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 651.0%. 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

Increased long-term mortality in women with high left ventricular ejection fraction: data from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) long-term registry

Aims: There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men. Methods and results: A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 \ub1 13.2 years in men and 59.5 \ub1 13.3 years in women, P = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55-65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41-0.98, P = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD). Conclusion: Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD

Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? results from the multinational coronary ct angiography evaluation for clinical outcome: An international multicenter registry (confirm)

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome

Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing

Background and aims: Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA. Methods: From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA. Results: Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9-5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1-2.9, p = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3-4.9) and 2.2 (95% CI 1.6-3.0), respectively]. Conclusions: Patients without luminal narrowing but with CAC experienc

Coronary dominance and prognosis in patients undergoing coronary computed tomographic angiography: Results from the CONFIRM (COronary CTAngiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter) registry

Aims: Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA. Methods and results: The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9±12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD(HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance. Conclusion: In our study population, survival after 5 years of follow-up did not differ significantly between patientswith left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations

1-year impact on medical practice and clinical outcomes of FFRCT the ADVANCE registry

OBJECTIVES The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes.BACKGROUND Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes.METHODS Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured.RESULTS At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT 0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p 0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT 0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT 0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01).CONCLUSIONS The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679) (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Cardiolog

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults

Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? results from the multinational coronary CT angiography evaluation for clinical outcome : an international multicenter registry (CONFIRM)

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent 6564-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome

Topological data analysis of coronary plaques demonstrates the natural history of coronary atherosclerosis

OBJECTIVES This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).BACKGROUND Coronary CTA can noninvasively assess coronary plaques quantitatively.METHODS Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.RESULTS Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a dosed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm(3) [interquartile range (IQR): 0.0 to 39.6 mm(3)]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm(3) [IQR: 0.0 to 127.4 mm(3)]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm(3) [IQR: 96.7 to 306.4 mm(3)]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p< 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p= 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.CONCLUSIONS The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque Determined by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411) (C) 2021 by the American College of Cardiology Foundation.Cardiolog

Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

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