Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study.

BACKGROUND: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals. METHODS: This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU. RESULTS: In the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (-76.9 HU vs. -73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10-2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21-2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score). CONCLUSIONS: MetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification. Trial registration NCT00927693.

Prediction of revascularization by coronary CT angiography using a machine learning ischemia risk score.

OBJECTIVES: The machine learning ischemia risk score (ML-IRS) is a machine learning-based algorithm designed to identify hemodynamically significant coronary disease using quantitative coronary computed tomography angiography (CCTA). The purpose of this study was to examine whether the ML-IRS can predict revascularization in patients referred for invasive coronary angiography (ICA) after CCTA. METHODS: This study was a post hoc analysis of a prospective dual-center registry of sequential patients undergoing CCTA followed by ICA within 3 months, referred from inpatient, outpatient, and emergency department settings (n = 352, age 63 ± 10 years, 68% male). The primary outcome was revascularization by either percutaneous coronary revascularization or coronary artery bypass grafting. Blinded readers performed semi-automated quantitative coronary plaque analysis. The ML-IRS was automatically computed. Relationships between clinical risk factors, coronary plaque features, and ML-IRS with revascularization were examined. RESULTS: The study cohort consisted of 352 subjects with 1056 analyzable vessels. The ML-IRS ranged between 0 and 81% with a median of 18.7% (6.4-34.8). Revascularization was performed in 26% of vessels. Vessels receiving revascularization had higher ML-IRS (33.6% (21.1-55.0) versus 13.0% (4.5-29.1), p < 0.0001), as well as higher contrast density difference, and total, non-calcified, calcified, and low-density plaque burden. ML-IRS, when added to a traditional risk model based on clinical data and stenosis to predict revascularization, resulted in increased area under the curve from 0.69 (95% CI: 0.65-0.72) to 0.78 (95% CI: 0.75-0.81) (p < 0.0001), with an overall continuous net reclassification improvement of 0.636 (95% CI: 0.503-0.769; p < 0.0001). CONCLUSIONS: ML-IRS from quantitative coronary CT angiography improved the prediction of future revascularization and can potentially identify patients likely to receive revascularization if referred to cardiac catheterization. KEY POINTS: • Machine learning ischemia risk from quantitative coronary CT angiography was significantly higher in patients who received revascularization versus those who did not receive revascularization. • The machine learning ischemia risk score was significantly higher in patients with invasive fractional flow ≤ 0.8 versus those with > 0.8. • The machine learning ischemia risk score improved the prediction of future revascularization significantly when added to a standard prediction model including stenosis.

Machine learning integration of circulating and imaging biomarkers for explainable patient-specific prediction of cardiac events: A prospective study.

BACKGROUND AND AIMS: We sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects. METHODS: We studied 1069 subjects (age 58.2 ± 8.2 years, 54.0% males) from the prospective EISNER trial who underwent coronary artery calcium (CAC) scoring CT, serum biomarker assessment, and long-term follow-up. Epicardial adipose tissue (EAT) was quantified from CT using fully automated deep learning software. Forty-eight serum biomarkers, both established and novel, were assayed. An ML algorithm (XGBoost) was trained using clinical risk factors, CT measures (CAC score, number of coronary lesions, aortic valve calcium score, EAT volume and attenuation), and circulating biomarkers, and validated using repeated 10-fold cross validation. RESULTS: At 14.5 ± 2.0 years, there were 50 hard cardiac events (myocardial infarction or cardiac death). The ML risk score (area under the receiver operator characteristic curve [AUC] 0.81) outperformed the CAC score (0.75) and ASCVD risk score (0.74; both p = 0.02) for the prediction of hard cardiac events. Serum biomarkers provided incremental prognostic value beyond clinical data and CT measures in the ML model (net reclassification index 0.53 [95% CI: 0.23-0.81], p < 0.0001). Among novel biomarkers, MMP-9, pentraxin 3, PIGR, and GDF-15 had highest variable importance for ML and reflect the pathways of inflammation, extracellular matrix remodeling, and fibrosis. CONCLUSIONS: In this prospective study, ML integration of novel circulating biomarkers and noninvasive imaging measures provided superior long-term risk prediction for cardiac events compared to current risk assessment tools.

