Machine learning of clinical variables and coronary artery calcium scoring for the prediction of obstructive coronary artery disease on coronary computed tomography angiography: analysis from the CONFIRM registry.

AIMS: Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA). METHODS AND RESULTS: The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD. A boosted ensemble algorithm (XGBoost) was used, with data split into a training set (80%) on which 10-fold cross-validation was done and a test set (20%). Performance was assessed of the (1) ML model (using 25 clinical and demographic features), (2) ML + CACS, (3) CAD consortium clinical score, (4) CAD consortium clinical score + CACS, and (5) updated Diamond-Forrester (UDF) score. The study population comprised of 13 054 patients, of whom 2380 (18.2%) had obstructive CAD (≥50% stenosis). Machine learning with CACS produced the best performance [area under the curve (AUC) of 0.881] compared with ML alone (AUC of 0.773), CAD consortium clinical score (AUC of 0.734), and with CACS (AUC of 0.866) and UDF (AUC of 0.682), P < 0.05 for all comparisons. CACS, age, and gender were the highest ranking features. CONCLUSION: A ML model incorporating clinical features in addition to CACS can accurately estimate the pretest likelihood of obstructive CAD on CCTA. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry.

BACKGROUND: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA). METHODS: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year. RESULTS: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors. CONCLUSION: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.

Determinants of Rejection Rate for Coronary CT Angiography Fractional Flow Reserve Analysis.

Background Coronary artery fractional flow reserve (FFR) derived from CT angiography (FFTCT) enables functional assessment of coronary stenosis. Prior clinical trials showed 13%-33% of coronary CT angiography studies had insufficient quality for quantitative analysis with FFRCT. Purpose To determine the rejection rate of FFRCT analysis and to determine factors associated with technically unsuccessful calculation of FFRCT. Materials and Methods Prospectively acquired coronary CT angiography scans submitted as part of the Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care (ADVANCE) registry (https://ClinicalTrials.gov: NCT02499679) and coronary CT angiography series submitted for clinical analysis were included. The primary outcome was the FFRCT rejection rate (defined as an inability to perform quantitative analysis with FFRCT). Factors that were associated with FFRCT rejection rate were assessed with multiple linear regression. Results In the ADVANCE registry, FFRCT rejection rate due to inadequate image quality was 2.9% (80 of 2778 patients; 95% confidence interval [CI]: 2.1%, 3.2%). In the 10 621 consecutive patients who underwent clinical analysis, the FFRCT rejection rate was 8.4% (n = 892; 95% CI: 6.2%, 7.2%; P < .001 vs the ADVANCE cohort). The main reason for the inability to perform FFRCT analysis was the presence of motion artifacts (63 of 80 [78%] and 729 of 892 [64%] in the ADVANCE and clinical cohorts, respectively). At multivariable analysis, section thickness in the ADVANCE (odds ratio [OR], 1.04; 95% CI: 1.001, 1.09; P = .045) and clinical (OR, 1.03; 95% CI: 1.02, 1.04; P < .001) cohorts and heart rate in the ADVANCE (OR, 1.05; 95% CI: 1.02, 1.08; P < .001) and clinical (OR, 1.06; 95% CI: 1.05, 1.07; P < .001) cohorts were independent predictors of rejection. Conclusion The rates for technically unsuccessful CT-derived fractional flow reserve in the ADVANCE registry and in a large clinical cohort were 2.9% and 8.4%, respectively. Thinner CT section thickness and lower patient heart rate may increase rates of completion of CT fractional flow reserve analysis. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sakuma in this issue.

Clinical Impact of Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve on Japanese Population in the ADVANCE Registry.

BACKGROUND: Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFRCT) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFRCTin Japan are scarce, so we assessed the clinical impact of using FFRCTin a Japanese population.Methods and Results:The ADVANCE registry is an international prospective FFRCTregistry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFRCT, treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFRCToccurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFRCT≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFRCT>0.80) (20.5% vs. 46.1%, P=0.0001). After FFRCT, 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFRCTwere medically treated. MACE occurred in 5 patients with positive FFRCT, but none occurred in patients with negative FFRCTwithin 90 days. CONCLUSIONS: In this Japanese population, FFRCTmodified the treatment strategy in more than half of the patients. FFRCTshowed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

Real-world clinical utility and impact on clinical decision-making of coronary computed tomography angiography-derived fractional flow reserve: lessons from the ADVANCE Registry.

