Coronary Computed Tomography Angiography Research Articles

Influence of coronary plaque characteristics on lesion-specific ischemia assessed by coronary computed tomography angiography and fractional flow reserve - a systematic review and meta-analysis

Abstract Background Characterization of atherosclerotic plaque features by coronary computed tomography angiography (CCTA) carries profound prognostic value. Previous studies indicate that coronary plaque burden and certain plaque features are associated to lesion-specific ischemia by invasive fractional flow reserve (FFR). However, the existing literature is limited by small sample sizes, and provide inconsistent results. Purpose We performed a meta-analysis in order to delineate further the potential association between coronary plaque phenotype by CCTA and FFR. Methods A comprehensive systematic literature review and meta-analysis was conducted. PubMed and Embase databases were searched for studies that investigated the association between coronary plaque characteristics and FFR between January 2010 and August 2023. Study search, evaluation, and data extraction were performed independently by two researchers. Weighted mean difference (WMD) method for WMD was used for comparison of pooled per-lesion plaque parameters and presence of specific plaque features against presence of lesion-specific ischemia (FFR ≤0.80). Lesions with stenosis severity of 25-90% were included. Extracted data from eligible studies were analysed using random effects model for WMD and to estimate odds ratios (OR) with 95% confidence intervals (CI). Results A total of 12 studies were deemed eligible with 1,318 patients and available data on 1,915 coronary lesions. Of these, 626 lesions caused ischemia. Significantly greater total plaque volume (TPV) and non-calcified plaque volume (NCPV) occurred in lesions with abnormal FFR compared to normal FFR (WMD 83.0 mm3, 95% CI: 44.27; 121.81, p<0.001; WMD 83.63 mm3, 95% CI: 55.0; 112.24, p <0.001, respectively). Similar findings were observed for aggregate plaque volume (%APV) and plaque burden (%PB) with WMD 9.18, 95% CI: 6.08; 12.28, p<0.001; WMD 8.83, 95% CI: 4.32; 14.24, p=0.001, respectively. Napkin ring-sign and spotty calcification appeared more frequent in ischemia-causing lesions compared to those with FFR >0.80 (OR 4.25, 95% CI: 1.39; 13.00, p=0.011; OR 1.92, 95% CI: 1.33; 2.75, p=0.001, respectively). A summary of the meta-analysis findings regarding the association between plaque burden and plaque characteristics and FFR is provided in Figure 1 and 2. Conclusion CCTA-derived TPV and NCPV as well as %APV, %PB and the presence of napkin-ring sign and spotty calcification are associated with presence of lesion-specific ischemia. Coronary plaque assessment from CCTA images provide improved discrimination of lesion-specific ischaemia.

Noninvasive predictors of residual coronary microvascular dysfunction after elective percutaneous coronary intervention

Abstract Backgrounds Coronary computed tomographic angiography (CCTA) provides noninvasive assessments of coronary plaque morphologies and perivascular inflammation. Morphological features associated with residual coronary microvascular dysfunction (CMD) after elective percutaneous coronary intervention (PCI) remains unknown. Purpose This study aimed to examine prevalence and predictors of residual CMD and its phenotypes after elective PCI. Methods We investigated consecutive patients who were scheduled for elective fractional flow reserve (FFR)-guided PCI for de novo single lesions with pre-PCI CCTA data. Pre- and post-PCI comprehensive physiological assessments including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed by using pressure temperature sensor-tipped guidewire in all patients. Patients with periprocedural myocardial infarction were excluded. Residual CMD was defined as lesions with post-PCI coronary flow reserve (CFR) <2.0, which was further categorized as functional (IMR<25) or structural (IMR ≥25) CMD. Results A total of 198 de novo lesions in 198 patients were included in the final dataset. Pre- and post-PCI mean CFR were 1.79 [1.27, 2.53] and 2.72 [2.00, 4.04], respectively. Residual CMD was observed in 24.7% (49/198) of patients, categorized as functional (n=26) or structural (n=23). Patients with residual CMD showed older age, less frequent diabetes mellitus, current smoking and a culprit lesion in left anterior descending artery (LAD), and higher CCTA-defined calcium score in the culprit vessel compared with those in patients without residual CMD. Multivariable logistic regression analysis showed that age (adjusted odds ratio [OR]:1.04; 95% confidence interval [CI]: 1.00 to 1.08; p=0.04) and non-LAD (adjusted OR: 2.18; 95%CI: 1.03 to 4.63; p=0.04) were independently associated with residual CMD. In patients with residual CMD, patients with structural CMD tended to have more frequent diabetes mellitus (43.5% vs 19.2%, P=0.13) and atrial fibrillation (26.1% vs 7.7%) and showed significantly lower pericoronary adipose tissue attenuation (PCATA) in right coronary artery (RCA) by CCTA (-79.9 HU vs -74.6 HU, P=0.04) compared with patients with functional CMD. CCTA-detected epicardial fat volume and attenuation showed no significant differences between patients with residual functional CMD, those with residual structural CMD, and those without residual CMD. Multivariable analysis revealed that diabetes mellitus (adjusted OR: 5.18; 95%CI: 1.14 to 23.7; p=0.03) and PCATA in RCA (adjusted OR: 0.93; 95% CI: 0.85 to 1.00; p=0.05) were independently predictive of residual structural CMD. Conclusions Residual CMD was observed in approximately 25% of patients undergoing elective PCI. CCTA-defined calcium score and PCATA, along with clinical factors could be potential predictors of post-PCI residual CMD and its phenotypes.

