Coronary Computed Tomography Angiography Research Articles

Enhancing computational fluid dynamics simulation for coronary artery disease analysis through spatial iterative modeling

Abstract Background Endothelial shear stress (ESS) critically influences the pathogenesis of coronary artery disease (CAD) by modulating the formation and progression of atherosclerotic lesions. Despite the use of 3D modeling in computational fluid dynamics (CFD) simulations to calculate ESS, the precision of these models significantly depends on the method of reconstruction. Spatial Iterative Method (SIM) extends the iterative approach in computer science to spatial data, using recurring algorithms to refine 3D models and analyses. Iterative approach executes a sequence of instructions repeatedly until a certain condition is met, enabling progressive problem-solving. Purpose In this study, we investigated the application of the SIM to estimate ESS in coronary arteries and explored Atherosclerotic Plaque Areas (APA) in patients with CAD. Methods We analyzed fifteen patients (9 males, mean age of 63 ± 10.56 years) with atherosclerotic plaque on coronary arteries. The eighteen images captured from an anterior viewpoint in 10-degree increments of the coronary artery obtained from Coronary Computed Tomography Angiography at the best diastolic phase for each patient were used. We implemented the SIM for 3D model reconstruction, facilitating ninety comparisons across all iterations to evaluate ESS estimations accurately. (Figure 1.) Results In our study, we evaluated ESS contours from CFD simulations for a total of 282 APA (200 calcified and 82 soft plaques) across ninety spatial iterations. We categorized ESS into three groups: low (162 APA cases with ESS of less than 1 Pascal (Pa)), medium (67 APA cases with ESS between 1 and 2 Pa), and high (53 APA cases with ESS greater than 2 Pa). There was a significant association between ESS categories and plaque types (p < 0.0001, Figure 2.). The calcified plaques were formed in areas with low ESS (%80 of calcified plaques) and soft plaques in areas with medium and high ESS (%97 percent of soft plaques). Conclusion The significant association between ESS categories and plaque types shows the potential of SIM in hemodynamic analysis. This finding highlights the potential of SIM in enhancing the understanding of hemodynamic influences on plaque formation, offering a promising direction for future cardiovascular research.Figure 1.Sample Iteration of the SIMFigure 2.Heatmap of ESS vs. APA

Pericoronary adipose tissue computed tomography attenuation (PCAT) as a marker of premature CVD in asymptomatic people living with HIV (PLWH) without traditional risk factors: H-ART to heart study

Abstract Background Controversy exists regarding the contribution of HIV, ART or traditional risk factors to CVD risk in PLWH. The H-ART to Heart study investigates the prevalence of subclinical CVD in asymptomatic PLWH without cardiovascular risk factors compared to negative controls(-). Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and thus can be detected on coronary computed tomography angiography (CTCA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). Methods This cross-sectional study compared PLWH aged 35-55yrs (diagnosed >10 yrs, on ART) to matched controls. Included were Caucasian men who have sex with men(MSM) and Black African/Caribbean women (BW) with traditional risk factors excluded (hypertension, hyperlipidaemia, diabetes, kidney disease, smoking, depression, inflammatory conditions, etc.). Detailed vitals, 10 year CVD risk calculation (Q-RISK 3) were recorded. CTCA were performed with novel analysis using PCAT to assess for coronary inflammation (Figure 1.) Results 98 participants were recruited (49M; 51 PLWH). Mean Q Risk 3 (10yr CVD risk - %) was low across the groups (HIV+MSM 4.65±2.1, HIV-MSM 3.88±2.7;p=0.29; HIV+BW 2.03±1.3, HIV-BW 1.38±0.98 p=0.66). 79 participants (42 PLWH; 37 controls) completed a CTCA with only 2 PLWH having clinically significant disease (CAD-RAD 3+ ie. >50% luminal stenosis) and none in the control group. (p=0.49) The CT scans of 69 patients were assessed for peri-coronary adipose tissue (PCAT) density, 2 were ruled out due to a small non-dominant RCA. The PCAT density of PLWH was higher than that of the controls (-71.2±27.6 vs -75.5±30.3 P=<0.05). Multivariate linear regression demonstrated that HIV status was an independent predictor of coronary inflammation (p=0.037) after adjusting for age, gender and BMI. Conclusion PWLH without traditional CV risk factors did not have significant evidence of more clinically relevant stenosis than controls on CTCA. However PCAT demonstrated a higher signal of coronary inflammation, despite stable disease, compliance with ART and low CVD risk scores. PLWH remain at risk of CV disease, this study supports the rationale for early preventative strategies for CVD prevention in PLWH.PCAT showing HIV inflammation Vs Control

Prediction of the burden and characteristics of coronary plaques by cardiorespiratory fitness

Abstract Background Cardiorespiratory fitness (CRF) and coronary plaque burden are both important predictors of mortality. Although mortality of coronary heart disease (CHD) is reduced, prevalence remains high and there is a need to improve early detection and preventive measures. How CRF relates to coronary plaque burden and composition in the general population is largely unknown. Purpose The aim was to study the relationship between CRF and the total coronary plaque burden, including subgroups of coronary plaques, in subjects without known CHD. Methods A random sample of participants from a large population-based echocardiographic reference range study aged 55-70 at baseline was included. Coronary plaque burden was assessed, on average, 4.0 years after the baseline evaluation using coronary computed tomography angiography (CCTA). The burden and characteristics of the coronary plaques were evaluated using a validated, commercially available, semi-automatic software that assessed all coronary territories including the left main, left anterior descending, circumflex, and right arteries. Coronary plaques were classified as dense calcified plaques, plaques with necrotic core, fibrous, and fibrous-fatty plaques. Baseline measures included cardiovascular risk factor assessment and measurement of peak oxygen consumption (VO2peak) assessed by treadmill cardiopulmonary exercise testing. Linear regression models were used to assess the impact of VO2peak on coronary plaque burden. In Model 1, we adjusted for sex and age, while Model 2 also included adjustments for non-HDL cholesterol, HbA1c, systolic blood pressure, smoking status, and body mass index. Results Of 845 invited to undergo CCTA, 707 (51% females) underwent CT scanning. Of these, 699 scans had acceptable quality for further analyses. Table 1 shows baseline characteristics and Table 2 shows the associations of VO2peak with coronary plaque burden. In the fully adjusted Model 2, there was a significant negative association of VO2peak with total plaque burden (β -0.18, R2 15%, p<0.001), while the association was not significant in Model 1 (p=0.54). Similarly, higher VO2peak significantly predicted a lower burden of dense calcified plaques, plaques with necrotic core, and fibrofatty plaques in both models (R2 3-17%, p≤0.01). The results were consistent whether the coronary plaques were evaluated across the entire coronary arteries (down to a diameter of 1.5 mm) or solely in the proximal segments. However, the predictive power of the models was relatively low with R2 of maximum 17%. Conclusion In a population without known CHD, CRF explained a modest part of the variation in coronary plaque burden. Considering CRF in risk prediction may enhance coronary artery disease prevention beyond traditional risk factors.

