Patient‐Specific Hemodynamic Analysis of Coronary Arteries

Background and Objectives: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary stenosis. However, it does not take into consideration the presence or severity of peri-coronary inflammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors, and peri-coronary inflammation in the coronary arteries of patients with coronary artery disease. Materials and Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1-patients with low index, ≤3 (n = 107), and group 2-patients with high index, >3 (n = 65). Demographic, clinical, and CCTA data were collected for all patients, and FAI analysis of coronary inflammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia, or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score, 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, 13.26 ± 10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84% ± 25.86% vs. 16.87% ± 15.80%; p < 0.0001). ROC analysis identified a cut-off value of 12.1% of the CaRi-Heart® risk score for predicting a high severity of coronary lesions, with an AUC of 0.69. Conclusions: The CT-derived modified Duke index correlates well with local perilesional inflammation as assessed using the FAI score at different levels of the coronary circulation.

ObjectivesTo evaluate computed tomography fractional flow reserve (FFRCT) values in distal parts of the coronaries in an asymptomatic cohort of marathon runners without any coronary stenosis for potentially false-positive values.MethodsNinety-eight asymptomatic male marathon runners (age 53 ± 7 years) were enrolled in a prospective monocentric study and underwent coronary computed tomography angiography (CCTA). CCTA data were analyzed for visual coronary artery stenosis. FFRCT was evaluated in 59 participants without coronary artery stenosis in proximal, mid, and distal coronary sections using an on-site software prototype.ResultsIn participants without coronary artery stenosis, abnormal FFRCT values ≤ 0.8 in distal segments were found in 22 participants (37%); in 19 participants in the LAD; in 5 participants in the LCX; and in 4 participants in the RCA. Vessel diameters in participants with FFRCT values > 0.80 compared to ≤ 0.80 were 1.6 ± 0.3 mm versus 1.5 ± 0.3 mm for distal LAD (p = 0.025), 1.8 ± 0.3 mm versus 1.6 ± 0.5 mm for distal LCX (p = 0.183), and 2.0 ± 0.4 mm versus 1.5 ± 0.2 mm for distal RCA (p < 0.001).ConclusionsAbnormal FFRCT values of ≤ 0.8 frequently occurred in distal coronary segments in subjects without any anatomical coronary artery stenosis. This effect is only to some degree explainable by small distal vessel diameters. Therefore, the validity of hemodynamic relevance evaluation using FFRCT in distal coronary artery segment stenosis is reduced.Key Points• Abnormal FFRCT values (≤ 0.8) occurred in over a third of the subjects in the distal LAD despite the absence of coronary artery stenosis..• Therefore, the validity of hemodynamic relevance evaluation in distal coronary artery segment stenosis is reduced.• Decision-making based on abnormal FFRCT values in distal vessel sections should be performed with caution and only in combination with visual assessment of the grade of stenosis..

Efficacy of Coronary Calcium Score in Predicting Coronary Artery Morphology in Patients With Obstructive Coronary Artery Disease

Efficient and reliable extraction of coronary artery centerline from computed tomography angiography data is a prerequisite for a variety of medical imaging applications. Many authors have combined minimum-cost path algorithms and vesselness measures to extract coronary centerlines. We propose a modular decomposition of this extraction process, in order to facilitate the implementation and comparison of different minimum-cost path strategies allowing users (radiologists and developers) to focus on subsequent image analysis tasks. Evaluation results show a good overlap (> 84%), and small distances with regard to reference centerlines (on average, not larger than the voxel size) in multi-vendor datasets, for two combinations of algorithms that follow this framework. Therefore, it can serve as a starting point to subsequent image analysis stages that require coronary centerlines.