Associate variables of coronary computed tomographic angiography-derived extracellular volume fraction and cardiac magnetic resonance-derived late-gadolinium enhancement

Abstract Background Coronary computed tomographic angiography (CCTA) with late-iodine enhancement enables the segmental quantification of extracellular volume (ECV) fraction which represents myocardial fibrosis. However, its association with cardiac magnetic resonance (CMR)-derived late gadolinium enhancement (LGE) has not been fully elucidated. Purpose We aimed to assess the concordance and discordance between CCTA-derived ECV and CMR-derived LGE and to investigate associated variables of each index. Methods This retrospective analysis included a total of 123 segments from 41 patients (anterior, inferior and lateral segments per patient) with known or suspected coronary artery disease (CAD) who underwent both clinically indicated CCTA and CMR. Patients with cardiomyopathy such as amyloidosis were excluded. Myocardial fibrosis was evaluated by CCTA-derived segmental ECV and by CMR-LGE with ischemic pattern on a per-segment basis (AHA 16 segments). Clinical and echocardiographic variables associated with CCTA-derived segmental ECV and CMR-LGE were studied by univariable linear and logistic regression analyses, respectively. Results Among the 123 segments, 21 segments showed ischemic CMR-LGE pattern. CCTA-ECV was significantly higher in segments with versus without CMR-LGE (42 [39, 47] % versus 34 [29, 39] %, P<0.01). Receiver-operating characteristic curve analysis showed that the best cut-off of CCTA-ECV to predict CMR-LGE was 38.9% (area under the curve 0.82 [95% confidence interval 0.74, 0.90], positive predictive value: 40.0%, negative predictive value: 96.2%). Univariable analyses revealed that male sex, prior history of revascularization, usage of statin, aspirin, angiotensin-converting enzyme inhibitor and beta-blockade, higher C-reactive protein, NT-pro BNP, lower left ventricular ejection fraction, greater left ventricular chamber size, shorter deceleration time, and larger segmental and global longitudinal strain were associated with both higher CCTA-ECV and the presence of CMR-LGE. Lower lipid profiles, higher high-sense troponin I, and greater left atrial volume index were associated with higher CCTA-ECV, while not with the presence of CMR-LGE. The frequency of CMR-LGE were significantly different according to CCTA-ECV tertiles. (P<0.05) Statin use and higher NT-proBNP were determinants of the highest ECV tertile without LGE. Conclusion We found a strong interrelationship between variables associated with ECV and the presence of LGE, although high ECV may not necessarily indicate the presence of LGE in patients with known or suspected CAD. Clinical factors associated with discordance, such as high-ECV without CMR-LGE, should be taken into account in the assessment of ECV and LGE. Further studies are needed to elucidate clinical significance of the concordance and discordance between ECV and LGE.

The paradox of CAC score and plaque vulnerability

Abstract Introduction The effect of coronary artery calcification on plaque vulnerability remains unclear. The coronary artery calcium (CAC) score, quantified using coronary computed tomography, has a strong correlation with total atherosclerotic burden and risk of adverse cardiac events. Nevertheless, different patterns in the distribution of coronary artery calcium have been reported to convey different effects on plaque stability. Some biomechanical models suggest that microcalcifications can intensify stress in the fibrous cap, promoting plaque rupture. On the other hand, large calcium deposits are hypothesized to promote plaque stability, as statin therapy has been shown to promote the calcification of atherosclerotic lesions. The purpose of this study is to investigate the relationship between CAC score and vulnerable plaque using coronary computed tomographic angiography (CCTA) in patients with an acute coronary syndrome (ACS). Methods CCTA was performed in 444 patients; these patients were divided into two groups (those with vulnerable plaque and those without). CAC score of each patient was obtained. We calculated median value of CAC score of both groups and compared them using Two Sample Mann-Whitney U Test. All tests were 2-sided, p values below a threshold of 0.05 were considered to be significant. All statistical analyses were performed using IBM SPSS Statistics 29.0 (SPSS Inc, Chicago, IL). Results Out of 444 patients with an ACS and evaluated with CCTA, vulnerable plaques were found in 57 patients (13%). The median value of CAC score in patients with vulnerable plaques was significantly higher compared with patients without vulnerable plaques (mean CAC score 1065,07 AU (95% Confidence Intervals 526,26-2656,40 AU) vs 444,03 AU (95% CI 120,18-766,88 AU, p < 0.001). Using Mann–Whitney U test, we found a statistically significant difference between CAC score of patients with vulnerable plaques and those that did not have such plaques. Conclusion Although CAC score is a reliable marker of atherosclerosis it is still uncertain whether CAC score is an indicator of plaque vulnerability. In our study, CAC score was higher in patients with vulnerable plaque compared to those without such plaques. A highly statistically significant difference was found between the median value of CAC score between these two groups of patients.Boxplot

