Coronary Computed Tomography Angiography Measures Research Articles

Association of coronary inflammation with plaque vulnerability and fractional flow reserve in coronary artery disease

BackgroundThe fat attenuation index (FAI) measured using coronary computed tomography angiography (CCTA) enables the direct evaluation of pericoronary adipose tissue composition and vascular inflammation. We aimed to investigate the association of fractional flow reserve (FFR) and plaque vulnerability with coronary inflammation. MethodsPatients with suspected coronary artery disease (CAD) who underwent CCTA and invasive FFR measurements within 90-day were included. A cloud-based medical device, CaRi-Heart, serves as a surrogate tool for evaluating coronary inflammation based on FAI by analyzing CCTA images. The correlations between CCTA-defined plaque characteristics, invasive coronary angiographic and physiologic assessments, and CaRi-Heart risk were analyzed. The primary endpoint was the patient-oriented composite outcome (POCO) consisting of all-cause death, any myocardial infarction, and any revascularization. ResultsA total of 564 patients (median age 67.0 years; 75.4 ​% men) were included. There were no significant differences in quantitative and qualitative plaque characteristics or FFR between the high- and low-CaRi-Heart risk groups (i.e., ≥5 ​% and <5 ​%). During the median follow-up of 3.2 years [1.13–4.73 years], CaRi-Heart risk ≥5 ​% was associated with a significantly higher rate of POCO compared to CaRi-Heart risk <5 ​% (0.9 ​% vs. 10.1 ​%, P ​= ​0.037). The CaRi-Heart risk was an independent predictor of POCO as a continuous (adjusted HR 1.016, 95 ​% CI 1.005–0.027, P ​= ​0.004) and categorical variable (CaRi-Heart risk ≥5 ​%, adjusted HR 2.949, 95 ​% CI 1.182–7.360, P ​= ​0.021), regardless of high-risk plaque characteristics and FFR. ConclusionCoronary inflammation risk assessed using CaRi-Heart risk provides independent prognostic information regardless of plaque vulnerability and physiologic stenosis in patients with CAD.

Characteristic findings of microvascular dysfunction on coronary computed tomography angiography in patients with intermediate coronary stenosis.

We aimed to assess the prevalence of coexistence of coronary microvascular dysfunction (CMD) in patients with intermediate epicardial stenosis and to explore coronary computed tomography angiography (CCTA)-derived lesion-, vessel-, and cardiac fat-related characteristic findings associated with CMD. A retrospective cross-sectional single-center study included a total of 177 patients with intermediate stenosis in the left anterior descending artery (LAD) who underwent CCTA and invasive physiological measurements. The 320-slice CCTA analysis included qualitative and quantitative assessments ofplaque, vessel, epicardial fat volume (ECFV) and epicardial fat attenuation (ECFA), and pericoronary fat attenuation (FAI). CMD was defined by the index of microcirculatory resistance (IMR) ≥ 25. In the entire cohort, median fractional flow reserve (FFR) and median IMR values were 0.77 (0.69-0.84) and 19.0 (13.7-27.7), respectively. The prevalence of CMD was 32.8 % (58/177) in the total cohort. The coexistence of CMD and functionally significant stenosis was 34.3 % (37/108), whereas CMD in nonsignificant intermediate stenosis was 30.4 % (21/69). CMD was significantly associated with greater lumen volume (p = 0.031), greater fibrofatty and necrotic component (FFNC) volume (p = 0.030), and greater ECFV (p = 0.030), but not with FAI (p = 0.832) and ECFA (p = 0.445). On multivariable logistic regression analysis, vessel volume, vessel lumen volume, lesion remodeling index, ECFV, and lesion FFNC volume were independent predictors of CMD. The prevalence of CMD was about one-third in patients with intermediate stenosis in LAD regardless of the presence or absence of functional stenosis significance. The integrated CCTA assessment may help in the identification of CMD. • The coexistence of coronary microvascular dysfunction (CMD) and functionally significant stenosis was 34.3 %, whereas CMD in nonsignificant intermediate stenosis was 30.4 %. • Coronary computed tomography angiography (CCTA)-derived CMD characteristics were vessel volume, vessel lumen volume, remodeling index, epicardial fat volume, and fibrofatty necrotic core volume. • Integrated CCTA assessment may help identify the coexistence of CMD and epicardial stenosis.

Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study.

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.Clinical Trial Registration: ClinicalTrials.gov NCT0280341.

Hemodynamic Change of Coronary Atherosclerotic Plaque After Statin Treatment: A Serial Follow-Up Study by Computed Tomography-Derived Fractional Flow Reserve.