ObjectivesThe primary objective was to determine which of the following angular insertion depth (AID) estimation methods showed the strongest correlation with the postoperative AID (AIDpostop) of a lateral wall (LW) electrode: the Escudé formula, based on the largest distance from the round window (RW) to the LW (distance A); the elliptic-circular approximation (ECA) method, based on both distance A and the perpendicular distance (distance B); and a three-dimensional (3D) reconstruction method. The secondary objective was to assess the impact of using the actual electrode insertion length on the evaluation of AID estimation methods.MethodsThis study included 45 cochleae implanted with the Advanced Bionics SlimJ electrode, with all 16 active electrode contacts positioned intracochlear. Distance A, distance B, and a 3D reconstruction along the LW were evaluated on preoperative magnetic resonance imaging using 3D Slicer. The AIDpostop and insertion length were assessed using cone-beam computed tomography. Two sets of estimated AID values were obtained: assuming a perfect 23-mm insertion length with the reference electrode at the RW (AID23mm); and using the actual insertion length (AIDinsertionlength). Spearman’s rank correlation coefficient was used to assess the association between the estimated AID values and AIDpostop.ResultsA moderately positive correlation was observed between AID23mm and AIDpostop for all three approaches, with no statistically significant differences among them (rs=0.410–0.579). When the analysis was repeated using AIDinsertionlength, the strength of the correlation with AIDpostop increased significantly for all three methods, with the 3D reconstruction method showing a stronger correlation (rs=0.952) than the Escudé formula (rs=0.734) or the ECA method (rs=0.787) (P<0.001).ConclusionThe 3D reconstruction approach has the potential to improve prediction of the AID for LW electrode arrays compared to spiral formulae based on 2D cochlear dimensions. Accurate assessment of the actual insertion length is important for the proper evaluation of AID estimation methods.

BackgroundThere are few data on the clinical significance of coronary computed tomography angiography (CCTA) in asymptomatic type 2 diabetes mellitus (T2DM) patients. We performed a retrospective study to evaluate coronary heart disease (CHD) screening in asymptomatic patients with T2DM using CCTA and CHD risk stratification prediction.Materials and methodsData from 141 T2DM patients (58 ± 8 years, 57% males) without known symptoms suggestive of CHD who underwent CCTA were retrospectively analyzed. The patients were classified into three subgroups based on United Kingdom prospective diabetes study (UKPDS) CHD risk stratification prediction. Seventy-four patients without diabetes mellitus and CHD who underwent CCTA successively were chosen as the control group. The segment involvement score (SIS), segment stenosis score (SSS), stenosis coefficient (SC), severe proximal plaque (SPP) positive ratio and CCTA-adapted Leaman score (CT-LeSc) based on CCTA data were evaluated and compared among the groups.ResultsCompared with the patients in the control group, patients in the moderate-high risk DM groups had higher scores on the SIS, SSS, SC, CT-LeSc, and a higher SPP positive ratio (all p-values < 0.001), and no difference was observed between the low-risk group and the control group (p = 0.136, p = 0.088, p = 0.0.067, p = 0.225, p = 1.000, respectively). Compared with patients in the control group, the patients in the moderate-high risk DM groups had increased odds of SIS > 3 [odds ratio (OR) = 6.557, p < 0.001; OR = 4.455, p < 0.001, respectively], SSS > 5 (OR = 5.727, p < 0.001; OR = 5.144, p < 0.001, respectively), CT-LeSc > 8.7 (OR = 3.780, p = 0.001; OR = 2.804, p = 0.007, respectively), and obstructive stenosis (OR = 7.233, p < 0.001; OR = 5.787, p < 0.001, respectively).ConclusionThe moderate-high CHD risk patients had increased odds of obstructive coronary artery stenosis, and the distribution of coronary artery stenosis was more extensive and more severe in that group compared to the patients without diabetes mellitus and CHD. CHD can be effectively screened in moderate-high risk asymptomatic T2DM patients using CCTA.