Interscan reproducibility of computed tomography derived coronary plaque volume measurements using a semi-automated analysis software

Abstract Background Coronary computed tomography angiography (CCTA) enables detailed quantification and characterization of coronary atherosclerotic plaque, offering diagnostic and prognostic value. Despite the growing demand for accurate plaque analysis, studies on interscan reproducibility of automated plaque quantification are limited in number and size. Moreover, impact of clinical and technical factors on the reproducibility of plaque assessment tools are scarce. Purpose The objective of this study was to assess the interscan reproducibility of CCTA-derived plaque volume measurements and the implications of clinical and technical characteristics on interscan reproducibility. Methods A total of 101 patients with known coronary artery disease underwent two CCTA scans within hour interval using identical CT acquisition protocol. Coronary plaque volume measurements were quantified on a per-patient level using a contemporary semi-automated plaque analysis software. Results There was no statistically significant difference in median plaque volumes between the first and second scan. The direct correlation was excellent for volumes of non-calcified plaque (NCP), calcified plaque (CP), and total plaque (TP) across all analyses (Pearson’s coefficient 0.96 to 0.99), while moderate for low-density non-calcified plaque (LD-NCP) volumes (Pearson’s coefficient 0.77). Bland Altman analyses demonstrated high interscan agreement with narrow absolute and relative limits of agreement (LoA) across plaque subtypes, except for LD-NCP volumes (Table 1). Interscan reproducibility on CP volumes was affected by CT image quality with narrower LoA in scans with the highest image quality score (p = 0.003), or lowest image reconstructive iteration level (p <0.001). Limits of agreement were significantly narrower for NCP, CP, and TP volumes in lesions located in LAD compared to non-LAD lesions (p <0.001). However, no significant difference in LoA was present when comparing patients according to BMI (<27 and ≥27 kg/m2), heart rate (<65 and ≥65 beats per minute), or Agatston score (<193 and ≥193). Conclusions This comprehensive interscan reproducibility study revealed good agreement in the measurement of plaque subtypes. Adding new insight to existing literature, we have demonstrated that factors such as image quality, image reconstructive algorithms, and lesion location affect the reproducibility of plaque volume measurements. CT-derived plaque quantification using a semi-automated plaque analysis software holds potential for monitoring disease progression or regression in patients with CAD, provided high CCTA image quality.

Association between high versus low cardiovascular risk in individuals with corresponding unexpected absent versus severe subclinical coronary atherosclerosis, a nationwide, multicenter study

Abstract Background It remains unclear as to why some individuals at low risk of cardiovascular disease (CVD) develop severe coronary atherosclerosis, while those at high CVD risk may remain free from coronary atherosclerosis. Purpose Using Coronary Computed Tomography Angiography (CCTA), we aimed to identify factors associated with absence and severe coronary atherosclerosis in subjects from the general population with very high and low-moderate CVD risk, respectively. Methods We assessed cross-sectionally a nationwide, multicenter population-based cohort, consisting of 30,154 individuals randomly recruited from the general population (age range 50-64 years, 51.4% women). Coronary calcified plaque burden was estimated by coronary artery calcium score (CACS) assessed by CCTA. Absent coronary atherosclerosis was defined as CACS 0 and severe coronary atherosclerosis was defined as CACS ≥301. We investigated only individuals with low-moderate (<5%) and very high CVD risk (≥10%) according to SCORE2 were included. Individuals with CACS 0 and prevalent CVD were excluded, as well as those with moderate CACS (1-300) or SCORE2 risk 5-9%. Out of 26 722 subjects with complete data on CACS and SCORE2, 13 075 were included. Logistic regression was performed adjusted for age and sex. Results The overall distribution of CACS in relation to SCORE2 CVD risk is illustrated in the Figure. Study characteristics are displayed in Table 1. Severe-extensive CACS in combination with low-moderate CVD risk was present in 2.3% (n=296). A further 2.3% (n=311) had very high CVD risk but CACS 0. Factors associated with CACS 0 despite a very-high estimated CVD risk included: lower age, being female, being born in Sweden, not having hypertension or hyperlipidemia, fewer pack-years of smoking, and lower waist circumference in men. On the contrary, severe-extensive CACS despite a low-moderate estimated CVD risk was associated with higher age, being male, being an ex-smoker, reporting more pack-years of smoking, having higher HbA1c, higher BMI, higher waist circumference, and prevalent hyperlipidemia and hypertension (Table 2). Conclusions We identified extreme cardiovascular risk phenotypes (subgroups) in the general population that either lacked coronary calcifications despite being at very high estimated CVD risk or had severe subclinical coronary atherosclerosis despite being at estimated low-moderate CVD risk. Further studies are warranted to elucidate putative enhancing or protective mechanisms explaining this unexpected phenomenon.