Reduced inflammation assessed by pericoronary adipose tissue is associated with coronary plaque calcification

Abstract Introduction Pericoronary adipose tissue attenuation (PCAT) quantified from coronary computed tomography angiography (CCTA) is increasingly recognized as an inflammation marker in coronary artery disease (CAD). Inflamed PCAT has been linked to non-calcified plaque (NCP) and cardiovascular morbidity and mortality. Nevertheless, gaps remain in understanding how PCAT behaves during plaque stabilization. Purpose We investigated associations between coronary artery inflammation assessed by PCAT and the presence and type of coronary plaques, plaque burden, and coronary calcification. Methods An observational study involving 506 patients with suspected chronic coronary syndrome who underwent CCTA. PCAT was averaged across the proximal 40 mm segments of all three coronary vessels to represent the patient level. Plaque presence and types (calcified, mixed, and soft) were assessed. Total, NCP, and calcified plaque (CP) burdens were measured as normalized atheroma volumes. Coronary calcification was quantified using Agatson coronary artery calcification (CAC) score and categorized based on cut-offs of 0, 100, 400. Results The mean PCAT was -81.1 ±6.3 Hounsfield Unit (HU) without plaque and -79.7 ±6.0 HU with plaque (p= 0.01). PCAT differed between calcified (-81.8 HU), mixed (-79.8 HU), and soft (-77.0 HU) plaques (p<0.0001). Multivariate linear analysis (adjusted for clinical risk factors, cardiovascular medication, and tube voltage) showed PCAT positively associated with total plaque burden (estimate= 1.1 [95% CI: 0.3-1.8], p=0.004) and NCP burden (estimate= 2.4 [95% CI: 1.4-3.4]; p<0.0001), while the association with CP burden was negative, but not statistically significant (estimate= -1.7 [95%CI : -4.1-0.7], p=0.2). Multivariate linear analysis, which accounted for both calcified and non-calcified plaque, reaffirmed the positive association to NCP burden (estimate= 2.7 [95% CI: 1.7-3.7]; p<0.0001) and a significant negative association between CP burden (estimate= - 3.3 [95% CI: -5.8- -1.0]; p=0.007) and PCAT. No significant differences in PCAT levels were found among patients with a CAC score of 0 and those with CAC scores exceeding 400, or across different stages of CAC score categories (p>0.8). Conclusion PCAT increased with plaque presence, rising from calcified to mixed to soft plaques. Increased NCP burden associated with higher PCAT, while higher CP burden seemed to reduce PCAT, though not statistical significant. Interestingly, when NCP was absent, higher levels of CP burden were associated with reduced inflammation. This supports the hypothesis of plaque stabilization, proposing that calcification might stabilize the vessel and indirectly contribute to reducing inflammation.Figure 1 PCAT by plaque typesTable 1 PCAT & plaque burden

Comparison between coronary calcium score and segment involvement score when used in clinical routine

Abstract Data from a nationwide registry on coronary computer tomography angiography. Background The Coronary Artery Calcium Score (CACS) and segment involvement score (SIS) are crucial factors in assessing the severity of coronary artery disease (CAD) and determining the likelihood of future cardiovascular events. However, there are few large multicenter studies comparing the predictive value of CACS and SIS when used in the clinical routine. Objectives To compare CACS and SIS ability to predict cardiovascular outcomes when used in the clinical routine. Methods This retrospective cohort study included patients who underwent Coronary Computed Tomography Angiography (CCTA) for CAD evaluation between 2006-2022 in 29 different centers in Sweden. CACS was calculated using the Agatston method, and SIS was determined based on the number of coronary segments exhibiting plaque. For SIS, patients were categorized into SIS=0, SIS=1, SIS=2, SIS=3, SIS³4, for CACS patients were categorized into CACS=0, CACS=1-9, CACS=10-99, CACS=100-299, CACS³300. Patients were followed regarding the primary outcome of death or myocardial infarction. Multivariable Cox proportional hazards models were used for adjusting for potential confounders. Results A total of 23034 patients underwent CCTA and were followed for up to ten years. Median age (IQR) was 58 (49–67) years, 50% were women, 9% had diabetes mellitus, 42% had hypertension, 25% had hyperlipidemia, 5% had previously known CAD. There were 955 patients (4.1%) with myocardial infarction (MI) and 409 patients (2.2%) died during follow up. There was an increase in cardiovascular events with increasing SIS. When comparing SIS and presence of obstructive stenosis, SIS was a better predictor of outcome (Figure 1). There was also an increase cardiovascular events with increasing CACS (Figure 2). When adjusted for age, sex, risk factors, previous cardiovascular disease and intervention, both SIS and CACS were independently associated with outcome. When SIS and CACS were compared in a receiver operating characteristic curve, CACS had significantly larger AUC than SIS, (0.70[0.67-0.73] vs 0.62[0.60-0.63]). Conclusion Our findings show that both CACS and SIS are important and independent predictors of cardiovascular outcomes thereby offering a valuable tool for personalized risk stratification and management in clinical settings. When used in the clinical routine, CACS appears to be more strongly associated with outcome than SIS.Figure1 Survival SISFigure 2 Survival CACS

