Prognostic Value of Follow-up Measures of Left Ventricular Global Longitudinal Strain in Patients With ST-Segment Elevation Myocardial Infarction.

INTRODUCTION: After ST-segment elevation myocardial infarction (STEMI), follow-up imaging is currently recommended only in patients with left ventricular ejection fraction (LVEF) <40%. Left ventricular global longitudinal strain (LVGLS) was shown to improve risk stratification over LVEF in these patients but has not been thoroughly studied during follow-up. The aim of this study was to explore the changes in LVGLS after STEMI and their potential prognostic value. MATERIALS AND METHODS: Data were analyzed from an ongoing STEMI registry. Echocardiography was performed during the index hospitalization and 1 year after STEMI; LVGLS was expressed as an absolute value and the relative LVGLS change (ΔGLS) was calculated. The study end point was all-cause mortality. RESULTS: A total of 1,409 STEMI patients (age 60 ± 11 years; 75% men) who survived at least 1 year after STEMI and underwent echocardiography at follow-up were included. At 1-year follow-up, LVEF improved from 50% ± 8% to 53% ± 8% (P < .001) and LVGLS from 14% ± 4% to 16% ± 3% (P < .001). Median ΔGLS was 14% (interquartile range, 0.5%-32%) relative improvement. Starting 1 year after STEMI, a total of 87 patients died after a median follow-up of 69 (interquartile range, 38-103) months. The optimal ΔGLS threshold associated with the end point (derived by spline curve analysis) was a relative decrease >7%. Cumulative 10-year survival was 91% in patients with ΔGLS improvement or a nonsignificant decrease, versus 85% in patients with ΔGLS decrease of >7% (P = .001). On multivariate Cox regression analysis, ΔGLS decrease >7% remained independently associated with the end point (hazard ratio, 2.5 [95% CI, 1.5-4.1]; P < .001) after adjustment for clinical and echocardiographic parameters. CONCLUSIONS: A significant decrease in LVGLS 1 year after STEMI was independently associated with long-term all-cause mortality and might help further risk stratification and management of these patients during follow-up.

Plaque volume, composition, and fraction versus ischemia and outcomes in patients with coronary artery disease.

BACKGROUND: The various plaque components have been associated with ischemia and outcomes in patients with coronary artery disease (CAD). The main goal of this analysis was to test the hypothesis that, at patient level, the fraction of non-calcified plaque volume (PV) of total PV is associated with ischemia and outcomes in patients with CAD. This ratio could be a simple and clinically useful parameter, if predicting outcomes. METHODS: Consecutive patients with suspected CAD undergoing coronary computed tomography angiography with selective positron emission tomography perfusion imaging were selected. Plaque components were quantitatively analyzed at patient level. The fraction of various plaque components were expressed as percentage of total PV and examined among patients with non-obstructive CAD, suspected stenosis with normal perfusion, and those with reduced myocardial perfusion. Clinical outcomes included all-cause mortality and myocardial infarction. RESULTS: In total, 494 patients (age 63 â€‹± â€‹9 years, 55% male) were included. Total PV and all plaque components were significantly larger in patients with reduced myocardial perfusion compared to patients with normal perfusion and those with non-obstructive CAD. During follow-up 35 events occurred. Patients with any plaque component â€‹≥ â€‹median showed worse outcomes (log-rank p â€‹< â€‹0.001 for all). In addition, low-attenuation plaque â€‹≥ â€‹median was associated with worse outcomes independent of total PV (adjusted HR: 2.754, 95% CI: 1.022-7.0419, p â€‹= â€‹0.045). The fractions of the various plaque components were not associated with outcomes. CONCLUSION: Larger total PV or any plaque component at patient level are associated with abnormal myocardial perfusion and adverse events. The various plaque components as fraction of total PV lack additional prognostic value.

Clinical and Coronary Plaque Predictors of Atherosclerotic Nonresponse to Statin Therapy.

BACKGROUND: Statins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse. OBJECTIVES: This study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins. METHODS: The multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque. RESULTS: The authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively). CONCLUSIONS: In patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.

Incorporating coronary artery calcium scoring in the prediction of obstructive coronary artery disease with myocardial ischemia: a study with sequential use of coronary computed tomography angiography and positron emission tomography imaging.

BACKGROUND: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD. METHODS AND RESULTS: Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001). CONCLUSIONS: Adding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD.

Coronary computed tomography angiography-based endothelial wall shear stress in normal coronary arteries.

