BackgroundElevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk... Show moreBackgroundElevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk.ObjectivesThe authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event.MethodsThe authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD. In the multinational CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, the authors compared ASCVD event rates in persons without a history of myocardial infarction (MI) or revascularization (as categorized on CAC scores) to event rates in those with established ASCVD. They identified 4,511 individuals without known coronary artery disease (CAC) who were compared to 438 individuals with established ASCVD. CAC was categorized as 0, 1 to 100, 101 to 300, and >300. Cumulative major adverse cardiovascular events (MACE), MACE plus late revascularization, MI, and all-cause mortality incidence was assessed using the Kaplan-Meier method for persons with no ASCVD history by CAC level and persons with established ASCVD. Cox proportional hazards regression analysis was used to calculate HRs with 95% CIs, which were adjusted for traditional cardiovascular risk factors.ResultsThe mean age was 57.6 ± 12.4 years (56% male). In total, 442 of 4,949 (9%) patients experienced MACEs over a median follow-up of 4 years (IQR: 1.7-5.7 years). Incident MACEs increased with higher CAC scores, with the highest rates observed with CAC score >300 and in those with prior ASCVD. All-cause mortality, MACEs, MACE + late revascularization, and MI event rates were not statistically significantly different in those with CAC >300 compared with established ASCVD (all P > 0.05). Persons with a CAC score <300 had substantially lower event rates.ConclusionsPatients with CAC scores >300 are at an equivalent risk of MACE and its components as those treated for established ASCVD. This observation, that those with CAC >300 have event rates comparable to those with established ASCVD, supplies important background for further study related to secondary prevention treatment targets in subjects without prior ASCVD with elevated CAC. Understanding the CAC scores that are associated with ASCVD risk equivalent to stable secondary prevention populations may be important for guiding the intensity of preventive approaches more broadly. Show less
AimsTo investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression... Show moreAimsTo investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA).Methods and resultsWe analyzed mild stenosis (25–49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02–3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09–2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07–2.22; P = 0.020).ConclusionIn mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. Show less
BACKGROUND The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be... Show moreBACKGROUND The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be determined.OBJECTIVES The purpose of this study was to explore the association between the change in PVAT density and the progression of total and compositional plaque volume (PV). METHODS Patients were selected from a prospective multinational registry. Patients who underwent serial coronary computed tomography angiography studies with $2-year intervals and were scanned with the same tube voltage at baseline and follow-up were included. Total and compositional PV and PVAT density at baseline and follow-up were quantitatively analyzed for every lesion. Multivariate linear regression models using cluster analyses were constructed.RESULTS A total of 1,476 lesions were identified from 474 enrolled patients (mean age 61.2 +/- 9.3 years; 65.0% men). The mean PVAT density was-74.1 +/- 11.5 HU, and total PV was 48.1 +/- 83.5 mm3 (19.2 +/- 44.8 mm3 of calcified PV and 28.9 +/- 51.0 mm3 of noncalcified PV). On multivariate analysis (adjusted for clinical risk factors, medication use, change in lipid levels, total PV at baseline, luminal HU attenuation, location of lesions, and tube voltage), the increase in PVAT density was positively associated with the progression of total PV (estimate = 0.275 [95% CI: 0.004-0.545]; P = 0.047), driven by the association with fibrous PV (estimate = 0.245 [95% CI: 0.070-0.420]; P = 0.006). Calcified PV progression was not associated with the increase in PVAT density (P > 0.050). CONCLUSIONS Increase in vessel inflammation represented by PVAT density is independently associated with the progression of the lipid component of coronary atherosclerotic plaques. (Progression of AtheRosclerotic PlAque Deter-mIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411) (J Am Coll Cardiol Img 2022;15:1760-1767) (c) 2022 by the American College of Cardiology Foundation. Show less