Social differences in subclinical coronary artery atherosclerosis in Sweden

Abstract Most data indicate an inverse relation between socioeconomic status and clinically manifest coronary heart disease that is only partly explained by modifiable cardiovascular risk factors. Few population-based studies have investigated social factors with respect to differences in subclinical coronary atherosclerosis in a healthy population without prior manifest coronary disease. Purpose To examine socioeconomic differences in imaging-detected coronary atherosclerosis, and to which extent potential differences could be explained by modifiable risk factors. Methods The Swedish CArdioPulmonary bioImage Study (SCAPIS) randomly invited individuals aged 50 to 64 years from the general population. Out of 30,154 participants, we defined a population of healthy participants without prior myocardial infarction or coronary procedures, with technically satisfactory results from coronary computed tomography angiography (CCTA) and coronary artery calcification scoring (CACs). CCTA outcomes were recorded as 1. any coronary atherosclerosis, 2. coronary stenosis ≥50%, 3. segment involvement score (SIS) ≥4, and 4. coronary artery calcium score (CACs) ≥100. Results Among 24,616 participants (49.2% women, mean age 57.4 (SD 4.2) years), those with ≤9 compared to ≥12 years of education were heavier, with mean (SD) BMI 28.0 (4.5) compared to 26.1 (4.0) kg/m2, with more hypertension (23.3% vs 15.0%), and diabetes (9.6% vs 4.6%), and with more active smokers (17.4% vs 3.8%). The prevalence of plaque/significant stenosis is shown in the Figure. Findings with respect to low vs high education and odds ratios (ORs) adjusted for age and sex were: 48.8% vs 35.3% for any coronary atherosclerosis, OR 1.31; 95%CI 1.19-14.4; 6.8% vs 4.4% for coronary stenosis ≥50%, OR 1.21; 95%CI 0.99-1.47; 15.7% vs 9.8% for SIS≥4, OR 1.21; 95% CI 0.99-1.47; and 10.1% vs 7.1% for CACS≥100, 1.29; 95%CI 1.12-1.48 (Table). However, after adjustment for coronary risk factors no significant associations with subclinical coronary atherosclerosis persisted. Conclusions After adjustment for conventional modifiable risk factors there was no convincing evidence of any independent association between low education and subclinical coronary atherosclerosis. Further studies are needed to explore which other mechanisms could potentially explain an independent link between low socioeconomic status and clinically manifest coronary heart disease.Figure

Effects of nicorandil, isosorbide mononitrate or diltiazem on radial artery grafts after coronary artery bypass grafting: the randomized ASRAB-pilot trial

Abstract Background The optimal chronic oral antispastic medication after coronary artery bypass grafting (CABG) using radial artery (RA) grafts is controversial. Purpose This pilot trial aimed to preliminarily compare the efficacy and safety of nicorandil, isosorbide mononitrate, or diltiazem in patients who underwent CABG using RA grafts. Methods This was a single-center, randomized, open-label, parallel-group pilot trial. Eligible patients who underwent CABG using RA grafts within 3 days were randomized in a 1:1:1 ratio to receive oral doses of nicorandil (15 mg daily), isosorbide mononitrate (50 mg daily), or diltiazem (180 mg daily) for 24 weeks post-CABG. The primary outcomes were RA grafts failure (defined as modified FitzGibbon Grade B, S, or O) at 1- and 24-weeks, assessed by coronary computed tomography angiography (CCTA). The secondary outcomes include major adverse cardiovascular event (MACE, a composite of all-cause death, myocardial infarction, stroke, and unplanned revascularization) and angina recurrence. Results Among 150 randomized participants, 149 patients (full analysis set, mean age 56.8 years, 13.4% females, 83.9% with acute coronary syndrome, 49.7% with diabetes) with 177 RA grafts completed at least once CCTA assessment, including 50 patients with 64 RA grafts in the nicorandil group, 50 patients with 57 RA grafts in the isosorbide mononitrate group, and 49 patients with 56 RA grafts in the diltiazem group, respectively. (Figure 1). At 1-week post-CABG, the RA graft failure rates were numerically lower with nicorandil vs. diltiazem (19.4% vs. 25.0%, difference: -5.6% [95% CI -20.6% to 9.3%]; P = 0.49) and isosorbide mononitrate vs. diltiazem (18.2% vs. 25.0%, difference: -6.8% [95% CI -21.8% to 8.6%]; P =0.41). Nicorandil vs. isosorbide mononitrate showed similar rates (19.4% vs 18.2%, difference: 1.2% [95% CI −13.3% to 15.2%]; P =0.88). At 24 weeks, a numerically trend indicating a larger reduction in RA graft failure rates between nicorandil vs. diltiazem (16.1% vs 27.8%, difference: -11.7% [95% CI -26.6% to 3.4%]; P =0.17), and isosorbide mononitrate vs. diltiazem (12.5% vs 27.8%, difference: -15.3% [95% CI -29.8% to -0.2%]; P =0.06). Nicorandil vs. isosorbide mononitrate remained similar (16.1% vs 12.5%, difference: 3.6% [95% CI -9.6% to 16.4%]; P =0.59). Per-protocol set analysis results were consistent with full analysis set analysis (Table 1). During the follow-up, 6 patients with MACEs and 7 with angina recurrence were observed (MACE: 2 in nicorandil, 2 in isosorbide mononitrate, and 2 in diltiazem; angina recurrence: 1, 3, and 3 in the respective groups). Conclusions In this underpowered pilot trial, treatment with nicorandil or isosorbide mononitrate showed a numerically considerable but not statistically significant benefit on RA grafts outcome compared to diltiazem up to 24-week post-CABG. Larger hypothesis testing trial is warranted.Figure 1:The study flow diagramFigure 2:Primary outcomes in FAS and PP

The impact of hydrostatic pressure on fractional flow reserve in saphenous vein grafts