Gender differences in the use of coronary computed tomography angiography, functional testing, coronary angiography, revascularization, and outcomes - a 10-year Danish, nationwide, registry-based foll

Abstract Background and aims Coronary computed tomography angiography (CCTA) serves as a noninvasive imaging modality, that guides downstream preventive and invasive treatment. However, differences in its use in relation to gender has not been investigated. Methods This nationwide register-based cohort study investigated all residents in Denmark between 2008 and 2018, consisting of individuals aged 50-80 years without coronary artery disease (CAD). The study population was stratified into male and female cohorts (n = 1469724). The outcomes included CCTA, functional testing, invasive coronary angiography (ICA), myocardial infarction (MI), revascularization, and major adverse cardiovascular and cerebrovascular events (MACCE). Results Among individuals who underwent CCTA, a slightly higher use was observed among females (absolute risk [AR] 4.2% individuals aged ≥50-59 years, AR 4.1% individuals aged ≥60-69 years, and AR 2.3% individuals aged ≥70-80 years) compared to males (absolute risk [AR] 4.0% individuals aged ≥50-59 years, AR 3.6% individuals aged ≥60-69 years, and AR 2.3% individuals aged ≥70-80 years). Conversely, the use of functional testing, were lower among females (AR 4.5% individuals aged ≥50-59 years, AR 5.2% individuals aged ≥60-69 years, and AR 4.3% individuals aged ≥70-80 years) compared to males (AR 6.2% individuals aged ≥50-59 years, AR 7.1% individuals aged ≥60-69 years, and AR 6.3% individuals aged ≥70-80 years), similar differences were observed for ICA, revascularization, MI risks, and MACCE. Conclusion Men were less likely to undergo CCTA compared to women. Conversely, use of functional testing, ICA, and revascularization along with an increased risk of MI or MACCE were higher in men.Figure 1

Relationship between plaque burden and plaque vulnerability in patients with acute coronary syndromes versus chronic coronary syndrome

Abstract Background The relationship between plaque burden and plaque vulnerability based on clinical presentations has not been fully investigated. Objective The aim of this study was to compare the relationship between plaque burden and plaque vulnerability in patients with acute coronary syndromes (ACS) versus chronic coronary syndrome (CCS). Methods This is an observational, single-center cohort study. Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) before coronary intervention were enrolled. All OCT and CTA images were analyzed at the core laboratory. All plaques were detected in culprit vessels using CTA, and total plaque volume (TPV) and OCT features were assessed at the corresponding sites. A layered plaque was defined as a plaque with one or more layers of different optical densities and a clear demarcation from underlying components. The layer arc was measured at 1-mm intervals. The layer index, which is equivalent to layer volume, was defined as mean layer arc × layer length. All plaques were divided into three groups according to the tertile range of TPV (low TPV: <96.5 mm3, moderate TPV: 96.5 – 164.7 mm3, high TPV: ≥164.8 mm3). The effect modification of clinical presentations (CCS or ACS) on the association between TPV and OCT features was investigated. Results A total of 990 plaques were imaged by OCT in 419 patients: 445 plaques in 190 (45.3%) patients who presented with ACS and 545 in 229 (54.7%) with CCS. The prevalence of thin-cap fibroatheroma (TCFA) was higher as plaque volume increased in both groups (low vs. moderate vs. high TPV group: 18.4% vs. 37.8% vs. 52.3% in ACS; 16.2% vs. 19.9% vs. 30.6% in CCS; interaction P=0.066). However, the effect modification of clinical presentations on the associations of TPV with macrophage, lipid arc, and layer index was statistically significant. Macrophage was more prevalent in plaques with greater TPV in patients who presented with ACS but not in those who presented with CCS (low vs. moderate vs. high TPV group: macrophage 57.4% vs. 71.8% vs. 82.4% in ACS; 63.4% vs. 67.8% vs. 66.7% in CCS; interaction P=0.004). Lipid arc was more strongly associated with TPV in patients who presented with ACS than in those with CCS (low vs. moderate vs. high TPV group: 116 [76-157] vs. 166 [115-210] vs. 175 [140-221] in ACS; 118 [80-154] vs. 143 [102-187] vs. 150 [102-199] in CCS; interaction P=0.028). Conversely, layer index was more weakly associated with TPV in patients who presented with ACS than in those who presented with CCS (low vs. moderate vs. high TPV group: 0 [0-0] vs. 0 [0-365] vs. 0 [0-903] in ACS; 0 [0-756] vs. 235 [0-1266] vs. 552 [0-1704] in CCS; interaction P=0.046) (Figure 1). Conclusions Greater plaque burden was closely related to the level of plaque vulnerability in ACS, whereas this relationship was less obvious in CCS.Figure 1

