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... Show moreBackground: 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 & PLUSMN; 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 & GE; median showed worse outcomes (log-rank p < 0.001 for all). In addition, low-attenuation plaque & GE; median was associated with worse outcomes independent of total PV (adjusted HR: 2.754, 95% CI: 1.022-7.0419, p = 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. Show less
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... Show moreBackground: 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 [O-15]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. Show less
Schultz, J.; Hoogen, I.J. van den; Kuneman, J.H.; Graaf, M.A. de; Kamperidis, V.; Broersen, A.; ... ; Knuuti, J. 2022
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... Show moreEndothelial 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 (rho = 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. 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
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