Abstract Background Intracoronary physiological measurements can be subject to the influence of hydrostatic pressure. Saphenous vein grafts (SVGs) diverge in origin and trajectory from native coronary arteries, which may increase the susceptibility of fractional flow reserve (FFR) measurements to be impacted by the hydrostatic pressures. The precise impact of SVG anatomy on physiological pressure indices remains unknown at present. Purpose We sought to study the impact of SVG anatomy on FFR. Methods Included were symptomatic patients with prior coronary artery bypass grafting and at least one non-occluded SVG, who underwent coronary computed tomography angiography (CCTA) preceding invasive coronary angiography. SVG course and height excursion were reconstructed based on the CCTA images. Similarly to native coronary arteries, the impact of hydrostatic pressure on FFR was calculated by adding 0.077 mmHg to the distal coronary pressure for every millimeter height difference in a supine position between the SVG ostium and the position of the pressure wire tip. Results In total, 74 patients (mean age 71 ± 7 years; 85% male) with 87 SVGs were included. A total of 76 SVGs underwent interrogation by FFR. The height difference between SVG ostium and pressure wire tip position was largest for single SVGs to the circumflex artery (Cx; - 55.1 ± 17.0 mm), followed by sequential SVGs to the Cx (- 53.1 ± 17.7 mm) and to the right coronary artery (RCA; - 36.7 ± 21.6 mm). Corrected FFR was significantly lower as compared to uncorrected FFR in single SVGs to the Cx (0.85 ± 0.17 vs. 0.90 ± 0.18), and sequential SVGs to the Cx (0.92 ± 0.14 vs. 0.96 ± 0.15) and the RCA (0.82 ± 0.20 vs. 0.85 ± 0.21) (P<0.001 for all). Conclusions Hydrostatic pressure related to the course anatomy of SVGs notably affects FFR values, resulting in an overestimation of FFR in SVGs to the Cx and sequential SVGs to the RCA. In these SVGs, FFR values near the cutoff value should be interpreted cautiously.

Lipoprotein(a) as a predictive marker of coronary artery calcification (CAC). The results from the STAR-Lp(a) cohort study.

Abstract Background Lipoprotein(a) [Lp(a)] concentration is an independent risk factor for cardiovascular disease, including atherosclerosis. Purpose The aim of the study was to assess the relationship between the elevated Lp(a) levels, and the risk of developing atherosclerosis assessed using coronary artery calcium (CAC) score. Methods The analysis was conducted among 553 primary prevention patients (65.7% women, the average age was 65.8±10.1 years) from the outpatient specialist care who underwent coronary computed tomographic angiography (CTA). This group accounted for 22.3% of all patients (n=2475) included in the registry. Lp(a) levels were assessed in three groups: <30 mg/dL (<75 nmol/l) (normal level), 30-50 mg/dL (75-125 nmol/l) (moderate cardiovascular risk) and >50 (>125 nmol/l) (high cardiovascular risk). Patients were divided into groups: with normal CAC score (CAC=0), with CAC 1-100 (presence of atherosclerotic), and those with CAC>100 (advanced atherosclerosis). Statistical analysis was performed using STATISTICA 13.1. Quantitative variables were known by providing descriptive statistics (mean and standard deviation [SD]). The chi-square test was used to assess the relationship between quantitative variables and Mann-Whitney and Kruskal Wallis in the case of qualitative variables. Pearson's correlation coefficient was used to measure correlation. To determine the effect of factors on the probability of occurrence CAC=0 a multivariate logistic regression model was built. P<0.05 was judged as significant. Results Positive significant correlation between CAC score and age was revealed (r=0.266, p<0.001). An analogous relationship was observed regarding to glucose level (r=-0.123, p=0.012). This was not observed for Lp(a). However, we showed a significant relationship between the level of Lp(a) and CAC score (r=0.113, p=0.009) (Fig. 1). Lp(a) levels increased with the CAC score increase. For every 10 mg/dL (25 nmol/l) of Lp(a), CAC score increases by 15.7±0.57 (p=0.006). The mean CAC among patients with normal Lp(a) level was 203.1 (±412.6) and respectively 206.6 (±460.1) in those with moderate cardiovascular risk and 335.6 (±784.9) for people with high risk (p=0.183). In the regression model the factors determining the absence of atherosclerosis (CAC=0; "power of zero") included female gender (OR = 4.05; 95CI: 2.48-6.59), age under 65 (OR = 0.31; 95CI: 0.07-1.34 for aged 40-65), and Lp(A)≤50 mg/dl (≤125 nmol/l) (OR=2.26; 95CI: 1.12-4.61). People with hypertension had a significantly lower odds of CAC=0 (OR=0.58; 95CI: 0.38-0.89). Conclusions The study showed a significant linear relationship between increased Lp(a) levels, and the progression of atherosclerosis expressed by the CAC score. Results confirm some existing recommendations that if an elevated Lp(a) level is found in a patient for primary prevention, a CT scan of the coronary arteries with assessment of the CAC score should be considered for more appropriate risk stratification.

AI-enabled cardiac chambers volumetry in non-contrast coronary artery calcium CT scans vs. contrast-enhanced coronary CT angiography scans in the same patients

Abstract Introduction We have developed an AI-enabled automated volumetry of cardiac chambers (AutoChamber) that works both on non-contrast ECG-gated cardiac CT scans used for coronary artery calcium (CAC) score, and non-contrast non-gated lung cancer screening CT scans. We have recently reported the agreement between AutoChamber measurements vs cardiac MRI measurements. Here we report AutoChamber results on non-contrast CAC scans and contrast enhanced coronary CT angiography (CTA). Methods We have obtained CT images from a previously published study in which 131 cases underwent non-contrast CAC and contrast enhanced CCTA at research institute. The cases consisted of 52.4% women with ages 55.0 ± 10.1 years. The cardiac chambers volume in 131 cases of contrast enhanced CCTA were measured using automated chamber volumetry by Philips Brilliance Volume v 4.5; Philips Healthcare. Results The correlations between Philips’ automated chamber volumetry in contrast enhanced CCTA scans versus AutoChamber automated volumetry in non-contrast CAC scans for left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV), and left ventricular wall (LVW) volume were 0.73, 0.65, 0.85, 0.93, 0.90, respectively (P for all <0.01). Conclusion AI-enabled AutoChamber volumetry based on non-contrast cardiac scans is feasible, and correlates reasonably well with contrast-enhanced cardiac CT scans. Further studies are warranted to reproduce these results and explore the add-on value of AutoChamber to CAC scans.

