Efficacy of human experts and an automated segmentation algorithm in quantifying disease pathology in coronary computed tomography angiography: A head-to-head comparison with intravascular ultrasound imaging.

BACKGROUND: Coronary computed tomography angiography (CCTA) analysis is currently performed by experts and is a laborious process. Fully automated edge-detection methods have been developed to expedite CCTA segmentation however their use is limited as there are concerns about their accuracy. This study aims to compare the performance of an automated CCTA analysis software and the experts using near-infrared spectroscopy-intravascular ultrasound imaging (NIRS-IVUS) as a reference standard. METHODS: Fifty-one participants (150 vessels) with chronic coronary syndrome who underwent CCTA and 3-vessel NIRS-IVUS were included. CCTA analysis was performed by an expert and an automated edge detection method and their estimations were compared to NIRS-IVUS at a segment-, lesion-, and frame-level. RESULTS: Segment-level analysis demonstrated a similar performance of the two CCTA analyses (conventional and automatic) with large biases and limits of agreement compared to NIRS-IVUS estimations for the total atheroma (ICC: 0.55 vs 0.25, mean difference:192 (-102-487) vs 243 (-132-617) and percent atheroma volume (ICC: 0.30 vs 0.12, mean difference: 12.8 (-5.91-31.6) vs 20.0 (0.79-39.2). Lesion-level analysis showed that the experts were able to detect more accurately lesions than the automated method (68.2 â€‹% and 60.7 â€‹%) however both analyses had poor reliability in assessing the minimal lumen area (ICC 0.44 vs 0.36) and the maximum plaque burden (ICC 0.33 vs 0.33) when NIRS-IVUS was used as the reference standard. CONCLUSIONS: Conventional and automated CCTA analyses had similar performance in assessing coronary artery pathology using NIRS-IVUS as a reference standard. Therefore, automated segmentation can be used to expedite CCTA analysis and enhance its applications in clinical practice.

Novel near-infrared spectroscopy-intravascular ultrasound-based deep-learning methodology for accurate coronary computed tomography plaque quantification and characterization.

Aims: Coronary computed tomography angiography (CCTA) is inferior to intravascular imaging in detecting plaque morphology and quantifying plaque burden. We aim to, for the first time, train a deep-learning (DL) methodology for accurate plaque quantification and characterization in CCTA using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). Methods and results: Seventy patients were prospectively recruited who underwent CCTA and NIRS-IVUS imaging. Corresponding cross sections were matched using an in-house developed software, and the estimations of NIRS-IVUS for the lumen, vessel wall borders, and plaque composition were used to train a convolutional neural network in 138 vessels. The performance was evaluated in 48 vessels and compared against the estimations of NIRS-IVUS and the conventional CCTA expert analysis. Sixty-four patients (186 vessels, 22 012 matched cross sections) were included. Deep-learning methodology provided estimations that were closer to NIRS-IVUS compared with the conventional approach for the total atheroma volume (ΔDL-NIRS-IVUS: -37.8 ± 89.0 vs. ΔConv-NIRS-IVUS: 243.3 ± 183.7 mm3, variance ratio: 4.262, P < 0.001) and percentage atheroma volume (-3.34 ± 5.77 vs. 17.20 ± 7.20%, variance ratio: 1.578, P < 0.001). The DL methodology detected lesions more accurately than the conventional approach (Area under the curve (AUC): 0.77 vs. 0.67, P < 0.001) and quantified minimum lumen area (ΔDL-NIRS-IVUS: -0.35 ± 1.81 vs. ΔConv-NIRS-IVUS: 1.37 ± 2.32 mm2, variance ratio: 1.634, P < 0.001), maximum plaque burden (4.33 ± 11.83% vs. 5.77 ± 16.58%, variance ratio: 2.071, P = 0.004), and calcific burden (-51.2 ± 115.1 vs. -54.3 ± 144.4, variance ratio: 2.308, P < 0.001) more accurately than conventional approach. The DL methodology was able to segment a vessel on CCTA in 0.3 s. Conclusions: The DL methodology developed for CCTA analysis from co-registered NIRS-IVUS and CCTA data enables rapid and accurate assessment of lesion morphology and is superior to expert analysts (Clinicaltrials.gov: NCT03556644).

Inter- and intra-observer reproducibility of CT-Leaman score by an independent core lab.

