Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

OBJECTIVES: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. METHODS: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. RESULTS: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. CONCLUSIONS: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. CLINICAL RELEVANCE STATEMENT: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. KEY POINTS: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Patients With and Without Diabetes: Long-Term Outcomes From the CONFIRM Registry.

BACKGROUND: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known. METHODS: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis). RESULTS: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879). CONCLUSION: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.

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 (ß: 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.

Association between Aortic Valve Calcification Progression and Coronary Atherosclerotic Plaque Volume Progression in the PARADIGM Registry.

Background Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary -artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies. Purpose To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations. Materials and Methods A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed. Results Overall, 594 participants (mean age ± standard deviation, 62 years ± 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years ± 1.5). At baseline, the AVC score was 31 Agatston units ± 117, and the normalized total plaque volume at baseline was 122 mm3 ± 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized ß = 0.24; 95% CI: 0.16, 0.32; P < .001) and both calcified (ß = 0.26; 95% CI: 0.18, 0.34; P < .001) and noncalcified (ß = 0.17; 95% CI: 0.08, 0.25; P < .001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (ß = 0.13; 95% CI: 0.03, 0.22; P = .01), driven solely by calcified plaque volume (ß = 0.24; 95% CI: 0.14, 0.34; P < .001) but not noncalcified plaque volumes (ß = -0.06; 95% CI: -0.14, 0.03; P = .17). Conclusion The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. Clinical trial registration no. NCT02803411 © RSNA, 2021 See also the editorial by Sinitsyn in this issue.

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.

Association of hepatic steatosis with epicardial fat volume and coronary artery disease in symptomatic patients.

AIMS: This study aims to investigate whether HS-when associated with an excessive amount of epicardial adipose tissue-correlates with CAD in subjects with symptoms suggestive of CVD. METHODS AND RESULTS: CCTA images, demographic and clinical variables of 1.182 individuals were retrieved: semi-automated measurements for EFV, CAC, and MLD were obtained. Individuals were grouped into three categories according to the presence of CAD, resulting in absent (CAD0), non-obstructive (CAD1) or obstructive (CAD2) disease-groups, and into two categories based on the presence of HS (with no HS, named HS-, and with HS, named HS+). EFV was significantly higher in HS+ than in HS- group (p < 0.001), whereas MLD was lower in CAD+ than in CAD- subjects (p < 0.001). Two predictive models for CAD were tested: the former included clinical risk factors for CAD along with age, gender, EFV and MLD, whereas the latter did not include clinical variables. The logistic regression analysis of the second proposed model reliably discriminated CAD0 from CAD1 and CAD2 (AUC of 0.712, range 0.682-0.742). CONCLUSION: Lower MLD was associated with increased EFV, and MLD-as a marker of HS-discriminate symptomatic patients with CAD from whom without.

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.

Prognostic value of cardiac CT.

In the past decades, coronary computed tomography angiography (CCTA) has become a powerful tool in the management of coronary artery disease. The diagnostic and prognostic value of CCTA has been extensively demonstrated in both large observational studies and clinical trials among stable chest pain patients. The quantification of coronary artery calcium score (CACS) is a well-established predictor of cardiovascular morbidity and mortality in asymptomatic subjects. Besides CACS, the main strength of CCTA is the accurate assessment of the individual total atherosclerotic plaque burden, which holds important prognostic information. In addition, CCTA, by providing detailed information on coronary plaque morphology and composition with identification of specific high-risk plaque features, may further improve the risk stratification beyond the assessment of coronary stenosis. The development of new CCTA applications, such as stress myocardial CT perfusion and computational fluids dynamic applied to standard CCTA to derive CT-based fractional flow reserve (FFR) values have shown promising results to guide revascularization, potentially improving clinical outcomes in stable chest pain patients. In this review, starting from the role of CACS and moving beyond coronary stenosis, we evaluate the existing evidence of the prognostic effectiveness of the CCTA strategy in real-world clinical practice.

TAVI imaging: over the echocardiography.