Association between lipoprotein particle concentration and size and progression of coronary plaque: the MACS Longitudinal Coronary CT angiography study

Abstract Background People living with HIV have greater risk of cardiovascular diseases (CVD) than people without HIV and tend to have different risk profiles, including higher serum triglycerides and lower LDL cholesterol levels. Nuclear magnetic resonance (NMR) provides a detailed phenotype of lipoproteins. Purpose To examine the associations between lipoprotein particle concentrations and size and progression of coronary artery plaque among people living with and without HIV, and whether these associations differ by HIV serostatus. Methods Men with no clinical CVD in the Multicenter AIDS Cohort Study (MACS) who underwent a coronary CT angiography at baseline (2010-13) and follow-up (2015-17) were included. NMR spectroscopy was completed on fasting serum samples at baseline. Logistic regression models for the change in total coronary plaque volume (in tertiles) were estimated with NMR-derived lipoproteins as predictors. Levels were log-transformed and standardized to make results comparable. Models were adjusted for demographics, statin use and HIV serostatus (model 1) with addition of CVD risk factors (model 2). Interactions by HIV serostatus were also tested. Results A total of 549 men (314 with HIV; 235 without HIV) were included. Mean age was 53 ±7 years; 58% were White, 30% Black, and 12% Hispanic. Coronary plaque was present in 70% and plaque volume progressed in 79% of the cohort. Among men with HIV, 81% had undetectable HIV RNA and 12% had a diagnosis of AIDS at baseline. Men with HIV had significantly higher levels of small LDL-P, and total, medium and large VLDL-P levels compared to men without HIV, and lower levels of total, small and large HDL-P (Table 1). Men with HIV had significantly greater progression of plaque volume (37 mm3) compared to men without HIV (31 mm3, p<0.05). Levels of total and small LDL-P concentrations were directly associated with plaque progression, whereas large HDL-P was inversely associated with plaque progression in the combined sample (Model 2). Associations between total and small LDL-P with plaque progression were stronger in men with HIV than in men without HIV in models 1 and 2 (interaction p<0.01). While associations in fully adjusted models for total VLDL-P and small VLDL-P were significant in men without HIV, there were no significant associations between these particle concentrations with coronary plaque progression among men without HIV (interaction p< 0.01) (Model 2, Table 2). Conclusion Associations between lipid particle concentrations and coronary plaque progression differed between men with and without HIV, with stronger associations seen in men without HIV for total and small LDL-P. Despite having higher VLDL and lower HDL particle concentrations at baseline, these particle concentrations were only associated with plaque progression in men without HIV. Further research is needed to elucidate HIV specific factors for plaque progression to tailor risk reduction strategies.

Coronary CT angiography using photon counting CT for the detection of coronary artery stenoses and coronary atherosclerotic plaque: comparison of reconstructions with 0.2 mm and 0.4 mm slice thickness

Abstract Photon Counting CT allows the acquisition of high-resolution data sets with 0.2 mm reconstructed slice thickness. It is unknown whether the detection of coronary artery stenoses, of coronary plaque or of vulnerable plaque characteristics is improved in data sets that employ maximum resolution. We therefore compared the identification of above characteristics in data sets reconstructed with 0.2 mm and 0.4 mm slice thickness In 30 patients with suspected coronary artery disease, sinus rhythm, a heart rate ≤65 beats/min, and body weight ≤ 100 kg, high-resolution data sets were acquired by photon counting CT (60 ml contrast i.v. at 6 ml/s) after s.c. application of nitrates in inspiratory breathhold. Data were reconstructed with 0.2 mm slice thickness at 0.1 mm increment and 0.4 mm slice thickness at 0.2 mm increment. Next to quantitative analysis of image quality parameters, all data sets were evaluated by two independent expert reviewers concerning subjective image quality as well as the ability to determine the presence of coronary artery stenoses, calcified and non- calcified plaque, as well as parameters of plaque vulnerability (positive remodeling, necrotic core, density < 30 HU and napkin-ring sign) using a 5-point Likert scale (-2 to +2) and a dedicated 11-segment coronary model. Of the 30 patients, 47% were male (mean age 58±12 years, mean heart rate 53±6 bpm, mean body weight 80±15 kg). The median dose length product was 508 mGy*cm. Mean image noise was 42±7 HU vs. 34±7 HU for 0.2 mm vs. 0.4 mm reconstructions (p < 0.001). The median image quality score was significantly higher for 0.2 mm reconstructions (3.8±0.8 vs 3.6±0.7). Of 335 coronary segments, none were classified as "unevaluable" while 87% vs. 76% were classified as "perfect" in 0.2 mm vs. 0.4 mm reconstructions (p < 0.001). Full confidence to rule-in or rule out significant coronary stenoses was achieved in 93% of segments in both reconstructions. The number of non-calcified plaques identified in 0.2 mm reconstructions was numerically higher than in 0.4 mm reconstructions (77 vs. 71, p = n.s.). On the Likert scale, the confidence to identify parameters of plaque vulnerability was significantly higher for 0.2 mm reconstructions (1.93 vs. 1.85, p < 0.001). In a selected patient group, photon counting CT coronary angiography demonstrated excellent image quality and an extremely low rate of unevaluable coronary segments. High-resolution reconstructions improve subjective image quality as was as the assessment of vulnerable plaque characteristics.