Wang, X.; Hoogen, I.J. van den; Butcher, S.C.; Kuneman, J.H.; Graaf, M.A. de; Kamperidis, V.; ... ; Bax, J.J. 2022
Aims: Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque... Show moreAims: Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission tomography (PET). Methods and results: From a registry of symptomatic patients with suspected coronary artery disease and clinically indicated CCTA with sequential [O-15]H2O PET myocardial perfusion imaging, we quantitatively measured diameter stenosis, total and compositional plaque volumes on CCTA. Primary endpoint was myocardial ischaemia on PET, defined as an absolute stress myocardial blood flow <= 2.4 mL/g/min in >= 1 segment. Multivariable prediction models for myocardial ischaemia were consecutively created using logistic regression analysis (stenosis model: diameter stenosis >= 50%; plaque volume model: +total plaque volume; plaque composition model: +necrotic core volume). A total of 493 patients (mean age 63 +/- 8 years, 54% men) underwent sequential CCTA/PET imaging. In 153 (31%) patients, myocardial ischaemia was detected on PET. Diameter stenosis >= 50% (P < 0.001) and necrotic core volume (P = 0.029) were independently associated with myocardial ischaemia, while total plaque volume showed borderline significance (P = 0.052). The plaque composition model (chi(2) = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (chi(2) = 138, P < 0.001) and plaque volume model (chi(2) = 164, P = 0.021). Conclusion: The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone. Show less
Aims: The temporal instability of coronary atherosclerotic plaque preceding an incident acute coronary syndrome (ACS) is not well defined. We sought to examine differences in the volume and... Show moreAims: The temporal instability of coronary atherosclerotic plaque preceding an incident acute coronary syndrome (ACS) is not well defined. We sought to examine differences in the volume and composition of coronary atherosclerosis between patients experiencing an early (<= 90 days) versus late ACS (>90 days) after baseline coronary computed tomography angiography (CCTA). Methods and results: From a multicenter study, we enrolled patients who underwent a clinically indicated baseline CCTA and experienced ACS during follow-up. Separate core laboratories performed blinded adjudication of ACS events and quantification of CCTA including compositional plaque volumes by Hounsfield units (HU): calcified plaque >350 HU, fibrous plaque 131-350 HU, fibrofatty plaque 31-130 HU and necrotic core <30 HU. In 234 patients (mean age 62 +/- 12 years, 36% women), early and late ACS occurred in 129 and 105 patients after a mean of 395 +/- 622 days, respectively. Patients with early ACS had a greater maximal diameter stenosis and maximal cross-sectional plaque burden as compared to patients with late ACS (P < 0.05). Larger total, fibrous, fibrofatty, and necrotic core volumes were observed in the early ACS group (P < 0.05). Findings for total, fibrous, fibrofatty, and necrotic core volumes were reproduced in an external validation cohort (P < 0.05). Conclusions: Volumetric differences in composition of coronary atherosclerosis exist between ACS patients according to their timing antecedent to the acute event. These data support that a large burden of non-calcified plaque on CCTA is strongly associated with near-term plaque instability and ACS risk. Show less
Won, K.B.; Park, H.B.; Heo, R.; Lee, B.K.; Lin, F.Y.; Hadamitzky, M.; ... ; Chang, H.J. 2022
Background: Atherosclerosis-related adverse events are commonly observed even in conditions with low cardiovascular (CV) risk. Longitudinal data regarding the association of normal systolic blood... Show moreBackground: Atherosclerosis-related adverse events are commonly observed even in conditions with low cardiovascular (CV) risk. Longitudinal data regarding the association of normal systolic blood pressure maintenance (SBPmaintain) with coronary plaque volume changes (PVC) has been limited in adults without traditional CV disease. Hypothesis: Normal SBPmaintain is important to attenuate coronary atherosclerosis progression in adults without baseline CV disease. Methods: We analyzed 95 adults (56.7 +/- 8.5 years; 