimulus that is, for the beep tone for measuring ART, and red circle for measuring VRT was determined using Inquisit 4.0 (Computer Software) in the laptop. The task was to press the spacebar as soon as the stimulus is presented. Five readings of each stimulus were taken, and their respective fastest RT's for each stimuli were recorded. Statistical analysis was done.
In both the sexes’ RT to the auditory stimulus was significantly less (P < 0.001) as compared to the visual stimulus. Significant difference was found between RT of male and female medical students (P < 0.001) as well as between sedentary and regularly exercising healthy medical 1st year students.
The ART is faster than the VRT in medical students. Furthermore, male medical students have faster RTs as compared to female medical students for both auditory as well as visual stimuli. Regularly exercising medical students have faster RTs when compared with medical students with sedentary lifestyles.
PMCID: PMC4456887  PMID: 26097821
Auditory reaction time; exercise; females; males; medical students; visual reaction time
5.  Validity of the Surface Electrocardiogram Criteria for Right Ventricular Hypertrophy: The MESA - Right Ventricle Study 
We aimed to assess the diagnostic properties of ECG criteria for RVH measured by cardiac magnetic resonance imaging (cMRI) in adults without clinical cardiovascular disease.
Current electrocardiographic (ECG) criteria for right ventricular hypertrophy (RVH) were based on cadaveric dissection in small studies.
The Multi-Ethnic Study of Atherosclerosis performed cMRIs with complete right ventricle (RV) interpretation on 4,062 participants without clinical cardiovascular disease. Endocardial margins of the RV were manually contoured on diastolic and systolic images. The ECG screening criteria for RVH from the 2009 AHA Recommendations for Standardization and Interpretation of the ECG were examined in participants with and without left ventricular hypertrophy or reduced ejection fraction. RVH was defined using sex-specific normative equations based on age, height, and weight.
The study sample with normal left ventricular morphology and function (n = 3,719) was 61.3 ± 10.0 years old, 53.5% female, 39.6% Caucasian, 25.5% African-American, 21.9% Hispanic, and 13.0% Asian. The mean BMI was 27.9 ± 5.0 kg/m2. Six percent had RVH which was generally mild. Traditional ECG criteria were specific (many > 95%) but had low sensitivity for RVH by cMRI. The positive predictive values were not sufficiently high as to be clinically useful (maximum 12%). The results did not differ based on age, sex, race, smoking status, or with including participants with abnormal LV mass or function. Classification and regression tree analysis revealed that no combination of ECG variables was better than the criteria used singly.
The recommended ECG screening criteria for RVH are not sufficiently sensitive or specific for screening for mild RVH in adults without clinical cardiovascular disease.
PMCID: PMC3944058  PMID: 24080107
Right Ventricular Hypertrophy; Magnetic Resonance Imaging; Electrocardiogram
6.  Attitude of Medical and Dental First Year Students Towards Teaching Methods in a Medical College of Northern India. 
Background: Teaching in most Asian countries is still dominated by teacher-centered classrooms in which students passively receive information from the teacher. Studies have shown that students’ inactivity in traditional teacher-centered classes makes them bored that consequently decrease their concentration and learning. To counter these problems active learning methods are being promoted to enhance their interest in studying. This present study was done to explore effective teaching system from a student’s perspective. The aim of the study was to examine the attitude of medical and dental first year students towards teaching methods.
Materials and Methods: The study was undertaken at on 150 Medical and Dental first year students. The study was conducted using general questionnaires along with feedback form to know their opinion about different teaching methodology.
Results: A 94.67% of the students were unsatisfied with traditional Lecture teaching. 89.33% favoured combination of traditional lectures and active learning techniques, 74.67% students find active learning methods to be interesting, 77.33% found them as attention seekers, 89.33% are motivated for in-depth study and 85.33% students are motivated for independents learning. 100% students agreed that active learning methods provide opportunities of student interaction while 86.67% students are happy with the teacher–student interaction it provides. Audio-visual aids are the most favoured (94.67%) and test questions are most criticized active teaching method.
Conclusion: Our study disclosed that the majority of student’s positively believe in using different active learning techniques for classroom activities.
