Pre-Coronary Artery Bypass Grafting Computed Tomography-Based Fractional Flow Reserve Predicts Graft Failure: Implications for Planning Invasive Treatment of Coronary Artery Disease.

OBJECTIVE: The aim of the study is to evaluate whether a pre-coronary artery bypass grafting (CABG) coronary computed tomography-based fractional flow reserve (FFR-CT) result at the site of a future anastomosis would predict the graft failure in patients undergoing CABG. METHODS: In 43 patients who had coronary computed tomography angiography (CCTA) prior to the CABG, follow-up CCTA were acquired >12 months post-CABG procedure. The FFR-CT values were simulated on the basis of the pre-CABG CCTA. Based on follow-up CCTA, the anastomosis sites and the graft patency were determined. The graft failure was defined as either its stenosis >50% or occlusion. RESULTS: Ninety eight (44 saphenous, 54 left or right internal mammary artery) grafts were assessed. Eighteen grafts from 16 patients were dysfunctional on follow-up CCTA. The FFR-CT values at the location of future anastomosis were higher in dysfunctional than in normal grafts (0.77 [0.71-0.81] vs 0.60 [0.56-0.66], respectively, P = 0.0007). Pre-CABG FFR-CT (hazard ratio = 1.1; 95% CI: 1.012-1.1, P = 0.0230), and bypass graft to right coronary artery (hazard ratio = 3.7; 95% CI: 1.4-9.3 vs left anterior descending artery) were independent predictors of graft dysfunction during follow-up. The optimal threshold of FFR-CT to predict graft failure was >0.68 (sensitivity 88.9% (95% CI: 65.3-98.6), specificity 63.7% (95% CI: 52.2-74.2), positive predictive value 35.6% (95% CI: 28.3%-43.5%), negative predictive value 96.2% (95% CI: 87.2%-99.0%)). CONCLUSIONS: Pre-CABG functional FFR-CT predicts future coronary bypass graft failure. This shows utility of FFR-CT for guiding coronary revascularization and also suggests significance of physiological assessment prior to CABG.

DASH diet decreases CXCL4 plasma concentration in patients diagnosed with coronary atherosclerotic lesions.

BACKGROUND AND AIMS: Aim of this study involved assessment of the intensive intervention concerning lifestyle based on the DASH diet model on plasma concentration of CXCL4 chemokine among patients with coronary atherosclerosis. METHODS AND RESULTS: The Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography Study randomized patients with stable CAD to an interventional group (n = 41), where DASH diet was implemented and the control group (n = 40) without dietary intervention. Dietary counselling was provided to DASH group during all 6 control visits within 6 months of observation. During the study, body weight and body composition were controlled using the bioimpedance method. CXCL4 concentration was determined with the use of ELISA test. Within the DASH group, a significant decrease in body weight, a decrease in high sensitivity C-reactive protein concentration (-0.32 ± 2.8 mg/l; p < 0.05), as well as a decrease in CXCL4 concentration (-3.35 ± 3.4 ng/ml; p < 0.0001) were observed. Occurring changes were not statistically significant within the control group. CONCLUSIONS: DASH diet lessens CXCL4 concentration among patients with a stable CAD, however, further research is necessary in order to confirm aforementioned results and evaluate the impact on atherosclerotic plaque. THIS TRIAL WAS REGISTERED AT: www.clinicaltrials.gov as NCT02571803.

Diet and Lifestyle Intervention-Induced Pattern of Weight Loss Related to Reduction in Low-Attenuation Coronary Plaque Burden.

