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Objectives:Successful and safe percutaneous closure of atrial septal defects (ASD) is contingent upon the accurate measurement of defect size and adjacent rim tissue, as well as the spatial relationship to other cardiac structures. Previous studies utilizing three-dimensional echocardiography have found significant changes in ASD defect size throughout the cardiac cycle. Cardiac computed tomography (CT) provides excellent spatial and temporal resolution of cardiac structures. Our study examines the efficacy of cardiac CT as a modality for evaluating dynamic changes in ASD defect size throughout the cardiac cycle.Methods:Thirty patients with an ostium secundum ASD underwent cardiovascular CT imaging prior to percutaneous or surgical repair. Cardiovascular CT was performed with a multidetector scanner and images were analyzed using a GE Advantage Workstation capable of advanced image processing and manipulation. ASD defect size was measured in the axial, coronal, and sagittal views at (end-systolic phase) 35% and (end-diastolic phase) 95% of the cardiac cycle.Results:In 30 participants the mean defect size was not significantly different across the three planes, axial mean was 22.4±15.3, coronal 23.7±16.2, and sagittal at 22.3±16.9, p=0.923. However, the change in defect size during the cardiac cycle was significantly different in all three views, P<0.0001 for all. On the axial view, the mean change from 35% to 95% was 6.5±4.9, while the coronal view change was 7.4±5.7, and the sagittal view change was 4.3±3.9. Additionally, the change in size increases with the defect size (figure 1).Conclusions:Cardiac CT imaging accurately depicts dynamic changes in ASD defect size throughout the cardiac cycle, and as such, may be considered a valuable and non-invasive imaging modality for patients undergoing pre-procedural evaluation.

Introduction:Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 polyunsaturated fatty acids (PUFAs) extensively studied in atherosclerosis. Clinical endpoint and imaging studies have yielded convergent findings favoring pure EPA over mixed EPA/DHA formulations. The effects of EPA and DHA dose on coronary plaque dynamics, however, remain unknown, and could yield insights into the utility of these PUFAs in coronary artery disease.Methods:We considered longitudinal studies that compared coronary plaque change in patients receiving statin versus statin+PUFA therapy. Outcomes were % change in total and lipid plaque volume. Treatment effects were calculated as standardized mean difference (SMD), the mean % plaque volume change between statin and statin+PUFA cohorts divided by their pooled standard error. To isolate effects of EPA or DHA dose respectively, treatment arms were pooled by dosage of the PUFA of interest. To account for dependent samples, we fit hierarchical mixed effects models using robust variance estimation, assuming a correlation of 0.5 among treatment effects within multi-arm studies.Results:Among 555 screened articles, 11 studies met inclusion criteria. Among 1,070 patients, there were 14 treatment arms stratified by EPA dose, and 15 treatment arms stratified by DHA dose. Meta-regression revealed that EPA dose (g/day) correlated positively with treatment effect (β = 0.3 [0.1, 0.6], P = 0.02), while daily DHA dose correlated negatively with treatment effect (β = -0.4 [-0.7, -0.1], P = 0.01). We found no associations between EPA (β = 0.1 [-0.2, 0.4], P = 0.44) or DHA (β = -0.1 [-0.3, 0.2], P = 0.59) dose and treatment effects for lipid volume (Figure 1).Conclusions:Among cohorts receiving statin+PUFA therapy, we found a dose-dependent benefit of administered EPA on coronary plaque volume; the opposite was true for DHA. This adds to a growing body of evidence suggesting DHA may blunt beneficial effects of EPA in atherosclerosis.