BackgroundWhether statin treatment can improve hemodynamic status of coronary atherosclerotic plaque remains unknown. It is of clinical interest to explore the hemodynamic change of coronary lesions after statin treatment.Methods and ResultsConsecutive patients with intermediate pre‐test probability of coronary artery disease were prospectively enrolled and underwent baseline coronary computed tomography angiography (CCTA) as well as follow‐up CCTA. The primary end point was to determine the lesion‐specific change of △computed tomography‐derived fractional flow reserve (△CT‐FFR, defined as the change of CT‐FFR value across each lesion) after rosuvastatin treatment. The secondary end point was to compare the change of other plaque characteristics according to serial CCTA findings. 152 patients (mean age: 67.1±9.7 years, 100 men, mean follow‐up duration of 13.9±2.5 months) were finally included. In non‐calcified plaque subgroup, △CT‐FFR was significantly lower at follow‐up compared with baseline (0.051±0.010 versus 0.035±0.012, P=0.013). All other parameters were not found to be significantly different between baseline and follow‐up CCTA measurements. In calcified plaque and mixed plaque subgroups, all parameters showed no significant differences between baseline and follow‐up CCTA groups (P>0.05 for all). According to multivariate regression analysis, non‐calcified plaque was >2 times more likely than calcified plaque to observe the decrease of △CT‐FFR (adjusted hazard ratio: 2.05 [1.03–4.09], P=0.042).ConclusionsIn patients with mild to intermediate coronary stenosis, rosuvastatin treatment resulted in a reduction in lesion‐specific △CT‐FFR at mid‐term follow‐up. This hemodynamic improvement was mainly observed for non‐calcified lesions.

Quantitative coronary computed tomography angiography for the detection of cardiac allograft vasculopathy

ObjectivesTo associate coronary wall volume and composition, derived from coronary computed tomography angiography (CTA), with cardiac allograft vasculopathy (CAV) detected on invasive coronary angiography (ICA) in heart-transplanted (HTX) patients.MethodsWe included consecutive adults who received ICA and coronary CTA for evaluation of CAV ≥ 10 months after HTX. In all coronary segments, we assessed lumen and wall volumes and segmental length, calculated volume-length ratio (VLR) (volumes indexed by segmental length; mm3/mm), wall burden (WB) (wall/wall + lumen volumes; %), and assessed proportions of calcified, fibrotic, fibro-fatty, and low-attenuation tissue (%) in coronary wall. We rendered independent CTA measures associated with CAV by ICA, tested their discriminatory capacity, and assessed concordance between CTA and ICA.ResultsAmong 50 patients (84% men; 53.6 ± 11.9 years), we analyzed 632 coronary segments. Mean interval between HTX and CTA was 6.7 ± 4.7 years and between ICA and CTA 1 (0–1) day. Segmental VLR, WB, and proportion of fibrotic tissue were independently associated with CAV (OR = 1.06–1.27; p ≤ 0.002), reaching a high discriminatory capacity (combination of all three: AUC = 0.84; 95%CI, 0.75–0.90). Concordance between CTA and ICA was higher in advanced CAV (88%) compared with that in none (37%) and mild (19%) CAV. Discordance was primarily driven by a large number of segments with coronary wall changes on CTA but without luminal stenoses on ICA (177/591; 25%).ConclusionCTA-derived coronary wall VLR, WB, and the proportion of fibrotic tissue are independent markers of CAV. Combination of these three parameters may aid the detection of early CAV not detected by ICA, the current standard of care.Key Points• Coronary CTA detects CAV in HTX patients.• Coronary wall volume-length ratio, wall burden, and proportion of fibrotic tissue are independently associated with CAV.• In contrast to ICA, coronary CTA may identify the early stages of CAV.

In This Issue of the Journal

I want to welcome you to the July 2018 issue of Circulation: Cardiovascular Imaging . The original articles and imaging cases highlight the fundamental role imaging plays in a variety of cardiovascular diseases as well as signals future advances to the field. Detailed below are short summaries of each of these offerings. Lee and colleagues have attempted to address the key question of whether coronary computed tomography angiography–derived measures of atherosclerosis assessment (eg, total atheroma burden or high-risk plaque assessment) provide any additional information with respect to disease progression or clinical events compared with more traditional measures of coronary artery stenosis evaluation. Data mining the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, these authors demonstrate that coronary computed tomography angiography measures of plaque burden and evidence of high-risk plaque features further improved the prediction of plaque progression and major averse cardiac evens. In his editorial, Arbab-Zadeh contextualizes these results, pointing out that although the magnitude of incremental risk prediction was small and of unclear clinical significance, such information may prove useful in guiding the …

Patterns of Coronary Calcification and Their Impact on the Diagnostic Accuracy of Computed Tomography Coronary Angiography.

