Objectives

The goal of this study was to compare the diagnostic performance of coronary computed tomography angiography (CTA) versus quantitative coronary angiography (QCA) for the detection of lesion-specific ischemia using fractional flow reserve (FFR) as the gold standard.

Background

Coronary CTA has emerged as a noninvasive method for accurate detection and exclusion of high-grade coronary stenoses. FFR is the gold standard for determining lesion-specific ischemia and has been shown to improve clinical outcomes when guiding revascularization.

Methods

A total of 252 patients from 5 countries were prospectively enrolled (mean age 63 years; 71% male). Patients underwent coronary CTA and invasive coronary angiography (ICA) with FFR in 407 lesions. Coronary CTA, QCA, and FFR were interpreted by independent core laboratories. Stenosis severity according to coronary CTA and QCA were graded as 0% to 29%, 30% to 49%, 50% to 69%, and 70% to 100%; stenosis ≥50% was considered anatomically obstructive. Lesion-specific ischemia was defined according to FFR ≤0.8, whereas QCA and coronary CTA stenosis ≥50% were considered obstructive. Diagnostic accuracy and areas under the receiver-operating characteristics curve (AUC) for lesion-specific ischemia was assessed.

Results

According to FFR, ischemia was present in 151 (37%) of 407 lesions. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 79%, 63%, 55%, and 83% for coronary CTA; and 71%, 74%, 70%, 59%, and 82% for QCA. AUC for identification of ischemia-causing lesions was similar: 0.75 for coronary CTA and 0.77 for QCA (p = 0.6). No differences between CTA and QCA existed for discrimination of ischemia within the left anterior descending artery (AUC 0.71 vs. 0.73; p = 0.6), left circumflex artery (AUC 0.78 vs. 0.85; p = 0.4), and right coronary artery (AUC 0.80 vs. 0.83; p = 0.6).

Conclusions

CTA and ICA exhibited similar diagnostic performance for the detection and exclusion of lesion-specific ischemia. Using a true reference standard to determine appropriate revascularization targets, 3-dimensional coronary CTA performed as well as 2-dimensional ICA.

Background

Studies have shown that quantitative evaluation of coronary artery plaque on Coronary Computed Tomography Angiography (CCTA) can identify patients at risk of cardiac events. Recent demonstration of artificial intelligence (AI) assisted CCTA shows that it allows for evaluation of CAD and plaque characteristics. Based on publications to date, we are the first group to perform AI augmented CCTA serial analysis of changes in coronary plaque characteristics over 13 years. We evaluated whether AI assisted CCTA can accurately assess changes in coronary plaque progression, which has potential clinical prognostic value in CAD management.

Case presentation

51-year-old male with hypertension, hyperlipidemia and family history of myocardial infarction, underwent CCTA exams for anginal symptom evaluation and CAD assessment. 5 CCTAs were performed between 2008 and 2021. Quantitative atherosclerosis plaque characterization (APC) using an AI platform (Cleerly), was performed to assess CAD burden. Total plaque volume (TPV) change-over-time demonstrated decreasing low-density non-calcified plaque (LD-NCP) with increasing overall NCP and calcified-plaque (CP). Examination of individual segments revealed a proximal-LAD lesion with decreasing NCP over-time and increasing CP. In contrast, although the D2/D1/ramus lesions showed increasing stenosis, CP, and total plaque, there were no significant differences in NCP over-time, with stable NCP and increased CP. Remarkably, we also consistently visualized small plaques, which typically readers may interpret as false positives due to artifacts. But in this case, they reappeared each study in the same locations, generally progressing in size and demonstrating expected plaque transformation over-time.

Conclusions

We performed the first AI augmented CCTA based serial analysis of changes in coronary plaque characteristics over 13 years. We were able to consistently assess progression of plaque volumes, stenosis, and APCs with this novel methodology. We found a significant increase in TPV composed of decreasing LD-NCP, and increasing NCP and CP, with variations in the evolution of APCs between vessels. Although the significance of evolving APCs needs to be investigated, this case demonstrates AI-based CCTA analysis can serve as valuable clinical tool to accurately define unique CAD characteristics over time. Prospective trails are needed to assess whether quantification of APCs provides prognostic capabilities to improve clinical care.

