OBJECTIVE: To assess coronary inflammation by measuring the volume and density of the epicardial adipose tissue (EAT), perivascular fat attenuation index (FAI) and coronary plaque burden in patients with Cushing\'s syndrome (CS) based on coronary computed tomography angiography (CCTA).
METHODS: This study included 29 patients with CS and 58 matched patients without CS who underwent CCTA. The EAT volume, EAT density, FAI and coronary plaque burden were measured. The high-risk plaque (HRP) was also evaluated. CS duration from diagnosis, 24-h urinary free cortisol (UFC), and abdominal visceral adipose tissue volume (VAT) of CS patients were recorded.
RESULTS: The CS group had higher EAT volume (146.9 [115.4, 184.2] vs. 119.6 [69.0, 147.1] mL, P = 0.006), lower EAT density (- 78.79 ± 5.89 vs. - 75.98 ± 6.03 HU, P = 0.042), lower FAI (- 84.0 ± 8.92 vs. - 79.40 ± 10.04 HU, P = 0.038), higher total plaque volume (88.81 [36.26, 522.5] vs. 44.45 [0, 198.16] mL, P = 0.010) and more HRP plaques (7.3% vs. 1.8%, P = 0.026) than the controls. The multivariate analysis suggested that CS itself (β [95% CI], 29.233 [10.436, 48.03], P = 0.014), CS duration (β [95% CI], 0.176 [0.185, 4.242], P = 0.033), and UFC (β [95% CI], 0.197 [1.803, 19.719], P = 0.019) were strongly associated with EAT volume but not EAT density, and EAT volume (β [95% CI] - 0.037[- 0.058, - 0.016], P = 0.001) not CS was strongly associated with EAT density. EAT volume, FAI and plaque burden increased (all P < 0.05) in 6 CS patients with follow-up CCTA. The EAT volume had a moderate correlation with abdominal VAT volume (r = 0.526, P = 0.008) in CS patients.
CONCLUSIONS: Patients with CS have higher EAT volume and coronary plaque burden but less inflammation as detected by EAT density and FAI. The EAT density is associated with EAT volume but not CS itself.

OBJECTIVE: Familial hypercholesterolaemia (FH) patients are subjected to a high lifetime exposure to low density lipoprotein cholesterol (LDL-C), despite use of lipid-lowering therapy (LLT). This study aimed to quantify the extent of subclinical atherosclerosis and to evaluate the association between lifetime cumulative LDL-C exposure and coronary atherosclerosis in young FH patients.
RESULTS: Familial hypercholesterolaemia patients, divided into a subgroup of early treated (LLT initiated <25 years) and late treated (LLT initiated ≥25 years) patients, and an age- and sex-matched unaffected control group, underwent coronary CT angiography (CCTA) with artificial intelligence-guided analysis. Ninety genetically diagnosed FH patients and 45 unaffected volunteers (mean age 41 ± 3 years, 51 (38%) female) were included. Familial hypercholesterolaemia patients had higher cumulative LDL-C exposure (181 ± 54 vs. 105 ± 33 mmol/L ∗ years) and higher prevalence of coronary plaque compared with controls (46 [51%] vs. 10 [22%], OR 3.66 [95%CI 1.62-8.27]). Every 75 mmol/L ∗ years cumulative exposure to LDL-C was associated with a doubling in per cent atheroma volume (total plaque volume divided by total vessel volume). Early treated patients had a modestly lower cumulative LDL-C exposure compared with late treated FH patients (167 ± 41 vs. 194 ± 61 mmol/L ∗ years; P = 0.045), without significant difference in coronary atherosclerosis. Familial hypercholesterolaemia patients with above-median cumulative LDL-C exposure had significantly higher plaque prevalence (OR 3.62 [95%CI 1.62-8.27]; P = 0.001), compared with patients with below-median exposure.
CONCLUSIONS: Lifetime exposure to LDL-C determines coronary plaque burden in FH, underlining the need of early as well as potent treatment initiation. Periodic CCTA may offer a unique opportunity to monitor coronary atherosclerosis and personalize treatment in FH.
This study reveals that young patients with familial hypercholesterolaemia (FH), as compared with individuals without FH, have a higher build-up of coronary artery plaque, linked directly to their increased lifetime exposure to LDL cholesterol. Genetically confirmed FH patients have a higher coronary plaque burden than those without FH, with every 75 mmol/L ∗ years increase in lifetime cumulative LDL cholesterol exposure resulting in a two-fold increase in total plaque volume. Early and potent LDL cholesterol lowering treatments are crucial for FH patients to prevent future cardiovascular diseases.