To assess the reproducibility of CT-based Leaman score (CT-LeSc). CT-LeSc can non-invasively quantify total coronary atherosclerotic burden and is an independent long-term predictor of cardiac events. Its calculation however relies on the subjective assessment of lesions using coronary computed tomography angiography and therefore is subject to intra- and inter-observer variability. Inter-observer reproducibility was assessed by calculating the CT-LeSc in 50 patients randomly selected from the SYNTAX III REVOLUTION and ABSORB trials by two separate teams, each made up of two cardiologists, who reported results by consensus. For intra-observer reproducibility, the CT-LeSc was calculated in same 50 patients on two occasions eight weeks apart, by the same team of two cardiologists. The level of agreement was measured by the weighted kappa statistic, with intra- and inter-observer variability used to evaluate the CT-LeSc's reproducibility. The variables evaluated by weighted kappa statistics were total number of lesions; number of calcified lesions; number of non-calcified lesions; number of mixed lesions; number of obstructive lesions; number of non-obstructive lesions; and the total CT-LeSc in increments of ten and five. During assessment of inter-observer variability the mean ± standard deviation (SD) CT-LeSc calculated by the first and second team was 15.36 ± 5.57 versus 15.24 ± 5.16. The mean of the differences (precision) was 0.97, with a SD (accuracy) 1.17. The inter-observer variability was lowest for Leaman score in increments of five (weighted kappa 0.93), and highest for the total number of calcified lesions (weighted kappa 0.66). During assessment of intra-observer variability, the mean ± SD CT-LeSc were 16.61 ± 5.28 versus 16.82 ± 5.55. The mean ± SD of the differences was 1.28 ± 1.02. The intra-observer variability was the lowest for Leaman score in increments of five (weighted kappa 0.93), and the highest for the total number of lesions and calcified lesions (weighted kappa 0.65). CT-LeSc has substantial to near-perfect agreement for reproducibility.

Angiography and optical coherence tomography derived shear stress: are they equivalent in my opinion?

Advances in image reconstruction using either single or multimodality imaging data provide increasingly accurate three-dimensional (3D) patient's arterial models for shear stress evaluation using computational fluid dynamics (CFD). We aim to evaluate the impacts on endothelial shear stress (ESS) derived from a simple image reconstruction using 3D-quantitative coronary angiography (3D-QCA) versus a multimodality reconstruction method using optical coherence tomography (OCT) in patients' vessels treated with bioresorbable scaffolds. Seven vessels at baseline and five-year follow-up of seven patients from a previous CFD investigation were retrospectively selected for a head-to-head comparison of angiography-derived versus OCT-derived ESS. 3D-QCA significantly underestimated the minimum stent area [MSA] (-2.38mm2) and the stent length (-1.46 mm) compared to OCT-fusion method reconstructions. After carefully co-registering the region of interest for all cases with a sophisticated statistical method, the difference in MSA measurements as well as the inability of angiography to visualise the strut footprint in the lumen surface have translated to higher angiography-derived ESS than OCT-derived ESS (1.76 Pa or 1.52 times for the overlapping segment). The difference in ESS widened with a more restricted region of interest (1.97 Pa or 1.63 times within the scaffold segment). Angiography and OCT offer two distinctive methods of ESS calculation. Angiography-derived ESS tends to overestimate the ESS compared to OCT-derived ESS. Further investigations into ESS analysis resolution play a vital role in adopting OCT-derived ESS.

An optical coherence tomography and endothelial shear stress study of a novel bioresorbable bypass graft.

Endothelial shear stress (ESS) plays a key role in the clinical outcomes in native and stented segments; however, their implications in bypass grafts and especially in a synthetic biorestorative coronary artery bypass graft are yet unclear. This report aims to examine the interplay between ESS and the morphological alterations of a biorestorative coronary bypass graft in an animal model. Computational fluid dynamics (CFD) simulation derived from the fusion of angiography and optical coherence tomography (OCT) imaging was used to reconstruct data on the luminal anatomy of a bioresorbable coronary bypass graft with an endoluminal "flap" identified during OCT acquisition. The "flap" compromised the smooth lumen surface and considerably disturbed the local flow, leading to abnormally low ESS and high oscillatory shear stress (OSI) in the vicinity of the "flap". In the presence of the catheter, the flow is more stable (median OSI 0.02384 versus 0.02635, p < 0.0001; maximum OSI 0.4612 versus 0.4837). Conversely, OSI increased as the catheter was withdrawn which can potentially cause back-and-forth motions of the "flap", triggering tissue fatigue failure. CFD analysis in this report provided sophisticated physiological information that complements the anatomic assessment from imaging enabling a complete understanding of biorestorative graft pathophysiology.