Although coronary computed tomographic angiography (CCTA) has been a robust diagnostic tool to identify anatomical significance of coronary artery disease (CAD), the utility of CCTA to assess hemodynamic significance of CAD remains unclear. We investigated the diagnostic performance of transluminal attenuation gradient (TAG) and fractional flow reserve derived from CCTA (FFRCT) to predict lesion-specific ischemia by invasive FFR. We identified 103 patients with suspected or known CAD enrolled from the DISCOVER-FLOW and DeFACTO studies who underwent invasive coronary angiography with FFR and high quality ≥64-slice CCTA. Diagnostic performance for predicting abnormal invasive FFR (≤0.80) was assessed for TAG [≤-1.1 HU/mm by the area under the curve (AUC) by receiver-operating characteristic curve analysis (ROC)], FFR(CT) (≤0.80), and CCTA stenosis (≥50%). On a per-vessel analysis (n = 146), 52 vessels (35.6%) had ischemia by invasive FFR. The sensitivity, specificity, positive predictive value and negative predictive value were 53.8, 45.7, 35.4, 64.2% for TAG, 82.7, 74.5, 64.2, 88.6% for FFR(CT), 84.6, 39.4, 43.6, 82.2% for CCTA stenosis, respectively. The AUC by ROC curve analysis for FFR(CT) (0.79) demonstrated greater discrimination of hemodynamic ischemia compared to TAG (0.50, p < 0.0001 vs. FFR(CT)), CCTA stenosis (0.62, p = 0.0004 vs. FFR(CT)) and the combination of the two (0.63, p = 0.004 vs. FFR(CT)). These results remained consistent regardless of the number of CCTA slices. FFR(CT) allows identification of lesion-specific ischemia using invasive FFR as a reference standard with greater diagnostic accuracy than TAG, CCTA stenosis, or the combination of the two.

Background

Myocardial CT perfusion (CTP) is a promising tool for the detection of myocardial ischemia. We hypothesize that regadenoson CTP is noninferior to regadenoson single photon emission CT (SPECT) for detecting or excluding myocardial ischemia.

Methods

Patients (men ≥ 45 years; women ≥ 50 years) with known or suspected coronary artery disease (n = 124) were randomized to 1 of 2 diagnostic sequences: rest and regadenoson SPECT on day 1, then regadenoson CTP and rest CTP (and coronary CT angiography [CTA]) (CTA; same acquisition) on day 2 or regadenoson CTP and rest CTP (and CTA) on Day 1, then rest and regadenoson SPECT on day 2. Scanning platforms included 64-, 128-, 256-, and 320-slice systems. The primary analysis examined the agreement rate between CTP and SPECT for detecting or excluding reversible ischemia in ≥ 2 myocardial segments as assessed by independent, blinded readers.

Results

Complete and interpretable CTP and SPECT scans were obtained for 110 patients. Regadenoson CTP was noninferior to SPECT for detecting or excluding reversible ischemia with an agreement rate of 0.87 (95% confidence interval [CI], 0.77-0.97) and sensitivity and specificity of 0.90 (95% CI, 0.71-1.00) and 0.84 (95% CI, 0.77-0.91), respectively. The agreement rate for detecting or excluding ≥ 1 fixed defects by regadenoson CTP and SPECT was 0.86 (95% CI, 0.74-0.98). With SPECT as the reference standard, the diagnostic accuracies for detecting or excluding ischemia by regadenoson CTP and CTA alone were 0.85 (95% CI, 0.78-0.91) and 0.69 (95% CI, 0.60-0.77), respectively.

Conclusions

This study establishes the noninferiority of regadenoson CTP to SPECT for detecting or excluding myocardial ischemia.

Background

Fractional flow reserve (FFR) is the gold standard for determining lesion-specific ischemia. Computed FFRCT derived from coronary CT angiography (coronary CTA) correlates well with invasive FFR and accurately differentiates between ischemia-producing and nonischemic lesions. The diagnostic performance of FFRCT when applied in a clinically relevant way to all vessels ≥ 2 mm in diameter stratified by sex and age has not been previously examined.