UNASSIGNED: Epicardial adipose tissue (EAT) accumulation has been associated with inflammation, atherosclerosis and microvascular dysfunction. Whether increased EAT volume is associated with coronary plaque vulnerability and demand myocardial ischemia in patients with non-obstructive coronary artery disease (CAD) is less explored.
UNASSIGNED: In 125 patients (median age 63[58, 69] years and 58% women) with chest pain and non-obstructive CAD, EAT volume was quantified on non-contrast cardiac CT images. EAT volume in the highest tertile (>125 ml) was defined as high EAT volume. Total coronary plaque volume and plaque vulnerability were quantified by coronary CT angiography (CCTA). Demand myocardial ischemia was detected by contrast dobutamine stress echocardiography.
UNASSIGNED: High EAT volume was more common in men and associated with higher BMI, hypertension, increased left ventricular mass index (LVMi), C-reactive protein (CRP) and positive remodelling (all p < 0.05). There was no difference in age, coronary calcium score, total and non-calcified plaque volume or presence of demand myocardial ischemia between groups (all p ≥ 0.34). In a multivariable model, obesity (p = 0.006), hypertension (p = 0.007) and LVMi (p = 0.016) were independently associated with high EAT volume. Including plaque vulnerability in an alternative model, positive remodelling (p = 0.038) was independently associated with high EAT volume.
UNASSIGNED: In non-obstructive CAD, high EAT volume was associated with cardiometabolic risk factors, inflammation and plaque vulnerability, while there was no association with demand myocardial ischemia or coronary plaque volume. Following our results, the role of EAT volume as a biomarker in non-obstructive CAD remains unclear.

To assess and correlate pulmonary involvement and outcome of SARS-CoV-2 pneumonia with the degree of coronary plaque burden based on the CAC-DRS classification (Coronary Artery Calcium Data and Reporting System).
This retrospective study included 142 patients with confirmed SARS-CoV-2 pneumonia (58 ± 16 years; 57 women) who underwent non-contrast CT between January 2020 and August 2021 and were followed up for 129 ± 72 days. One experienced blinded radiologist analyzed CT series for the presence and extent of calcified plaque burden according to the visual and quantitative HU-based CAC-DRS Score. Pulmonary involvement was automatically evaluated with a dedicated software prototype by another two experienced radiologists and expressed as Opacity Score.
CAC-DRS Scores derived from visual and quantitative image evaluation correlated well with the Opacity Score (r=0.81, 95% CI 0.76-0.86, and r=0.83, 95% CI 0.77-0.89, respectively; p<0.0001) with higher correlation in severe than in mild stage SARS-CoV-2 pneumonia (p<0.0001). Combined, CAC-DRS and Opacity Scores revealed great potential to discriminate fatal outcomes from a mild course of disease (AUC 0.938, 95% CI 0.89-0.97), and the need for intensive care treatment (AUC 0.801, 95% CI 0.77-0.83). Visual and quantitative CAC-DRS Scores provided independent prognostic information on all-cause mortality (p=0.0016 and p<0.0001, respectively), both in univariate and multivariate analysis.
Coronary plaque burden is strongly correlated to pulmonary involvement, adverse outcome, and death due to respiratory failure in patients with SARS-CoV-2 pneumonia, offering great potential to identify individuals at high risk.

OBJECTIVE: Whether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD.
METHODS: We included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis < 50%) by CCTA, who were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. Total plaque burden was quantified by CCTA as the total plaque volume in the main coronary arteries, and positive remodelling was defined as remodelling index > 1.10.
RESULTS: Patients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00-1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling.
CONCLUSIONS: Total coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies.ClinicalTrials.gov: Identifier NCT01853527.

