Comparative effectiveness of coronary artery stenosis and atherosclerotic plaque burden assessment for predicting 30-day revascularization and 2-year major adverse cardiac events.

PURPOSE: To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD). METHODS: We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction. RESULTS: Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67-0.78) but improved after excluding patients with known CAD (AUC range 0.73-0.86, p < 0.05 for all). Similarly, prediction of MACE improved after excluding patients with known CAD (AUC range 0.58-0.73 vs. 0.63-0.77). CT metrics of atherosclerosis burden performed overall similarly but stenosis assessment was superior for predicting 30-day revascularization. CONCLUSIONS: Angiographic and coronary atherosclerotic plaque metrics perform only modestly well for predicting 30-day revascularization and 2-year MACE in high risk patients but improve after excluding patients with known CAD. Atherosclerotic plaque metrics did not yield incremental value over stenosis assessment for predicting events that predominantly consisted of revascularization procedures. CLINICAL TRIAL REGISTRATION: NCT00934037.

Comparative Effectiveness of CT-Derived Atherosclerotic Plaque Metrics for Predicting Myocardial Ischemia.

OBJECTIVES: This study sought to investigate the performance of various cardiac computed tomography (CT)-derived atherosclerotic plaque metrics for predicting provocable myocardial ischemia. BACKGROUND: The association of coronary arterial diameter stenosis with myocardial ischemia is only modest, but cardiac CT provides several other, readily available atherosclerosis metrics, which may have incremental value. METHODS: The study analyzed 873 nonstented coronary arteries and their myocardial perfusion territories in 356 patients (mean 62 years of age) enrolled in the CORE320 (Coronary Artery Evaluation using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) study. Myocardial perfusion defects in static CT perfusion imaging were graded at rest and after adenosine in 13 myocardial segments using a 4-point scale. The summed difference score was calculated by subtracting the summed rest score from the summed stress score. Reversible ischemia was defined as summed difference score ≥1. In a sensitivity analysis, results were also provided using single-photon emission computed tomography (SPECT) as the reference standard. Vessel based predictor variables included maximum percent diameter stenosis, lesion length, coronary calcium score, maximum cross-sectional calcium arc, percent atheroma volume (PAV), low-attenuation atheroma volume, positive (external) vascular remodeling, and subjective impression of "vulnerable plaque." The study used logistic regression models to assess the association of plaque metrics with myocardial ischemia. RESULTS: In univariate analysis, all plaque metrics were associated with reversible ischemia. In the adjusted logistic model, only maximum percent diameter stenosis (1.26; 95% confidence interval: 1.15 to 1.38) remained an independent predictor. With SPECT as outcome variable, PAV and "vulnerable" plaque remained predictive after adjustment. In vessels with intermediate stenosis (40% to 70%), no single metric had clinically meaningful incremental value. CONCLUSIONS: Various plaque metrics obtained by cardiac CT predict provocable myocardial ischemia by CT perfusion imaging through their association with maximum percent stenosis, while none had significant incremental value. With SPECT as reference standard, PAV and "vulnerable plaque" remained predictors of ischemia after adjustment but the predictive value added to stenosis assessment alone was small.

Total coronary atherosclerotic plaque burden assessment by CT angiography for detecting obstructive coronary artery disease associated with myocardial perfusion abnormalities.