BACKGROUND: Despite extensive research on body weight and cardiovascular risk, the mechanistic relationship between weight loss and coronary plaque modification has not been adequately addressed. This study aimed to determine the association between body composition dynamics and low-attenuation coronary plaque (LAP) burden. METHODS: Eighty-nine participants (40% women, 60 ± 7.7 years) of the Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography (DISCO-CT) study with non-obstructive atherosclerosis with nonobstructive atherosclerosis confirmed in computed tomography angiography (CCTA), a randomized (1:1), prospective, single-center study were included into the analysis. Patients were randomly assigned to either experimental arm (intensive diet and lifestyle intervention atop optimal medical therapy, n = 45) or control arm (optimal medical therapy alone, n = 44) over 66.8 ± 13.7 weeks. Changes (∆) in body mass (BM) and body composition parameters, including total body fat (TBF), skeletal muscle mass (SMM), and fat-to-muscle ratio (FMR), measured with bioimpedance analyzer were compared with CCTA-measured ∆LAP. Coronary plaque analysis was performed using the 2 × 192 dual-energy scanner (Somatom Force, Siemens, Germany), while quantitative coronary plaque measurements were performed using a semi-automated plaque analysis software system (QAngioCT v3.1.3.13, Medis Medical Imaging Systems, Leiden, The Netherlands). RESULTS: Significant intergroup differences were found for ∆BM (-3.6 ± 4.9 kg in the experimental vs. -1.4 ± 2.9 kg in the control group, p = 0.015), ∆TBF (-3.4 ± 4.8% in the experimental vs. 1.1 ± 5.5% in the control arm, p < 0.001), ∆SMM (1.9 ± 2.8% in the experimental vs. -0.7 ± 3.2% in the control arm, p < 0.001), and FMR [-12.9 (-21.2; -4.3)% in the experimental vs. 3.1 (-5.3; 10.7)% in the control arm, p < 0.001]. ∆LAP did not differ significantly between the study arms; however, in the whole study population, ∆LAP was positively correlated with ∆BM, ∆TBF, and ∆FMR (r = 0.45, p < 0.001; r = 0.300, p = 0.004; r = 0.233, p = 0.028, respectively), and negatively with ∆SMM (r = -0.285, p = 0.007). Multivariate linear regression analysis revealed the association of ∆LAP with ∆BM, ∆TBF, and ∆FMR. CONCLUSIONS: The study intervention resulted in BM reduction characterized by fat loss, skeletal muscle gain, and increased FMR. This weight loss pattern may lead to a reduction in high-risk coronary plaque. Compared to a simple weight control, tracking body composition changes over time can provide valuable information on adverse coronary plaque modification.

Identification of noncalcified coronary plaque characteristics using machine learning radiomic analysis of non-contrast high-resolution computed tomography.

BACKGROUND: Novel imaging and analysis techniques may offer the ability to detect noncalcified or high-risk coronary plaques on a non-contrast computer tomography (CT) scan, advancing cardiovascular diagnostics. AIMS: We aimed to explore whether machine learning (ML) radiomic analysis of low-dose high-resolution non-contrast electrocardiographically (ECG) gated cardiac CT scan allows for the identification of noncalcified coronary plaque characteristics. METHODS: We prospectively enrolled 125 patients with noncalcified plaques and adverse plaque characteristics (APC) and 25 controls without visible atherosclerosis on coronary CT angiography (CCTA). All patients underwent non-contrast CT exam before CCTA. Four hundred and nineteen radiomic features were calculated to identify the presence of any coronary artery disease (CAD), obstructive CAD (stenosis >50%), plaque with ≥2 APC, degree of calcification, and specific APCs. ML models were trained on a training set (917 segmentations) and tested (validation) on a separate set (292 segmentations). RESULTS: Among the radiomic features, 88.3% were associated with a plaque, 0.9% with obstructive CAD, and 76.4% with the presence of at least two APCs. Overall, 80.2%, 88.5%, and 36.5%, of features were associated with calcified, partially calcified, and noncalcified plaques, respectively. Regarding APCs, 61.1%, 61.8%, 84.2%, and 61.3% of features were associated with low attenuation (LAP), napkin-ring sign (NRS), spotty calcification (SC), and positive remodeling (PR), respectively. ML models outperformed conventional methods for the presence of plaque obstructive stenosis, and the presence of 2 APCs, as well as for noncalcified plaques and partially calcified plaques, but not for calcified plaques. ML models also significantly outperformed identification of LAP and PR, but neither NRS nor SC. CONCLUSION: Radiomic analysis of non-contrast cardiac CT exams may allow for the identification of specific noncalcified coronary plaque characteristics displaying the potential for future clinical applications.

