Comparison of Coronary Artery Calcium and Quantitative Coronary Plaque in Predicting Obstructive Coronary Artery Disease: Subgroup Analysis of the CLARIFY Study.

Background: Agatston coronary artery calcium (CAC) score is a strong predictor of mortality. However, the relationship between CAC and quantitative calcified plaque volume (CPV), which is measured on coronary computed tomography angiography (CCTA), is not well understood. Furthermore, there is limited evidence evaluating the difference between CAC versus CPV and CAC versus total plaque volume (TPV) in predicting obstructive coronary artery disease (CAD). Methods: This study included 147 subjects from the CLARIFY registry, a multicentered study of patients undergoing assessment using CCTA and CAC score as part of acute and stable chest pain evaluation. Automated software service (Cleerly.Inc, Denver, CO, USA) was used to evaluate the degree of vessel stenosis and plaque quantification on CCTA. CAC was measured using the standard Agatston method. Spearman correlation and receiver operating characteristic curve analysis was performed to evaluate the diagnostic ability of CAC, CPV and TPV in detecting obstructive CAD. Results: Results demonstrated a very strong positive correlation between CAC and CPV (r=0.76, p=0.0001) and strong correlation between CAC and TPV (r=0.72, p<0.001) at per-patient level analysis. At per-patient level analysis, the sensitivity of CAC (68%) is lower than CPV (77%) in predicting >50% stenosis, but negative predictive value is comparable. However, the sensitivity of TPV is higher compared with CAC in predicting >50% stenosis, and the negative predictive value of TPV is also higher. Conclusion: CPV and TPV are more sensitive in predicting the severity of obstructive CAD compared with the CAC score. However, the negative predictive value of CAC is comparable to CPV, but is lower than TPV. This study elucidates the relationship between CAC and quantitative plaque types, and especially emphasizes the differences between CAC and CPV which are two distinct plaque measurement techniques that are utilized in predicting obstructive CAD.

Comparison of risk profiles of participants in the Women's IschemiA TRial to Reduce events In non-ObstRuctive CAD (WARRIOR) trial, using Coronary Computed Tomography Angiography vs Invasive Coronary Angiography.

OBJECTIVE: To compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). METHODS: The WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. RESULTS: An initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. CONCLUSIONS: Among this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

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.

Quantitative imaging biomarkers of coronary plaque morphology: insights from EVAPORATE.

Aims: Residual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result. Methods and Results: EVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm3 vs. an increase of 41 mm3, p = 0.008), widening at 18 months (6 mm3 vs. 58 mm3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p < 0.01 (sustained at 18 months), generalizing well to a validation cohort. Conclusion: Plaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response.

What Is New in Risk Assessment in Nuclear Cardiology?

Nuclear cardiology techniques allow in-depth evaluation of cardiac patients. A body of literature has established the use of nuclear cardiology. The results obtained with traditional cameras have been reinforced by those obtained with a series of innovations that have revolutionized the field of nuclear cardiology. This article highlights the role of nuclear cardiology in the risk assessment of patients with cardiac disease and sheds light on advancements of nuclear imaging techniques in the cardiovascular field. Patient risk stratification has a key role in modern precision medicine. Nuclear cardiac imaging techniques may quantitatively investigate major disease mechanisms of different cardiac pathologies.

Benefit of icosapent ethyl on coronary physiology assessed by computed tomography angiography fractional flow reserve: EVAPORATE-FFRCT.

AIMS: Icosapent ethyl (IPE) significantly reduced ischaemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides in REDUCE-IT, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. However, the mechanisms driving this clinical benefit are not fully known. The EVAPORATE trial demonstrated that IPE significantly reduced plaque burden. No study to date has assessed the impact of IPE on coronary physiology. Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) data sets (FFRCT) applies computational fluid dynamics to calculate FFR values in epicardial coronary arteries. Our objective was to assess the impact of IPE on coronary physiology assessed by FFRCT using imaging data from EVAPORATE. METHODS AND RESULTS: A total of 47 patients and of 507 coronary lesions at baseline, 9 months, and 18 months with coronary CTA and FFRCT were studied in a blinded core lab. The pre-specified primary endpoint was the FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using IPE compared with placebo. The pre-specified secondary endpoint was the change in translesional FFRCT (ΔFFRCT) across the most severe (minimum 30% diameter stenosis) coronary lesion per vessel. Baseline FFRCT was similar for IPE compared with placebo (0.83 ± 0.08 vs. 0.84 ± 0.08, P = 0.55). There was significant improvement in the primary endpoint, as IPE improved mean distal segment FFRCT at 9- and 18-month follow-up compared with placebo (0.01 ± 0.05 vs. -0.05 ± 0.09, P = 0.02, and -0.01 ± 0.09 vs. -0.09 ± 0.12, P = 0.03, respectively). ΔFFRCT in 140 coronary lesions was improved, although not statistically significant, with IPE compared with placebo (-0.06 ± 0.08 vs. -0.09 ± 0.1, P = 0.054). CONCLUSION: Icosapent ethyl demonstrated significant benefits in coronary physiology compared with placebo. This early and sustained improvement in FFRCT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial. Furthermore, this is the first assessment of FFRCT to determine drug effect.