Endothelial wall shear stress (ESS) is a biomechanical force which plays a role in the formation and evolution of atherosclerotic lesions. The purpose of this study is to evaluate coronary computed tomography angiography (CCTA)-based ESS in coronary arteries without atherosclerosis, and to assess factors affecting ESS values. CCTA images from patients with suspected coronary artery disease were analyzed to identify coronary arteries without atherosclerosis. Minimal and maximal ESS values were calculated for 3-mm segments. Factors potentially affecting ESS values were examined, including sex, lumen diameter and distance from the ostium. Segments were categorized according to lumen diameter tertiles into small (< 2.6 mm), intermediate (2.6-3.2 mm) or large (≥ 3.2 mm) segments. A total of 349 normal vessels from 168 patients (mean age 59 ± 9 years, 39% men) were included. ESS was highest in the left anterior descending artery compared to the left circumflex artery and right coronary artery (minimal ESS 2.3 Pa vs. 1.9 Pa vs. 1.6 Pa, p < 0.001 and maximal ESS 3.7 Pa vs. 3.0 Pa vs. 2.5 Pa, p < 0.001). Men had lower ESS values than women, also after adjusting for lumen diameter (p < 0.001). ESS values were highest in small segments compared to intermediate or large segments (minimal ESS 3.8 Pa vs. 1.7 Pa vs. 1.2 Pa, p < 0.001 and maximal ESS 6.0 Pa vs. 2.6 Pa vs. 2.0 Pa, p < 0.001). A weak to strong correlation was found between ESS and distance from the ostium (ρ = 0.22-0.62, p < 0.001). CCTA-based ESS values increase rapidly and become widely scattered with decreasing lumen diameter. This needs to be taken into account when assessing the added value of ESS beyond lumen diameter in highly stenotic lesions.

Importance of plaque volume and composition for the prediction of myocardial ischaemia using sequential coronary computed tomography angiography/positron emission tomography imaging.

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 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 [15O]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 (χ2 = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (χ2 = 138, P < 0.001) and plaque volume model (χ2 = 164, P = 0.021). CONCLUSION: The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone.

Vessel and sex differences in pericoronary adipose tissue attenuation obtained with coronary CT in individuals without coronary atherosclerosis.

Pericoronary adipose tissue (PCAT) attenuation, derived from coronary computed tomography angiography (CCTA), is associated with coronary artery inflammation. Values for PCAT attenuation in men and women without atherosclerosis on CCTA are lacking. The aim of the current study was to assess the mean PCAT attenuation in individuals without coronary artery atherosclerosis on CCTA. Data on PCAT attenuation in men and women without coronary artery atherosclerosis on CCTA were included in this retrospective analysis. The PCAT attenuation was analyzed from the proximal part of the right coronary artery (RCA), the left anterior descending artery (LAD), and the left circumflex artery (LCx). For patient level analyses the mean PCAT attenuation was defined as the mean of the three coronary arteries. In 109 individuals (mean age 45 ± 13 years; 44% men), 320 coronary arteries were analyzed. The mean PCAT attenuation of the overall population was - 64.4 ± 8.0 HU. The mean PCAT attenuation was significantly lower in the LAD compared with the LCx and RCA (- 67.8 ± 7.8 HU vs - 62.6 ± 6.8 HU vs - 63.6 ± 7.9 HU, respectively, p < 0.001). In addition, the mean PCAT attenuation was significantly higher in men vs. women in all three coronary arteries (LAD: - 65.7 ± 7.6 HU vs - 69.4 ± 7.6 HU, p = 0.014; LCx: - 60.6 ± 7.4 HU vs - 64.3 ± 5.9 HU, p = 0.008; RCA: -61.7 ± 7.9 HU vs - 65.0 ± 7.7 HU, p = 0.029, respectively). The current study provides mean PCAT attenuation values, derived from individuals without CAD. Moreover, the mean PCAT attenuation is lower in women vs. men. Furthermore, the mean PCAT attenuation is significantly lower in the LAD vs LCx and RCA.

Early versus late acute coronary syndrome risk patterns of coronary atherosclerotic plaque.

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 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.

Age related compositional plaque burden by CT in patients with future ACS.