PMCID: PMC4316323  PMID: 25654017
Active learning; Dental; Medical; Passive learning; Teaching
7.  Current overview on challenges in regenerative endodontics 
Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment.
The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice.
Materials and Methods:
A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were “regenerative endodontics,” “dental stem cells,” “growth factor regeneration,” “scaffolds,” and “challenges in regeneration.” This review article screened about 150 articles and then the relevant information was compiled.
Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes.
Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth.
PMCID: PMC4313471  PMID: 25657518
Endodontics; regeneration; stem cells; tissue engineering
8.  Current overview on dental stem cells applications in regenerative dentistry 
Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental stem cells were shortlisted and the facts are compiled. The objective of this review article is to discuss the history of stem cells, different stem cells relevant for dentistry, their isolation approaches, collection, and preservation of dental stem cells along with the current status of dental and medical applications.
PMCID: PMC4367063  PMID: 25810631
Cell culture techniques; stem cells; stem cell research; tissue banks; tissue engineering
9.  Regenerative Endodontics: A Road Less Travelled 
Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients’ quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering.
PMCID: PMC4253294  PMID: 25478476
Endodontics; Regeneration; Revascularization; Scaffolds; Stem cells; Tissue engineering
10.  Reference ranges of PR duration and P-wave indices in individuals free of cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Journal of electrocardiology  2013;46(6):10.1016/j.jelectrocard.2013.05.006.
In this brief report, we provide normal reference ranges for PR duration [unadjusted and heart rate adjusted] and P-wave indices [duration, amplitude and terminal force in V1] in individuals free of cardiovascular disease and its risk factors. We used automatically processed digital ECG data from 1252 US participants [mean age 59 (± 10) years, 738 women, 588 whites, 207 African-Americans, 217 Hispanics, 240 Chinese] from the Multi-Ethnic Study of Atherosclerosis [MESA]. In multivariable adjusted linear regression models with PR and each P-wave variable as a separate outcome, significant age, sex and race differences in these markers were observed. Subsequently, we report reference ranges for abnormal [2nd and 98th percentiles], borderline abnormal [5th and 95th percentiles] and mean [SD] values of PR and P-wave indices stratified by age [middle age (45–64 years) and seniors (65–84 years)], sex [men and women] and race [whites, African Americans, Hispanics and Chinese].
PMCID: PMC3795794  PMID: 23806475
P-wave indices; PR interval; MESA
11.  Full Mouth Rehabilitation in a Medically Compromised Patient with Fluorosis 
Severely worn out dentition needs to be given definite attention as it not only affects aesthetics but can also cause psychological distress to the affected individual. It can cause chewing difficulty, temporomandibular joint problems, headaches, pain and facial collapse. Before any attempt to restore severely worn dentition, aetiology of excessive tooth wear should be established. Severe wear can result from chemical cause, mechanical cause or a combination of various causes. Dental fluorosis can also result in severe wear of teeth. Teeth sometimes become extremely porous and friable with a mottled appearance ranging from yellow to brown-black. There occurs loss of tooth substance and anatomic dental deformities resulting in un-aesthetic dentition requiring full mouth rehabilitation. Here a similar case of full mouth rehabilitation of severely worn dentition due to dental fluorosis in a 27-year-old patient is presented. This case report conjointly presents the uncommon association of diabetes insipidus with dental fluorosis. Diabetes insipidus through its characteristic symptom of polydipsia can result in intake of more than permitted dose of fluoride thus causing dental fluorosis. In literature only few cases have been reported of dental fluorosis in association of diabetes insipidus. Full mouth rehabilitation of the patient was successfully accomplished through well-planned systematic approach to simultaneously fulfill aesthetic, occlusal and functional parameters.
PMCID: PMC4149160  PMID: 25177654
Dental fluorosis; Diabetes insipidus; Rehabilitation; Tooth wear; Vertical dimension of occlusion
12.  N-terminal Pro-B-Type Natriuretic Peptide, Left Ventricular Mass, and Incident Heart Failure: Multi-Ethnic Study of Atherosclerosis 
Circulation. Heart failure  2012;5(6):727-734.
Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population.
