Methods and Reproducibility of Liver Fat Measurement Using 3-Dimensional Liver Segmentation From Noncontrast Computed Tomography in EVAPORATE Cohort.

OBJECTIVE: Nonalcoholic fatty liver disease not only shares multiple risk factors with cardiovascular disease but also independently predicts its increased risk and related outcomes. Here, we evaluate reproducibility of 3-dimensional (3D) liver volume segmentation method to identify fatty liver on noncontrast cardiac computed tomography (CT) and compare measures with previously validated 2-dimensional (2D) segmentation CT criteria for the measurement of liver fat. METHODS: The study included 68 participants enrolled in the EVAPORATE trial and underwent serial noncontrast cardiac CT. Liver attenuation < 40 Hounsfield units (HU) was used for diagnosing fatty liver, as done in the MESA study. Two-dimensional and 3D segmentation of the liver were performed by Philips software. Bland-Altman plot analysis was used to assess reproducibility. RESULTS: Interreader reproducibility of 3D liver mean HU measurements was 96% in a sample of 111 scans. Reproducibility of 2D and 3D liver mean HU measurements was 93% in a sample of 111 scans. Reproducibility of change in 2D and 3D liver mean HU was 94% in 68 scans. Kappa, a measure of agreement in which the 2D and 3D measures both identified fatty liver, was excellent at 96.4% in 111 scans. CONCLUSIONS: Fatty liver can be reliably diagnosed and measured serially in a stable and reproducible way by 3D liver segmentation of noncontrast cardiac CT scans. Future studies need to explore the sensitivity and stability of measures for low liver fat content by 3D segmentation, over the current 2D methodology. This measure can serve as an imaging biomarker to understand mechanistic correlations between atherosclerosis, fatty liver, and cardiovascular disease risk.

Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. METHODS: A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. RESULTS: In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR = 1.33, 95% CI = 1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. CONCLUSIONS: The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.

Association between coronary artery calcium and thoracic spine bone mineral density: Multiethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Previously, osteoporosis and coronary artery disease were considered unrelated. However, beyond age, these two conditions appear to share common etiologies that are not yet fully understood. We examined the relationship between thoracic spine bone mineral density (BMD) and severity of coronary artery calcium (CAC) score. METHODS AND RESULTS: MESA is a prospective cohort study of 6814 men and women between the ages of 45 and 84 years, without clinical cardiovascular disease. This study included participants who underwent non-contrast chest CT scans to determine CAC score and thoracic spine BMD. The thoracic spine BMD was categorized into osteoporosis (defined as T score: ≤ -2.5), osteopenia (T-score between: -2.5 and -1) and normal BMD (T-score ≥ -1). There were 3392 subjects who had CAC >0 at baseline. The prevalence of CAC >0 was 36% in normal BMD group, 49% in the osteopenia and 68% in osteoporosis group. After adjusting for risk factors of atherosclerosis, in multivariate regression models we found a significant association between CAC and osteoporosis (OR: 1.40, 95% CI 1.16-1.69, p value < 0.0004). Furthermore, we stratified our results by gender and found a statistically significant association in both men and women. CONCLUSION: Results from this cross-sectional analysis of a large population based ethnically diverse cohort indicate a significant inverse relationship between thoracic BMD and CAC in both genders independent of other cardiovascular risk factors. Future studies need to explore the underlying pathophysiological mechanisms relating BMD and coronary artery calcification.

Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction.

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT. METHODS: A total of 2412 participants who underwent both chest CT and ECG-gated cardiac CT at the same period were included in the Multi-Ethnic Study of Atherosclerosis Exam 5. All participants were monitored for incident atherosclerotic cardiovascular disease (ASCVD) events. TAC is defined as calcification in the ascending aorta, aortic arch and descending aorta on chest CT. The quantification of TAC was measured using the Agatston method. Time-dependent receiver-operating characteristic (ROC) curves were used to compare the prognostic value of TAC and CAC scores. RESULTS: Participants were 69±9 years of age and 47% were male. The Spearman correlation between TAC and CAC scores was 0.46 (p<0.001). During the median follow-up period of 8.8 years, 234 participants (9.7%) experienced ASCVD events. In multivariable Cox regression analysis, TAC score was independently associated with increased risk of ASCVD events (HR 1.31, 95% CI 1.09 to 1.58) as well as CAC score (HR 1.82, 95% CI 1.53 to 2.17). However, the area under the time-dependent ROC curve for CAC score was greater than that for TAC score in all participants (0.698 and 0.641, p=0.031). This was particularly pronounced in participants with borderline/intermediate and high 10-year ASCVD risk scores. CONCLUSION: Our study demonstrated a significant association between TAC and CAC scores but a superior prognostic value of CAC score for ASCVD events. These findings suggest TAC on chest CT provides supplementary data to estimate ASCVD risk but does not replace CAC on ECG-gated cardiac CT.

Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

The impact of carbohydrate restriction-induced elevations in low-density lipoprotein cholesterol on progression of coronary atherosclerosis: the ketogenic diet trial study design.

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.

A Rare Case of Radiation-Associated Aortic and Mitral Valve Stenosis Treated With Transcatheter Valve Replacements.

Radiation therapy is the standard of care for achieving cure for many thoracic malignancies, but it can result in long-term cardiovascular sequelae such as valve disease. We describe a rare case of severe aortic and mitral stenosis due to prior radiation therapy for giant cell tumor treated successfully with percutaneous aortic and off-label mitral valve replacements. (Level of Difficulty: Intermediate.).

Incremental value of ABI and CAC beyond traditional risk markers in long-term prediction of cardiovascular disease incidence in participants with diabetes and impaired fasting glucose: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Subclinical atherosclerosis (SA) diagnosis is key to primary prevention of atherosclerotic cardiovascular disease (ASCVD). SA is common among diabetics. Ankle brachial index (ABI) and coronary artery calcium (CAC) are markers of SA. This study examined whether adding ABI and CAC to diabetic individuals improved ASCVD risk prediction beyond established risk factors. METHODS: MESA is an observational cohort of 6814 participants without clinical cardiovascular disease. All participants with diabetes and impaired fasting glucose were included in the analysis. The association between CAC, ABI, and incident ASCVD, and all-cause mortality was examined using Cox proportional hazard regression. The risk prediction models including ABI and/or CAC in addition to standard risk factors alone were compared. RESULTS: Of the 1719 participants, 55% were male and average age was 64 (±9.6) years old. Participants with diabetes or impaired fasting glucose with higher CAC and lower ABI had higher ASCVD and all-cause mortality. ABI and CAC enhanced ASCVD discrimination over standard risk factors, with C-index (95% CI) of 0.689 (0.66, 0.718) for risk factors alone, 0.696 (0.668, 0.724) for ABI, 0.719 (0.691, 0.747) for CAC, and 0.721 (0.693, 0.749) for CAC + ABI. Similarly, for all-cause mortality, both CAC and ABI improved risk discrimination in addition to standard risk factors alone. CONCLUSIONS: In a large population-based study of individuals with diabetes or impaired fasting glucose, the addition of ABI and CAC to conventional risk factors improved 10-year ASCVD risk prediction. ABI and CAC are non-invasive and cost-effective tests; therefore, these markers should be included into ASCVD risk stratification for primary prevention in the diabetic and impaired fasting glucose population.

Artificial intelligence using a deep learning versus expert computed tomography human reading in calcium score and coronary artery calcium data and reporting system classification.

BACKGROUND: Artificial intelligence (AI) applied to cardiac imaging may provide improved processing, reading precision and advantages of automation. Coronary artery calcium (CAC) score testing is a standard stratification tool that is rapid and highly reproducible. We analyzed CAC results of 100 studies in order to determine the accuracy and correlation between the AI software (Coreline AVIEW, Seoul, South Korea) and expert level-3 computed tomography (CT) human CAC interpretation and its performance when coronary artery disease data and reporting system (coronary artery calcium data and reporting system) classification is applied. METHODS: A total of 100 non-contrast calcium score images were selected by blinded randomization and processed with the AI software versus human level-3 CT reading. The results were compared and the Pearson correlation index was calculated. The CAC-DRS classification system was applied, and the cause of category reclassification was determined using an anatomical qualitative description by the readers. RESULTS: The mean age was age 64.5 years, with 48% female. The absolute CAC scores between AI versus human reading demonstrated a highly significant correlation (Pearson coefficient R  = 0.996); however, despite these minimal CAC score differences, 14% of the patients had their CAC-DRS category reclassified. The main source of reclassification was observed in CAC-DRS 0-1, where 13 were recategorized, particularly between studies having a CAC Agatston score of 0 versus 1. Qualitative description of the errors showed that the main cause of misclassification was AI underestimation of right coronary calcium, AI overestimation of right ventricle densities and human underestimation of right coronary artery calcium. CONCLUSION: Correlation between AI and human values is excellent with absolute numbers. When the CAC-DRS classification system was adopted, there was a strong correlation in the respective categories. Misclassified were predominantly in the category of CAC = 0, most often with minimal values of calcium volume. Additional algorithm optimization with enhanced sensitivity and specificity for low values of calcium volume will be required to enhance AI CAC score utilization for minimal disease. Over a broad range of calcium scores, AI software for calcium scoring had an excellent correlation compared to human expert reading and in rare cases determined calcium missed by human interpretation.