Despite coronary calcifications being a major factor affecting the diagnostic accuracy of coronary computed tomography angiography (CTA), there is a lack of established criteria for categorizing calcifications. We aimed to evaluate patterns of coronary calcification based on quantitative radiodensity and size parameters to provide coronary calcium categories and assess their impact on the accuracy of coronary CTA. We analyzed length, maximum thickness, volume, mean density, and maximum density of coronary calcium and divided each of these parameters into tertiles. Subsequently, we summarized the tertiles for each individual calcification and divided them into 3 equal groups of: mild, moderate, and severe calcification. The accuracy of coronary CTA was defined as the difference between the measurements obtained on coronary CTA versus the reference of intravascular ultrasound (IVUS). We evaluated 252 coronary calcifications within 97 arteries of 60 patients. There was an expected increase in size and density values for mild versus moderate versus severe calcifications, but there was no difference in IVUS measured minimum lumen area among the 3 groups. Of note, coronary CTA significantly underestimated IVUS minimum lumen area measurement by 1.2 ± 1.6 mm (14.6 ± 23.1%, P < 0.001) for severe calcifications and by 0.5 ± 2.0 mm (3.7 ± 32.1%, P = 0.021) for moderate calcifications. Within mild calcifications, the difference was not significant. Based on their dimensional and radiodensity characteristics, our analysis revealed patterns of individual coronary artery calcifications that affected the accuracy of coronary CTA measurements; coronary CTA inaccuracy was associated with the presence of moderate or severe calcifications, but not mild calcifications.

Prognostic value of segment involvement score compared to other measures of coronary atherosclerosis by computed tomography: A systematic review and meta-analysis

BackgroundThe segment involvement score (SIS) is a semiquantitative measure of the extent of atherosclerosis burden by coronary computed tomography angiography (CTA). We sought to evaluate by meta-analysis the prognostic value of SIS, and to compare it with other CTA measures of coronary artery disease (CAD). MethodsElectronic databases from 1946 to January 2016 were searched. Studies reporting SIS, or an equivalent measure by coronary CTA, and clinical outcomes were included. Maximally adjusted hazard ratios (HR), predominantly for clinical variables, were extracted for SIS, obstructive CAD, Agatston coronary artery calcium score, and plaque composition. These were pooled using DerSimonian-Laird random effects models. ResultsEleven nonrandomized studies with good methodological quality enrolling 9777 subjects (mean age 61 ± 11 years, 57% male, mean follow up 3.3 years) who had 472 (4.8%) MACE (cardiac or all cause death, non-fatal myocardial infarction or late revascularization), were included. SIS (per segment increase) had pooled HR of 1.25 (95% CI: 1.16,1.35; I2 = 71.4%, p < 0.001) for MACE. HR for MACE was 1.37 (95% CI: 1.32,1.42; I2 = 95.6%, p < 0.001) for number of segments with stenosis (per segment increase), 3.39 (95% CI: 1.65,6.99; I2 = 87.8%, p = 0.001) for obstructive CAD (binary variable) and 1.00 (95% CI: 1.00,1.01; I2 = 75.0%, p = 0.490) for Agatston score (per unit increase). HRs by plaque composition (calcified, non-calcified and mixed; per segment change) were 1.24 (95% CI: 1.10,1.39; I2 = 81.6%, p = 0.001), 1.20 (95% CI: 0.97,1.48; I2 = 92.9%, p = 0.093) and 1.27 (95% CI: 1.03,1.58; I2 = 89.8%, p = 0.029), respectively. ConclusionDespite heterogeneity in endpoints, extent of CAD as quantified by SIS on coronary CTA is a strong, independent predictor of cardiovascular events.

The Prognostic Value of Percentage Total Plaque Score Adjusted to Age.

Total plaque score (TPS) on coronary computed tomography angiography (CCTA) has been validated as a surrogate measure of coronary artery disease (CAD) burden and is prognostic. We propose a novel measure, percentage TPS adjusted to age (%TPS/age), that may reflect vascular age and potentially more rapidly progressive atherosclerosis and evaluate its potential prognostic value. %TPS/age was calculated for consecutive patients prospectively enrolled into our institutional CCTA registry and evaluated for primary composite outcome of cardiac death, nonfatal myocardial infarction, and late revascularization. Of 1896 patients identified (mean age 57.7 ± 11.4 years, 50.1% male, median follow-up 18.6 months [interquartile range: 15.3, 32.4]), 552 (29%) had %TPS/age = 0 (no atherosclerosis), with 1 (0.2%) primary outcome observed (annual event rate [AER] = 0.1%). Two events (0.4%, AER = 0.3%) were observed in %TPS/age < 0.314 category, 22 (5.0%, AER = 2.2%) in %TPS/age 0.314 to 0.699 category, and 54 (12.0%, AER = 5.7%) in %TPS/age ≥ 0.700 category. After adjusting for clinical predictors and obstructive CAD, higher %TPS/age category was associated with hazard ratio 1.95 (1.31-2.88, P < .001) for primary outcome on multivariable analysis, Harrell-C-Statistic 0.87 (confidence interval 95%: 0.84-0.90), and net reclassification improvement of 0.71 ( P < .001). %TPS/Age has incremental prognostic value to traditional risk factors and CCTA measures of CAD and improves evaluation of burden of coronary atherosclerosis and clinical risk.