Impact of waist circumference and abdominal fat distribution on coronary artery disease severity stratified by computed tomography-derived SYNTAX score

Abstract Background Waist circumference (WC) is the most convenient anthropometric measure of obesity. Recently, abdominal fat distribution (AFD) has been identified as a more important risk factor for coronary artery disease (CAD) than the absolute amount of adipose tissue. However, studies examining the impact of body composition indicators (BCIs) on CAD severity are lacking. The computed tomography (CT)-derived SYNTAX score (CT-SXscore) is a feasible method for grading CAD severity based on coronary CT angiography (CTA) findings. Purpose This study was aimed to evaluate the association between BCI and CAD severity using the CT-SXscore. Methods We enrolled consecutive patients with suspected CAD who underwent CTA using a 320-row multidetector CT scanner between October 2014 and March 2020. Plain abdominal CT was also performed at the umbilical level to measure the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas. The total adipose tissue (TAT) area was calculated as the sum of VAT and SAT. To assess the AFD, the VAT/SAT (V/S) ratios were also calculated as the VAT area divided by the SAT area in each case. WC was measured by tracing the body contour at the umbilical level in CT images. The severity of coronary artery stenosis was assessed using CTA. Significant stenosis was defined as a stenosis diameter of ≥50%. The CT-SXscore was calculated in patients with more than one significant stenoses. Each stenotic lesion was evaluated to calculate the CT-SXscore in the same manner as the invasive coronary angiography assessment. We assessed the effects of BCI [i.e., WC, body mass index (BMI), each adipose tissue area, and V/S ratios] on the CT-SXscores. Results 308 eligible patients (mean age, 70.9 ± 10.6 years; 69.5% males) were evaluated. The median values of WC, BMI, TAT, SAT, VAT, and V/S ratio were 84.8 cm, 23.6 kg/m2, 198.2 cm2, 111.8 cm2, 81.0 cm2, and 0.67, respectively. Although WC showed a significant correlation with BMI, TAT, SAT, and VAT area, no correlation was observed between WC and V/S ratio (Figure1). The CT-SXscore showed no association with WC, BMI, and TAT area; however, it exhibited a weak negative correlation with the SAT area and a weak positive correlation with the VAT area. Additionally, a strong correlation was observed between the CT-SXscore and V/S ratio. In the multivariate regression analysis, WC, BMI, TAT, SAT, and VAT were no longer associated with the CT-SXscore after adjusting for traditional coronary risk factors, whereas the V/S ratio remained as the only independent predictor of CAD severity based on the CT-SXscore (Figure2). Conclusions WC was strongly correlated with other BCIs, except for the V/S ratio; however, it could not be identified as a predictive factor of CAD severity. Among the BCIs, only the V/S ratio was an independent predictor of CAD severity, indicating that the AFD revealed by the V/S ratio may be a more important risk factor for progression of CAD than other BCIs.Figure1Figure2

Favorable impact of FFRCT on myocardial revascularization outcomes: results from an observational real-world registry

