Analysis of Three-Dimensional Scar Architecture and Conducting Channels by High-Resolution Contrast-Enhanced Cardiac Magnetic Resonance Imaging in Chagas Heart Disease

We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events.Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range).A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60).High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events

Automatic segmentation of multiple cardiovascular structures from cardiac computed tomography angiography images using deep learning.

OBJECTIVES:To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. BACKGROUND:Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. METHODS:Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split. RESULTS:The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups. CONCLUSIONS:An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level

Machine Learning Framework to Identify Individuals at Risk of Rapid Progression of Coronary Atherosclerosis: From the PARADIGM Registry.

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P<0.001; statistical model, 0.81 [0.75-0.87], P=0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP

Percent atheroma volume: Optimal variable to report whole-heart atherosclerotic plaque burden with coronary CTA, the PARADIGM study.

BACKGROUND AND AIMS:Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex. METHODS:The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm3, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAVnorm) in mm3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed. RESULTS:The study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11-13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAVnorm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex. CONCLUSIONS:PAV was less affected by patient's body surface area then PV and TAVnorm and may be the preferred method to report coronary atherosclerotic burden

a retrospective case–control study from the PARADIGM registry

Funding Information: Dr. Jonathon A. Leipsic serves as a consultant and has stock options in HeartFlow and Circle Cardiovascular Imaging; he also receives grant support from GE Healthcare and speaking fees from Philips. Dr. Habib Samady has an equity interest in Covanos. Dr. Daniel Berman receives software royalties from Cedars-Sinai Medical Center. Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare and has an equity interest in Cleerly. All other authors declare that they have no competing interests. Funding Information: This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (Ministry of Science and ICT; Ministry of Trade, Industry and Energy; Ministry of Health & Welfare, Republic of Korea; and Ministry of Food and Drug Safety; Project Number: 202016B02). Publisher Copyright: © 2022, The Author(s).Background: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. Methods: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV). Results: During a median inter-scan period of 3.6 years (interquartile range: 2.7–5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (β: 0.098, 95% confidence interval [CI]: 0.048–0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574–0.999]; P = 0.017). Conclusion: In this retrospective case–control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. Trial registration: ClinicalTrials.gov NCT02803411.publishersversionpublishe

a cluster analysis of PARADIGM registry data

Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm3), with necrotic core and fibro-fatty PV regression (− 5.7 mm3 and − 5.6 mm3, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (− 2.4 mm3). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm3). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm3), predominantly increasing in calcified PV (+ 35.9 mm3). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.publishersversionpublishe

Results from the PARADIGM registry

Funding Information: This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (Ministry of Science and ICT; Ministry of Trade, Industry and Energy; Ministry of Health & Welfare, Republic of Korea; and Ministry of Food and Drug Safety; Project Number: 202016B02) and funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging and the Michael Wolk Foundation. This work was also supported by the National Research Foundation of Korea [RS‐2022‐00165404, 2022R1A5A6000840, 2020R1I1A1A01073151]. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Publisher Copyright: © 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.Background and Hypothesis: The recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner. Methods: From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model. Results: The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%–50% and 5.6%–7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis. Conclusions: This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.publishersversionepub_ahead_of_prin