Major Global Coronary Artery Calcium Guidelines.

This review summarizes the framework behind global guidelines of coronary artery calcium (CAC) in atherosclerotic cardiovascular disease risk assessment, for applications in both the clinical setting and preventive therapy. By comparing similarities and differences in recommendations, this review identifies most notable common features for the application of CAC presented by different cardiovascular societies across the world. Guidelines included from North America are as follows: 1) the 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease; and 2) the 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for Prevention of Adult Cardiovascular Disease. The authors also included European guidelines: 1) the 2019 European Society for Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias; and 2) the 2016 National Institute for Health and Care Excellence Clinical Guidelines. In this comparison, the authors also discuss: 1) the Cardiac Society of Australia and New Zealand Guidelines on CAC; 2) the Chinese Society of Cardiology Guidelines; and 3) the Japanese Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. Last, they include statements made by specialty societies including the National Lipid Association, Society of Cardiovascular Computed Tomography, and U.S. Preventive Services Task Force. Utilizing an in-depth review of clinical evidence, these guidelines emphasize the importance of CAC in the primary and secondary prevention of atherosclerotic cardiovascular disease. International guidelines all empower a dynamic clinician-patient relationship and advocate for individualized discussions regarding disease management and pharmacotherapy treatment. Some differences in precise coronary artery calcium score intervals, risk cut points, treatment thresholds, and stratifiers of specific patient subgroups do exist. However, international guidelines employ more similarities than differences from both a clinical and functional perspective. Understanding the parallels among international coronary artery calcium guidelines is essential for clinicians to correctly adjudicate personalized statin and aspirin therapy and further medical management.

Achieving coronary plaque regression: a decades-long battle against coronary artery disease.

INTRODUCTION: Traditionally atherosclerosis was thought to be progressive and medical treatment solely focused on delaying the progression of atherosclerosis rather than treating the disease itself. Multiple recent studies, however, have demonstrated a significant decrease in cardiovascular mortality with the use of additional anti-atherosclerotic therapies beyond statins. Consistent with these observations, mechanistic studies indicate that these additional anti-atherosclerotic therapies have a positive effect on both halting and reversing the course of atherosclerosis. AREAS COVERED: We examine the progression of atherosclerosis and the efficacy of various anti-atherosclerotic treatment classes in this review utilizing multimodality imaging techniques. Searches were conducted in electronic databases: PubMed and EMBASE for all peer reviewed publications that examined coronary plaque progression, regression and stabilization using different imaging modalities and antiatherosclerosis therapies. All relevant published articles on this topic were identified and their reference lists were screened for relevance. EXPERT OPINION: Though lipoprotein levels have traditionally been the target for antiatherosclerosis medication, several newer strategies have emerged creating novel targets in the treatment of coronary atherosclerosis. Using a combination of antiatherosclerosis therapies in conjunction with noninvasive imaging modalities like CCTA to directly visualize the plaque, is currently the focus of the future, with the aim of preventing and reversing atherosclerosis.

Multimodality Imaging Trials Evaluating the Impact of Omega-3 Fatty Acids on Coronary Artery Plaque Characteristics and Burden.

Treatment of established risk factors, especially low-density lipoprotein (LDL) cholesterol, is the cornerstone of preventing atherosclerotic coronary artery disease. Despite reducing LDL cholesterol, there remains a significant risk of cardiovascular disease. Inflammatory and metabolic pathways contribute to recurrence of cardiovascular events, and are often missed in clinical practice. Eicosapentaenoic acid (EPA) may play a crucial role in reducing residual risk of cardiovascular disease. In this review we discuss the clinical applications of omega-3 fatty acids (OM3FAs), their mechanism of action, the difference between pure EPA and docosahexaenoic acid components, and the latest cardiovascular outcome trials and imaging trials evaluating coronary plaque. PubMed and EMBASE were searched to include all the remarkable clinical trials investigating OM3FAs and cardiovascular disease. Beyond statins, additional medications are required to reduce the risk of cardiovascular disease. EPA has shown cardiovascular benefit in addition to statins in large outcome trials. Additionally, multiple serial-imaging studies have demonstrated benefits on plaque progression and stabilization. Due to its pleotropic properties, icosapent ethyl outperforms other OM3FAs in decreasing cardiovascular disease risk in both patients with and without high triglycerides, and is currently recommended as an adjunct to statins. To further strengthen the current evidence, additional research is required to elucidate the inconsistencies between the effects of pure EPA and EPA plus docosahexaenoic acid.