Imaging-defined atherosclerosis represents an intermediate phenotype of atherosclerotic cardiovascular disease (ASCVD). Genome-wide association studies (GWAS) on directly measured coronary plaques using coronary computed tomography angiography (CCTA) are scarce. In the so far largest population-based cohort with CCTA data, we performed a GWAS on coronary plaque burden as determined by the segment involvement score (SIS) in 24,811 European individuals. We identified 20 significant independent genetic markers for SIS, three of which were found in loci not implicated in ASCVD before. Further GWAS on coronary artery calcification showed similar results to that of SIS, whereas a GWAS on ultrasound-assessed carotid plaques identified both shared and non-shared loci with SIS. In two-sample Mendelian randomization studies using SIS-associated markers in UK Biobank and CARDIoGRAMplusC4D, one extra coronary segment with atherosclerosis corresponded to 1.8-fold increased odds of myocardial infarction. This GWAS data can aid future studies of causal pathways in ASCVD.

Diagnostic Performance of a Novel Method for Fractional Flow Reserve Computed from Noninvasive Computed Tomography Angiography (NOVEL-FLOW Study)

Background and AimsThe aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)–derived atherosclerotic plaque analysis in ISCHEMIA.MethodsAtherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2–4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis.ResultsAnalysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25–1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model’s predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes.ConclusionsIn ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Introduction Spontaneous Coronary Artery Dissection (SCAD) may be at the origin of up to 25% of acute coronary events in women &amp;lt;50 yo with no or few risk factors. The diagnosis of SCAD is challenging and in some cases it may be ascertained only by intracoronary imaging such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT). IVUS is widely available and has a better depth penetration compared to OCT, showing the extent of the false lumen and the aspect of the adventitia but its lower resolution does not always allow the visualization of smaller structures such as fenestrations. In a previous study we investigated the role of OCT in understanding the pathophysiology of SCAD and we reported a number of OCT complications. It is not known if these also apply to IVUS but since IVUS does not require additional contrast injection, the risk of false lumen (FL) propagation should be lower. Aim of the study To analyze the value of IVUS in the assessment of key features of SCAD and to explore the feasibility of three-dimensional (3D) reconstruction using IVUS imaging. Methods We collated the imaging findings of 15 cases of SCAD for which IVUS was used as part of routine clinical care. Images were assessed to determine the visualisation of the true lumen, the false lumen extent and its contents, the intima-media membrane, the presence of fenestrations, the external elastic lamina and underlying adventitia. Furthermore, we performed a 3D reconstruction of a type 2a dissection of the right coronary artery. The IVUS images were exported in DICOM format. The segmentation of the true and false lumens in the regions of interest was manually done using the ImageJ software. Subsequent images were processed using 3D Slicer and Paraview in order to obtain the 3D reconstruction of the dissected segment. Results The false lumen was entirely visible in 13/15 cases (87%) and the external elastic lamina in 12/15 cases (80%). In 3/15 cases (20%) the dissection was circumferential. The false lumen content had lower echogenicity compared to the surrounding tissue in all 15 cases. There was no visible fenestration. The 3D reconstruction (Figure 1) showed that the false lumen was larger than the true lumen. The general cross-sectional appearance was that of a “horseshoe” dissection but there was also a short segment of circumferential dissection and the intima-media membrane looked thickened. Conclusion Despite its resolution being lower than OCT, IVUS has a deep penetration and provides adequate imaging of the key features of SCAD. Perspectives We plan to further expand these findings in a larger series, intending to better characterize the false lumen and the adventitia in SCAD. IVUS findings in SCAD, 3D reconstruction Funding Acknowledgement Type of funding source: None