Epicardial adipose tissue is associated with extent of pneumonia and adverse outcomes in patients with COVID-19.

AIM: We sought to examine the association of epicardial adipose tissue (EAT) quantified on chest computed tomography (CT) with the extent of pneumonia and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a post-hoc analysis of a prospective international registry comprising 109 consecutive patients (age 64 ±â€¯16 years; 62% male) with laboratory-confirmed COVID-19 and noncontrast chest CT imaging. Using semi-automated software, we quantified the burden (%) of lung abnormalities associated with COVID-19 pneumonia. EAT volume (mL) and attenuation (Hounsfield units) were measured using deep learning software. The primary outcome was clinical deterioration (intensive care unit admission, invasive mechanical ventilation, or vasopressor therapy) or in-hospital death. RESULTS: In multivariable linear regression analysis adjusted for patient comorbidities, the total burden of COVID-19 pneumonia was associated with EAT volume (ß = 10.6, p = 0.005) and EAT attenuation (ß = 5.2, p = 0.004). EAT volume correlated with serum levels of lactate dehydrogenase (r = 0.361, p = 0.001) and C-reactive protein (r = 0.450, p < 0.001). Clinical deterioration or death occurred in 23 (21.1%) patients at a median of 3 days (IQR 1-13 days) following the chest CT. In multivariable logistic regression analysis, EAT volume (OR 5.1 [95% CI 1.8-14.1] per doubling p = 0.011) and EAT attenuation (OR 3.4 [95% CI 1.5-7.5] per 5 Hounsfield unit increase, p = 0.003) were independent predictors of clinical deterioration or death, as was total pneumonia burden (OR 2.5, 95% CI 1.4-4.6, p = 0.002), chronic lung disease (OR 1.3 [95% CI 1.1-1.7], p = 0.011), and history of heart failure (OR 3.5 [95% 1.1-8.2], p = 0.037). CONCLUSIONS: EAT measures quantified from chest CT are independently associated with extent of pneumonia and adverse outcomes in patients with COVID-19, lending support to their use in clinical risk stratification.

Myocardial Infarction Associates With a Distinct Pericoronary Adipose Tissue Radiomic Phenotype: A Prospective Case-Control Study.

OBJECTIVES: This study sought to determine whether coronary computed tomography angiography (CCTA)-based radiomic analysis of pericoronary adipose tissue (PCAT) could distinguish patients with acute myocardial infarction (MI) from patients with stable or no coronary artery disease (CAD). BACKGROUND: Imaging of PCAT with CCTA enables detection of coronary inflammation. Radiomics involves extracting quantitative features from medical images to create big data and identify novel imaging biomarkers. METHODS: In a prospective case-control study, 60 patients with acute MI underwent CCTA within 48 h of admission, before invasive angiography. These subjects were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, sex, risk factors, medications, and CT tube voltage. PCAT was segmented around the proximal right coronary artery (RCA) in all patients and around culprit and nonculprit lesions in patients with MI. PCAT segmentations were analyzed using Radiomics Image Analysis software. RESULTS: Of 1,103 calculated radiomic parameters, 20.3% differed significantly between MI patients and controls, and 16.5% differed between patients with MI and stable CAD (critical p < 0.0006); whereas none differed between patients with stable CAD and controls. On cluster analysis, the most significant radiomic parameters were texture or geometry based. At 6 months post-MI, there was no significant change in the PCAT radiomic profile around the proximal RCA or nonculprit lesions. Using machine learning (XGBoost), a model integrating clinical features (risk factors, serum lipids, high-sensitivity C-reactive protein), PCAT attenuation, and radiomic parameters provided superior discrimination of acute MI (area under the receiver operator characteristic curve [AUC]: 0.87) compared with a model with clinical features and PCAT attenuation (AUC: 0.77; p = 0.001) or clinical features alone (AUC: 0.76; p < 0.001). CONCLUSIONS: Patients with acute MI have a distinct PCAT radiomic phenotype compared with patients with stable or no CAD. Using machine learning, a radiomics-based model outperforms a PCAT attenuation-based model in accurately identifying patients with MI.