Pericoronary Adipose Tissue Attenuation in Patients With Acute Coronary Syndrome Versus Stable Coronary Artery Disease.

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation has been associated with coronary inflammation and can be evaluated with coronary computed tomography angiography. The aims of this study were to compare the PCAT attenuation across precursors of culprit and nonculprit lesions of patients with acute coronary syndrome versus stable coronary artery disease (CAD). METHODS: In this case-control study, patients with suspected CAD who underwent coronary computed tomography angiography were included. Patients who developed an acute coronary syndrome within 2 years after the coronary computed tomography angiography scan were identified, and patients with stable CAD (defined as any coronary plaque ≥30% luminal diameter stenosis) were 1:2 propensity score matched for age, sex, and cardiac risk factors. The mean PCAT attenuation was analyzed at lesion level and compared between precursors of culprit lesions, nonculprit lesions, and stable coronary plaques. RESULTS: In total, 198 patients (age 62±10 years, 65% male) were selected, including 66 patients who developed an acute coronary syndrome and 132 propensity matched patients with stable CAD. Overall, 765 coronary lesions were analyzed (culprit lesion precursors: n=66; nonculprit lesion precursors: n=207; and stable lesions: n=492). Culprit lesion precursors had larger total plaque volume, fibro-fatty plaque volume, and low-attenuation plaque volume compared to nonculprit and stable lesions. The mean PCAT attenuation was significantly higher across culprit lesion precursors compared to nonculprit and stable lesions (-63.8±9.7 Hounsfield units versus -68.8±10.6 Hounsfield units versus -69.6±10.6 Hounsfield units, respectively; P<0.001), whereas the mean PCAT attenuation around nonculprit and stable lesions was not significantly different (P=0.99). CONCLUSIONS: The mean PCAT attenuation is significantly increased across culprit lesion precursors in patients with acute coronary syndrome, compared to nonculprit lesions of these patients and to lesions of patients with stable CAD, which may suggest a higher intensity of inflammation. PCAT attenuation on coronary computed tomography angiography may be a novel marker to identify high-risk plaques.

Feature-tracking computed tomography left atrial strain and long-term survival after transcatheter aortic valve implantation.

AIMS: Aortic stenosis (AS) induces left atrial (LA) remodelling through the increase of left ventricular (LV) filling pressures. Peak LA longitudinal strain (PALS), reflecting LA reservoir function, has been proposed as a prognostic marker in patients with AS. Feature-tracking (FT) multi-detector computed tomography (MDCT) allows assessment of LA strain from MDCT data. The aim of this study is to investigate the association between PALS using FT MDCT and survival in patients with severe AS who underwent transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: A total of 376 patients (mean age 80 ± 7 years, 53% male) who underwent MDCT before TAVI and had suitable data for assessment of PALS using dedicated FT software, were included. The patients were classified into four groups according to PALS quartiles; PALS > 19.3% (Q1, highest reservoir function), 15.0-19.3% (Q2), 9.1-14.9% (Q3), and ≤9.0% (Q4, lowest reservoir function). The primary outcome was all-cause mortality. During a median of 45 (22-68) months follow-up, 148 patients (39%) died. On multivariable Cox regression analysis, PALS was independently associated with all-cause mortality [hazard ratio (HR): 1.044, 95% confidence interval (CI): 1.012-1.076, P = 0.006]. Compared with patients in Q1, patients in Q3 and Q4 were associated with higher risk of mortality after TAVI [HR: 2.262 (95% CI: 1.335-3.832), P = 0.002 for Q3, HR: 3.116 (95% CI: 1.864-5.210), P < 0.001 for Q4]. CONCLUSION: PALS assessed with FT MDCT is independently associated with all-cause mortality after TAVI.

Introduction to hemodynamic forces by echocardiography.

Hemodynamic force (HDF) analysis represents a novel approach to quantify intraventricular pressure gradients, responsible for blood flow. A new mathematical model allows the derivation of HDF parameters from routine transthoracic echocardiography, making this tool more accessible for clinical use. HDF analysis is considered the fluid dynamics correlate of deformation imaging and may be even more sensitive to detect mechanical abnormalities. This has the potential to add incremental clinical value, allowing earlier detection of pathology or immediate evaluation of response to treatment. In this article, the theoretical background and physiological patterns of HDF in the left ventricle are provided. In pathological situations, the HDF pattern might alter, which is illustrated with a case of ST segment elevation myocardial infarction and non-ischemic cardiomyopathy with typical left bundle branch block.