40.0% men) without baseline CV disease who underwent serial coronary computed tomographic angiography with mean 3.5 years of follow-up. All participants were divided into two groups of normal SBPmaintain (follow-up SBP < 120 mm Hg) and >= elevated SBPmaintain (follow-up SBP >= 120 mm Hg). Annualized PVC was defined as PVC divided by the interscan period. Results: Compared to participants with normal SBPmaintain, those with >= elevated SBPmaintain had higher annualized total PVC (mm(3)/year) (0.0 [0.0-2.2] vs. 4.1 [0.0-13.0]; p < .001). Baseline total plaque volume (beta = .10) and the levels of SBPmaintain (beta = .23) and follow-up high-density lipoprotein cholesterol (beta = -0.28) were associated with annualized total PVC (all p < .05). The optimal cutoff of SBPmaintain for predicting plaque progression was 118.5 mm Hg (sensitivity: 78.2%, specificity: 62.5%; area under curve: 0.700; 95% confidence interval [CI]: 0.59-0.81; p < .05). SBPmaintain >= 118.5 mm Hg (odds ratio [OR]: 4.03; 95% CI: 1.51-10.75) and baseline total plaque volume (OR: 1.03; 95% CI: 1.01-1.06) independently influenced coronary plaque progression (all p < .05). Conclusion: Normal SBPmaintain is substantial to attenuate coronary atherosclerosis progression in conditions without established CV disease. Show less
Hoogen, I.J. van den; Schultz, J.; Kuneman, J.H.; Graaf, M.A. de; Kamperidis, V.; Broersen, A.; ... ; Knuuti, J. 2022
Aims Evolving evidence suggests that endothelial wall shear stress (ESS) plays a crucial role in the rupture and progression of coronary plaques by triggering biological signalling pathways. We... Show moreAims Evolving evidence suggests that endothelial wall shear stress (ESS) plays a crucial role in the rupture and progression of coronary plaques by triggering biological signalling pathways. We aimed to investigate the patterns of ESS across coronary lesions from non-invasive imaging with coronary computed tomography angiography (CCTA), and to define plaque-associated ESS values in patients with coronary artery disease (CAD). Methods and results: Symptomatic patients with CAD who underwent a clinically indicated CCTA scan were identified. Separate core laboratories performed blinded analysis of CCTA for anatomical and ESS features of coronary atherosclerosis. ESS was assessed using dedicated software, providing minimal and maximal ESS values for each 3 mm segment. Each coronary lesion was divided into upstream, start, minimal luminal area (MLA), end and downstream segments. Also, ESS ratios were calculated using the upstream segment as a reference. From 122 patients (mean age 64 +/- 7 years, 57% men), a total of 237 lesions were analyzed. Minimal and maximal ESS values varied across the lesions with the highest values at the MLA segment [minimal ESS 3.97 Pa (IQR 1.93-8.92 Pa) and maximal ESS 5.64 Pa (IQR 3.13-11.21 Pa), respectively]. Furthermore, minimal and maximal ESS values were positively associated with stenosis severity (P < 0.001), percent atheroma volume (P < 0.001), and lesion length (P <= 0.023) at the MLA segment. Using ESS ratios, similar associations were observed for stenosis severity and lesion length. Conclusions: Detailed behaviour of ESS across coronary lesions can be derived from routine non-invasive CCTA imaging. This may further improve risk stratification. Show less
Aims: Atherosclerosis develops progressively and worsens over time, yet event risk patterns vary in the left circumflex (LCx), right coronary artery (RCA) and left anterior descending (LAD). The... Show moreAims: Atherosclerosis develops progressively and worsens over time, yet event risk patterns vary in the left circumflex (LCx), right coronary artery (RCA) and left anterior descending (LAD). The aim of this analysis was to examine varying progressive disease alterations between the three major coronary arteries. Methods and results: Patients were included from a prospective, international registry of consecutive patients who underwent serial CCTA at a median interval of 3.3 years. Annual progression of quantitative total and compositional plaque volume were compared between the three coronary arteries (LCx, LAD, and RCA). Other analyses compared stenosis >= 50% and new high-risk plaque (HRP; >= 2 of the following: spotty calcification, positive remodelling, napkin-ring sign, and low-attenuation plaque) on follow-up. Generalized estimating equations and marginal Cox regression models were used to compare progression, with covariate adjustment