Heterozygous familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease. Semi-automated plaque characterization (SAPC) by coronary computed tomographic angiography (CTA) provides information regarding coronary plaque burden and plaque characterization. Our aim was to quantify and characterize the coronary plaque burden of patients with FH using SAPC analysis and to identify which factors are related to plaque burden and plaque characteristics. A second aim was to analyse the prognostic implications of these parameters.
Two hundred and fifty-nine asymptomatic individuals with molecularly determined FH were enrolled in this follow-up cohort study and underwent a coronary CTA analysed with SAPC.
Mean follow-up time after coronary CTA was 3.9 ± 2 years. Mean age was 46.9 (10.7) years (130 women, 50.2%). Median plaque burden was 25.0% (19.0-29.0), non-calcified plaque burden 22.83% (17.94-26.88), calcified plaque-burden 1.12% (0.31-2.86) and CCS 8.9 (0-93). Five-year risk was independently related to plaque burden, non-calcified plaque burden, calcified plaque burden and coronary calcium score (B:3.75, 95%CI:2.92-4.58; p < 0.001, B:2.9, 95%CI:2.15-3.66; p < 0.001, B:0.75, 95%CI 0.4-1.1; p < 0.001 and B:82.2, 95%CI:49.28-115.16; p < 0.001 respectively). During follow-up, there were 15 (5.81%) nonfatal events and 1 (0.4%) fatal event. Plaque burden was significantly related to event-free survival during follow-up (HR:1.11; 95%CI:1.05-1.18; p < 0.001).
Coronary atherosclerosis and its qualitative components may be quantified by means of SAPC in patients with FH. Plaque burden, calcified plaque burden and non-calcified plaque burden were independently related to the estimated cardiovascular risk. Plaque burden was also related to prognosis.

OBJECTIVE: We aimed to evaluate the relationship between fragmented QRS complex and plaque burden in patients presented with typical chest pain and deemed to have intermediate pretest probability of CAD using coronary computed tomography angiography (CCTA).
METHODS: We studied electrocardiograms (ECGs) obtained from 172 subjects (47.5 ± 9.5 years, 125 were men) presented with chest pain and had intermediate pretest probability for CAD. The presence was found and evaluation of CAD was performed with CCTA.
RESULTS: Seventy four (43%) of the study cohort had CCTA-documented CAD. Meanwhile the frequency of fQRS in our cohort was (57%). 70 (71.4%) patients with fQRS had CAD compared with only 4 (5.4%) patients without fQRS (p < 0.001). The number of leads with fQRs was correlated with the calcium score (p < 0.005), segment stenosis score, segment involvement score, total plaque score (TPS), and E/e ratio (p < 0.001, for all). Multivariate analysis demonstrated that fQRS was a strong independent predictor for CAD (or = 2.15, p < 0.001). ROC analysis showed that the number of leads ≥3 was the optimal number for predicting CAD (AUC = 0.89, sensitivity 88%, and specificity 83%, p < 0.001).
CONCLUSIONS: Fragmented QRS was seen more often in patients with high plaque burden. We suggest that fQRS might provide a useful noninvasive prognosticator for subjects with intermediate pretest probability of CAD for further investigation.

UNASSIGNED: Coronary artery disease continues to be the most important cause of morbidity and mortality. Obstructive sleep apnea (OSA) is independently associated with subclinical atherosclerosis. In this study, we aimed to assess the relationship between the presence of coronary plaques and OSA and between coronary plaque burden and the severity of OSA according to plaque type.
UNASSIGNED: In this cross-sectional study, we enrolled 214 consecutive patients who were divided into four groups of 43 patients (age: 52.3 ± 6.4 years) without OSA, 51 patients (age: 53.9 ± 6.7 years) with mild OSA, 40 patients (age: 55.2 ± 5.9 years) with moderate OSA, and 80 patients (age: 54.9 ± 7.2 years) with severe OSA according to the apnea-hypopnea index (AHI). We performed coronary computed tomographic angiography (CCTA) and evaluated plaque positivity, the presence of non-calcified/mixed plaques, and total stenosis score for each group.
UNASSIGNED: The prevalence of non-calcified/mixed plaques was three times higher in the severe OSA (41.3%) group and two times higher in the moderate OSA (30.0%) group compared to the patients without OSA (14.0%). When the four groups were examined in terms of plaque burden, the total stenosis score was found to increase with the presence and severity of OSA (0.27 ± 0.85, 1.07 ± 2.44, 1.75 ± 2.85, and 2.55 ± 3.96 respectively, p = 0.001). In addition, AHI and age were independent predictors of the presence of non-calcified/mixed plaques (p < 0.001 and p = 0.007, respectively).
UNASSIGNED: The presence of coronary artery plaques, especially non-calcified/mixed plaques, and coronary artery stenosis as measured by CCTA was significantly associated with the severity of sleep-disordered breathing in symptomatic patients at low to intermediate risk of coronary artery disease. Prospective studies are needed to establish the relationship between plaque burden and OSA.