Introduction:South Asians (SA) have greater atherosclerotic cardiovascular disease (ASCVD) rates than non-Hispanic whites (NHW). SA ethnicity is a risk factor for cardiovascular disease, according to ACC/AHA guidelines. However, data on pattern of atherosclerosis in SA is limited. This study examines plaque burden in SA using quantitative plaque analysis from coronary CT angiography (CCTA).Methods:This is a cross-sectional study comparing the prevalence of atherosclerosis in SA to that of NHW. We identified 104 South Asians who underwent CCTA and quantitative plaque analysis. We then matched 1:1 with 104 non-Hispanic whites. Age, gender, diabetes, hypertension and smoking were utilized to perform a 1: 1 covariate match. Quantification of coronary plaque was conducted using automated plaque analysis software (Cleerly, NY, NY). Percentage atheroma volume (PAV), which is a measure of total plaque divided by total vessel volume, was calculated for each plaque subtypes.Results:A total of 208 subjects formed the study population. The mean age was 71.2±4.9, 66% being male, 38% had DM, 72% reported hypertension, and 10% were past smokers in each group. The SA cohort had significantly higher calcified plaque PAV compared to NHW cohort, median (IQR), 7.6(1.9, 15.5) versus 3.9(1.3, 9.6), (p=0.027). Noncalcified plaque PAV was higher in SA 5.2 (3.0, 7.9) versus 4.5 (2.6,7.2), but not statistically significant (p=0.35). The number of subjects with obstructive disease (&gt50% stenosis) trended higher in the SA cohort (71% of SA versus 60% of NHW) (p=0.08).Conclusions:South Asians had significantly higher calcified plaque PAV and a higher prevalence of obstructive disease compared to the NHW cohort. These results are suggestive of a unique plaque burden and distinctive characteristics in the SA population, which may explain the greater incidence of cardiovascular events and supports the current guidelines.

Introduction:Cardiovascular (CV) disease is the leading cause of death for on-duty firefighters. According to the National Fire Protection Association (NFPA), 44% of all fatalities were due to sudden cardiac deaths, and 90% of which were due to coronary artery disease. Furthermore, firefighters are prone to occupational behaviors, conditions, and environmental exposures that may increase their adverse outcomes. In this study, we will attempt to explore the atherosclerotic differences between firefighters and non-firefighter individuals.Methods:302 firefighters from the Los Angeles fire department who underwent coronary computed tomography angiogram from 2008 to 2021 were matched 1:1 for age, gender, race, diabetes mellitus (DM), hyperlipidemia (HLD), hypertension (HTN), and past smoking to a control cohort for comparison of semi-quantitative coronary plaque burden. Each coronary segment was assessed by a semi-quantify plaque severity (0 for no plaque, 1 for minimal or mild, 2 for moderate, 3 for severe) and luminal stenosis (0: none, 1: <30%, 2: 30-49%, 3: 50-69%, 4: 70-99% and 5:100%). The total plaque severity score (TPS) was calculated by the sum of the individual segment plaque severity score. The total segment stenosis score (TSS) was calculated by adding all the individual segment stenosis score (SSS). Segment involvement score (SIS) was calculated by summing the total number of coronary segments with plaque.Results:Mean (SD) age was 51.3 (6.6); 2% were diabetic; 34% had hyperlipidemia; 19% were hypertensive; 10% were prior smokers in each cohort. The Fire Fighter cohort had significantly higher coronary calcium scores (mean 42.5 vs 12); p<0.0001, TPS at 3 (IQR (1,6) vs 2 (IQR (0,5)); p<0.0001, TSS 3 (IQR (1,5) vs 2 (IQR (0,5)); p<0.0001 , and SIS 2 (IQR (1,4) vs 2 (IQR (0,4)); p<0.0001.Conclusions:After matching for age, gender, race, DM, HTN, HLD, and past smoking. Firefighters had more plaque burden, more stenosis, and more diffuse disease when compared to nonfirefighters, illustrating the occupational effects on the atherosclerotic process