by the baseline atherosclerotic cardiovascular disease risk score, statin use, and plaque burden. Quantitative plaque measurements were calculated in 1344 patients (age 60 +/- 9 years, 57% men). Plaque progression occurred less often in the LCx (41.0%) as compared to the RCA (52.7%) and LAD (77.4%, P < 0.001). Odds for annual plaque burden increase >= population mean were 1.98- and 1.43-fold as high in the LAD (P < 0.001) and RCA (P < 0.001) as compared to the LCx. Similarly, the LAD was associated with a 2.45 higher risk of progression to obstructive CAD (P < 0.001), as compared to the LCx; with no differences between the RCA and LCx (P = 0.13). New HRP lesions formed least often in the LCx (3.4%), followed by the RCA (8.1%) and most often in the LAD (10.1%; P < 0.001). Conclusions: Our findings reveal novel insights into varied patterns of atherosclerotic plaque progression within the LCx as compared to the other epicardial coronary arteries. These varied patterns reflect differing stages in the disease process or differing pathogenic milieu across the coronary arteries. Show less
Aims: The relationship between AtheroSclerotic CardioVascular Disease (ASCVD) risk and vessel-specific plaque evaluation using coronary computed tomography angiography (CCTA), focusing on plaque... Show moreAims: The relationship between AtheroSclerotic CardioVascular Disease (ASCVD) risk and vessel-specific plaque evaluation using coronary computed tomography angiography (CCTA), focusing on plaque extent and composition, has not been examined. To evaluate differences in quantified plaque characteristics (using CCTA) between the three major coronary arteries [left anterior descending (LAD), right coronary (RCA), and left circumflex (LCx)] among subgroups of patients with varying ASCVD risk.Methods and results: Patients were included from a prospective, international registry of consecutive patients who underwent CCTA for evaluation of coronary artery disease. ASCVD risk groups were <7.5% (low), 7.5-20% (intermediate), and ≥20% (high). Among the ASCVD risk groups, the three coronary arteries were compared regarding quantified plaque volume and composition. Whole-heart plaque quantification was performed in 1340 patients (age 60 ± 9 years, 58% men). Across low, intermediate, and high ASCVD risk patients, the volume of plaque increased proportionally but was least in the LCx (7.4, 9.0, and 25.3 mm3, respectively) as compared with the RCA (19.3, 32.6, and 67.0 mm3, respectively, all P ≤ 0.006) and LAD (39.9, 60.8, and 93.3 mm3, respectively, all P < 0.001). In each ASCVD risk group, the composition of plaque in the LCx exhibited the least necrotic core and fibrofatty plaque (P < 0.05 vs. LAD and RCA).Conclusion: Among patients with varying risk of ASCVD, plaque in the LCx is decidedly less and is comprised of less non-calcified plaque supporting prior evidence of the lower rates of acute coronary events in this vessel. Show less
Aims The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the... Show moreAims The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea. Methods and results: From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for >= 5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 +/- 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1-6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29-1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02-1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD. Conclusion: In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk. Show less
Cipriani, A.; Dall'Aglio, P.B.; Mazzotta, L.; Sirico, D.; Sarris, G.; Hazekamp, M.; ... ; Padalino, M.A. 2022
Background: Anomalous aortic origin of a coronary artery (AAOCA) is a congenital heart disease with a 0.3%-0.5% prevalence. Diagnosis is challenging due to nonspecific clinical presentation. Risk... Show moreBackground: Anomalous aortic origin of a coronary artery (AAOCA) is a congenital heart disease with a 0.3%-0.5% prevalence. Diagnosis is challenging due to nonspecific clinical presentation. Risk stratification and treatment are currently based on expert consensus and single-center case series. Methods: Demographical and clinical data of AAOCA patients from 17 tertiary-care centers were analyzed. Diagnostic imaging studies (Bidimensional echocardiography, coronary computed tomography angiography [CCTA] were collected. Clinical correlations with anomalous coronary course and origin were evaluated. Results: Data from 239 patients (42% males, mean age 15 y) affected by AAOCA were collected; 154 had AAOCA involving the right coronary artery (AAORCA), 62 the left (AAOLCA), 23 other anomalies. 