Usefulness of MCP-1 Chemokine in the Monitoring of Patients with Coronary Artery Disease Subjected to Intensive Dietary Intervention: A Pilot Study.

Monocyte chemotactic protein-1 (MCP-1) plays an important role in the entire atherosclerotic process, from atherogenesis to destabilisation of the atherosclerotic plaque. The purpose of this study is to evaluate the effect of the dietary approaches to stop hypertension (DASH) diet in patients with coronary artery disease on the MCP-1 plasma concentration and to evaluate the potential usefulness of this chemokine as a marker of change in the volume and composition of coronary plaque. MATERIAL AND METHOD: As part of the dietary intervention to stop coronary atherosclerosis in computed tomography (DISCO-CT) study, patients were randomised to an intervention group (n = 40) in which the DASH diet was introduced, and to a control group (n = 39) with no dietary intervention. In the DASH group, dietary counselling was provided at all follow-up visits within 12 months of the follow-up period. MCP-1 plasma concentration was determined using enzyme-linked immunosorbent assay (ELISA). Coronary plaque analysis was performed using a semi-automated plaque analysis software system (QAngioCT, Medis, The Netherlands). RESULTS: In the DASH group, MCP-1 plasma concentration significantly decreased by 34.1 pg/mL (p = 0.01), while in the control group, the change in MPC-1 was not significant. Significant inverse correlations were revealed for the change in MCP-1 plasma concentration and change in the consumption of vitamin C and dietary fibre both in the DASH (r = -0.519, p = 0.0005; r = -0.353, p = 0.025, respectively) and in the control group (r = -0.488 p = 0.001; r = -0.502, p = 0.001, respectively). In patients with the highest decrease in percent atheroma volume (PAV), a significant positive correlation was observed between the change in MCP-1 plasma concentration and changes in PAV (r = 0.428, p = 0.033) and calcified plaque component (r = 0.468, p = 0.018), while the change in noncalcified plaque component correlated inversely with change in MCP1 (r = -0.459, p = 0.021). CONCLUSION: Dietary intervention based on the DASH diet model reduces the MCP-1plasma concentration, mostly due to an increased intake of plant-derived, fibre-rich foods and antioxidants. The change in MCP-1 plasma concentration seems to reflect changes in the atheroma volume and proportions between the calcified and non-calcified plaque elements.

The Effect of Intensive Dietary Intervention on the Level of RANTES and CXCL4 Chemokines in Patients with Non-Obstructive Coronary Artery Disease: A Randomised Study.

BACKGROUND: Inflammation is the key pathophysiological mechanism of the initiation and progression of atherosclerosis. The study objective was to assess the effects of a dietary intervention based on the model of the dietary approaches to stop hypertension (DASH) diet on the levels of chemokines RANTES and CXCL4 in patients with non-obstructive coronary artery disease. METHODS: As part of Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography (DISCO-CT) study, patients were randomised to an intervention group (n = 40), where the DASH diet was introduced along with optimal pharmacotherapy, and to a control group (n = 39), with optimal pharmacotherapy alone. In the DASH group, systematic dietary counselling was provided for the follow-up period. RANTES and CXCL4 levels were determined using ELISA. RESULTS: In the DASH group, the RANTES level insignificantly reduced from 42.70 ± 21.1 ng/mL to 38.09 ± 18.5 ng/mL (p = 0.134), and the CXCL4 concentration significantly reduced from 12.38 ± 4.1 ng/mL to 8.36 ± 2.3 ng/mL (p = 0.0001). At the same time, an increase in the level of both chemokines was observed in the control group: RANTES from 34.69 ± 22.7 to 40.94 ± 20.0 ng/mL (p = 0.06) and CXCL4 from 10.98 ± 3.6 to 13.0 5± 4.8 ng/mL (p = 0.009). The difference between the changes in both groups was significant for both RANTES (p = 0.03) and CXCL4 (p = 0.00001). The RANTES/CXCL4 ratio reduced in the control group (from 3.52 ± 2.8 to 3.35 ± 2.8; p = 0.006), while in the DASH group, an increase was observed (from 3.54 ± 1.7 to 4.77 ± 2.4; p = 0.001). CONCLUSIONS: A 12-month-long intensive dietary intervention based on DASH diet guidelines as an addition to optimal pharmacotherapy causes changes in the levels of chemokines CXCL4 and RANTES and their mutual relationship in comparison to conventional treatment.