Introduction:Despite the best risk prediction tools, there seems to be a significant amount of residual risk of atrial fibrillation (AF) that justifies new risk prediction strategies. The CHARGE- AF simple model outperforms other existing models. This study aims to evaluate the predictive ability of cardiac MRI-based imaging biomarkers in addition to the CHARGE AF simple model.Methods:MESA is an observational cohort study of 6,814 men and women from six U.S. communities between the ages of 45 and 84 years, who were initially free of clinical CVD. We included 4185 participants after excluding baseline AF (n=70) and missing values of imaging biomarkers (n=2559) at the baseline exam. Left atrial (LA) volume and left ventricular (LV) volumes were obtained from cardiac MRI measurements. Multivariable Cox regression was used to assess the independent 5/10-year AF predictive ability of imaging biomarkers in addition to the baseline model while adjusting for confounders.Results:4,185 participants were included in the study. The average age (SD) was 61(±10) years, 47% male, 13% current smokers, and 39% White with a median follow-up of 17 years. Of this population, 19% developed AF. In multivariable regression models, a 1 ml increase in LA volume was significantly associated with a 3 to 10% higher risk of developing AF. Compared to the baseline model (M1, with no imaging biomarker), the 5 /10-year risk prediction of atrial fibrillation was improved after adding the imaging biomarkers for models 2, 3, and 6 (Table 1). The 5 /10 years concordance index for assessing risk prediction increased marginally from 80 / 79% in M1 to 84 / 81%, 84 / 81%, and 84 / 81% in M2, M3 and M6 respectively (all p values &lt 0.0001).Conclusions:The incorporation of MRI-based LA volume index into the CHARGE AF simple model demonstrated a modest improvement in the 5/10-year risk prediction of AF. The clinical benefit should be interpreted with caution due to marginal improvement in risk prediction.

Objectives:Coronary artery calcium (CAC) has been demonstrated as a non-invasive, low-cost means of assessing atherosclerotic burden and risk of major cardiovascular events in asymptomatic individuals. While it has been previously shown that CAC progression predicts all-cause mortality, we sought to further quantify this association by examining a large cohort of individuals over a follow-up period of between 1 to 22 years.Methods:We studied 3,260 persons aged 30 to 89 years who were referred by their primary care physician for CAC measurement, and had a follow-up scan at least 12 months from initial scan. CAC change was evaluated by absolute change between baseline and follow-up scan. Multivariate analyses using Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between CAC progression and death after adjusting for age, gender, race and other risk factors. Participants were considered at risk from the date of exam 1 to the first occurrence of an event of death or lost to follow-up. The occurrence of death across the follow-up period was verified with the National Death Index.Results:The average time between scans was 4.7±3.2 years with an additional average of 9.1±4.0 years of follow-up time. The average age of the cohort was 58.1 ±10.5 years, 70% being male. A total of 164 deaths occurred. A clinical cut point of CAC progression of 100 units was significantly associated with mortality, hazard ratio 1.51 (95% CI 1.10 -2.13) P=0.017, while adjusting for age, gender, race, diabetes mellitus, hypertension, hyperlipidemia, smoking, baseline CAC and family history. Figure 1.Conclusions:CAC progression of greater than 100 units predicts all-cause mortality. This may add clinical value in encouraging close surveillance and aggressive treatment of individuals within this range.

Introduction and Hypothesis:There is a disproportionately higher incidence of atherosclerotic cardiovascular disease (ASCVD) and associated adverse outcomes in South Asians (SA), compared to other races. SA ancestry has been identified as a risk enhancer in the US cholesterol guidelines. Coronary artery calcium (CAC), a validated marker of sub clinical atherosclerosis offers a robust assessment of CVD risk. We sought to compare the distribution of CAC scores as a marker of CVD risk, across various age groups in SA and other races/ethnicities.Methods:Our analyses included 33,663 individuals (517 SA, 24,060 whites, 1,509 African Americans (AA), 3,759 Hispanics, 3,818 Asians), who underwent CAC scoring at our center. CAC scores were stratified by age, across various races/ethnic sub-groups. Age groups were classified into quartiles as follows: <51 years, 51-59 years, 59-67 years and >67 years of age. Differences in median CAC across races/ethnicities were tested with the Kruskal-Wallis Test, by age quartiles as described.Results:Mean (SD) age was 59 (11.6) years and 63% were men in the entire cohort. SA over 67 years of age, had significantly higher median CAC score 354.0, Interquartile Range (IQR) 36 - 1476, compared to other race/ethnicities (Median CAC (IQR): whites, 195, (21-762), Hispanics 167.5, (19-779), Asians 144, (14-642), AA 159 (8.5-676) (P=0.0019). In age groups from 50-67 years of age, median CAC scores were not significantly different between these groups (Figure 1).Conclusions:In older age groups, SA have higher median CAC scores compared to whites and other racial/ethnic groups including AAs, Hispanics and other Asians. The observed differences in atherosclerotic burden provide mechanistic insights to higher CVD risk, in the vulnerable SA groups. Future studies should explore the effects of CAC screening on treatment strategies, such as initiation of statins and prognosis in SA.