Prognostic Value of Serial Coronary CT Angiography in Atherosclerotic Plaque Modification: What have we learnt?

Purpose of review: To provide an update and to outline the status of coronary computer tomography angiography (CCTA) in evaluation of coronary plaques and discuss the relevance of serial CCTA in guiding cardiovascular risk stratification and anti- atherosclerotic medical therapy. Recent Findings: Coronary CTA is now the imaging modality of choice in monitoring changes in coronary plaque. It has been used in innumerable clinical trials which have demonstrated the benefits of several therapeutic agents and has excellent correlation with previously used invasive imaging modalities. It is safe, fast, less cumbersome, and a cost-effective testing method compared to other invasive imaging modalities for coronary plaque analysis. Summary: The emergence of a noninvasive imaging modality such as CCTA, now permits quantification not only of plaque burden but also allows for further distinction of plaque components and identification of vulnerable plaques. Application of these findings continues to extend the prospect of coronary CTA in evaluation and management of atherosclerotic coronary artery disease (CAD) in clinical practice. In the future artificial intelligence and machine learning will play a significant role in plaque analysis allowing for high accuracy and reproducibility which will lead to a substantial increase in the utilization of coronary CTA.

Assessment of left main coronary artery disease: a comparison between invasive and noninvasive.

Left main coronary artery disease has significant therapeutic as well as prognostic implications. The presence of left main coronary artery stenosis is strongly associated with poor short- and long-term prognoses. Accurate identification of left main stenosis is extremely important since it would be the main factor to guide management. There are several modalities used to determine the presence of atherosclerosis and the degree of stenosis in a left main coronary artery. Newer modalities allow for an accurate evaluation of left main stenosis and atherosclerosis. In this review, we go through different invasive and noninvasive modalities to diagnose left main stenosis, shedding more light into coronary computed tomography angiography, and its accuracy in this specific diagnosis.

Coronary computed tomography angiography evaluation of plaque morphology and its relationship to HDL and total cholesterol to HDL ratio.

BACKGROUND: While population studies have demonstrated that high density lipoprotein cholesterol (HDL-C) and the ratio of total cholesterol to HDL (TC/HDL) improve cardiovascular risk prediction, the mechanism by which these parameters protect the cardiovascular system remains uncertain. OBJECTIVE: To investigate the relationship between the HDL-C level and the total cholesterol to HDL (TC/HDL) ratio with the morphology of coronary artery plaque as determined by coronary computed tomography angiography (CCTA). METHODS: This is a cross-sectional study involving 190 subjects with stable coronary artery disease. Semi-automated plaque analysis software was utilized to quantify plaque and plaque volumes are presented as total atheroma volume normalized (TAVnorm). Multivariate regression models were used to evaluate the association of HDL-C and TC/HDL ratio with coronary plaque volumes. RESULTS: Of the 190 subjects the average (SD) age was 58.9 (9.8) years, with 63% being male. After adjustment for cardiovascular risk factors, HDL- C (>40 mg/dl) is inversely associated with fibrous (p = 0.003), fibrous fatty (p = 0.007), low attenuation plaque (LAP) (p = 0.007), total non-calcified plaque (TNCP) (p = 0.002) and total plaque (TP)(p = 0.004) volume. Furthermore, the TC/HDL ratio (> 4.0) is associated with fibrous (p = 0.047) and total non-calcified plaque (p = 0.039), but not with fibrofatty, LAP, dense calcified plaque, or TP volume. CONCLUSION: There is a strong association between low HDL-C levels and increasing TC/HDL ratio with certain types of coronary plaque characteristics, independent of traditional risk factors. The findings of this study suggest mechanistic evidence supporting the protective role of HDL-C and the TC/HDL ratio's clinical relevance in coronary artery disease management.

Serial Changes in Troponin I in COVID-19 Vaccine-Associated Myocarditis.

A 63-year-old woman presented with atypical chest pain after a third dose of the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine. Serial cardiac troponin measurements were performed to evaluate the trajectory of her time-concentration curve which showed a typical myocarditis curve with rapid normalization. The diagnosis of myocarditis was confirmed by cardiac magnetic resonance imaging and follow-up imaging showed resolution. All symptoms resolved with weeks.