211 (88%) presented with an inter-arterial course. Basal electrocardiogram (ECG) was abnormal in 37 (16%). AAOCA was detected by transthoracic echocardiography and CCTA in 53% and 92% of patients, respectively. Half of the patients reported cardiac symptoms (119/239; 50%), mostly during exercise in 121/178 (68%). An ischemic response was demonstrated in 37/106 (35%) and 16/31 (52%) of patients undergoing ECG stress test and stress-rest single positron emission cardiac tomography. Compared with AAORCA, patients with AAOLCA presented more frequently with syncope (18% vs. 5%, P = 0.002), in particular when associated with inter-arterial course (22% vs. 5%, P < 0.001). Conclusion: Diagnosis of AAOCA is a clinical challenge due to nonspecific clinical presentations and low sensitivity of first-line cardiac screening exams. Syncope seems to be strictly correlated to AAOLCA with inter-arterial course. Show less
Coronary computed tomography angiography (CTA) has shown great technological improvements over the last 2 decades. High accuracy of CTA in detecting significant coronary stenosis has promoted CTA... Show moreCoronary computed tomography angiography (CTA) has shown great technological improvements over the last 2 decades. High accuracy of CTA in detecting significant coronary stenosis has promoted CTA as a substitute for conven-tional invasive coronary angiography in patients with suspected coronary artery disease. In patients with coronary stenosis, CTA-derived physiological assessment is surrogate for intracoronary pressure and velocity wires, and renders possible decision-making about revascularization solely based on computed tomography. Computed tomography coro-nary anatomy with functionality assessment could potentially become a first line in diagnosis. Noninvasive imaging assessment of plaque burden and morphology is becoming a valuable substitute for intravascular imaging. Recently, wall shear stress and perivascular inflammation have been introduced. These assessments could support risk management for both primary and secondary cardiovascular prevention. Anatomy, functionality, and plaque composition by CTA tend to replace invasive assessment. Complete CTA assessment could provide a 1-stop-shop for diagnosis, risk management, and decision-making on treatment. (J Am Coll Cardiol 2021;78:713-736) (c) 2021 by the American College of Cardiology Foundation. Show less
Bodini, A.; Michelucci, E.; Giorgi, N. di; Caselli, C.; Signore, G.; Neglia, D.; ... ; Rocchiccioli, S. 2021
Background: Lipidomics is emerging for biomarker discovery in cardiovascular disease, and circulating lipids are increasingly incorporated in risk models to predict cardiovascular events. Moreover,... Show moreBackground: Lipidomics is emerging for biomarker discovery in cardiovascular disease, and circulating lipids are increasingly incorporated in risk models to predict cardiovascular events. Moreover, specific classes of lipids, such as sphingomyelins, ceramides, and triglycerides, have been related to coronary artery disease (CAD) severity and plaque characteristics. To avoid unnecessary testing, it is important to identify individuals at low CAD risk. The only pretest model available so far to rule out the presence of coronary atherosclerosis in patients with chest pain, but normal coronary arteries, is the minimal risk tool (MRT).Aim: Using state-of-the-art statistical methods, we aim to verify the additive predictive value of a set of lipids, derived from targeted plasma lipidomics of suspected CAD patients, to a re-estimated version of the MRT for ruling out the presence of coronary atherosclerosis assessed by coronary CT angiography (CCTA).Methods: Two hundred and fifty-six subjects with suspected stable CAD recruited from five European countries within H2020-SMARTool, undergoing CCTA and blood sampling for clinical biochemistry and lipidomics, were selected. The MRT was validated by regression methods and then re-estimated (reMRT). The reMRT was used as a baseline model in a likelihood ratio test approach to assess the added predictive value of each lipid from 13 among ceramides, triglycerides, and sphingomyelins. Except for one lipid, the analysis was carried out on more than 240 subjects for each lipid. A sensitivity analysis was carried out by considering two alternative models developed on