Aortic valve stenosis (AS) is a common valvular heart disease. Recently, transcatheter aortic valve implantation (TAVI) has changed the treatment of severe AS in elderly patients with contraindications to traditional surgical replacement. Echocardiography is conventionally used as the first imaging modality to assess the presence and severity of AS and to provide anatomical and functional information. Nowadays, imaging techniques play a crucial role in the planning of TAVI to define suitable candidates. Computed tomography (CT) is essential to display the anatomy of the aortic valve complex (including aortic annulus, Valsalva sinuses, coronary arteries ostia, sinotubular junction), thoracoabdominal aorta, and vascular access. Cardiac CT may also provide the evaluation of coronary arteries in alternative to conventional coronary angiography. Magnetic resonance imaging may be alternative or supplementary in selected cases, providing detailed information of cardiac function and myocardial wall characteristics. More recently, advanced computer modeling image-based techniques can be used to support the evaluation of the feasibility and safety of TAVI procedures.

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.

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.

Integrated non-invasive approach to atherosclerosis with cardiac CT and carotid ultrasound in patients with suspected coronary artery disease.

OBJECTIVE: The aim of the study was to compare the atherosclerotic disease in the coronary and carotid arteries in patients who underwent non-invasive imaging for suspected stable coronary artery disease (CAD). MATERIALS AND METHODS: 107 patients (64 men, age 59 ± 12) with atypical chest pain underwent cardiac CT (CCT) and carotid ultrasound (US) on the same day. Severity (obstructive or not-obstructive disease), location, shape, and composition of atherosclerotic plaques in the two districts were evaluated. RESULTS: Patients presented normal coronary arteries in 36 % (n = 38), not-obstructive CAD in 36 % (n = 39), and obstructive CAD in 28 % (n = 30), while had normal carotid arteries in 53 % (n = 57), not-obstructive disease in 44 % (n = 47), and obstructive disease in 3 % (n = 3) (p < 0.05). The coronary plaques were located in 7 % at ostial sites, in 29 % at non-ostial sites, and in 64 % at both locations. The carotid plaques were located at the origin of the internal and external carotid arteries in 56 %, at the bifurcation in 20 %, and at both locations in 24 % (p < 0.05). Coronary plaques were calcified in 25 %, non-calcified in 19 %, and mixed in 56 %; carotid plaques were calcified in 8 %, non-calcified in 8 %, and mixed in 84 % of patients (p < 0.05). CONCLUSION: Atherosclerotic disease presents different imaging findings in the coronary tree and in the carotid district with respect to lesion severity, position along the vessel course, and composition of plaque.

Rationale and design of the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry: A comprehensive exploration of plaque progression and its impact on clinical outcomes from a multicenter serial coronary computed tomographic angiography study.

BACKGROUND: The natural history of coronary artery disease (CAD) in patients with low-to-intermediate risk is not well characterized. Although earlier invasive serial studies have documented the progression of atherosclerotic burden, most were focused on high-risk patients only. The PARADIGM registry is a large, prospective, multinational dynamic observational registry of patients undergoing serial coronary computed tomographic angiography (CCTA). The primary aim of PARADIGM is to characterize the natural history of CAD in relation to clinical and laboratory data. DESIGN: The PARADIGM registry (ClinicalTrials.govNCT02803411) comprises ≥2,000 consecutive patients across 9 cluster sites in 7 countries. PARADIGM sites were chosen on the basis of adequate CCTA volume, site CCTA proficiency, local demographic characteristics, and medical facilities to ensure a broad-based sample of patients. Patients referred for clinically indicated CCTA will be followed up and enrolled if they had a second CCTA scan. Patients will also be followed up beyond serial CCTA performance to identify adverse CAD events that include cardiac and noncardiac death, myocardial infarction, unstable angina, target vessel revascularization, and CAD-related hospitalization. SUMMARY: The results derived from the PARADIGM registry are anticipated to add incremental insight into the changes in CCTA findings in accordance with the progression or regression of CAD that confer prognostic value beyond demographic and clinical characteristics.

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.

Role of Cardiac Computed Tomography in the Evaluation of Coronary Artery Stenosis in Patients With Ascending Aorta Aneurysm Detected at Transthoracic Echocardiography.