Relation Between Coronary Plaque Composition Assessed by Intravascular Ultrasound Virtual Histology and Myocardial Ischemia Assessed by Quantitative Flow Ratio.

Coronary plaque composition may play an important role in the induction of myocardial ischemia. Our objective was to further clarify the relation between coronary plaque composition and myocardial ischemia in patients with chest pain symptoms. The study population consisted of 103 patients who presented to the outpatient clinic or emergency department with chest pain symptoms and were referred for diagnostic invasive coronary angiography. Intravascular ultrasound virtual histology was used for the assessment of coronary plaque composition. A noncalcified plaque was defined as a combination of necrotic core and fibrofatty tissue. Quantitative flow ratio (QFR), which is a coronary angiography-based technique used to calculate fractional flow reserve without the need for hyperemia induction or for a pressure wire, was used as the reference standard for the evaluation of myocardial ischemia. Coronary artery plaques with QFR of ≤0.80 were considered abnormal-that is, ischemia-generating. In total, 149 coronary plaques were analyzed, 21 of which (14%) were considered abnormal according to QFR. The percentage of noncalcified tissue was significantly higher in plaques with abnormal QFR (38.2 ± 6.5% vs 33.1 ± 9.0%, p = 0.014). After univariable analysis, both plaque load (odds ratio [OR] per 1% increase 1.081, p <0.001) and the percentage of noncalcified tissue (OR per 1% increase 1.070, p = 0.020) were significantly associated with reduced QFR. However, after multivariable analysis, only plaque load remained significantly associated with abnormal QFR (OR per 1% increase 1.072, p <0.001). In conclusion, the noncalcified plaque area was significantly higher in hemodynamically significant coronary lesions than in nonsignificant lesions. Although an increase in the noncalcified plaque area was significantly associated with a reduced QFR, this association lost significance after adjustment for localized plaque load.

Vessel and sex differences in pericoronary adipose tissue attenuation obtained with coronary CT in individuals without coronary atherosclerosis.

Pericoronary adipose tissue (PCAT) attenuation, derived from coronary computed tomography angiography (CCTA), is associated with coronary artery inflammation. Values for PCAT attenuation in men and women without atherosclerosis on CCTA are lacking. The aim of the current study was to assess the mean PCAT attenuation in individuals without coronary artery atherosclerosis on CCTA. Data on PCAT attenuation in men and women without coronary artery atherosclerosis on CCTA were included in this retrospective analysis. The PCAT attenuation was analyzed from the proximal part of the right coronary artery (RCA), the left anterior descending artery (LAD), and the left circumflex artery (LCx). For patient level analyses the mean PCAT attenuation was defined as the mean of the three coronary arteries. In 109 individuals (mean age 45 ± 13 years; 44% men), 320 coronary arteries were analyzed. The mean PCAT attenuation of the overall population was - 64.4 ± 8.0 HU. The mean PCAT attenuation was significantly lower in the LAD compared with the LCx and RCA (- 67.8 ± 7.8 HU vs - 62.6 ± 6.8 HU vs - 63.6 ± 7.9 HU, respectively, p < 0.001). In addition, the mean PCAT attenuation was significantly higher in men vs. women in all three coronary arteries (LAD: - 65.7 ± 7.6 HU vs - 69.4 ± 7.6 HU, p = 0.014; LCx: - 60.6 ± 7.4 HU vs - 64.3 ± 5.9 HU, p = 0.008; RCA: -61.7 ± 7.9 HU vs - 65.0 ± 7.7 HU, p = 0.029, respectively). The current study provides mean PCAT attenuation values, derived from individuals without CAD. Moreover, the mean PCAT attenuation is lower in women vs. men. Furthermore, the mean PCAT attenuation is significantly lower in the LAD vs LCx and RCA.

Association Between Changes in Perivascular Adipose Tissue Density and Plaque Progression.