Aims: Non-invasive assessment of stable chest pain patients is a critical determinant of resource utilization and clinical outcomes. Increasingly coronary computed tomography angiography (CCTA) with selective CCTA-derived fractional flow reserve (FFRCT) is being used. The ADVANCE Registry, is a large prospective examination of using a CCTA and FFRCT diagnostic pathway in real-world settings, with the aim of determining the impact of this pathway on decision-making, downstream invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular events (MACE). Methods and results: A total of 5083 patients with symptoms concerning for coronary artery disease (CAD) and atherosclerosis on CCTA were enrolled at 38 international sites from 15 July 2015 to 20 October 2017. Demographics, symptom status, CCTA and FFRCT findings, treatment plans, and 90 days outcomes were recorded. The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management plans occurred in 66.9% [confidence interval (CI): 64.8-67.6] of patients. Non-obstructive coronary disease was significantly lower in ICA patients with FFRCT ≤0.80 (14.4%) compared to patients with FFRCT >0.80 (43.8%, odds ratio 0.19, CI: 0.15-0.25, P < 0.001). In total, 72.3% of subjects undergoing ICA with FFRCT ≤0.80 were revascularized. No death/myocardial infarction (MI) occurred within 90 days in patients with FFRCT >0.80 (n = 1529), whereas 19 (0.6%) MACE [hazard ratio (HR) 19.75, CI: 1.19-326, P = 0.0008] and 14 (0.3%) death/MI (HR 14.68, CI 0.88-246, P = 0.039) occurred in subjects with an FFRCT ≤0.80. Conclusions: In a large international multicentre population, FFRCT modified treatment recommendation in two-thirds of subjects as compared to CCTA alone, was associated with less negative ICA, predicted revascularization, and identified subjects at low risk of adverse events through 90 days.

Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study.

Aim: The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown. Methods and results: From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental χ2 range 20.7-25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA findings when added to a base model containing both traditional RF and CACS (C-statistics P > 0.05, for all). Conclusions: Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 2: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 1: Radiation Physics and Radiation Biology: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Developed in Collaboration With Mended Hearts.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.

Prognostic value of age adjusted segment involvement score as measured by coronary computed tomography: a potential marker of vascular age.

Extent of coronary atherosclerotic disease (CAD) burden on coronary computed tomography angiography (CCTA) as measured by segment involvement score (SIS) has a prognostic value. We sought to investigate the incremental prognostic value of 'age adjusted SIS' (aSIS), which may be a marker of premature atherosclerosis and vascular age. Consecutive patients were prospectively enrolled into the CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicentre) multinational observational study. Patients were followed for the outcome of all-cause death. aSIS was calculated on CCTA for each patient, and its incremental prognostic value was evaluated. A total of 22,211 patients [mean age 58.5 ± 12.7 years, 55.8% male) with a median follow-up of 27.3 months (IQR 17.8, 35.4)] were identified. After adjustment for clinical factors and presence of obstructive CAD, higher aSIS was associated with increased death on multivariable analysis, with hazard ratio (HR) 2.40 (1.83-3.16, p < 0.001), C-statistic 0.723 (0.700-0.756), net reclassification improvement (NRI) 0.36 (0.26-0.47, p < 0.001), and relative integrated discrimination improvement (IDI) 0.33 (p = 0.009). aSIS had HR 3.48 (2.33-5.18, p < 0.001) for mortality in those without obstructive CAD, compared to HR 1.79 (1.25-2.58, p = 0.02) in those with obstructive CAD. In conclusion, aSIS has an incremental prognostic value to traditional risk factors and obstructive CAD, and may enhance CCTA risk stratification.

Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease: a 5-year multicentre prospective registry analysis.

AIMS: Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. METHODS AND RESULTS: The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P< 0.001). CONCLUSIONS: Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone.

Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry) registry.

OBJECTIVE: We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. APPROACH AND RESULTS: Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque. CONCLUSIONS: The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/. Unique identifier NCT01443637.

Current but not past smoking increases the risk of cardiac events: insights from coronary computed tomographic angiography.

AIMS: We evaluated coronary artery disease (CAD) extent, severity, and major adverse cardiac events (MACEs) in never, past, and current smokers undergoing coronary CT angiography (CCTA). METHODS AND RESULTS: We evaluated 9456 patients (57.1 ± 12.3 years, 55.5% male) without known CAD (1588 current smokers; 2183 past smokers who quit ≥3 months before CCTA; and 5685 never smokers). By risk-adjusted Cox proportional-hazards models, we related smoking status to MACE (all-cause death or non-fatal myocardial infarction). We further performed 1:1:1 propensity matching for 1000 in each group evaluate event risk among individuals with similar age, gender, CAD risk factors, and symptom presentation. During a mean follow-up of 2.8 ± 1.9 years, 297 MACE occurred. Compared with never smokers, current and past smokers had greater atherosclerotic burden including extent of plaque defined as segments with any plaque (2.1 ± 2.8 vs. 2.6 ± 3.2 vs. 3.1 ± 3.3, P < 0.0001) and prevalence of obstructive CAD [1-vessel disease (VD): 10.6% vs. 14.9% vs. 15.2%, P < 0.001; 2-VD: 4.4% vs. 6.1% vs. 6.2%, P = 0.001; 3-VD: 3.1% vs. 5.2% vs. 4.3%, P < 0.001]. Compared with never smokers, current smokers experienced higher MACE risk [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.4-2.6, P < 0.001], while past smokers did not (HR 1.2, 95% CI 0.8-1.6, P = 0.35). Among matched individuals, current smokers had higher MACE risk (HR 2.6, 95% CI 1.6-4.2, P < 0.001), while past smokers did not (HR 1.3, 95% CI 0.7-2.4, P = 0.39). Similar findings were observed for risk of all-cause death. CONCLUSION: Among patients without known CAD undergoing CCTA, current and past smokers had increased burden of atherosclerosis compared with never smokers; however, risk of MACE was heightened only in current smokers.

Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.

AIM: Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown. METHODS AND RESULTS: From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0-10, 11-100, 101-400, 401-1000, >1000. For CCTA analysis, the number of obstructive vessels-as defined by the per-patient presence of a ≥50% luminal stenosis-was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) χ(2), C-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th-75th percentile, 17-30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LRχ(2), 25.34; increment in C-statistic, 0.24; NRI, 0.62, all P < 0.001), but not among those with CACS ≤100 (all P > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS. CONCLUSION: Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS.

The role of jet eccentricity in generating disproportionately elevated transaortic pressure gradients in patients with aortic stenosis.

In patients with aortic stenosis (AS) and eccentric transaortic flow, greater pressure loss occurs as the jet collides with the aortic wall together with delayed and diminished pressure recovery. This leads to the elevated transaortic valve pressure gradients noted on both Doppler and cardiac catheterization. Such situations may present a diagnostic dilemma where traditional measures of stenosis severity indicate severe AS, while imaging modalities of the aortic valve geometric aortic valve area (GOA) suggest less than severe stenosis. In this study, we present a series of cases exemplifying this clinical dilemma and demonstrate how color M-mode, 2D and 3D transthoracic (TTE) and transesophageal (TEE) echocardiography, cardiac computed tomography angiography (CTA), and magnetic resonance imaging (MRI), may be used to resolve such discrepancies.

Left ventricular function and volume with coronary CT angiography improves risk stratification and identification of patients at risk for incident mortality: results from 7758 patients in the prospective multinational CONFIRM observational cohort study.

PURPOSE: To assess whether gradations of left ventricular (LV) ejection fraction (LVEF) and volumes measured with coronary computed tomography (CT) would augment risk stratification and discrimination for incident mortality. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained when required. Subjects without known coronary artery disease (CAD) who underwent cardiac CT angiography with quantitative LV measurements were categorized according to LVEF (≥ 55%, 45%-54.9%, 35%-44.9%, or <35%). LV end-systolic volume (LVESV) and LV end-diastolic volume (LVEDV) were classified as normal (≥ 90 mL) or abnormal (≥ 200 mL). CAD extent and severity was categorized as none, nonobstructive, obstructive (≥ 50%), one-vessel, two-vessel, and three-vessel or left main disease. LVEF and volumes were assessed for risk prediction and discrimination of future mortality by using Cox hazards model and receiver operating characteristic curve analysis, respectively. RESULTS: During a follow-up of 2.0 years ± 0.9, 7758 patients (mean age, 58.5 years ± 13.0; 4220 male patients [54.4%]) were studied. At multivariable analysis, worsening LVEF was independently associated with mortality for moderately (hazard ratio = 3.14, P < .001) and severely (hazard ratio = 5.19, P < .001) abnormal ejection fraction. LVEF demonstrated improved discrimination for mortality (Az = 0.816) when compared with CAD risk factors alone (Az = 0.781) or CAD risk factors plus extent and severity. At multivariable analysis of a subgroup of 3706 individuals, abnormal LVEDV (hazard ratio = 4.02) and LVESV (hazard ratio = 6.46) helped predict mortality (P < .001). Similarly, LVESV and LVEDV demonstrated improved discrimination when compared with CAD risk factors or CAD extent and severity (P < .05). CONCLUSION: LV dysfunction and volumes measured with cardiac CT angiography augment risk prediction and discrimination for future mortality.

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study.

PURPOSE: To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. MATERIALS AND METHODS: Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. RESULTS: At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). CONCLUSION: When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease.