OBJECTIVE: The aim of our study was to evaluate the diagnostic performance of cardiac computed tomography (CCT) in the evaluation of coronary artery stenosis in patients with ascending aorta aneurysm detected at transthoracic echocardiography. METHODS: We conducted a retrospective analysis of patients with an aneurysm 45 mm or greater at transthoracic echocardiography who underwent CCT from 2012 to 2014 in our hospital. We calculated the sensitivity, specificity, and positive and negative predictive values of CCT for the assessment of coronary artery stenosis (<50% or ≥50% stenosis) in patients who underwent conventional coronary angiography. RESULTS: We included 104 patients (73 men, aged 64 [SD, 10.8] years) in our study. Obstructive coronary artery disease was found in 22.1% of patients. Sensitivity, specificity, and positive and negative predictive values of CCT for detecting significant stenoses were 100%, 98%, and 82% and 100% on a segment-by-segment analysis and 100%, 83%, and 65% and 100% on a per-patient analysis, respectively. CONCLUSIONS: Cardiac computed tomography provides a comprehensive evaluation of ascending aorta aneurysms and coronary artery tree.

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.

Under-reporting of cardiovascular findings on chest CT.

PURPOSE: It is unclear whether (and, to what extent) radiologists look at and report cardiovascular abnormalities on non-cardio-synchronized standard chest computed tomography (CT). In this study, the frequency and the reporting rate of cardiovascular findings in chest CT examinations were retrospectively assessed. MATERIALS AND METHODS: This study was approved by the institutional review board of each participating center. Four academic centers provided data on 447 subjects who underwent non-ECG-synchronized chest CT examinations for evaluating pulmonary fibrosis (161/447, 36 %), suspected pulmonary embolism (140/447, 31.3 %), or lung cancer staging (146/447, 32.7 %). A total of 220/447 (53.7 %) and 227/447 CT (46.3 %) examinations were evaluated and reported by junior and senior chest radiologists, respectively. Two radiologists with training in cardiac imaging reviewed the same chest CT images looking for the presence of incidental cardiovascular abnormalities using a preformatted score sheet. Inter-observer agreement was assessed using the kappa coefficient of agreement (k). RESULTS: Inter-observer agreement between the study reviewers was moderate to good (0.4-0.73) for most of the incidental cardiovascular findings. At least one incidental cardiovascular finding not documented in the original report was identified by the study reviewers in 225/409 (55 %) of chest CT examinations. A total of 168/266 (63.2 %) potentially clinically significant cardiovascular findings were unreported in the original reports of 177/447 (39.6 %) subjects (p < 0.0001). Senior radiologists tended to more frequently report coronary artery calcification (p = 0.0006), cardiac valves calcification (p = 0.0003), and ascending aorta enlargement (p = 0.01) compared to junior radiologists. CONCLUSIONS: Several cardiovascular abnormalities can be reliably identified on standard chest CT. Yet, they are often under-reported, even when they might be relevant to the patient's work-up.

Collateral non cardiac findings in clinical routine CT coronary angiography: results from a multi-center registry.

PURPOSE: The aim of the study was to evaluate the prevalence of collateral findings detected in computed tomography coronary angiography (CTCA) in a multi-center registry. MATERIALS AND METHODS: We performed a retrospective review of 4303 patients (2719 males, mean age 60.3 ± 10.2 years) undergoing 64-slice CTCA for suspected or known coronary artery disease (CAD) at various academic institutions between 01/2006 and 09/2010. Collateral findings were recorded and scored as: non-significant (no signs of relevant pathology, not necessary to be reported), significant (clear signs of pathology, mandatory to be reported), or major (remarkable pathology, mandatory to be reported and further investigated). RESULTS: We detected 6886 non-cardiac findings (1.6 non cardiac finding per patient). Considering all centers, only 865/4303 (20.1 %) patients were completely without any additional finding. Overall, 2095 (30.4 %) non-significant, 4486 (65.2 %) significant, and 305 (4.4 %) major findings were detected. Among major findings, primary lung cancer was reported in 21 cases. In every center, most prevalent significant findings were mediastinal lymph nodes >1 cm. In 256 patients, collateral findings were clinically more relevant than coexisting CAD and justified the symptoms of patients. CONCLUSIONS: The prevalence of significant and major collateral findings in CTCA is high. Radiologists should carefully evaluate the entire scan volume in each patient.