the cohort as baseline models.Results: In 205 subjects, coronary atherosclerosis ranged from minimal lesions to overt obstructive CAD, while in 51 subjects (19.9%) the coronary arteries were intact. Four triglycerides and seven sphingomyelins were significantly (p < 0.05) and differentially expressed in the two groups and, at a lesser extent, one ceramide (p = 0.067). The probability of being at minimal risk was significantly better estimated by adding either Cer(d18:1/16:0) (p = 0.01), SM(40:2) (p = 0.04), or SM(41:1) at a lesser extent (p = 0.052) to reMRT than by applying the reMRT alone. The sensitivity analysis confirmed the relevance of these lipids. Furthermore, the addition of SM(34:1), SM(38:2), SM(41:2), and SM(42:4) improved the predictive performance of at least one of the other baseline models. None of the selected triglycerides was found to provide an added value.Conclusions: Plasma lipidomics can be a promising source of diagnostic and prognostic biomarkers in cardiovascular disease, exploitable not only to assess the risk of adverse events but also to identify subjects without coronary atherosclerosis, thus reducing unnecessary further testing in normal subjects. Show less
Aims Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque... Show moreAims Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries.Methods and results A total of 1271 patients (age 60 +/- 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 +/- 29.4 mm(3)), followed by the RCA (32.8 +/- 82.7 mm(3); P < 0.001), and LAD (58.6 +/- 83.3 mm(3); P < 0.001), even when correcting for vessel length or volume. The prevalence of >= 2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P<0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P<0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001).Conclusion Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries.[GRAPHICS]. Show less
OBJECTIVES The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque... Show moreOBJECTIVES The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.BACKGROUND Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.METHODS This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) x 100 at a per-plaque and per-patient level (summation of all individual plaques).RESULTS CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis.CONCLUSIONS Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (C) 2021 by the American College of Cardiology Foundation. Show less
OBJECTIVES This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BACKGROUND It is unclear whether sex has an impact on PV progression in... Show moreOBJECTIVES This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BACKGROUND It is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).METHODS The study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at $2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed.RESULTS Of the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 +/- 9 years of age vs. 59 +/- 9 years of age; p < 0.001) and had higher total cholesterol levels (195 +/- 41 mg/dl vs. 187 +/- 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm(3) [interquartile range (IQR): 0 to 121.8 mm(3)] vs. 56.7 mm(3) [IQR: 6.8 to 152.1 mm(3)] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (b = 2.83; p = 0.004) but slower noncalcified PV progression (b = -3.39; p = 0.008) and less development of high-risk plaques (b = -0.18; p = 0.049) than in men.CONCLUSIONS The compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (c) 2020 by the American College of Cardiology Foundation. Show less
OBJECTIVES This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque... Show moreOBJECTIVES This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics.BACKGROUND Coronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known.METHODS Utilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested casecontrol study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of thismodel was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion.RESULTS CL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs.CONCLUSIONS In a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA. (c) 2020 by the American College of Cardiology Foundation. Show less