Methods and Results
A total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54–2.46, P<0.001). This relationship held among different ethnic groups, non-Hispanic whites, African-Americans, and Hispanics. Most importantly, NT-proBNP provided additive prognostic value beyond both traditional risk factors and LV mass index for predicting incident HF (integrated discrimination index=0.046, P<0.001; net reclassification index; 6-year risk probability categorized by <3%, 3–10%, >10% =0.175, P=0.019; category-less net reclassification index=0.561, P<0.001).
Plasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population.
Clinical Trial Registration
URL: Unique identifier: NCT00005487.
PMCID: PMC4124746  PMID: 23032197
N-terminal pro-B-type natriuretic peptide; heart failure; left ventricular mass
13.  Overview on the Current Antibiotic Containing Agents Used in Endodontics 
Antibiotics are systemically and locally used extensively in endodontics. However, local antibiotic application mode is considered more effective than systemic administration. The local mode enables the dentist to target bacteria in every nook and corner of root canal system, which is otherwise beyond reach if targeted by instrumentation or conventional root canal treatment protocols. Therefore, they are an important adjunct to conventional treatment of root canal. The present study reviews the various antibiotic containing dental agents used in endodontics. A web-based research on MedLine was performed with terms Review Articles published in the last 10 year's dental journals in English for literature researching, extracting, and synthesizing data. Relevant articles were shortlisted. Important cross-reference articles were also reviewed.
PMCID: PMC4158642  PMID: 25210667
Antibiotics; Intracanal medicaments; Irrigants; Obturation; Regeneration
14.  Minor Isolated Q Waves and Cardiovascular Events in the MESA Study 
The American journal of medicine  2013;126(5):450.e9-450.e16.
The significance of minor isolated Q waves in the resting electrocardiograms (ECGs) of apparently healthy individuals is unknown.
To examine the association between minor isolated Q waves and incident cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA).
This analysis included 6551 MESA participants (38% white, 28% black, 22% Hispanic, 12% Chinese) who were free of cardiovascular disease at enrollment. Cox proportional hazards models were used to examine the association between minor isolated Q waves defined by the Minnesota ECG Classification with adjudicated incident cardiovascular events.
During up to 7.8 years of follow-up, 423 events occurred, with a rate of 10.7 events per 1000 person-years. A significant interaction between minor isolated Q waves and race/ethnicity was observed (P = .030). In models stratified by race/ethnicity and adjusted for demographics, socioeconomic status, common cardiovascular risk factors, and other ECG abnormalities, presence of isolated minor Q waves was significantly associated with incident cardiovascular events in Hispanics (hazard ratio [HR] 2.62; 95% confidence interval [CI], 1.42-4.82), but not in whites (HR 0.65; 95% CI, 0.32-1.33) or blacks (HR 1.46; 95% CI, 0.74-2.89). Despite the statistically significant association in the Chinese population, the small number of events precluded solid conclusions in this race/ethnicity.
The prognostic significance of minor isolated Q waves varies across races/ethnicities; they carry a high risk for future cardiovascular events in apparently healthy Hispanics, but not in whites or blacks.
PMCID: PMC3741651  PMID: 23582938
Electrocardiography; MESA; Minor isolated Q waves; Race/ethnicity
15.  Relations of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA) 
The British journal of nutrition  2012;109(8):1490-1497.
Type 2 diabetes is a highly prevalent but preventable disorder. We assessed the association between an a priori Mediterranean diet score (MeDiet) and fasting glucose and insulin at baseline and incident type 2 diabetes after 6-year follow-up in MESA. Dietary intake was measured at baseline by a 127-item food frequency questionnaire in 5,390 men and women aged 45-84 years free of prevalent diabetes and clinical CVD. A MeDiet score was created based on intake of 10 food components: vegetables, whole grains, nuts, legumes, fruits, ratio of monounsaturated to saturated fat, red and processed meat, dairy, fish and alcohol. Multivariable linear and proportional hazard models were used to estimate the association of MeDiet, categorized in quintiles, with baseline insulin and glucose, and incident diabetes, respectively. Models adjusted for demographic, physiologic and behavioral characteristics. After multivariable adjustment, individuals with a higher MeDiet score had lower baseline mean (95% CI) insulin levels [mean Q1: = 5.8 (5.6-6.0) umol/l; mean Q5: = 4.8 (4.6-5.0) umol/l; p-trend= <0.0001]. A higher MeDiet score was also associated with significantly lower glucose levels after basic adjustment, but was attenuated after adjustment for waist circumference. During follow-up, 412 incident diabetes events accrued. MeDiet was not significantly related to risk of incident diabetes (p-trend=0.64). In summary, greater consistency with a Mediterranean-style diet, reflected by a higher a priori Mediterranean diet score, was cross-sectionally associated with lower insulin levels among non-diabetics, and lower blood glucose prior to adjustment for obesity, but not with lower incidence of diabetes.
