Invasive coronary plaque imaging such as intravascular ultrasound and optical coherence tomography has been widely used to observe culprit or non-culprit coronary atherosclerosis, as well as optimize stent sizing, apposition and deployment. Coronary computed tomographic angiography (CTA) is non-invasively available to assess coronary artery disease (CAD) and has become an appropriate strategy to evaluate patients with suspected CAD. Given recent technologies, semi-automated plaque software is available to identify coronary plaque stenosis, volume and characteristics and potentially allows to be used for the assessment of more details of plaque information, progression and future risk as a surrogate tool of the invasive imaging modalities. This review article aims to focus on various evidence in coronary plaque imaging by coronary CTA and describes how accurate coronary CTA can classify coronary atherosclerosis.

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

Regional left ventricular (LV) mechanics in mitral regurgitation (MR) patients, and local changes in function after transcatheter mitral valve implantation (TMVI) have yet to be evaluated. Herein, we introduce a method for creating high resolution maps of endocardial function from 4DCT images, leading to detailed characterization of changes in local LV function. These changes are particularly interesting when evaluating the effect of the Tendyne^™ TMVI device in the region of the epicardial pad.

Methods

Regional endocardial shortening from CT (RS_CT) was evaluated in Tendyne (Abbott Medical) TMVI patients with 4DCT exams pre- and post-implantation. Regional function was evaluated in 90 LV segments (5 longitudinal × 18 circumferential). LV volumes and ejection fraction (EF) were also computed. A reproducibility study was performed in a subset of patients to determine the precision of RS_CT measurements in this population.

Results

Baseline and local changes in RS_CT post TMVI were highly variable and extremely spatially heterogeneous. Both inter- and intra-observer variability were low and demonstrated the high precision of RS_CT for evaluating regional LV function.

Conclusion

RS_CT is a reproducible metric which can be evaluated in patients with highly abnormal regional LV function and geometry. After TMVI, significant spatially heterogeneous changes in RS_CT were observed in all subjects; therefore, it is unlikely that the functional state of TMVI patients can be fully described by changes in LV volume or EF. Measurement of RS_CT provides precise characterization of the spatially heterogeneous effects of MR and TMVI on LV function and remodeling.

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.

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.

Objectives

This study evaluated the association between atherosclerotic plaque characteristics (APCs) by coronary computed tomographic angiography (CTA), and lesion ischemia by fractional flow reserve (FFR).

Background

FFR is the gold standard for determining lesion ischemia. Although APCs by CTA-including aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation plaque (LAP), and spotty calcification (SC)-are associated with future coronary syndromes, their relationship to lesion ischemia is unclear.

Methods

252 patients (17 centers, 5 countries; mean age 63 years; 71% males) underwent coronary CTA, with FFR performed for 407 coronary lesions. Coronary CTA was interpreted for <50% and ≥50% stenosis, with the latter considered obstructive. APCs by coronary CTA were defined as: 1) PR, lesion diameter/reference diameter >1.10; 2) LAP, any voxel <30 Hounsfield units; and 3) SC, nodular calcified plaque <3 mm. Odds ratios (OR) and net reclassification improvement of APCs for lesion ischemia, defined by FFR ≤0.8, were analyzed.

Results

By FFR, ischemia was present in 151 lesions (37%). %APV was associated with a 50% increased risk of ischemia per 5% additional APV. PR, LAP, and SC were associated with ischemia, with a 3 to 5 times higher prevalence than in nonischemic lesions. In multivariable analyses, a stepwise increased risk of ischemia was observed for 1 (OR: 4.0, p < 0.001) and ≥2 (OR: 12.1, p < 0.001) APCs. These findings were APC dependent, with PR (OR: 5.3, p < 0.001) and LAP (OR: 2.1, p = 0.038) associated with ischemia, but not SC. When examined by stenosis severity, PR remained a predictor of ischemia for all lesions, whereas %APV and LAP were associated with ischemia for only ≥50%, but not for <50%, stenosis.

Conclusions

%APV and APCs by coronary CTA improve identification of coronary lesions that cause ischemia. PR is associated with all ischemia-causing lesions, whereas %APV and LAP are only associated with ischemia-causing lesions ≥50%. (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography; NCT01233518).

Bicuspid aortic valve disease (BAVD) is present in up to half of all patients referred for surgical aortic valve replacement (SAVR) yet was an exclusion criterion for all randomized controlled trials (RCTs) comparing transcatheter aortic valve replacement (TAVR) to SAVR. Nonetheless, approximately 10% of patients currently treated with TAVR have BAVD and available observational data for performing TAVR in these patients are limited by selection bias. Many in the cardiovascular community have advocated for RCTs in this population, but none have been performed. The Heart Valve Collaboratory (HVC) is a multidisciplinary community of stakeholders with the aim of creating significant advances in valvular heart disease by stimulating clinical research, engaging in educational activities, and advancing regulatory science. In December 2020, the HVC hosted a Global Multidisciplinary workshop involving over 100 international experts in the field. Following this 2-day symposium, working groups with varied expertise were convened to discuss BAVD, including the need for and design of RCTs. This review, conducted under the auspices of the HVC, summarizes available data and knowledge gaps regarding procedural therapy for BAVD, outlining specific challenges for trials in this population. We also propose several potential studies that could be performed and discuss respective strengths and weaknesses of each approach. Finally, we present a roadmap for future directions in clinical research in TAVR for BAVD with an emphasis both on RCTs and also prospective registries focused on disease phenotyping to develop parameters and risk scores that could ultimately be applied to patients to inform clinical decision-making.

The intent of CAD-RADS - Coronary Artery Disease Reporting and Data System is to create a standardized method to communicate findings of coronary CT angiography (coronary CTA) in order to facilitate decision-making regarding further patient management. The suggested CAD-RADS classification is applied on a per-patient basis and represents the highest-grade coronary artery lesion documented by coronary CTA. It ranges from CAD-RADS 0 (Zero) for the complete absence of stenosis and plaque to CAD-RADS 5 for the presence of at least one totally occluded coronary artery and should always be interpreted in conjunction with the impression found in the report. Specific recommendations are provided for further management of patients with stable or acute chest pain based on the CAD-RADS classification. The main goal of CAD-RADS is to standardize reporting of coronary CTA results and to facilitate communication of test results to referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will provide a framework of standardization that may benefit education, research, peer-review and quality assurance with the potential to ultimately result in improved quality of care.

Background

The natural history of coronary artery disease (CAD) in patients with low-to-intermediate risk is not well characterized. Although earlier invasive serial studies have documented the progression of atherosclerotic burden, most were focused on high-risk patients only. The PARADIGM registry is a large, prospective, multinational dynamic observational registry of patients undergoing serial coronary computed tomographic angiography (CCTA). The primary aim of PARADIGM is to characterize the natural history of CAD in relation to clinical and laboratory data.

Design

The PARADIGM registry (ClinicalTrials.govNCT02803411) comprises ≥2,000 consecutive patients across 9 cluster sites in 7 countries. PARADIGM sites were chosen on the basis of adequate CCTA volume, site CCTA proficiency, local demographic characteristics, and medical facilities to ensure a broad-based sample of patients. Patients referred for clinically indicated CCTA will be followed up and enrolled if they had a second CCTA scan. Patients will also be followed up beyond serial CCTA performance to identify adverse CAD events that include cardiac and noncardiac death, myocardial infarction, unstable angina, target vessel revascularization, and CAD-related hospitalization.

Summary

The results derived from the PARADIGM registry are anticipated to add incremental insight into the changes in CCTA findings in accordance with the progression or regression of CAD that confer prognostic value beyond demographic and clinical characteristics.