Abstract Background Based on excellent clinical outcomes data, coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) is endorsed by guidelines to diagnose obstructive coronary artery disease (OCAD)(1). Dedicated outcome analyses in revascularized patients are essential to assess the additional value of FFRCT in revascularization. Purpose To assess the impact of FFRCT use on the postprocedural myocardial injury (PMI) and long-term outcomes of patients with OCAD undergoing myocardial revascularization. Methods Patients with suspected OCAD on CCTA (at least one stenosis of >50% in any vessel) were included from a 2013-2021 tertiary hospital registry. Propensity score adjusted Cox- regression and logistic regression analysis were used to assess the impact of FFRCT on the outcomes of OCAD patients post-revascularization. PMI was defined as cardiac troponin (cTn)>5 times the 99th percentile URL for percutaneous coronary intervention (PCI) and cTn>10 times the 99th percentile URL for coronary artery bypass graft (CABG) (2). Major adverse cardiovascular events (MACE) comprised all – cause mortality, acute myocardial infarction (AMI), stroke, hospitalization for heart failure (HHF) and new revascularization. Results From a registry of 7541 patients, suspected CCTA - derived OCAD was reported in 1601 cases. 559 OCAD patients were revascularized: 386(69.05%) by PCI, 166(29.7%) by CABG and 7(1.25%) by PCI and CABG. FFRCT was performed in 252(45.1%) patients. During a follow-up of 4.4±2.2 years, MACE occurred in 137(24.5%) patients: 43(7.7%) died, 21(3.8%) patients were hospitalized for AMI, 14(2.5%) patients had a stroke, 12 (2.1%) patients had HHF and 77(13.8%) patients had a new revascularization. Survival analysis indicated significant differences in MACE and all-cause mortality–rates between FFRCT use and no FFRCT use (log- rank p = 0.033 and 0.004, Fig 1). Multivariable propensity–adjusted Cox–regression analysis showed a non–significant trend towards reduced MACE risk by using FFRCT (HR 0.736, 95% CI 0.513-1.055, P=0.095) and a significant reduction in all-cause mortality risk (HR 0.476, 95% CI 0.230–0.985, P=0.046). Sub-analysis in the PCI and CABG groups showed no significant association between FFRCT and MACE. Among the 477 patients with available cTn values, 203 (42.5%) had PMI. In the CABG group, FFRCT use correlated with low PMI incidence (5.3% vs. 15.6%, p=0.044). However, multivariable Cox regression analysis revealed no significant association between FFRCT use and PMI(Fig 2). Conclusion This observational designed study reveals for the first time that FFRCT reduces post-myocardial revascularization MACE, primarily driven by reduced all-cause mortality. No clear reduction of PMI was observed suggesting that FFRCT value extends beyond procedural enhancements. Although derived from a large real-world registry, these promising observations need to be confirmed by randomized studies.Figure 1Figure 2

Increased prevalence of coronary atherosclerosis in cancer survivors: a matched cross-sectional study with coronary CT angiography

Abstract Background Cancer and atherosclerosis share many risk factors. Although cardiovascular disease is highly prevalent among cancer survivors, it is unknown whether coronary atherosclerosis is present at a younger age in patients with a history of cancer. Purpose The purpose of this study is to evaluate the prevalence of coronary atherosclerosis in different age groups of patients with a history of cancer compared to matched controls. Methods Consecutive patients with a history of cancer aged >30 years who underwent evaluation for coronary artery disease with coronary computed tomography angiography (CCTA) between 2010 and 2023 were included in this cross-sectional study. Patients with a history of cancer were matched 1:2 to a control population without oncological history using propensity score matching. Patients were matched on age, gender, body mass index, hypercholesterolemia, hypertension, diabetes, use of statins and smoking status. The presence of atherosclerosis in the main coronary arteries was compared between the groups. Results The study population consisted of 313 patients with an oncological history and 626 matched control patients. The median age during CCTA scan was 59.4 [50.4-67.5] years and 66.1% of the patients were female. Coronary atherosclerosis was observed in 258 (82.4%) patients with a history of cancer compared to 461 (73.6%) control patients with a risk ratio of 1.12 [95% CI: 1.04-1.20], p<0.01. Mainly younger patients with a history of cancer aged between 30-59 years had a significant increased prevalence of coronary atherosclerosis with a risk ratio of 1.18 [1.04-1.33] compared to healthy controls (p=0.02). In our study population, thoracic radiotherapy was not associated with an increased prevalence of coronary atherosclerosis. Calcified plaques were observed more frequently in patients with a history of cancer (14.4% vs. 9.3% respectively, p=0.018). Conclusion Patients with a history cancer have a higher prevalence of coronary atherosclerosis as observed on CCTA compared to matched patients without cancer. This effect was most pronounced in younger patients aged 30-59 years. There is an unmet need to define strategies for cardiovascular disease monitoring and prevention in this growing patient population of patients with a history of cancer.Presence of coronary atherosclerosisRadiotherapy and atherosclerosis

Coronary inflammation stratifies risk in patients undergoing coronary CT angiography: the Oxford Risk Factors and Non-Invasive Imaging (ORFAN) study