Diagnostic performance of computed tomography-derived fractional flow reserve in patients with severe aortic stenosis

Abstract Background Computed tomography-derived fractional flow reserve (FFR-CT) is a clinical modality for assessing coronary artery disease; however, its use has not been validated in patients with severe aortic stenosis (AS). Purpose This study assessed the diagnostic performance of FFR-CT in patients with severe AS. Methods Retrospectively recruited patients with severe AS underwent standard-protocol invasive fractional flow reserve (FFR) and coronary CT angiography. The FFR-CT values were compared with the invasive FFR values (ischemia defined as invasive FFR ≦0.80). Results Among 46 patients (105 vessels), the mean age was 82.8 ± 5.9 years (37% male). Mean invasive FFR and FFR-CT values were 0.86 ± 0.11 and 0.83 ± 0.10, respectively. In a per-vessel analysis, there was a positive correlation between invasive FFR and FFR-CT values (Pearson correlation coefficient, R= 0.64; P<0.0001). In addition, the sensitivity, specificity, positive predictive, and negative predictive values were 100%, 86%, 43%, and 100% with 88% diagnostic accuracy, respectively. The Bland-Altman plot showed that the mean bias between invasive FFR and FFR-CT values was 0.031 (-0.146 to 0.209). The per vessels area under the receiver-operating characteristic curve analysis was 0.97 (95 % CI: 0.94-1.00, P<0.0001). Importantly, among another 58 patients who deferred invasive coronary angiography (ICA) because the FFR-CT value was negative (> 0.80), none experienced deterioration of condition during transcatheter aortic valve replacement (TAVR) or major adverse cardiac events (all-cause death, myocardial infarction, and unplanned hospitalization with urgent revascularization) within 30 days after TAVR. Conclusions FFR-CT values were significantly correlated with invasive FFR values and had a high negative predictive value in patients with severe AS. Patients with a negative FFR-CT value and deferred ICA had an excellent short-term prognosis after TAVR. FFR-CT is expected to serve as a gatekeeper for unnecessary ICA prior to TAVR.

Real world economic evaluation of CT-FFR in patients with suspected coronary artery disease

Abstract Background Incorporation of CT-derived fractional flow reserve (CT-FFR) enhances the precision of Coronary CT Angiography (CCTA) to detect hemodynamically significant coronary artery disease (CAD). However, the financial consequences remain unclear. Purpose Our objective is to assess the economic implications of CT-FFR in the Dutch Healthcare system. Methods This retrospective, single-center cost effectiveness analysis includes patient data of a previously published study assessing the impact of routine CT-FFR availability on clinical management. We collected medical resource use for both diagnostic and therapeutic cardiovascular care with a follow-up duration of 1 year. Costs of CT-FFR analysis were set at €1000, its current price for Dutch hospitals. Median total costs at were compared using the Wilcoxon rank sum test, including a sensitivity analysis in which cost estimations (without registered maximum tariffs) were increased or decreased with 10%. Results A total of 360 patients, classified as having low to intermediate risk of CAD, were enrolled in the study – 224 in the CCTA group and 136 in the CT-FFR group. In addition to undergoing more (invasive) diagnostic testing and revascularization procedures over the studied period, patients in the CCTA-group had more outpatient clinic consultations (p<0.001), presented more frequently to the emergency department (p=0.035) and spend more nights in the hospital (p=0.11). Median costs were €3.347 (IQR €1.066 – €4.862) in the CCTA-group and €1.436 (IQR €1.362 - €3.943) in the CT-FFR group (p=0.091). Increasing cost estimation with 10% revealed a median of €3.431 in the CCTA-group versus €1.479 in the CT-FFR group (p=0.078), decreasing with 10% showed median costs of €3.263 in the CCTA-group and €1.392 in the CT-FFR group (p=0.118). In our sample, CT-FFR guided care would have been significantly cheaper than CCTA-guided care at or below a market price of €770. Conclusion Despite the significant reduction in additional diagnostic testing and hospital visits in the CT-FFR group, CT-FFR guided care was not cheaper than CCTA-guided care at its current market price of €1.000. Economic cost-effectiveness would have occurred from a price of €770 per analysis. The large difference between medians suggests that the lack of significance might partially be attributed to insufficient power in this relatively small sample size. Additionally, this study did not account for costs associated with loss of productivity and quality of life. However, less additional diagnostic testing, less revascularization procedures and less hospital consultations and admissions leads to reduction in hospital resource consumption and patient burden, which is an important advantage of CT-FFR as the number of referred patients increases yearly.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction

Abstract Background Heart failure (HF) with improved ejection fraction (EF, HFimpEF) gains increasing attention as a distinct HF subtype, characterized by left ventricular reverse remodeling and myocardial recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. Methods A total of 203 hospitalized HF patients with reduced EF (HFrEF, EF≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute EF improvement ≥10% and (2) a second EF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. Results During a median follow-up of 8.6 (4.9~13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (126.03 ± 57.71 cm3 vs 182.74 ± 82.99 cm3 , P< 0.001) and higher EAT density (-74.92 ± 6.84 HU vs -78.76 ± 6.28 HU, P< 0.001) both in ischemic and non-ischemic HF patients. EAT density was inversely correlated with EAT volume (r= -0.33, P< 0.001). Multivariate analysis showed lower EAT volume (OR: 0.881 [95% CI 0.821~0.939]) and higher density (OR: 2.354 [95% CI 1.314~4.415]) were both independently associated with the incidence of HFimpEF, after adjusting for conventional risk factors, pharmacological therapies and baseline anthropometric parameters including body mass index. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. Conclusions This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

The impact of transcatheter aortic valve replacement on changes of coronary computed tomography-derived fractional flow reserve