Background:Traditionally, osteoporosis and coronary artery disease were considered unrelated. Beyond age, these two conditions appear to share common etiologies that are not yet fully understood.Objective:We sought to evaluate the relationship between thoracic spine bone mineral density (BMD) and severity of coronary artery calcium (CAC) score.Methods:MESA is a cohort study of 6,814 men and women from six U.S. cities between the ages of 45 and 84 years, who were free of clinical CVD. Included participants had thoracic spine BMD and CAC that was assessed by non-contrast chest CT, using methods previously described by Budoff et al 2010. Multivariate regression analysis was performed to examine the association of thoracic spine BMD and CAC score after adjusting for conventional risk factors of atherosclerosis including age, gender, BMI, race/ethnicity, diabetes, hypertension medications, lipid lowering medications, smoking history and family history of CAD.Results:Correlation coefficient, r, was -0.29 (p<0.0001), indicating inverse relationship between CAC and BMD. BMD was categorized as normal (T-score>-1), osteopenia (-2.50 was 36% in normal group, 49% in the osteopenia group and 68% in the osteoporosis group. In adjusted regression models, the odds of CAC were significantly higher in those with osteoporosis (OR: 1.57 95% CI: 1.31,1.88) p<0.0001 and trending higher in those with osteopenia (OR: 1.15; 95% CI:1.00,1.32) p=0.049. Analysis stratified based on gender, the odds of CAC in men with osteoporosis is higher (OR: 1.61; 95% CI: 1.24,2.09) p=0.0004 compared to women with osteoporosis (OR: 1.48; 95% CI: 1.15,1.90) p=0.002.Conclusion:The prevalence of CAC was significantly higher in osteoporosis group compared to normal BMD. There is an inverse relationship between BMD and CAC independent of cardiovascular risk factors.

Introduction:Multiple trials demonstrate efficacy of eicosapentaenoic acid (EPA) for lowering cardiovascular risk. Imaging studies suggest this benefit may relate to measurable effects on coronary plaque. Interestingly, EPA mixed with docosahexaenoic acid (DHA) has largely failed to show clinical benefit. The differential effects of EPA and EPA/DHA on coronary plaque burden and characteristics, including prognostically significant features such as lipid volume, remain unclear.Methods:We performed a systematic review of clinical trials that longitudinally measured coronary plaque volume in patients randomized to statin+EPA or statin+EPA/DHA versus statin alone, and performed network meta-analysis to estimate the standardized mean difference (SMD) of these treatments in percent change of total plaque volume and plaque lipid volume.Results:Ten trials comprising 860 patients met inclusion criteria among 535 articles. Four studies used intravascular ultrasound, three used coronary CTA, and three used optical coherence tomography. Among statin, statin+EPA, and statin+EPA/DHA treatments, random effects analysis yielded changes of +1.7% [-2.8%, +6.3%], -11.0% [-20.7%, -1.3%], and -3.4% [-14.5%, +7.8%] in total plaque volume and +3.1% [-1.6%, +7.8%], -19.8% [-27.5%, -12.1%], and -6.4% [-20.3%, +7.5%] in plaque lipid volume. Compared with statin, statin+EPA achieved greater percent reduction in coronary plaque volume (total volume: SMD = 0.92, P =0.002; lipid volume: SMD = 1.04, P= 0.003) but statin+EPA/DHA showed no difference (total volume: SMD = 0.19, P= 0.58; lipid volume: SMD = 0.42, P =0.38).Conclusions:In this most up-to-date meta-analysis, EPA as an adjunct to statins is associated with significant reductions in coronary plaque burden, including plaque lipid volume - unlike EPA/DHA combinations. These differential effects on coronary atherosclerosis offer mechanistic insights to observed clinical benefits of statin+EPA therapy.