Abstract Background Patients with chest pain symptoms often undergo coronary CT angiography (CCTA) for the diagnosis of obstructive coronary artery disease (CAD) to guide revascularisation. However, acute cardiac events could occur in the absence of obstructive CAD. Further risk stratification of patients could potentially be useful by quantifying coronary inflammation using the Fat Attenuation Index (FAI) Score, and an artificial intelligence (AI)-assisted prognostic model that captures the inflammatory risk by integrating CCTA-derived metrics (including FAI Score and plaque burden) and the patient’s clinical risk factors. Purpose To evaluate the risk of cardiac events among patients without obstructive CAD, and the prognostic value of integrating coronary inflammation in risk stratifying this patient group. Methods From the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, patients undergoing CCTA in 7 UK Hospitals (n=40,091) were followed up for the incidence of cardiac mortality over a median(IQR) of 2.7(1.4-5.3) years. In a nested cohort of 3,393 patients with long-term follow up, we evaluated the long-term prognostic value of FAI Score and the performance of AI-Risk algorithm over a median(IQR) follow up of 7.7(6.4-9.1) years. Reclassification of risk category from AI-Risk was compared with contemporary clinical risk score (QRISK3). Results Patients without obstructive CAD (n=32,533, 81.1%) accounted for 63.7% of all cardiac deaths (n=1,754) during follow up, highlighting the substantial proportion of cardiac events in absolute terms given a large proportion of patients without obstructive CAD. In the nested cohort with long-term follow up, FAI Score in any of the 3 epicardial coronary arteries was significantly associated with cardiac mortality with or without obstructive CAD. In the whole cohort, the highest quartile of FAI Score in LAD showed 20-times higher risk of cardiac death compared with the lowest quartile (Panel A). Integrating coronary inflammation with clinical risk factors and plaque burden, patients with very-high AI-Risk classification showed 6-fold higher risk of cardiac mortality compared to low/medium risk, with good alignment of the incident predicted events from AI-Risk and observed events. (Panel B) The predicted cardiac mortality from AI-Risk also demonstrated good calibration with the observed events in the whole population. (Panel C) Finally, AI-Risk significantly reclassify the risk above clinical risk factor-based prediction (QRISK3) (Panel D). Conclusion Patients with high coronary inflammation measured by FAI Score showed significantly elevated risk for cardiac mortality. The AI-enabled absolute risk prediction algorithm leads to significant reclassification of patients undergoing routine CCTA, and can be used as a precision medicine tool.

Prognostic value of quantitative anatomical and functional measures of coronary artery disease in diabetic and non-diabetic patients

Abstract Background Diabetes is associated with increased risk of coronary artery disease (CAD). However, the relative prognostic importance of anatomical and functional findings of CAD in the presence vs. absence of diabetes is incompletely understood. Technological advances have made quantitative analysis of coronary artery plaques and stenosis feasible by coronary computed tomography angiography (CTA). In turn, positron emission tomography (PET) enables absolute quantification of myocardial blood flow (MBF). Purpose To study long-term prognostic value of quantified severity of coronary atherosclerosis and myocardial perfusion in non-diabetic vs. diabetic patients with suspected CAD. Methods From two academic medical centres, we identified symptomatic patients with suspected CAD who had undergone coronary CTA and [15O]H2O PET myocardial perfusion imaging during adenosine stress. Based on artificial intelligence -guided quantitative analysis of coronary CTA scans, the anatomical severity of CAD was measured as the presence of obstructive CAD (≥50% diameter stenosis) and percent atheroma volume (PAV; higher vs. lower than median). The functional severity of CAD was measured as the presence of regional myocardial ischemia (≥2 adjacent segments with stress MBF <2.3 ml/g/min) and global stress MBF (<2.2 ml/g/min vs. ≥ 2.2 ml/g/min) by PET. Annual rates of adverse events (AER) including all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP) were evaluated. Results Among 1311 patients, 251 (19%) had diabetes. Patients with diabetes had more frequently obstructive CAD (55% vs. 43%, p<0.001) and regional myocardial ischemia (51% vs. 43%, p=0.015), higher plaque burden by PAV (12% vs. 7%, p<0.001), and lower global stress MBF (2.78 ml/g/min vs. 3.05 ml/g/min, p<0.001). During median follow-up of 7.1 years, 171 (13.0%) patients experienced AE (85 deaths, 56 MIs, and 30 UAPs). Patients with diabetes had higher AER than non-diabetic patients (3.1% vs. 1.6%, p<0.001). The presence of obstructive stenosis was associated with increased AER in non-diabetic (2.6% vs. 1.0%, p<0.001) and diabetic patients (4.2% vs. 1.9%, p<0.001). High plaque burden by PAV was associated with increased AER in non-diabetic (2.8% vs. 0.7%, p<0.001) and diabetic patients (3.9% vs. 1.7%, p<0.001). The presence of regional myocardial ischemia was associated with increased AER in non-diabetic (2.5% vs. 1.1%, p<0.001), but not in diabetic patients (3.4% vs. 2.7%, p=0.238). Low global stress MBF was associated with increased AER in non-diabetic (2.9% vs. 1.3%, p<0.001), but not among diabetic patients (3.2% vs. 3.0%, p=0.286). Conclusions Diabetes was associated with more advanced CAD. Quantified severity of anatomical findings predicted long-term adverse outcome in non-diabetic and diabetic patients. In contrast, functional imaging risk stratified non-diabetic patients, whereas diabetic patients had impaired long-term outcome irrespective of perfusion findings.