High-Risk Coronary Plaque Regression After Intensive Lifestyle Intervention in Nonobstructive Coronary Disease: A Randomized Study.

OBJECTIVES: The authors sought to study the impact of diet and lifestyle intervention on changes in atherosclerotic plaque volume and composition. BACKGROUND: Lifestyle and diet modification are the leading strategies to manage coronary artery disease; however, their direct impact on atherosclerosis remains unknown. Coronary plaque composition is related to the risk of future cardiovascular events independent of stenosis severity and can be conveniently evaluated with computed tomography angiography (CTA). METHODS: We enrolled 92 patients (41% women; mean age 60 ± 7.7 years) with nonobstructive (<70% stenosis) coronary atherosclerosis identified by CTA. Participants were randomized (1:1) to either the DISCO (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography) intervention group (systematic follow-up by a dietitian to adhere to the Dietary Approaches to Stop Hypertension nutrition model together with optimal medical therapy [OMT]) or the control group (OMT alone). In all patients, CTA was repeated after 66.9 ± 13.7 weeks. The outcome was change (Δ) in atheroma volume and plaque composition. Based on atherosclerotic tissue attenuation ranges in Hounsfield units (HU), the following components of coronary plaque were distinguished: dense calcium (>351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque combined with necrotic core (-30 to 150 HU), referred to as noncalcified plaque. RESULTS: Percent atheroma volume increased in the control arm (Δ = +1.1 ± 3.4%; p = 0.033) versus no significant change in the experimental arm (Δ = +1.0% ± 4.2%; p = 0.127; intergroup p = 0.851). There was a reduction in noncalcified plaque in both the experimental arm (Δ = -51.3 ± 79.5 mm3 [-1.7 ± 2.7%]; p < 0.001) and the control arm (Δ = -21.3 ± 57.7 [-0.7 ± 1.9%]; p = 0.018), which was greater in the DISCO intervention group (intergroup p = 0.045). No differences in fibrous component or dense calcium changes were observed between the groups. CONCLUSIONS: Controlled diet and lifestyle intervention together with OMT may slow the progression of atherosclerosis and reduce noncalcified plaque volume compared to OMT alone. (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography [DISCO-CT]; NCT02571803).

Coronary CTA enhanced with CTA based FFR analysis provides higher diagnostic value than invasive coronary angiography in patients with intermediate coronary stenosis.

BACKGROUND: CTA based FFR, a software based application, enhances diagnostic value of coronary computed tomography angiography (CTA) examination. However it remains unknown whether it improves accuracy over the gold standard of invasive coronary angiography (ICA) in predicting functionally significant coronary stenosis. The aim of our study was to compare diagnostic accuracies of coronary CTA, CTA based FFR, and ICA, with invasive FFR as the reference standard in patients with intermediate stenosis on CTA. METHODS: 96 intermediate stenoses (50-90%) from 90 subjects, with intermediate pre-test probability of CAD, who underwent coronary CTA were analyzed. Each patient had subsequent ICA with FFR. CTA based FFR (cFFR v2.1, Siemens) analysis was performed on-site. The stenoses with invasive FFR≤0.8 were considered hemodynamically significant. RESULTS: 41/96 stenoses were hemodynamically significant (FFR≤0.8). While the area under ROC curves (AUC) for identification of significant stenosis evaluated on QCA (0.653), visual ICA (0.652), qCTA (0.690) and visual CTA (0.660) did not significantly differ, the AUC for CTA based FFR (0.835) was significantly higher (p = 0.004, p = 0.004, p = 0.010, p = 0.007, respectively). The accuracies of CTA based FFR, qCTA and QCA were 76%, 63% and 58% respectively. CONCLUSION: Our results suggest that diagnostic potential of routine coronary CTA, augmented with CTA based FFR analysis, is superior to ICA in patients with intermediate stenosis.