Introduction:Type 2 diabetes (T2D) has long been known to increase the risk for cardiovascular disease (CVD), partly due to its association with hypertension, dyslipidemia, and obesity. However, T2D alone also confers a higher risk for CVD and increased cardiovascular mortality. The mechanism by which T2D confers this higher risk of CVD is yet to be completely understood.Hypothesis:We hypothesized that people with T2D have decreased coronary lumen volume in comparison with nondiabetics, likely as a result of the decreased ability to undergo coronary vascular remodeling in diabetes.Methods:In a case-controlled study of patients without symptoms of cardiovascular disease, 71 people with T2D and 71 matched patients without T2D underwent coronary CT angiogram. Commercially available software was used to derive number of calcified lesions, atherosclerotic plaque volume, and coronary lumen volume. Spearman and Pearson correlations were used to analyze relationships between plaque, lumen volume and calcified lesions. Wilcoxon rank sum tests were used to analyze differences between number of calcified lesions in T2D and non-T2D. Multi-variate linear regression was use to analyze the relationship between lumen volume and T2D, gender and BMI.Results:Non-diabetics were found to have significantly more coronary lumen volume compared to diabetics (?=425?181 cubic mm, P=0.02) despite similar levels of atherosclerosis after adjusting for BMI and gender.Conclusions:We have found in our sample population, diabetics have significantly less coronary lumen volume than their nondiabetic counterparts even with similar amounts of atherosclerosis. To our knowledge, this is the first time it has been shown diabetics have decreased coronary lumen volume in comparison to nondiabetics. This finding is significant because it can in part explain the mechanism by which T2D results in increased rates of cardiovascular events and poorer outcomes. Future research can be directed toward studying the mechanism by which T2D results in poorer endovascular remodeling and ultimately decreased coronary volume.

Introduction:Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions.Hypothesis:There is a negative correlation between Coronary Artery Calcium (CAC) and Bone Mineral Density (vBMD), and Menopausal Hormonal Therapy (MHT) has a positive effect on both of them.Methods:Healthy perimenopausal women (n=374, age 42-58 years) underwent serial cardiac CT scans over four years to establish eligibility for the Kronos Early Estrogen Prevention Study (KEEPS), a randomized, controlled trial to investigate the relationship between CVD and early initiation of MHT. 104 subjects received oral conjugated equine estrogens (o-CEE), 119 subjects received transdermal 17?-estradiol (t-E2), and 151 subjects received the placebo. We measured CAC and vBMD from thoracic vertebrae using validated software. Multiple linear regression was used to analyze the effect of incident CAC or progression of CAC (an increase of 1 or more), on vBMD among the MHT groups.Results:In 40 subjects (10 o-CEE, 15 t-E2, and 15 placebo) with CAC greater than 0 at baseline, vBMD decreased significantly more than the 334 subjects (94 o-CEE, 104 t-E2, and 136 placebo) with 0 CAC at baseline. In the 66 subjects that showed progression of CAC >1, the same trend is noted, those with CAC progression also had more vBMD loss, than those with no CAC progression. Most notable was the average decrease of vBMD of 11.7 ? 26.2 in the CAC>0 tE-2 group, versus an average increase in vBMD of 5.7 ? 26.2 treated with t-E2 with CAC=0, p=<0.0001.Conclusions:Incidence and progression of CAC are associated with worsening osteoporosis. Osteoporosis worsens in patients with CAC, and MHT slows the progression of CAC and osteoporosis.