BACKGROUND: Total atherosclerotic plaque burden assessment by CT angiography (CTA) is a promising tool for diagnosis and prognosis of coronary artery disease (CAD) but its validation is restricted to small clinical studies. We tested the feasibility of semi-automatically derived coronary atheroma burden assessment for identifying patients with hemodynamically significant CAD in a large cohort of patients with heterogenous characteristics. METHODS: This study focused on the CTA component of the CORE320 study population. A semi-automated contour detection algorithm quantified total coronary atheroma volume defined as the difference between vessel and lumen volume. Percent atheroma volume (PAV = [total atheroma volume/total vessel volume] × 100) was the primary metric for assessment (n = 374). The area under the receiver operating characteristic curve (AUC) determined the diagnostic accuracy for identifying patients with hemodynamically significant CAD defined as ≥50% stenosis by quantitative coronary angiography and associated myocardial perfusion abnormality by SPECT. RESULTS: Of 374 patients, 139 (37%) had hemodynamically significant CAD. The AUC for PAV was 0.78 (95% confidence interval [CI] 0.73-0.83) compared with 0.84 [0.79-0.88] by standard expert CTA interpretation (p = 0.02). Accuracy for both CTA (0.91 [0.87, 0.96]) and PAV (0.86 [0.81-0.91]) increased after excluding patients with history of CAD (p < 0.01 for both). Bland-Altman analysis revealed good agreement between two observers (bias of 280.2 mm(3) [161.8, 398.7]). CONCLUSIONS: A semi-automatically derived index of total coronary atheroma volume yields good accuracy for identifying patients with hemodynamically significant CAD, though marginally inferior to CTA expert reading. These results convey promise for rapid, reliable evaluation of clinically relevant CAD.

Incremental diagnostic accuracy of computed tomography myocardial perfusion imaging over coronary angiography stratified by pre-test probability of coronary artery disease and severity of coronary artery calcification: The CORE320 study.

BACKGROUND: Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis. OBJECTIVES: To assess the diagnostic performance of CTA and CTP alone versus combined CTA-CTP stratified by Morise's pre-test probability and coronary artery calcium (CAC, Agatston) score. METHODS: 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1-399 and ≥400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA≥50% stenosis+corresponding SPECT summed stress score ≥1. RESULTS: In both pre-test risk groups with an Agatston score of 1-399, AUCs of CTA-CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1-399, AUC for CTA-CTP (89) was higher than that for CTP (76, p=0.003) alone. In the same group with CAC score ≥400, AUCs were higher for CTA-CTP (97) than that for CTA (88, p=0.030) and CTP (83, p=0.033). In high risk/known CAD patients with CAC 1-399, diagnostic performance for CTA-CTP (77) was superior to CTP (71, p=0.037) alone. In the high risk/known CAD group with CAC score ≥400, AUCs for combined imaging were higher (86) than that for CTA (75, p<0.001) as well as CTP (78, p=0.020). CONCLUSIONS: The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score≥400), combined CTA-CTP has better diagnostic accuracy than CTA and CTP alone.

Combined coronary angiography and myocardial perfusion by computed tomography in the identification of flow-limiting stenosis - The CORE320 study: An integrated analysis of CT coronary angiography and myocardial perfusion.

BACKGROUND: The combination of coronary CT angiography (CTA) and myocardial CT perfusion (CTP) is gaining increasing acceptance, but a standardized approach to be implemented in the clinical setting is necessary. OBJECTIVES: To investigate the accuracy of a combined coronary CTA and myocardial CTP comprehensive protocol compared to coronary CTA alone, using a combination of invasive coronary angiography and single photon emission CT as reference. METHODS: Three hundred eighty-one patients included in the CORE320 trial were analyzed in this study. Flow-limiting stenosis was defined as the presence of ≥50% stenosis by invasive coronary angiography with a related perfusion defect by single photon emission CT. The combined CTA + CTP definition of disease was the presence of a ≥50% stenosis with a related perfusion defect. All data sets were analyzed by 2 experienced readers, aligning anatomic findings by CTA with perfusion defects by CTP. RESULTS: Mean patient age was 62 ± 6 years (66% male), 27% with prior history of myocardial infarction. In a per-patient analysis, sensitivity for CTA alone was 93%, specificity was 54%, positive predictive value was 55%, negative predictive value was 93%, and overall accuracy was 69%. After combining CTA and CTP, sensitivity was 78%, specificity was 73%, negative predictive value was 64%, positive predictive value was 0.85%, and overall accuracy was 75%. In a per-vessel analysis, overall accuracy of CTA alone was 73% compared to 79% for the combination of CTA and CTP (P < .0001 for difference). CONCLUSIONS: Combining coronary CTA and myocardial CTP findings through a comprehensive protocol is feasible. Although sensitivity is lower, specificity and overall accuracy are higher than assessment by coronary CTA when compared against a reference standard of stenosis with an associated perfusion defect.