A prospective two-center study on the associations between microalbuminuria, coronary atherosclerosis and long-term clinical outcome in asymptomatic patients with type 2 diabetes mellitus: evaluation by coronary CT angiography.

This study assessed the associations between microalbuminuria in asymptomatic patients with type 2 diabetes and the presence, extent, and severity of coronary atherosclerosis, as measured by coronary computed tomography angiography (CCTA), and the long-term clinical outcomes. In total, the study enrolled 284 consecutive eligible asymptomatic patients with type 2 diabetes and without known coronary artery disease (CAD), who then underwent CCTA and 24h urine albumin measurements. Microalbuminuria was defined as 30-300mg/day urinary albumin excretion. Obstructive CAD, as measured by CCTA, was defined as maximum intra-luminal stenosis ≥50%. Patients with and without microalbuminuria were compared in terms of obstructive CAD prevalence, and the extent and severity of coronary atherosclerosis. They were evaluated using the following data: coronary artery calcium score (CACS), atheroma burden obstructive score (ABOS), segment involvement score (SIS) and segment stenosis score (SSS). All-cause mortality within a follow-up period of 5years was also compared. Compared to patients without microalbuminuria, patients with microalbuminuria were more likely to have obstructive CAD (p=0.004). Microalbuminuria was associated with higher ABOS (p=0.010), SIS (p=0.029), and SSS (p=0.011), except for CACS (p=0.058). Multivariable analyses adjusted for conventional cardiovascular risk factors revealed that microalbuminuria was an independent predictor of obstructive CAD [odds ratio 2.255, confidence intervals (CI) 1.121-4.538, p=0.023] and all-cause mortality (hazard ratio 3.469, CI 1.319-9.121, p=0.012). In asymptomatic patients with type 2 diabetes, microalbuminuria was associated with increased risk of CAD and poorer clinical outcomes.

Aggregate Plaque Volume by Coronary Computed Tomography Angiography Is Superior and Incremental to Luminal Narrowing for Diagnosis of Ischemic Lesions of Intermediate Stenosis Severity

This study examined the performance of percent aggregate plaque volume (%APV), which represents cumulative plaque volume as a function of total vessel volume, by coronary computed tomography angiography (CTA) for identification of ischemic lesions of intermediate stenosis severity. Coronary lesions of intermediate stenosis demonstrate significant rates of ischemia. Coronary CTA enables quantification of luminal narrowing and %APV. We identified 58 patients with intermediate lesions (30% to 69% diameter stenosis) who underwent invasive angiography and fractional flow reserve. Coronary CTA measures included diameter stenosis, area stenosis, minimal lumen diameter (MLD), minimal lumen area (MLA) and %APV. %APV was defined as the sum of plaque volume divided by the sum of vessel volume from the ostium to the distal portion of the lesion. Fractional flow reserve ≤ 0.80 was considered diagnostic of lesion-specific ischemia. Area under the receiver operating characteristic curve and net reclassification improvement (NRI) were also evaluated. Twenty-two of 58 lesions (38%) caused ischemia. Compared with nonischemic lesions, ischemic lesions had smaller MLD (1.3 vs. 1.7 mm, p = 0.01), smaller MLA (2.5 vs. 3.8 mm(2), p = 0.01), and greater %APV (48.9% vs. 39.3%, p < 0.0001). Area under the receiver operating characteristic curve was highest for %APV (0.85) compared with diameter stenosis (0.68), area stenosis (0.66), MLD (0.75), or MLA (0.78). Addition of %APV to other measures showed significant reclassification over diameter stenosis (NRI 0.77, p < 0.001), area stenosis (NRI 0.63, p = 0.002), MLD (NRI 0.62, p = 0.001), and MLA (NRI 0.43, p = 0.01). Compared with diameter stenosis, area stenosis, MLD, and MLA, %APV by coronary CTA improves identification, discrimination, and reclassification of ischemic lesions of intermediate stenosis severity.