OBJECTIVES This study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP).BACKGROUND It is... Show moreOBJECTIVES This study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP).BACKGROUND It is still debatable whether HRP simply represents a certain phase during the natural history of coronary atherosclerotic plaques or if disease progression would differ according to the presence of HRP.METHODS Patients with nonobstructive coronary artery disease, defined as percent diameter stenosis (%DS) <50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an interscan interval of >= 2 years. HRP was defined as lesions with >= 2 features of positive remodeling, spotty calcification, or low-attenuation plaque. Quantitative total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions.RESULTS A total of 3,049 nonobstructive lesions were identified from 1,297 patients (mean age 60.3 +/- 9.3 years; 56.8% men). There were 2,624 non-HRP and 425 HRP lesions. HRP lesions had a greater total PAV and all noncalcified components of PAV and %DS at baseline compared with non-HRP lesions. However, the annualized total PAV changes were greater in non-HRP lesions than in HRP lesions. On multivariate analysis adjusted for clinical risk factors, drug use, change in lipid level, total PAV, %DS, and HRP, only the baseline total PAV and %DS independently predicted the development of obstructive lesions (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07, and HR: 1.07; 95% CI: 1.04 to 1.10, respectively, all p < 0.05), whereas the presence of HRP did not (p > 0.05).CONCLUSIONS The pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV, not the presence of HRP features, was the most important predictor of lesions developing into obstructive lesions. (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411) (c) 2020 by the American College of Cardiology Foundation. Show less
Aims In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and results Patients from the long-term... Show moreAims In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and results Patients from the long-term CONFIRM registry without prior CAD and without obstructive (>50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N= 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 +/- 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) white HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of >= 1 traditional risk factors did not worsen prognosis (tog-rank P= 0.248), white it did in non-obstructive CAD (log-rank P=0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004).Conclusion Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both. Show less
OBJECTIVES This study designed and evaluated an end-to-end deep learning solution for cardiac segmentation and quantification.BACKGROUND Segmentation of cardiac structures from coronary computed... Show moreOBJECTIVES This study designed and evaluated an end-to-end deep learning solution for cardiac segmentation and quantification.BACKGROUND Segmentation of cardiac structures from coronary computed tomography angiography (CCTA) images is laborious. We designed an end-to-end deep-learning solution.METHODS Scans were obtained from multicenter registries of 166 patients who underwent clinically indicated CCTA. Left ventricular volume (LVV) and right ventricular volume (RVV), left atrial volume (LAV) and right atrial volume (RAV), and left ventricular myocardial mass (LVM) were manually annotated as ground truth. A U-Net-inspired, deep-learning model was trained, validated, and tested in a 70:20:10 split.RESULTS Mean age was 61.1 +/- 8.4 years, and 49% were women. A combined overall median Dice score of 0.9246 (interquartile range: 0.8870 to 0.9475) was achieved. The median Dice scores for LVV, RVV, LAV, RAV, and LVM were 0.938 (interquartile range: 0.887 to 0.958), 0.927 (interquartile range: 0.916 to 0.946), 0.934 (interquartile range: 0.899 to 0.950), 0.915 (interquartile range: 0.890 to 0.920), and 0.920 (interquartile range: 0.811 to 0.944), respectively. Model prediction correlated and agreed well with manual annotation for LVV (r = 0.98), RVV (r = 0.97), LAV (r = 0.78), RAV (r = 0.97), and LVM (r = 0.94) (p < 0.05 for all). Mean difference and limits of agreement for LVV, RVV, LAV, RAV, and LVM were 1.20 ml (95% CI: -7.12 to 9.51), -0.78 ml (95% CI: -10.08 to 8.52), -3.75 ml (95% CI: -21.53 to 14.03), 0.97 ml (95% CI: -6.14 to 8.09), and 6.41 g (95% CI: -8.71 to 21.52), respectively.CONCLUSIONS A deep-learning model rapidly segmented and quantified cardiac structures. This was done with high accuracy on a pixel level, with good agreement with manual annotation, facilitating its expansion into areas of research and clinical import. (C) 2020 by the American College of Cardiology Foundation. Show less