Previous studies reporting that statin increases coronary artery calcium (CAC) were conducted exclusively on patients with statin as a prevention, regardless of the presence or absence of dyslipidemia. The impact of sex on CAC has not been fully evaluated. We aimed to determine the association of dyslipidemia and sex with CAC using 320-row multi-detector computed tomography (MDCT).Of the 356 consecutive patients who underwent coronary MDCT, 251 patients were enrolled, after excluding those with prior stenting and/or coronary bypass grafting or images showing motion artifacts. The primary outcome measures were the percent calcium volume (PCV) and percent atheroma volume (PAV) per coronary vessel.Multivariable analyses indicated that PCV was significantly higher in dyslipidemia patients without statins than in the subjects without dyslipidemia [partial regression coefficient (PRC): 2.59, 95% confidence interval (CI): 0.83 to 4.34, P = 0.004]. In contrast, PCV was similar in dyslipidemia patients taking statins and those without dyslipidemia (PRC: -1.09, 95% CI: -2.82 to 0.65, P = 0.22). There was no significant difference in PCV between men and women, although women exhibited a significantly lower PAV (PRC: -2.87, 95% CI: -4.54 to -1.20, P = 0.001).In low-risk patients, these results could be translated into hypotheses, which should be tested in future prospective studies. Furthermore, there was no significant difference in CAC between men and women, but women had lower PAV than men.

OBJECTIVE: The purpose of this study was to determine whether use of iterative image reconstruction algorithms improves the accuracy of coronary CT angiography (CCTA) compared with intravascular ultrasound (IVUS) in semiautomated plaque burden assessment.
METHODS: CCTA and IVUS images of seven coronary arteries were acquired ex vivo. CT images were reconstructed with filtered back projection (FBP) and adaptive statistical (ASIR) and model-based (MBIR) iterative reconstruction algorithms. Cross-sectional images of the arteries were coregistered between CCTA and IVUS in 1-mm increments. In CCTA, fully automated (without manual corrections) and semiautomated (allowing manual corrections of vessel wall boundaries) plaque burden assessments were performed for each of the reconstruction algorithms with commercially available software. In IVUS, plaque burden was measured manually. Agreement between CCTA and IVUS was determined with Pearson correlation.
RESULTS: A total of 173 corresponding cross sections were included. The mean plaque burden measured with IVUS was 63.39% ± 10.63%. With CCTA and the fully automated technique, it was 54.90% ± 11.70% with FBP, 53.34% ± 13.11% with ASIR, and 55.35% ± 12.22% with MBIR. With CCTA and the semiautomated technique mean plaque burden was 54.90% ± 11.76%, 53.40% ± 12.85%, 57.09% ± 11.05%. Manual correction of the semiautomated assessments was performed in 39% of all cross sections and improved plaque burden correlation with the IVUS assessment independently of reconstruction algorithm (p < 0.0001). Furthermore, MBIR was superior to FBP and ASIR independently of assessment method (semiautomated, r = 0.59 for FBP, r = 0.52 for ASIR, r = 0.78 for MBIR, all p < 0.001; fully automated, r = 0.40 for FBP, r = 0.37 for ASIR, r = 0.53 for MBIR, all p < 0.001).
CONCLUSIONS: For the quantification of plaque burden with CCTA, MBIR led to better correlation with IVUS than did traditional reconstruction algorithms such as FBP, independently of the use of a fully automated or semiautomated assessment approach. The highest accuracy for quantifying plaque burden with CCTA can be achieved by using MBIR data with semiautomated assessment.