This study is an initial evaluation of a validation platform for computational fluid dynamics (CFD) pipelines made for human intra-cardiac flow estimation. The pipelines use image-based prescribed geometry CFD from computed tomography angiography (CTA). In this study the CTA provides approximately 20 volumetric images within one cardiac cycle. The validation platform consists of a dynamic heart phantom which mimics the human heart in CTA and ultrasound (US) measurements. The flow inside the phantom right ventricle (RV) was measured using two methods: 1) a novel CFD pipeline applied using the CTA data (3D+time). 2) US vector flow imaging (VFI) measured directly on the phantom (2D+time). The CFD and VFI are compared quantitatively by comparing point evaluations (line averages) of the in-plane fluid velocity magnitude. The similarity of the line averages, assessed from plots, is found to be depending on the spatial position of the lines. Some positions are very similar in CFD and VFI and some are not. Furthermore a qualitatively comparison is made by plotting the corresponding 2D slices of the vector fields which confirms the quantitative assessment: the overall flow patterns are similar but not everywhere.

Coronary arteries hemodynamics: effect of arterial geometry on hemodynamic parameters causing atherosclerosis.

The high quality three-dimensional (3D) presentation of computed tomography (CT) data has become a common technique since fast imaging systems and 3D software became widely available at the beginning of the 1980s. Unfortunately, the quality of the 3D images produced by standard 3D packages depends not only on several basic scanning parameters like voltage, amperage, slice, and imcrernent, but also on the primary reconstruction algorithm, image separation, and 3D reconstruction and shading method. Therefore, no standard 3D scanning method providing a high quality 3D display combined with an acceptable acquisition and reconstruction time has been established. New volume scanning methods such as the spiral CT offer additional methods to shorten the examination time. There are some problems for 3D imaging in the use of spiral CT. The aim of our study was to compare different scanning — and 3D — reconstruction methods in order to develop standard scanning sequences for routine 3D CT imaging.

Fractal Analysis of Dynamic Stress CT-Perfusion Imaging for Detection of Hemodynamically Relevant Coronary Artery Disease

BackgroundThe interplay between branched‐chain amino acid (BCAA) metabolism, an important pathway in adiposity and cardiometabolic disease, and visceral adipose depots such as hepatic steatosis (HS) and epicardial adipose tissue is unknown. We leveraged the PROMISE clinical trial with centrally adjudicated coronary computed tomography angiography imaging to determine relationships between adipose depots, BCAA dysregulation, and coronary artery disease (CAD).Methods and ResultsThe PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial randomized 10 003 outpatients with stable chest pain to computed tomography angiography versus standard‐of‐care diagnostics. For this study, we included 1798 participants with available computed tomography angiography data and biospecimens. Linear and logistic regression were used to determine associations between a molar sum of BCAAs measured by nuclear magnetic resonance spectroscopy with body mass index, adipose traits, and obstructive CAD. Mendelian randomization was then used to determine if BCAAs are in the causal pathway for adipose depots or CAD. The study sample had a mean age of 60 years (SD, 8.0), body mass index of 30.6 (SD, 5.9), and epicardial adipose tissue volume of 57.3 (SD, 21.3) cm3/m2; 27% had HS, and 14% had obstructive CAD. BCAAs were associated with body mass index (multivariable beta 0.12 per SD increase in BCAA [95% CI, 0.08–0.17]; P=4×10−8). BCAAs were also associated with HS (multivariable odds ratio [OR], 1.46 per SD increase in BCAAs [95% CI, 1.28–1.67]; P=2×10−8), but BCAAs were associated only with epicardial adipose tissue volume (odds ratio, 1.18 [95% CI, 1.07–1.32]; P=0.002) and obstructive CAD (OR, 1.18 [95% CI, 1.04–1.34]; P=0.009) in univariable models. Two‐sample Mendelian randomization did not support the role of BCAAs as within the causal pathways for HS or CAD.ConclusionsBCAAs have been implicated in the pathogenesis of cardiometabolic diseases, and adipose depots have been associated with the risk of CAD. Leveraging a large clinical trial, we further establish the role of dysregulated BCAA catabolism in HS and CAD, although BCAAs did not appear to be in the causal pathway of either disease. This suggests that BCAAs may serve as an independent circulating biomarker of HS and CAD but that their association with these cardiometabolic diseases is mediated through other pathways.