Relationship of left ventricular mass to coronary atherosclerosis and myocardial ischaemia: the CORE320 multicenter study.

AIMS: The aim of this study was to investigate the association of left ventricular mass (LVM) with coronary atherosclerosis and myocardial infarction (MI). METHODS AND RESULTS: Patients (n = 338) underwent 320 × 0.5 mm detector row coronary computed tomography (CT) angiography, invasive coronary angiography (ICA), and single-photon emission CT (SPECT) myocardial perfusion imaging. Quantitative coronary atheroma volume was obtained from the CT images for the entire coronary tree (19-segment model) with an arterial contour detection algorithm. Normalized total atheroma volume (NormTAV) was analysed to reflect quantitative total atheroma volume. LVM was measured on myocardial CT images and indexed to height to the power of 2.7 (LVMi). Patients with obstructive coronary artery disease (CAD) were defined as those with ≥50% diameter stenosis by quantitative ICA. Abnormal perfusion defect was defined as ≥1 abnormal myocardial segment by SPECT. The association of LVMi with coronary atherosclerosis and myocardial perfusion defect on SPECT at the patient level was determined with uni- and multivariable linear and logistic regression analyses. Obstructive CAD was present in 60.0% of enrolled patients. LVMi was independently associated with abnormal summed rest score [SRS; odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03-1.09] and summed stress score (OR, 1.04; 95% CI, 1.01-1.07). An increase in LVMi was also independently associated with that in NormTAV (coefficient, 10.44; 95% CI, 1.50-19.39) and SRS ≥1 (OR, 1.05; 95% CI, 1.01-1.10), even after adjusting for cardiovascular risk factors in patients without previous MI. CONCLUSIONS: LVM was independently associated with the presence of coronary artery atherosclerosis and MI.

Dipyridamole stress and rest transmural myocardial perfusion ratio evaluation by 64 detector-row computed tomography.

BACKGROUND: Myocardial stress CT perfusion (CTP) can detect myocardial ischemia. OBJECTIVE: We evaluated the transmural perfusion ratio (TPR) of dipyridamole stress CTP to detect significant coronary stenosis (>70%) defined by quantitative invasive coronary angiography (ICA). METHODS: Twenty-six patients (61.6 ± 8.0 years old; 14 males), without prior myocardial infarction, with positive single-photon emission computed tomography (SPECT; <2 months) and clinical indication for ICA, underwent a customized multidetector-row CT (MDCT) protocol with rest/stress myocardial perfusion evaluation and coronary CT angiography. TPR was defined as mean subendocardial divided by mean subepicardial attenuation and quantified on rest and stress MDCT images. Abnormal TPR was defined as 2 SDs below the mean rest TPR. RESULTS: All 26 patients completed the CT protocol with no adverse events. Rest TPR was measured in all patients with a mean of 1.06 ± 0.11, and abnormal TPR was considered <0.85. For 6 patients with normal coronary arteries by ICA, the mean TPR of territories with a previous positive perfusion defect in SPECT was 1.02 ± 0.18 (95% CI, 0.86-1.18; n = 6), and mean TPR of territories without perfusion defect in SPECT was 1.03 ± 0.09 (95% CI, -0.95 to 1.11; n = 12; P = 0.83). Mean stress TPR in territories with positive SPECT and significant coronary artery disease by quantitative ICA was 0.71 ± 0.13 (95% CI, -0.64 to 0.77) and in the remote myocardial was 1.01 ± 0.09 (95% CI, -0.96 to 1.06; P < 0001). In these territories, a significant Pearson's correlation was observed (r = -0.74, P < 0.001). CONCLUSION: TPR has a good correlation with SPECT and ICA to detect significant coronary stenosis.