BACKGROUND: We examined age differences in whole-heart volumes of non-calcified and calcified atherosclerosis by coronary computed tomography angiography (CCTA) of patients with future ACS. METHODS: A total of 234 patients with core-lab adjudicated ACS after baseline CCTA were enrolled. Atherosclerotic plaque was quantified and characterized from the main epicardial vessels and side branches on a 0.5 â€‹mm cross-sectional basis. Calcified plaque and non-calcified plaque were defined by above or below 350 Hounsfield units. Patients were categorized according to their age by deciles. Also, coronary artery calcium scores (CACS) were evaluated when available. RESULTS: Patients were on average 62.2 â€‹± â€‹11.5 years old. On the pre-ACS CCTA, patients showed diffuse, multi-site, predominantly non-obstructive atherosclerosis across all age categories, with plaque being detected in 93.5% of all ACS cases. The proportion calcified plaque from the total plaque burden increased significantly with older presentation (10% calcification in those <50 years, and 50% calcification in those >80 years old). Patients with ACS <50 years had remarkably lower atherosclerotic burden compared with older patients, but a high proportion of high risk markers such as low-attenuation plaque. CACS was >0 in 85% of the patients older than 50 years, and in 57% of patients younger than 50 years. CONCLUSION: The proportion of calcified plaque varied depending on patient age at the time of ACS. Only a small proportion of plaque was calcified when ACS occurred at <50 years old, while this increased gradually with older age. Purely non-calcified atherosclerotic plaque was not uncommon in patients <50 years.

Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease.

BACKGROUND: Among symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque. OBJECTIVES: Among patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume. METHODS: A total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up). RESULTS: Across baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm3 (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm3 increase in calcified plaque, there was a 5.5 mm3 increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001). CONCLUSIONS: CAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk.

Detailed behaviour of endothelial wall shear stress across coronary lesions from non-invasive imaging with coronary computed tomography angiography.

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 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.

Marked variation in atherosclerotic plaque progression between the major epicardial coronary arteries.

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 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.

Coronary volume to left ventricular mass ratio in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes. METHODS: Patients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes. RESULTS: Of the 3053 patients (age 66 â€‹± â€‹10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 â€‹± â€‹940 â€‹mm3 vs. 3040 â€‹± â€‹970 â€‹mm3, p â€‹< â€‹0.0001), whereas the myocardial mass was comparable between the 2 groups (122 â€‹± â€‹33 â€‹g vs. 122 â€‹± â€‹32 â€‹g, p â€‹= â€‹0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 â€‹± â€‹6.8 â€‹mm3/g vs. 25.7 â€‹± â€‹7.5 â€‹mm3/g, p â€‹< â€‹0.0001). Among subjects with obstructive CAD (n â€‹= â€‹2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 â€‹± â€‹6.7 â€‹mm3/g vs. 25.0 â€‹± â€‹7.3 â€‹mm3/g, p â€‹< â€‹0.0001 and 25.6 â€‹± â€‹6.9 â€‹mm3/g vs. 27.3 â€‹± â€‹7.6 â€‹mm3/g, respectively, p â€‹= â€‹0.006). CONCLUSION: The V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation.

Atherosclerotic plaque characteristics on quantitative coronary computed tomography angiography associated with ischemia on positron emission tomography in diabetic patients.

Patients with diabetes mellitus (DM) may show diffuse coronary artery atherosclerosis on coronary computed tomography angiography (CTA). The present study aimed at quantification of atherosclerotic plaque with CTA and its association with myocardial ischemia on positron emission tomography (PET) in DM patients. Of 922 symptomatic outpatients without previously known coronary artery disease who underwent CTA, 115 with DM (mean age 65 ± 8 years, 58% male) who had coronary atherosclerosis and underwent both quantified CTA (QCTA) and PET were included in the study. QCTA analysis was performed on a per-vessel basis and the most stenotic lesion of each vessel was considered. Myocardial ischemia on PET was based on absolute myocardial blood flow at stress ≤ 2.4 ml/g/min. Of the 345 vessels included in the analysis, 135 (39%) had flow-limiting stenosis and were characterized by having longer lesions, higher plaque volume, more extensive plaque burden and higher percentage of dense calcium (37 ± 22% vs 28 ± 22%, p = 0.001). On univariable analysis, QCTA parameters indicating the degree of stenosis, the plaque extent and composition were associated with presence of ischemia. The addition of the QCTA degree of stenosis parameters (x2 36.45 vs 88.18, p < 0.001) and the QCTA plaque extent parameters (x2 88.18 vs 97.44, p = 0.01) to a baseline model increased the association with ischemia. In DM patients, QCTA variables of vessel stenosis, plaque extent and composition are associated with ischemia on PET and characterize the hemodynamic significant atherosclerotic lesion.

Measurement of compensatory arterial remodelling over time with serial coronary computed tomography angiography and 3D metrics.