Deep Learning-Based Quantification of Epicardial Adipose Tissue Volume and Attenuation Predicts Major Adverse Cardiovascular Events in Asymptomatic Subjects.

BACKGROUND: Epicardial adipose tissue (EAT) volume (cm3) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography. METHODS: Our study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction. RESULTS: At 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01-1.04]; 1.25 [1.19-1.30]; and 1.35 [1.07-1.68], P<0.01 for all) and EAT attenuation was inversely associated with MACE (hazard ratio, 0.83 [95% CI, 0.72-0.96]; P=0.01), with corresponding Harrell C statistic of 0.76. MACE risk progressively increased with EAT volume ≥113 cm3 and coronary artery calcium ≥100 AU and was highest in subjects with both (P<0.02 for all). In 1317 subjects, EAT volume was correlated with inflammatory biomarkers C-reactive protein, myeloperoxidase, and adiponectin reduction; EAT attenuation was inversely related to these biomarkers. CONCLUSIONS: Fully automated EAT volume and attenuation quantification by deep learning from noncontrast cardiac computed tomography can provide prognostic value for the asymptomatic patient, without additional imaging or physician interaction.

Quantitative Burden of COVID-19 Pneumonia on Chest CT Predicts Adverse Outcomes: A Post-Hoc Analysis of a Prospective International Registry.

PURPOSE: To examine the independent and incremental value of CT-derived quantitative burden and attenuation of COVID-19 pneumonia for the prediction of clinical deterioration or death. METHODS: This was a retrospective analysis of a prospective international registry of consecutive patients with laboratory-confirmed COVID-19 and chest CT imaging, admitted to four centers between January 10 and May 6, 2020. Total burden (expressed as a percentage) and mean attenuation of ground glass opacities (GGO) and consolidation were quantified from CT using semi-automated research software. The primary outcome was clinical deterioration (intensive care unit admission, invasive mechanical ventilation, or vasopressor therapy) or in-hospital death. Logistic regression was performed to assess the predictive value of clinical and CT parameters for the primary outcome. RESULTS: The final population comprised 120 patients (mean age 64 ± 16 years, 78 men), of whom 39 (32.5%) experienced clinical deterioration or death. In multivariable regression of clinical and CT parameters, consolidation burden (odds ratio [OR], 3.4; 95% confidence interval [CI]: 1.7, 6.9 per doubling; P = .001) and increasing GGO attenuation (OR, 3.2; 95% CI: 1.3, 8.3 per standard deviation, P = .02) were independent predictors of deterioration or death; as was C-reactive protein (OR, 2.1; 95% CI: 1.3, 3.4 per doubling; P = .004), history of heart failure (OR 1.3; 95% CI: 1.1, 1.6, P = .01), and chronic lung disease (OR, 1.3; 95% CI: 1.0, 1.6; P = .02). Quantitative CT measures added incremental predictive value beyond a model with only clinical parameters (area under the curve, 0.93 vs 0.82, P = .006). The optimal prognostic cutoffs for burden of COVID-19 pneumonia as determined by Youden's index were consolidation of greater than or equal to 1.8% and GGO of greater than or equal to 13.5%. CONCLUSIONS: Quantitative burden of consolidation or GGO on chest CT independently predict clinical deterioration or death in patients with COVID-19 pneumonia. CT-derived measures have incremental prognostic value over and above clinical parameters, and may be useful for risk stratifying patients with COVID-19.