Additional value of dipyridamole stress myocardial perfusion by 64-row computed tomography in patients with coronary stents.

BACKGROUND: Coronary computed tomography angiography (CTA) is a well-established diagnostic tool for coronary artery disease (CAD). However, coronary segments with prior stent implantation visualized with CTA may have limited evaluation and reduced accuracy. OBJECTIVE: We assessed the incremental value of stress myocardial CT perfusion (CTP) over anatomical assessment by coronary CTA alone in patients with stents, using quantitative invasive coronary angiography (≥50%) as reference. METHODS: Forty-six patients (56.9 ± 7.2 years; 28 men) referred to invasive coronary angiography were evaluated, combining coronary CTA and dipyridamole stress myocardial CTP with 64 detector-row CT. Coronary CTA was evaluated for ≥50% coronary stenosis, and myocardial CTP was used to potentially reclassify coronary territories, including those with stents and poorly evaluated stents because of artifacts. RESULTS: We evaluated 138 coronary territories, 62 with ≥1 stent. From these, 21 (34%) territories had adequately evaluated stents, 28 (45%) had limitedly evaluated stents still allowing diagnosis, and 13 (21%) had inadequately evaluated stents (no luminal assessment possible). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for coronary CTA in stent territories were, respectively, 85%, 77%, 87%, 74%, and 81%, and the combined use of coronary CTA and myocardial CTP were 88%, 95%, 97%, 81%, and 91% (P = 0.0292). In territories with impaired stent evaluation (limited or inadequate), the diagnostic performance of coronary CTA alone was 83%, 72%, 79%, 76% and 77%, and combined with myocardial CTP were 87%, 94%, 95%, 85%, and 91% (P = 0.036). CONCLUSION: The combined evaluation of coronary CTA and stress myocardial CTP improved the diagnostic accuracy for the detection of significant obstructive CAD in patients with stents.

Dipyridamole stress and rest myocardial perfusion by 64-detector row computed tomography in patients with suspected coronary artery disease.

Recently, stress myocardial computed tomographic perfusion (CTP) was shown to detect myocardial ischemia. Our main objective was to evaluate the feasibility of dipyridamole stress CTP and compare it to single-photon emission computed tomography (SPECT) to detect significant coronary stenosis using invasive conventional coronary angiography (CCA; stenosis >70%) as the reference method. Thirty-six patients (62 +/- 8 years old, 20 men) with previous positive results with SPECT (<2 months) as the primary inclusion criterion and suspected coronary artery disease underwent a customized multidetector-row CT protocol with myocardial perfusion evaluation at rest and during stress and coronary CT angiography (CTA). Multidetector-row computed tomography was performed in a 64-slice scanner with dipyridamole stress perfusion acquisition before a second perfusion/CT angiographic acquisition at rest. Independent blinded observers performed analysis of images from CTP, CTA, and CCA. All 36 patients completed the CT protocol with no adverse events (mean radiation dose 14.7 +/- 3.0 mSv) and with interpretable scans. CTP results were positive in 27 of 36 patients (75%). From the 9 (25%) disagreements, 6 patients had normal coronary arteries and 2 had no significant stenosis (8 false-positive results with SPECT, 22%). The remaining patient had an occluded artery with collateral flow confirmed by conventional coronary angiogram. Good agreement was demonstrated between CTP and SPECT on a per-patient analysis (kappa 0.53). In 26 patients using CCA as reference, sensitivity, specificity, and positive and negative predictive values were 88.0%, 79.3%, 66.7%, and 93.3% for CTP and 68.8, 76.1%, 66.7%, and 77.8%, for SPECT, respectively (p = NS). In conclusion, dipyridamole CT myocardial perfusion at rest and during stress is feasible and results are similar to single-photon emission CT scintigraphy. The anatomical-perfusion information provided by this combined CT protocol may allow identification of false-positive results by SPECT.