Plaque Progression Differences Between Apixaban and Rivaroxaban in Patients With Atrial Fibrillation Measured With Cardiac Computed Tomography and Plaque Quantification.

BACKGROUND: Direct oral anticoagulants (DOACs) have been associated with less calcification and coronary plaque progression than warfarin. Whether different DOACs have different effects on coronary plaque burden and progression is not known. We compared the 12-month effects of apixaban and rivaroxaban on plaque characteristics and vascular morphology in patients with atrial fibrillation through quantitative cardiac computed tomographic angiography. STUDY QUESTION: In patients with nonvalvular atrial fibrillation using apixaban or rivaroxaban, are there differences in plaque quantification and progression measured with cardiac computed tomography? STUDY DESIGN: This is a post hoc analysis of 2 paired prospective, single-centered, randomized, open-label trials with blinded adjudication of results. In total, 74 patients were prospectively randomized in parallel trials: 29 to apixaban (2.5-5 mg BID) and 45 to rivaroxaban (20 mg QD). Serial cardiac computed tomographic angiography was performed at baseline and 52 weeks. MEASURES AND OUTCOMES: Comprehensive whole-heart analysis was performed for differences in the progression of percent atheroma volume (PAV), calcified plaque (CP) PAV, noncalcified plaque (NCP) PAV, positive arterial remodeling (PR) ≥1.10, and high-risk plaque (Cleerly Labs, New York, NY). RESULTS: Both groups had progression of all 3 plaque types (apixaban: CP 8.7 mm 3 , NCP 69.7 mm 3 , and LD-NCP 27.2 mm 3 ; rivaroxaban: CP 22.9 mm 3 , NCP 66.3 mm 3 , and LD-NCP 11.0 mm 3 ) and a total annual plaque PAV change (apixaban: PAV 1.5%, PAV-CP 0.12%, and PAV-NCP 0.92%; rivaroxaban: PAV 2.1%, PAV-CP 0.46%, and PAV-NCP 1.40%). There was significantly lower PAV-CP progression in the apixaban group compared with the rivaroxaban group (0.12% vs. 0.46% P = 0.02). High-risk plaque characteristics showed a significant change in PR of apixaban versus rivaroxaban ( P = 0.01). When the propensity score weighting model is applied, only PR changes are statistically significant ( P = 0.04). CONCLUSIONS: In both groups, there is progression of all types of plaque. There was a significant difference between apixaban and rivaroxaban on coronary calcification, with significantly lower calcific plaque progression in the apixaban group, and change in positive remodeling. With weighted modeling, only PR changes are statistically significant between the 2 DOACs.

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.

Coronary plaque progression is greater in systemic lupus erythematosus than rheumatoid arthritis.

BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with a high incidence of cardiovascular disease. Coronary atherosclerosis, particularly total plaque and noncalcified plaque on coronary computed tomography angiography (CCTA) has been correlated with cardiovascular events. We compared baseline coronary plaque burden and progression by serial CCTA in SLE and RA patients. METHODS: We prospectively evaluated 44 patients who underwent serial CCTA examinations to quantify coronary plaque progression, 22 SLE patients, and 22 age- and sex-matched RA patients. Semiautomated plaque software was used for quantitative plaque assessment. Linear regression examined the effect of SLE diagnosis (versus RA) on annualized change in natural log-transformed total normalized atheroma volume (ln-TAV norm ) for low-attenuation, fibrofatty, fibrous, total noncalcified, densely calcified, and total plaque. RESULTS: No quantitative differences for any plaque types were observed at baseline between SLE and RA patients ( P = 0.330-0.990). After adjustment for baseline plaque and cardiovascular risk factors, the increase in ln-TAV norm was higher in SLE than RA patients for fibrous [Exp-ß: 0.202 (0.398), P = 0.0003], total noncalcified [Exp-ß: 0.179 (0.393), P = 0.0001], and total plaque volume [Exp-ß: 0.154 (0.501), P = 0.0007], but not for low-attenuation, fibrofatty, or densely calcified plaque ( P = 0.103-0.489). Patients with SLE had 80% more fibrous, 82% more noncalcified, and 85% more total plaque increase than those with RA. CONCLUSION: Coronary plaque volume was similar in RA and SLE at baseline. Progression was greater in SLE, which may explain the greater cardiovascular risk in this disease. Further research to evaluate screening and management strategies for cardiovascular disease in these high-risk patients is warranted.