Increased prevalence of subclinical coronary atherosclerosis in young patients with ankylosing spondylitis.

Introduction There is substantial evidence that spondyloarthropathies, such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA), may increase cardiovascular risk. Objectives The study aimed to compare development of atherosclerotic lesions in coronary arteries between patients with AS and individuals without rheumatic dise ases. Patients and methods A total of 37 adult patients with AS (mean [SD] age, 40.4 [9.6] years; men, 26 [70.3%]), with disease duration of less than 10 years were enrolled. The control group consisted of 76 participants without rheumatic diseases. Controls were matched for age, sex, history of hypertension, dyslipidemia, and smoking status. Coronary computed tomography angiography was performed in both groups. Results Atherosclerotic lesions in the coronary arteries were present in 18 patients (48.7%) with AS compared with 20 controls (26.3%) (P = 0.02). Univariate analysis performed in the AS group demonstrated an association between the presence of lesions and age (P = 0.02), hypertension (P = 0.003), and dyslipidemia (P = 0.001). The multivariable logistic regression analysis showed a significant association between coronary atherosclerosis and hypertension (P = 0.008) and with dyslipidemia (P = 0.001). The average plaque burden was higher in patients with AS than in controls (mean [SD], 42.2% [4.7%] vs 36.5% [3.1%], P <0.0001). Conclusions Atherosclerotic plaques in the coronary arteries were significantly more prevalent in patients with AS. A strong association was demonstrated between atherosclerotic lesions and age, hypertension, and dyslipidemia. Our results confirm the need for cardiovascular risk assessment in patients with AS and cardiovascular prevention, if indicated.

What is the optimal anatomic location for coronary artery pressure measurement at CT-derived FFR?

BACKGROUND: CT-FFR is an area of growing interest in the field of cardiac imaging. However, the specific anatomic location distal to a lesion of interest where CT-FFR should be computed to yield the most valid results has not been examined. This study investigated the most appropriate anatomic location distal to a coronary artery stenosis for obtaining CT-FFR measurements. METHODS: 73 patients (60 ± 9 years; 58% male) with at least one coronary lesion with 40-90% stenosis on coronary CTA (either a 2 × 128 slice or a 2 × 192 slice dual-source CT scanner) underwent stress cardiac magnetic resonance (CMR) perfusion imaging for inducible ischemia. 133 coronary arteries and corresponding myocardial territories were analyzed. The most appropriate anatomic location for predicting lesion-specific ischemia via CT-FFR (cFFR version 1.4, Siemens) was determined as either the distance from the lesion of interest or as a multiple of the reference vessel diameter distal to the minimum lumen area (MLA). RESULTS: Inducible myocardial ischemia was found on MRI in 24 (18.1%) vessels/corresponding myocardial territories. The area under the ROC curve was A) 0.866 for CT-FFR measurement locations distal to the MLA expressed as a multiple of the reference diameter, B) 0.854 when expressed as a distance (mm) distal to the MLA, C) 0.803 for CT-FFR values measured in the distal vessel, and D) 0.725 according to stenosis severity on coronary CTA (A vs B p = 0.093; A vs D p = 0.003; A vs C p = 0.019; B vs D p = 0.006; B vs C p = 0.061; C vs D p = 0.082). The most optimal thresholds for agreement of CT-FFR with the reference CMR perfusion were at 41 mm or 10.9 times the proximal reference diameter distal to the MLA. CONCLUSIONS: Our results suggest that the best agreement of CT-FFR with the reference CMR perfusion study is provided when CT-FFR values are computed at 41 mm or 10.9 times the proximal reference diameter distal to the MLA.