BACKGROUND: The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be determined. OBJECTIVES: The purpose of this study was to explore the association between the change in PVAT density and the progression of total and compositional plaque volume (PV). METHODS: Patients were selected from a prospective multinational registry. Patients who underwent serial coronary computed tomography angiography studies with ≥2-year intervals and were scanned with the same tube voltage at baseline and follow-up were included. Total and compositional PV and PVAT density at baseline and follow-up were quantitatively analyzed for every lesion. Multivariate linear regression models using cluster analyses were constructed. RESULTS: A total of 1,476 lesions were identified from 474 enrolled patients (mean age 61.2 ± 9.3 years; 65.0% men). The mean PVAT density was -74.1 ± 11.5 HU, and total PV was 48.1 ± 83.5 mm3 (19.2 ± 44.8 mm3 of calcified PV and 28.9 ± 51.0 mm3 of noncalcified PV). On multivariate analysis (adjusted for clinical risk factors, medication use, change in lipid levels, total PV at baseline, luminal HU attenuation, location of lesions, and tube voltage), the increase in PVAT density was positively associated with the progression of total PV (estimate = 0.275 [95% CI: 0.004-0.545]; P = 0.047), driven by the association with fibrous PV (estimate = 0.245 [95% CI: 0.070-0.420]; P = 0.006). Calcified PV progression was not associated with the increase in PVAT density (P > 0.050). CONCLUSIONS: Increase in vessel inflammation represented by PVAT density is independently associated with the progression of the lipid component of coronary atherosclerotic plaques. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

Abnormal Diastolic Hemodynamic Forces: A Link Between Right Ventricular Wall Motion, Intracardiac Flow, and Pulmonary Regurgitation in Repaired Tetralogy of Fallot.

Background and Objective: The effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dysfunction in repaired Tetralogy of Fallot (RTOF) patients is well recognized by cardiac magnetic resonance (CMR). However, the link between RV wall motion, intracardiac flow and PR has not been established. Hemodynamic force (HDF) represents the global force exchanged between intracardiac blood volume and endocardium, measurable by 4D flow or by a novel mathematical model of wall motion. In our study, we used this novel methodology to derive HDF in a cohort of RTOF patients, exclusively using routine CMR imaging. Methods: RTOF patients and controls with CMR imaging were retrospectively included. Three-dimensional (3D) models of RV were segmented, including RV outflow tract (RVOT). Feature-tracking software (QStrain 2.0, Medis Medical Imaging Systems, Leiden, Netherlands) captured endocardial contours from long/short-axis cine and used to reconstruct RV wall motion. A global HDF vector was computed from the moving surface, then decomposed into amplitude/impulse of three directional components based on reference (Apical-to-Basal, Septal-to-Free Wall and Diaphragm-to-RVOT direction). HDF were compared and correlated against CMR and exercise stress test parameters. A subset of RTOF patients had 4D flow that was used to derive vorticity (for correlation) and HDF (for comparison against cine method). Results: 68 RTOF patients and 20 controls were included. RTOF patients had increased diastolic HDF amplitude in all three directions (p<0.05). PR% correlated with Diaphragm-RVOT HDF amplitude/impulse (r = 0.578, p<0.0001, r = 0.508, p < 0.0001, respectively). RV ejection fraction modestly correlated with global HDF amplitude (r = 0.2916, p = 0.031). VO2-max correlated with Septal-to-Free Wall HDF impulse (r = 0.536, p = 0.007). Diaphragm-to-RVOT HDF correlated with RVOT vorticity (r = 0.4997, p = 0.001). There was no significant measurement bias between Cine-derived HDF and 4D flow-derived HDF by Bland-Altman analysis. Conclusion: RTOF patients have abnormal diastolic HDF that is correlated to PR, RV function, exercise capacity and vorticity. HDF can be derived from conventional cine, and is a potential link between RV wall motion and intracardiac flow from PR in RTOF patients.

Angiography derived assessment of the coronary microcirculation: is it ready for prime time?

INTRODUCTION: Non-obstructive coronary arteries (NOCA) are present in 39.7% to 62.4% of patients who undergo elective angiography. Coronary microcirculation (<400 µm) is not visible on angiography therefore functional assessment, invasive or noninvasive plays a prior role to help provide a more personalized diagnosis of angina. AREA COVERED: In this review, we revisit the pathophysiology, clinical importance, and invasive assessment of the coronary microcirculation, and discuss angiography-derived indices of microvascular resistance. A comprehensive literature review over four decades is also undertaken. EXPERT OPINION: The coronary microvasculature plays an important role in flow autoregulation and metabolic regulation. Invasive assessment of microvascular resistance is a validated modality with independent prognostic value, nevertheless, its routine application is hampered by the requirement of intravascular instrumentation and hyperemic agents. The angiography-derived index of microvascular resistance has emerged as a promising surrogate in pilot studies, however, more data are needed to validate and compare the diagnostic and prognostic accuracy of different equations as well as to illustrate the relationship between angiography-derived parameters for epicardial coronary arteries and those for the microvasculature.