Background The effect of transcatheter aortic valve replacement (TAVR) on changes of computed tomography-derived fractional flow reserve (CT-FFR) values was controversial. Thus, we aimed to identify the impact of TAVR on changes of CT-FFR values, plaque characteristics, and the associated clinical impact. Methods This single-center observational study included 39 consecutive patients with severe aortic valve disease undergone TAVR between August 2019 and April 2023, whom were performed with preoperative and postoperative coronary CT angiography (CCTA). The computation of CT-FFR and plaque characteristics was performed by an independent central core laboratory. Results Each patient underwent CCTA and CT-FFR assessment without encountering any complications. Notably, both at discharge and six months post-TAVR, there was a significant improvement observed in the New York Heart Association (NYHA) functional classification, left ventricular fractional shortening, and ejection fraction compared to pre-operative levels. The CT-FFR for left anterior descending artery (LAD), left anterior descending artery (LCX), and right coronary artery (RCA) had no obvious change at discharge compared to pre-operation (0.92 ± 0.05 vs. 0.93 ± 0.05, p = 0.109; 0.96 ± 0.03 vs. 0.95 ± 0.03, p = 0.523; 0.97 ± 0.04 vs. 0.97 ± 0.03, p = 0.533; respectively). Furthermore, TAVR did not exert a significant impact on plaque burden during the perioperative period. Conclusions Our report suggested that TAVR did not significantly affect coronary CT-FFR measurements and plaque characteristics in the perioperative period, and furthermore, the patients’ cardiac function showed gradual improvement in the short-term following discharge.

The diagnostic role of myocardial work indices in stable coronary disease - global wasted work as a novel important non-invasive parameter?

Abstract Introduction Although the non-invasive diagnostic tools for stable coronary artery disease (CAD) have developed significantly over the past years, there is no resting parameter available to recognize functionally significant CAD. The role of the novel myocardial work index (myocardial work index - MWI) calculated by the pressure-strain loop created with the help of speckle-tracking analysis and blood pressure measurement in the diagnosis of ischemic heart disease is not yet fully clarified. In our research, we examined the parameters of myocardial work analysis in stable coronary disease patients. Purpose Clarification of the diagnostic role of the myocardial work analysis, in patients with stable coronary artery disease. Methods In our prospective, single-center study, we examined 13 patients who had at least moderate stenosis (≥50%) in one main coronary branch detected on coronary CTA. A fractional flow reserve (FFR) test was performed for functional coronary assessment. Based on this measurement, we divided our patients into FFRneg (FFR value>0.8) and FFRpos groups. Echocardiography was performed before coronary angiography in all patients. In addition to the standard echocardiographic parameters, global myocardial work index (GWI), global constructive work (GCW) and global wasted work (GWW) were calculated. In the case of the FFRpos group, we performed the above examination both before and after revascularization (2 months). Results Our results show that neither the standard parameters (GLS, EF), nor the GWI and GCW showed any difference between the FFRpos and FFRneg groups. However, there was a significant difference regarding GWW (172.3±21.8 FFRneg vs. 258.2±38.4 FFRpos, p=0.048) at baseline. In the case of the FFRpos group, the analysis of our data showed that there was no significant difference in EF, GLS, GWI and GWE parameters before and after revascularization. However, global wasted work (GWW) showed a significant improvement after revascularization (preGWW 258.2±38.4 vs. postGWW 139.5±14.5, p=0.041). NT-proBNP levels were normal in our patient population and we could not detect. Conclusion Based on our results, the GWW may be suitable for non-invasive assessment of the functional significance of stable coronary disease, as it showed a significant difference in the case of functionally significant and non-significant stenosis and improved after revascularization in patients with single-vessel CAD.

Predictive factors and gender insights into abnormal myocardial flow reserve in non-obstructive coronary artery disease: a CZT-SPECT analysis

Abstract Background Dynamic myocardial perfusion imaging (D-MPI) using cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT has emerged as a valuable method for assessing coronary microcirculation, particularly compared to conventional SPECT. Additionally, gender-specific disparities in microvascular dysfunction require further investigation. Objective This study aims to identify predictive factors for abnormal myocardial flow reserve (MFR) in non-obstructive coronary artery disease (CAD) using CZT-SPECT, with a focus on gender differences in MFR dysfunction. Methods A retrospective analysis was conducted on clinical data from 393 patients presenting with symptoms of "chest pain and/or tightness," all of whom were confirmed to lack obstructive CAD by coronary angiography or CT angiography. MFR was measured using CZT-SPECT, with values ≥2.5 considered normal and values <2.5 considered abnormal. Results Of the patients, 49.1% (193/393) demonstrated abnormal MFR, with females representing 56.7% (223/393). Females with abnormal MFR exhibited higher averages in age, total cholesterol, LDL-C, creatinine, left atrial diameter, left ventricular posterior wall (LVPW) thickness in diastole, and E/e’ ratio (P < 0.05). Additionally, MDRD-eGFR and mitral annular septal velocity e’ were lower in the abnormal MFR cohort (P < 0.05). Multivariate logistic regression analysis identified elevated LDL-C levels (OR = 1.513, 95%CI: 1.122–2.041, P = 0.007) and increased LVPW thickness (OR = 1.717, 95%CI: 1.140–2.585, P = 0.010) as independent predictors of abnormal MFR in females. ROC analysis suggested optimal cutoff for LDL-C at 3.68 mmol/L (sensitivity 31%, specificity 84%, AUC = 0.586; 95%CI: 0.511–0.661) and LVPW thickness at 9.5 mm (sensitivity 62%, specificity 52%, AUC = 0.576; 95%CI: 0.501–0.652). A combined ROC analysis of LDL-C and LVPW thickness showed a sensitivity of 50% and specificity of 73% (AUC = 0.632, 95%CI: 0.559–0.705). In males, greater left ventricular end-diastolic diameter (LVEDD) was significantly associated with abnormal MFR (P = 0.014), with LVEDD identified as a predictor (OR = 1.130, 95%CI: 1.016–1.258, P = 0.025) and an optimal cutoff at 44.5 mm (sensitivity 88%, specificity 37%, AUC = 0.609; 95%CI: 0.524–0.694). No significant gender differences were observed in overall left ventricular resting myocardial blood flow (MBF) among patients with abnormal MFR (P = 0.072); however, female patients exhibited higher resting MBF in specific territories supplied by the left circumflex and right coronary arteries, and higher E/e’ ratios (P < 0.05). Furthermore, a negative correlation was found between resting MBF in the territory supplied by the right coronary artery and E/e’ in females (r = -0.210, P = 0.030). Conclusion Predictors of abnormal MFR in non-obstructive CAD show gender disparities, implicating an association with left ventricular diastolic function.