Methods

Two hundred fifty-two patients and 407 vessels underwent coronary CTA, FFRCT, invasive coronary angiography, and invasive FFR. FFRCT and FFR ≤ 0.80 were considered ischemic, whereas CT stenosis ≥ 50% was considered obstructive. The diagnostic performance of FFRCT was assessed following a prespecified clinical use rule which included all vessels ≥ 2 mm in diameter, not just those assessed by invasive FFR measurements. Stenoses <30% were assigned an FFR of 0.90, and stenoses >90% were assigned an FFR of 0.50. Diagnostic performance of FFRCT was stratified by vessel diameter, sex, and age.

Results

By FFR, ischemia was identified in 129 of 252 patients (51%) and in 151 of 407 vessels (31%). Mean age (± standard deviation) was 62.9 ± 9 years, and women were older (65.5 vs 61.9 years; P = .003). Per-patient diagnostic accuracy (83% vs 72%; P < .005) and specificity (54% vs 82%, P < .001) improved significantly after application of the clinical use tool. These were significantly improved over standard coronary CTA values before application of the clinical use rule. Discriminatory power of FFRCT also increased compared with baseline (area under the receiver operating characteristics curve [AUC]: 0.93 vs 0.81, P < .001). Diagnostic performance improved in both sexes with no significant differences between the sexes (AUC: 0.93 vs 0.90, P = .43). There were no differences in the discrimination of FFRCT after application of the clinical use rule when stratified by age ≥ 65 or <65 years (AUC: 0.95 vs 0.90, P = .10).

Conclusions

The diagnostic accuracy and discriminatory power of FFRCT improve significantly after the application of a clinical use rule which includes all clinically relevant vessels >2 mm in diameter. FFRCT has similar diagnostic accuracy and discriminatory power for ischemia detection in men and women irrespective of age using a cut point of 65 years.

Serial measurements of coronary plaque volume have been used to evaluate drug efficacy in atherosclerotic progression. However, the usefulness of computed tomography for this purpose is unknown. We investigated whether the change in total plaque volume on coronary computed tomographic angiography is associated with the change in segment plaque volume on intravascular ultrasound. We prospectively enrolled 11 consecutive patients (mean age, 56.3 ± 5 yr; 6 men) who were to undergo serial invasive coronary angiographic examinations with use of grayscale intravascular ultrasound and coronary computed tomography, performed <180 days apart at baseline and from 1 to 2 years later. Subjects underwent 186 serial measurements of total plaque volume on coronary computed tomography and 22 of segmental plaque volume on intravascular ultrasound. We used semiautomated software to examine percentage relationships and changes between total plaque and segmental plaque volumes. No significant correlations were found between percentages of total coronary and segment coronary plaque volume, nor between normalized coronary plaque volume. However, in the per-patient analysis, there were strong correlations between the imaging methods for changes in total coronary and segment coronary plaque volume (r=0.62; P=0.04), as well as normalized plaque volume (r=0.82; P=0.002). Per-patient change in plaque volume on coronary computed tomography is significantly associated with that on intravascular ultrasound. Computed tomographic angiography may be safer and more widely available than intravascular ultrasound for evaluating atherosclerotic progression in coronary arteries. Larger studies are warranted.

Aims

We evaluated the association between atherosclerotic plaque characteristics (APCs) by CT -including positive remodelling (PR), low attenuation plaque (LAP) and spotty calcification (SC)- and lesion ischaemia by fractional flow reserve (FFR).

Methods and results

Two hundred and fifty-two patients (17 centres, five countries) underwent CT, FFR derived from CT (FFRCT) with invasive FFR performed for 407 coronary lesions. FFR ≤0.8 was indicative of lesion-specific ischaemia. CT diameter ≥50% stenosis was considered obstructive. APCs by CT were defined as: (1) PR, lesion diameter/reference diameter >1.10; (2) LAP, any voxel <30 HU; and (3) SC, nodular calcified plaque <3 mm. Odds ratios (OR) and area under the ROC curve (AUC) of APCs for lesion-specific ischaemia were analysed. PR, LAP and SC were associated with ischaemia, with a three to fivefold higher prevalence than in non-ischaemic lesions. Among individual APC, PR (OR 4.7, p<0.001), but not SC or LAP, was strongly associated with lesion-specific ischaemia and provided incremental prediction for lesion-specific ischaemia over CT stenosis plus FFRCT (AUC 0.87 vs. 0.83, p=0.002).

Conclusions

APCs' features -especially PR- by CT improve identification and reclassification of coronary lesions which cause ischaemia over CT stenosis and FFRCT.