A comparison of cardiovascular imaging practices in Africa, North America, and Europe: two faces of the same coin.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. There are significant differences in the burden of cardiovascular disease and associated risk factors, across high-income countries and low- and middle-income countries. Cardiac imaging by echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography myocardial perfusion imaging are well-established non-invasive tests that aid in the diagnosis, risk stratification, and management of various cardiac diseases. However, there are significant inequalities in availability and access to imaging modalities in low- and middle-income countries attributed to financial constraints, disparities in healthcare and technical infrastructure. In the post-COVID-19 pandemic era, these disparities are exaggerated by the continued technological advancements driving innovations in the field of cardiovascular (CV) imaging in high-income countries, while there is an urgent need to provide sustainable access to diagnostic imaging for patients in economically strained healthcare systems in regions like Africa. This review aims to highlight the inequalities in the burden of cardiac disease, associated risk factors, and access to diagnostic CV imaging tests, while also exploring the need for sustainable solutions to implementing CV imaging all over the world.

The effect of icosapent ethyl on left atrial and left ventricular morphology.

Atrial fibrillation (AF) is a common arrhythmia associated with poor outcomes. N-3 fatty acids have been shown to provide significant cardiovascular risk reduction, but they may exacerbate the risk of AF. The pathway by which N-3 fatty acids may be arrhythmogenic is unknown. One possible mechanism involves cardiac chamber morphology alteration. The purpose of this study was to investigate the effect of icosapent ethyl (IPE) on left atrial (LA) size and left ventricular (LV) mass. This study used coronary computed tomographic angiography images gathered from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis (EVAPORATE) trial. EVAPORATE was a randomised, double-blind, placebo-controlled study finding a significant reduction in coronary atherosclerosis progression in patients with residually elevated triglycerides despite statin therapy on 4 g IPE daily versus 4 g placebo daily. Computed tomography images were used to measure LA size and LV mass at 0 and 18 months. Of 80 enrolled patients, 68 were included in the final analysis. Baseline demographics and risk factors were similar between IPE and placebo cohorts. LA anterior- posterior diameter measured on axial (p=0.51) and sagittal (p=0.52) orientations were not different over time. Also, there was no difference between groups in the change in LA volume (p=0.84). Change in LV mass was similar between groups (p=0.13). In conclusion, this study did not detect differences in LA size or LV mass over 18 months between patients on 4 g daily IPE versus placebo.

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.

Obstructive coronary artery disease in symptomatic diabetics with zero coronary calcium score: are we missing something?

BACKGROUND: Prevalence and severity of coronary artery disease (CAD) in symptomatic patients with zero coronary artery calcium score (CACS) are unclear, particularly in regard to the diabetic population, which represents, per se, a subgroup at increased cardiovascular risk. The aim of this study was to investigate the prevalence and severity of CAD by coronary computed tomography angiography (CCTA) in a symptomatic diabetic cohort with zero CACS. METHODS: All consecutive symptomatic diabetics referred for CAD suspicion were included in this study. All subjects underwent a noncontrast coronary artery calcium scan followed by CCTA. CACS was quantified using the Agatston method. CAD was defined as a total plaque score (TPS) greater than zero. Obstructive and severe obstructive CAD were defined respectively as luminal stenosis >50% and >70% in at least one coronary segment. RESULTS: We identified 1722 symptomatic diabetics (mean age 62.5 ± 12.9 years, 62% men). One hundred and eleven subjects had zero CACS and TPS >0 (mean age was 49.5 ± 14.8, 58% women, 56% Hispanics). Sixty-five patients (58.5%) had one-vessel disease, followed by 30 (27%) with two-vessel disease and 14 (12.6%) with ≥ three-vessel disease. Obstructive CAD was found in 11 subjects and, among these, three were categorized as severe obstructive CAD. CONCLUSION: In symptomatic diabetic patients with zero CACS, CAD, including obstructive disease, can still occur and is predominant in middle-aged adults, women and Hispanics. In symptomatic diabetics CCTA is a critical step for accurate risk stratification even when CACS would have placed some of these individuals in a lower-risk category.