BACKGROUND: Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD. METHODS: From the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic angiography were prospectively enrolled and followed for a median of 2.1 years. Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary stenosis) a luminal stenosis. CAC scores were calculated using the Agatston method. Univariable and multivariable Cox proportional hazard models were employed to estimate all-cause mortality and/or myocardial infarction (MI). Four-year death and death or MI rates were 1.9% and 3.3%. RESULTS: Of the 4,380 patients with no luminal stenosis, 86% had CAC scores of <10 while those with a luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC score of ≥100. Among patients with no luminal stenosis, CAC was not predictive of all-cause mortality (P = .44). However, among patients with a luminal stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to ≥400 (P < .0001). The mortality hazard was 6.0 (P = .004) and 13.3 (P < .0001) for patients with a CAC score of 100-399 and ≥400. In patients with a luminal stenosis, CAC remained independently predictive in all-cause mortality (P < .0001) and death or MI (P < .0001) in multivariable models containing CAD risk factors and presenting symptoms. CONCLUSIONS: CAC allows for the identification of those at an increased hazard for death or MI in symptomatic patients with nonobstructive disease. From the CONFIRM registry, the extent of CAC was an independent estimator of long-term prognosis among symptomatic patients with luminal stenosis and may further define risk and guide preventive strategies in patients with nonobstructive CAD.

Calcium score, coronary artery disease extent and severity, and clinical outcomes among low Framingham risk patients with low vs high lifetime risk: results from the CONFIRM registry.

BACKGROUND: Short-term risk scores, such as the Framingham risk score (FRS), frequently classify younger patients as low risk despite the presence of uncontrolled cardiovascular risk factors. Among patients with low FRS, estimation of lifetime risk is associated with significant differences in coronary arterial calcium scores (CACS); however, the relationship of lifetime risk to coronary atherosclerosis on coronary CT angiography (CCTA) and prognosis has not been studied. METHODS AND RESULTS: We evaluated asymptomatic 20-60-year-old patients without diabetes or known coronary artery disease (CAD) within an international CT registry who underwent ≥64-slice CCTA. Patients with low FRS (<10%) were stratified as low (<39%) or high (≥39%) lifetime CAD risk, and compared for the presence and severity of CAD and prognosis for death, myocardial infarction, and late coronary revascularization (>90 days post CCTA). 1,863 patients of mean age of 47 years were included, with 48% of the low FRS patients at high lifetime risk. Median follow-up was 2.0 years. Comparing low-to-high lifetime risk, respectively, the prevalence of any CAD was 32% vs 41% (P < .001) and ≥50% stenosis was 7.4% vs 9.6% (P = .09). For those with CAD, subjects at low vs high lifetime risk had lower CACS (median 12 [IQR 0-94] vs 38 [IQR 0.05-144], P = .02) and less purely calcified plaque, 35% vs 45% (P < .001). Prognosis did not differ due to low number of events. CONCLUSION: Assessment of lifetime risk among patients at low FRS identified those with the increase in CAD prevalence and severity and a higher proportion of calcified plaque.

Cardiovascular risk among stable individuals suspected of having coronary artery disease with no modifiable risk factors: results from an international multicenter study of 5262 patients.

PURPOSE: To assess the prevalence, extent, severity, and risk of coronary artery disease (CAD) in patients suspected of having CAD but with no medically modifiable risk factors. MATERIALS AND METHODS: Institutional review board approval or waiver of consent was obtained at each center. This study was HIPAA compliant. From an international multicenter cohort study of 27 125 subjects undergoing coronary computed tomographic (CT) angiography from 12 centers, 5262 patients without known CAD and without modifiable risk factors were identified. CAD severity was defined as none (0%), mild (1%-49%), or obstructive (≥ 50%) on a per-patient, per-vessel, and per-segment basis. CAD presence, extent, and severity were related to incidence of major adverse cardiovascular event (MACE) by using Cox proportional hazards models. RESULTS: At a mean follow-up of 2.3 years ± 1.2 (standard deviation), MACE occurred in 106 patients. CAD was common for nonobstructive (n = 1452, 27%) and obstructive (n = 629, 12%) CAD. In risk-adjusted analysis, per-patient obstructive CAD (hazard ratio [HR], 6.64; 95% confidence interval [CI]: 3.68, 12.00; P ≤ .001) was related to MACE. MACE was associated with a dose-response relationship to the number of vessels exhibiting obstructive CAD, increasing risk for obstructive one-vessel (HR, 6.11; 95% CI: 3.22, 11.6; P ≤ .001), two-vessel (HR, 5.86; 95% CI: 2.75, 12.5; P ≤ .0001), or three-vessel or left main (HR, 11.69; 95% CI: 5.38, 25.4; P ≤ .001) CAD. The increased hazard for MACE of obstructive disease holds true for symptomatic (HR, 11.9; 95% CI: 4.81, 29.6; P ≤ .001) and asymptomatic (HR, 6.3; 95% CI: 2.4, 16.7; P ≤ .001) patients. No CAD at coronary CT angiography was associated with a low annualized MACE rate: 0.31% versus 2.06% with obstructive disease. CONCLUSION: Among individuals suspected of having CAD but without modifiable risk factors, CAD is common, with significantly increased hazards for MACE and mortality.