AIMS: The magnitude of alterations in which coronary arteries remodel and narrow over time is not well understood. We aimed to examine changes in coronary arterial remodelling and luminal narrowing by three-dimensional (3D) metrics from serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: From a multicentre registry of patients with suspected coronary artery disease who underwent clinically indicated serial CCTA (median interscan interval = 3.3 years), we quantitatively measured coronary plaque, vessel, and lumen volumes on both scans. Primary outcome was the per-segment change in coronary vessel and lumen volume from a change in plaque volume, focusing on arterial remodelling. Multivariate generalized estimating equations including statins were calculated comparing associations between groups of baseline percent atheroma volume (PAV) and location within the coronary artery tree. From 1245 patients (mean age 61 ± 9 years, 39% women), a total of 5721 segments were analysed. For each 1.00 mm3 increase in plaque volume, the vessel volume increased by 0.71 mm3 [95% confidence interval (CI) 0.63 to 0.79 mm3, P < 0.001] with a corresponding reduction in lumen volume by 0.29 mm3 (95% CI -0.37 to -0.21 mm3, P < 0.001). Serial 3D arterial remodelling and luminal narrowing was similar in segments with low and high baseline PAV (P ≥ 0.496). No differences were observed between left main and non-left main segments, proximal and distal segments and side branch and non-side branch segments (P ≥ 0.281). CONCLUSIONS: Over time, atherosclerotic coronary plaque reveals prominent outward arterial remodelling that co-occurs with modest luminal narrowing. These findings provide additional insight into the compensatory mechanisms involved in the progression of coronary atherosclerosis.

Associations between dyspnoea, coronary atherosclerosis, and cardiovascular outcomes: results from the long-term follow-up CONFIRM registry.

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 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.

Association of Statin Treatment With Progression of Coronary Atherosclerotic Plaque Composition.

Importance: The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques. Objective: To assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression. Design, Setting, and Participants: This cohort study enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree. The study was conducted from 2013 to 2016 at 13 sites in 7 countries. Main Outcomes and Measures: The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation (expressed in Hounsfield units [HU]): low attenuation (-30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU). The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density. Analysis was performed among lesions matched at baseline and follow-up. Data analyses were conducted from August 2019 through March 2020. Results: In total, 2458 coronary lesions in 857 patients (mean [SD] age, 62.1 [8.7] years; 540 [63.0%] men; 548 [63.9%] received statin therapy) were included. Untreated coronary lesions increased in volume over time for all 6 compositional types. Statin therapy was associated with volume decreases in low-attenuation plaque (ß, -0.02; 95% CI, -0.03 to -0.01; P = .001) and fibro-fatty plaque (ß, -0.03; 95% CI, -0.04 to -0.02; P < .001) and greater progression of high-density calcium plaque (ß, 0.02; 95% CI, 0.01-0.03; P < .001) and 1K plaque (ß, 0.02; 95% CI, 0.01-0.03; P < .001). When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, statin therapy was not associated with a change in overall calcified plaque volume (ß, -0.03; 95% CI, -0.08 to 0.02; P = .24) but was associated with a transformation toward more dense calcium. Interaction analysis between baseline plaque volume and calcium density showed that more dense coronary calcium was associated with less plaque progression. Conclusions and Relevance: The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium.

Progression of whole-heart Atherosclerosis by coronary CT and major adverse cardiovascular events.

BACKGROUND: The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE). METHODS: The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted. RESULTS: The study population comprised 1166 patients (age 60.5 â€‹± â€‹9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P â€‹< â€‹0.001. CONCLUSIONS: Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year.

The Clinical Spectrum of Myocardial Infarction and Ischemia With Nonobstructive Coronary Arteries in Women.

Women exhibit less burden of anatomic obstructive coronary atherosclerotic disease as compared with men of the same age, but contradictorily show similar or higher cardiovascular mortality rates. The higher prevalence of nonexertional cardiac symptoms and nonobstructive coronary atherosclerotic disease in women may lead to lack of recognition and appropriate management, resulting in undertesting and undertreatment. Leaders in women's health from the American College of Cardiology's Cardiovascular Disease in Women Committee present novel imaging cases that may provoke thought regarding the broad clinical spectrum of myocardial infarction and ischemia with nonobstructive coronary arteries in women. These unique imaging approaches are based on the concept of targeting sex-specific differences in acute and stable ischemic heart disease.

Comparative differences in the atherosclerotic disease burden between the epicardial coronary arteries: quantitative plaque analysis on coronary computed tomography angiography.

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 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 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; 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.