Workstation-Based Calculation of CTA-Based FFR for Intermediate Stenosis.

OBJECTIVES: This study sought to evaluate the proportion of patients with intermediate coronary stenosis diagnosed on computed tomography angiography (CTA), which may be saved from any further testing due to use of CTA-based fractional flow reserve (FFR). BACKGROUND: Coronary CTA often results in diagnosis of intermediate stenosis, triggering further physiological testing. CTA-based FFR (CTA-FFR) is a promising diagnostic tool, which may obviate the need for further testing. However, the specific thresholds for CTA-FFR values predicting ischemic versus nonischemic FFR with acceptable confidence are unknown, obscuring clinical utility of the diagnostic strategy using CTA-FFR. METHODS: We analyzed 96 lesions (mean CTA stenosis: 69.7 ± 11.7%) in 90 patients (63.4 ± 8.2 years, 32% were men) who underwent CTA for suspected CAD and were diagnosed with at least 1 intermediate coronary stenosis (50% to 90%) scheduled for further physiological testing. All patients underwent routine invasive FFR and CTA-FFR evaluation. The objective was to determine the proportion of patients falling between the lower and upper CTA-FFR thresholds that predict ischemic and nonischemic stenosis, respectively (on the basis of an invasive FFR cutpoint of ≤0.80), with ≥90% accuracy. RESULTS: The invasive FFR ≤0.8 was observed in 41 of 96 lesions (42.7%). According to Bland-Altman analysis, the CTA-FFR underestimated FFR by 0.01 and the 95% limits of agreement were ±0.19. Receiver-operating characteristic area under the curve was significantly higher for CTA-FFR than that for CTA (per lesion 0.835 vs. 0.660, respectively; p = 0.007). The CTA-FFR thresholds for which the positive and negative predictive values were each ≥90% (corresponding to an FFR of ≤0.80) were >0.87 or <0.74, respectively, encompassing 49 lesions (51%) and 45 of 90 patients. CONCLUSIONS: In around one-half of the patients diagnosed with intermediate stenosis, coronary CTA-based FFR may confidently discriminate between ischemic versus nonischemic stenoses. Our findings require validation in an independent cohort.

Accuracy of coronary computed tomography angiography vs intravascular ultrasound for evaluation of vessel area.

BACKGROUND: We evaluated the accuracy of commonly used thresholds for vessel area evaluation on coronary CT angiography (CTA) and assessed ability of CTA to image the adventitial border. METHODS: We evaluated 137 paired (coronary CTA and intravascular ultrasound [IVUS]) coronary artery cross-sections in 30 patients. CTA analysis included measurements of external vessel border area defined at Hounsfield unit (HU) thresholds of 0 (presumed adventitia), 50, and 70 (presumed external elastic membrane [EEM]). IVUS analysis included measurements of lumen, EEM, and outer border of the highly echogenic area adjacent to EEM (presumed adventitia area). RESULTS: High correlation was found between CTA and IVUS measurements for EEM areas (R(2) = 0.65, P < .001 and R(2) = 0.60, P < .001 for CTA thresholds of 50 and 70 HU, respectively). CTA and IVUS measurements of adventitia areas were significantly correlated (R(2) = 0.74; P < .001), with no significant difference between the 2 methods (20.2 ± 6.4 mm(2) vs 19.8 ± 6.4 mm(2), respectively; P = .278). Cross-sectional coronary lumen radiodensity on CTA images and plaque burden measured on IVUS significantly affected the accuracy of CTA in assessment of the EEM area but not the presumed adventitial area. CONCLUSIONS: We have demonstrated that use of a 50-HU threshold for vessel area determination by CTA led to its significant overestimation, whereas 70-HU threshold was close to that of EEM on IVUS. CTA may accurately delineate the coronary adventitial border by using a 0-HU threshold.