Prevalence of high-risk plaque features on cardiac computed tomography scans in patients with a coronary artery calcium score of zero

Abstract Introduction Coronary artery calcium (CAC) score of zero (so-called "power of zero") is associated with a very low rate of major adverse cardiac events (MACE), especially during short and midterm follow-up. However, a CAC score of zero does not definitively exclude the presence of atherosclerotic plaques or obstructive coronary artery disease (CAD). The composition of atherosclerotic plaques and the frequency of high-risk plaque features in this population are not well described. Purpose We sought to characterize the composition of atherosclerotic plaques and assess the frequency of high-risk plaque features on contrast-enhanced computed tomography (CT) images in patients with a zero CAC score. Methods The study enrolled patients with stable chest pain suspected of CAD referred for coronary CT imaging and having a CAC score of zero. Coronary CT angiography images were assessed by an expert reader to identify atherosclerotic plaques and high-risk plaque features in all coronary arteries with a diameter ≥1.5mm. The coronary artery lumen and plaques were manually segmented, and the degree of stenosis was evaluated following the Coronary Artery Disease Reporting and Data System (CAD-RADS) criteria. The presence of four high-risk plaque features was identified: positive remodeling, spotty calcification, low-attenuation plaque, and napkin ring sign. Total plaque volume, percent atheroma volume, and plaque composition were quantified using dedicated software (Figure 1). Results A total of 145 patients (mean age 54.2±12.1 years, 35.9% males) were included in the analysis. At least one coronary artery plaque was identified in 30 individuals (20.7%). 22 (15.2%), 7 (4.8%), and 1 (0.7%) patients were categorized into CAD-RADS 1, CAD-RADS 2, and CAD-RADS 3 categories, respectively. Among 30 patients with any coronary artery plaque, at least one high-risk feature was found in 10 individuals (33.3%), while 3 individuals (10.0%) had two features. Positive remodeling was found in 7 (23.3%), spotty calcification in 3 (10.0%), low-attenuation plaque in 3 (10.0%), and napkin ring sign in 0 patients, respectively (Figure 1). The mean total plaque volume was 48.2±54.3mm³, and the mean percent atheroma volume was 1.2±0.8%. Total plaque volume comprised low-attenuation (0.4%), fibro-fatty (58.9%), fibrous (39.4%), and calcified (1.3%) plaque volumes. Notably, in 3 (10.0%) individuals, the presence of calcified plaque was identified, which on non-contrast CT images did not meet the Agatston criteria for the CAC score. Conclusions Our study demonstrates a significant prevalence of atherosclerotic plaques and high-risk plaque features in patients with a CAC score of zero. Specifically, one in every five study participants had identifiable atherosclerotic plaque, with one in every three of those exhibiting one or more high-risk plaque features. The prognostic significance of these findings warrants further evaluation in studies with longitudinal follow-up.

Impact of ultra-high-resolution on cardiac CT assessment of coronary artery stenoses, plaque burden/composition, and pericoronary adipose tissue attenuation

Abstract Background Conventional coronary computed tomography angiography (CCTA) overestimates stenoses within stents and calcified arteries due to "blooming" artifacts. Ultra-high-resolution coronary CT (UHR-CT) may overcome this limitation because of higher spatial resolution. Purpose To investigate differences in coronary arterial lumen volume, stenosis severity, and plaque composition, between CCTA and UHRCT in patients with stents and/or high coronary calcium scores. Methods As part of a prospective pilot study, 14 patients referred for invasive coronary angiography for evaluation of obstructive CAD underwent UHRCT (Canon Precision, 160 x 0.25mm slices) prior to catheterization. Images of identical cardiac phases were reconstructed in two badges for comparison: 1) Ultra-high resolution using a 1,024 x 1,024 matrix, 0.25 mm, and 2) conventional resolution with a 524 x 524 matrix, 0.5 mm. All images were reconstructed using iterative reconstruction algorithm (AIDR 3D) and a sharp kernel (FC05). For the left main and three coronary arteries, an automated contour analysis using a dedicated software (QAngioCT RE 3.2, Medis, Netherlands) was performed to compare conventional CCTA vs. UHR-CT resolution images across common vascular and plaque metrics, including lumen and vessel volume, plaque burden/volume, plaque composition based upon predefined fixed intensity cut-off values of CT attenuation, minimal and maximal plaque thickness, pericoronary adipose tissue attenuation (PCAT), minimal lumen area and diameter, and diameter stenosis. All lumen and vessel contours were generated by the software, without manual editing. The segment model proposed by the SCCT was used as reference and the lesions classified as greater than 25% stenosis by visual assessment were recorded. The quality of the images was subjectively assessed using a 5-point Likert scale. Vessel segments with scores 1 (severe artifacts) and 2 (pronounced artifacts) were not included in the analysis. Results The mean patient age was 68.5 years (±6.8), 2 were female (14.3%), 6 patients had stents (11 stented segments) and the mean Agatston score was 947.6 (±449) among the 8 non-stented patients. A total of 56 vessels, 133 segments, and 57 lesions were analyzed. Eight segments (6%) were excluded from the analysis due to poor quality. Results on a per segment and per lesion basis were summarized in the table. The mean PCAT value was significantly lower for the UHRCT images compared to NR reconstruction in both segment (p<0.001) and lesion based (p=0.002) analyses. Plaque differentiation varied by UHRCT resulted in a lower fibrous plaque volumes but higher necrotic (low attenuation) plaque volumes. Conclusions Ultra-high-resolution CT image analysis results in significantly different coronary artery plaque volume and PCAT assessment vs. conventional resolution CCTA. These findings have implications for evaluating high-risk plaque features and perivascular inflammation in patients.Table 1