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.

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.

Association of High-Density Calcified 1K Plaque With Risk of Acute Coronary Syndrome.

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

Relation between quantitative coronary CTA and myocardial ischemia by adenosine stress myocardial CT perfusion.

BACKGROUND: Coronary-computed tomography angiography (CTA) has limited accuracy to predict myocardial ischemia. Besides luminal area stenosis, other coronary plaque morphology and composition parameters may help to assess ischemia. With the integration of coronary CTA and adenosine stress CT myocardial perfusion (CTP), reliable information regarding coronary anatomy and function can be derived in one procedure. This analysis aimed to investigate the association between coronary stenosis severity, plaque composition and morphology and the presence of ischemia measured with adenosine stress myocardial CTP. METHODS AND RESULTS: 84 patients (age, 62 ± 10 years; 48% men) who underwent sequential coronary CTA and adenosine stress myocardial CT perfusion were analyzed. Automated quantification was performed in all coronary lesions (quantitative CTA). Downstream myocardial ischemia was assessed by visual analysis of the rest and stress CTP images and defined as a summed difference score of ≥1. One or more coronary plaques were present in 146 coronary arteries of which 31 (21%) were ischemia-related. Of the lesions with a stenosis percentage <50%, 50%-70%, and >70%, respectively, 9% (6/67), 18% (9/51), and 57% (16/28) demonstrated downstream ischemia. Furthermore, mean plaque burden, plaque volume, lesion length, maximal plaque thickness, and dense calcium volume were significantly higher in ischemia-related lesions, but only stenosis severity (%) (OR 1.06; 95% CI 1.02-1.10; P = .006) and lesion length (mm) (OR 1.26; 95% CI 1.02-1.55; P = .029) were independent correlates. CONCLUSIONS: Increasing stenosis percentage by quantitative CTA is positively correlated to myocardial ischemia measured with adenosine stress myocardial CTP. However, stenosis percentage remains a moderate determinant. Lumen area stenosis and lesion length were independently associated with ischemia, adjusted for coronary plaque volume, mean plaque burden, maximal lesion thickness, and dense calcium volume.

The influence of clinical and acquisition parameters on the interpretability of adenosine stress myocardial computed tomography perfusion.

AIMS: The interpretation of adenosine stress myocardial computed tomography perfusion (CTP) is often hampered by image artefacts caused by cardiac motion, beam hardening, and cone beam. The aim of the present analysis was to assess the influence of the heart-rate response during adenosine infusion, patient characteristics, and medication use on the interpretability of stress myocardial CTP examinations. METHODS AND RESULTS: Interpretability of stress myocardial CTP examinations was evaluated in 120 patients who underwent sequentially coronary CTA and adenosine stress myocardial CTP (320-row CT scanner, temporal resolution 175 ms) and scored as follows: excellent = absence of any artefact (n = 27, 22%); good = presence of artefacts that do not interfere with the study interpretability (n = 56, 47%); fair = artefacts that do interfere with interpretability (n = 35, 29%); poor = uninterpretable study due to artefacts (n = 2, 2%). 'Fair' and 'poor' were merged into 'reduced' for comparisons. Increasing heart rate during stress myocardial CTP acquisition was related to worse interpretability (excellent: 61.7 ± 13.4 bpm vs. good: 69.8 ± 13.5 bpm vs. reduced: 78.1 ± 17.0 bpm, P < 0.001). Thirteen (11%) of all examinations were considered non-diagnostic. In patients with a heart rate exceeding 85 bpm, 76% of the studies were 'reduced' interpretable. In multivariate analysis, no use of beta blocker (baseline or additional use prior to coronary CTA) (OR: 0.2, P = 0.012), increasing heart rate during coronary CTA (OR: 1.09, P = 0.032), younger age (OR: 0.92, P = 0.021), and the use of calcium antagonist (OR: 6.48, P = 0.017) were independently associated with a heart rate ≥85 bpm during stress myocardial CTP. CONCLUSION: Higher heart rate during the acquisition of stress myocardial CTP was related to worse interpretability. Furthermore, increasing heart rate during and no beta blocker use prior to the previously performed coronary CTA, younger age, and the use of calcium antagonist were independently associated with a heart rate ≥85 bpm during stress myocardial CTP acquisition.