PMCID: PMC4002212  PMID: 22932232
16.  Psychosocial Risks: Is Risk Management Strategic Enough in Business and Policy Making? 
Safety and Health at Work  2013;4(2):87-94.
In times of continuous change and volatile markets, organizations are increasingly characterized by downsizing, work intensification, and resource rationalization. This has resulted in diversification, and the emergence of new risks within the field of occupational health and safety, with an important impact. This paper focuses on one such type of risk in the modern workplace—psychosocial risks. The current study aimed to explore stakeholder perspectives, regarding the extent to which psychosocial risks are incorporated into strategic risk management practices, at both the business and policy level.
Semi-structured interviews were conducted with 14 professionals, representing employer, expert, policy maker, and trade union stakeholder perspectives.
It was found that the majority of organizations do not sufficiently, if at all, understand and incorporate psychosocial risks into strategic decision making, whereby the key barrier related to practical difficulties of not knowing how to manage psychosocial risks adequately.
The study found that there is a need to close the gap between policy and practice on a number of levels. Future recommendations comprise a policy framework and infrastructure underpinned by educational initiatives, partnerships, and networks to drive a shift in attitudes toward recognizing the duality of the concept of risk (including both potential negative and positive outcomes) and moving beyond simple regulatory compliance.
PMCID: PMC3732138  PMID: 23961331
organizations; policy making; psychosocial risk; strategy
17.  Right Ventricular Morphology and the Onset of Dyspnea: The MESA-Right Ventricle Study 
PLoS ONE  2013;8(2):e56826.
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.
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.
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.
Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.
PMCID: PMC3574101  PMID: 23457622
18.  Myocardial Structure, Function and Scar in Patients with Type 1 Diabetes 
Circulation  2011;124(16):1737-1746.
We report relationships of cardiovascular disease (CVD) risk factors with myocardial structure, function and scar in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.
Cardiac magnetic resonance (CMR) was obtained in 1017 patients with type 1 diabetes. Gadolinium CMR was also obtained in 741 patients. The mean age was 49 ± 7 years, 52% were men, and mean diabetes duration was 28± 5 years. Associations of CVD risk factors with CMR parameters were examined using linear and logistic regression models. History of macroalbuminuria was positively associated with LV mass (by +14.8 g) leading to a significantly higher LV mass/EDV ratio (by 8%). Mean hemoglobin A1c (HbA1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (−3.0 ml per unit mean HbA1c %) and stroke volume (−2.3 ml per unit mean HbA1c %) and positively related to elevated LV mass/EDV ratio (0.02 g/ml per unit). The overall prevalence of myocardial scar was 4.3% by CMR and 1.4% by clinical adjudication of myocardial infarction. Both mean HbA1c (Odds ratio (O.R.) 1.5 [1.0–2.2] per unit) and macroalbuminuria (OR 3.5 [1.2–9.9]) were significantly associated with myocardial scar as well as traditional CVD risk factors.
In addition to traditional CVD risk factors, elevated mean HbA1c and macroalbuminuria were significantly associated with alterations in LV structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function.
PMCID: PMC3215589  PMID: 21947298
Myocardial function; myocardial scar; type 1 diabetes; delayed enhancement; CMR
19.  Sex and Race Differences in Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
Circulation  2011;123(22):2542-2551.
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.
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.
PMCID: PMC3111939  PMID: 21646505
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension
20.  Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
PLoS ONE  2012;7(2):e30480.
Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114).
SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex.
After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48–5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19–1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02–12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes.
SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study.
PMCID: PMC3281845  PMID: 22363441
21.  Physical Activity and Right Ventricular Structure and Function 
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.
PMCID: PMC3056232  PMID: 20813888
exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging
22.  Cardiovascular Imaging for Assessing Cardiovascular Risk in Asymptomatic Men Versus Women 
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).
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.
PMCID: PMC3037859  PMID: 21068189
imaging; cardiovascular diseases; sex
23.  Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are associated with right ventricular structure and function: The MESA-RV Study 
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.
PMCID: PMC3045574  PMID: 20923324
Inflammation; thrombosis; hypertension; pulmonary
24.  The Association of Chronic Kidney Disease and Metabolic Syndrome with Incident Cardiovascular Events: Multiethnic Study of Atherosclerosis 
Background. There is an association between chronic kidney disease (CKD) and metabolic syndrome (MetS). We examined the joint association of CKD and MetS with incident cardiovascular (CVD) events in the Multiethnic Study of Atherosclerosis (MESA) cohort. Methods. We analyzed 2,283 Caucasians, 363 Chinese, 1,449 African-Americans, and 1,068 Hispanics in the MESA cohort. CKD was defined by cystatin C estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 and MetS was defined by NCEP criteria. Cox proportional regression adjusting for age, ethnicity, gender, study site, education, income, smoking, alcohol use, physical activity, and total and LDL cholesterol was performed to assess the joint association of CKD and MetS with incident CVD events. Participants were divided into four groups by presence of CKD and/or MetS and compared to the group without CKD and MetS (CKD−/MetS−). Tests for additive and multiplicative interactions between CKD and MetS and prediction of incident CVD were performed. Results. During follow-up period of 5.5 years, 283 participants developed CVD. Multivariate Cox regression analysis demonstrated that CKD and MetS were independent predictors of CVD (hazard ratio, 2.02 for CKD, and 2.55 for MetS). When participants were compared to the CKD−/MetS− group, adjusted HR for the CKD+/MetS+ group was 5.56 (95% CI 3.72–8.12). There was no multiplicative interaction between CKD and MetS (P = 0.2); however, there was presence of additive interaction. The relative excess risk for additive interaction (RERI) was 2.73, P = 0.2, and the attributable portion (AP) was 0.49 (0.24–0.74). Conclusion. Our findings illustrate that the combination of CKD and MetS is a strong predictor of incident clinical cardiovascular events due to presence of additive interaction between CKD and MetS.
PMCID: PMC3154776  PMID: 21860804
25.  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) 
The American journal of cardiology  2010;106(1):110-116.
The impact of cardiovascular risk factors on the left ventricle is well known but their impact on right ventricle has not been studied using advanced imaging techniques. The purpose of this study was to determine the relation between cardiovascular risk factors and right ventricular (RV) structure and function and its interaction with the left ventricle. Cardiac magnetic resonance images were analyzed in 4204 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression models were used to study the cross sectional association between individual RV parameters and risk factors. All RV parameters except ejection fraction decreased with age (p<0.0001). RV mass was positively associated with systolic blood pressure (+0.4g, p<0.0001) and high density lipoprotein (HDL) cholesterol (+0.2g, p<0.0001); inversely with diastolic blood pressure (−0.3g, p<0.0001) and total cholesterol (−0.2g, p<0.01). RV end diastolic volume was positively associated with systolic blood pressure (+1.6ml, p<0.01) and HDL cholesterol (+1.8ml, p<0.0001); and inversely with diastolic blood pressure (−2.2 ml, p<0.0001), total cholesterol (−1.4ml, p<0.0001), current smoking (−2.7ml, p<0.05) and diabetes mellitus (−3.1ml, p<0.01). RV ejection fraction was positively related with systolic blood pressure (+1.0%, p<0.0001), HDL cholesterol (+0.4%, p<0.0001) and inversely with diastolic blood pressure (−0.7%, p<0.0001). In conclusion, the mass and volumes of the right ventricle decrease with age. Cardiovascular risk factors, especially blood pressure and HDL cholesterol are associated with subclinical changes in RV mass and volumes.
PMCID: PMC2901248  PMID: 20609657

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