Age stratified differences in coronary artery plaque phenotype in women and men with non-obstructive coronary artery disease

Abstract Background Development of coronary artery disease (CAD) and risk of acute cardiac events differ between women and men during the life span. The aim of this study was therefore to characterize sex differences in coronary artery plaque phenotype among patients with symptomatic non-obstructive CAD in different age groups. Methods Advanced coronary artery plaque phenotyping by coronary computed tomography angiography was performed in 606 patients (31% women) with symptomatic non-obstructive CAD from the Norwegian Registry of Invasive Cardiology. A 1:1 sex-matched study design ensured equal distribution of the sexes in the different age groups. We assessed total plaque burden adjusted for vessel volume and plaque composition consisting of dense calcium, fibrous, fibro-fatty, and necrotic core. Patients were further stratified into age groups of ≤50, 51-64, and ≥65 years to explore the relationship between age and sex on coronary artery plaque phenotype. Results In the study population, patients ≥65 years had a higher prevalence of hypertension, higher calcium score, coronary artery segment involvement score and total plaque burden, whereas the prevalence of obesity was lower compared to patients aged 51-64 and ≤50 years (all p<0.05). The prevalence of smoking, diabetes and statin treatment was similar between groups. A two-way analysis of variance demonstrated an interaction between sex and age group on total plaque burden (F [2, 600] =3.431, p=0.33), where women aged 51-64 and ≥65 years had a higher total plaque burden compared to men (p=0.002 and p<0.001, respectively, Figure 1). Plaque composition in women ≥65 years was characterized by an increased proportion of stable dense calcified plaques compared to men and younger women (all p<0.05), whereas men ≥65 years had a higher proportion of vulnerable necrotic core plaque phenotype (p<0.001). Women showed consistently lower proportions of more vulnerable fibro-fatty plaques compared to men across all age groups (all p<0.05, Figure 2). Conclusions In non-obstructive CAD, higher total plaque burden was associated with older age and female sex. Women had a lower proportion of vulnerable fibro-fatty plaques across all age groups and a higher proportion of stable dense calcified plaques at an older age compared to men. Future longitudinal studies on coronary artery plaque phenotype during the life span will increase the understanding of sex differences in CAD development and may contribute to customise risk stratification in women and men.Figure 1.Total plaque burdenFigure 2.Compositional plaque burden

Radiomics-based multimodality prediction of left atrial appendage thrombus using coronary computed tomography angiography

Abstract Background Timely detection of thrombus in the left atrial appendage (LAA) may help guide decision-making. However, existing models have challenges in extracting comprehensive image information. It has been shown that radiomics-based prediction models can be used for accurate identification. This study investigates potential radiomic markers and constructs a highly efficient multimodality prediction model for LAA thrombus in patients undergoing coronary computed tomography angiography (CCTA). Methods We retrospectively enrolled patients with nonvalvular atrial fibrillation (NVAF) who underwent CCTA and transesophageal echocardiography (TEE) from May 2015 to May 2020. These patients were classified into thrombus or non-thrombus groups based on TEE findings. The data were balanced by resampling and assigned to training or test sets. Radiomics was conducted on the extracted features, and a random forest algorithm was employed for feature selection and importance ranking. We constructed different multimodality thrombus prediction models and compared their performance using the area under the receiver operating characteristic curve (AUC) and other efficacy parameters. Results Among 670 patients (60.17±10.98 years, 70.1% male), 5.2% (n=35) had LAA thrombi. A total of 1232 radiomics features were extracted, with 25 features selected using a random forest for modeling. Two radiomics features (Ibp_3D_m1_firstorder Skewness and original_shape_Flatness) ranked the highest. The radiomics-based multimodality prediction model achieved an AUC of 0.964 (95% confidence interval [CI]: 0.947-0.982), an accuracy of 0.926 (95% CI: 0.925-0.926), and an F1 score of 0.924, outperforming other traditional prediction models. Decision curve analysis also indicated that this model provided the best net clinical benefit. Conclusions Radiomics facilitates a comprehensive exploration of predictors associated with LAA thrombi. A radiomics-based multimodality prediction model can significantly enhance the efficiency of non-invasively detecting thrombi.Receiver operating characteristic curveDecision curve analysis

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