CT or Invasive Coronary Angiography in Stable Chest Pain.

BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification.

BACKGROUND: Calcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling. METHODS: Human valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan (Bgn), Tlr3, and IFN-α/ß receptor alpha chain (Ifnar1)-deficient mice and a specific zebrafish model were used to study the implication of the biglycan (BGN)-TLR3-IFN axis in both CAVD and bone formation in vivo. Two large-scale cohorts (GERA [Genetic Epidemiology Research on Adult Health and Aging], n=55 192 with 3469 aortic stenosis cases; UK Biobank, n=257 231 with 2213 aortic stenosis cases) were examined for genetic variation at genes implicated in BGN-TLR3-IFN signaling associating with CAVD in humans. RESULTS: Here, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that Bgn-/-, Tlr3-/-, and Ifnar1-/- mice are protected against CAVD and display impaired bone formation. Meta-analysis of 2 large-scale cohorts with >300 000 individuals reveals that genetic variation at loci relevant to the XYLT1-BGN-TLR3-interferon-α/ß receptor alpha chain (IFNAR) 1 pathway is associated with CAVD in humans. CONCLUSIONS: This study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.

Effect of Body Mass Index on Effectiveness of CT versus Invasive Coronary Angiography in Stable Chest Pain: The DISCHARGE Trial.

Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m2, respectively. No interaction was found between CT or ICA and BMI for MACE (P = .29), the expanded MACE composite (P = .38), or major procedure-related complications (P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.

Coronary Artery Calcium Score Predicts Major Adverse Cardiovascular Events in Stable Chest Pain.

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques.

OBJECTIVE: To determine the association of cardiovascular atherosclerotic plaque monosodium urate deposits with the occurrence of major cardiovascular events in gout and hyperuricemia patients. METHODS: This retrospective cohort study included patients with clinically suspicion of gout, who performed a dual energy computed tomography of the affected limb and thorax between June 1st, 2012 and December 5th, 2019. Clinical and laboratory parameters were retrieved from patients charts. Established cardiovascular risk factors were evaluated. Medical history review identified the presence of major adverse cardiac events with a median follow up time of 33 months (range 0-108 months) after the performed computed tomography scan. RESULTS: Full data sets were available for 189 patients: 131 (69.3%) gout patients, 40 (21.2%) hyperuricemia patients, and 18 (9.5%) controls. Patients with cardiovascular monosodium urate deposits (n = 85/189, 45%) revealed increased serum acute phase reactants, uric acid levels and calcium scores in computed tomography compared with patients without cardiovascular monosodium urate deposits. Major adverse cardiac events were observed in 35 patients (18.5%) with a higher prevalence in those patients revealing cardiovascular monosodium urate deposits (n = 22/85, 25.9%) compared with those without cardiovascular monosodium urate deposits (n = 13/104, 12.5%, OR 2.4, p= 0.018). CONCLUSION: This is the first study demonstrating the higher hazard of major adverse cardiac events in patients with dual energy computed tomography-verified cardiovascular monosodium urate deposits. The higher prevalence of cardiac events in patients with cardiovascular monosodium urate deposits may facilitate risk stratification of gout patients, as classical cardiovascular risk scores or laboratory markers fail in their proper identification.

The interaction of lipomatous hypertrophy of the interatrial septum with pericardial adipose tissue biomarkers by computed tomography.

OBJECTIVE: Novel pericardial adipose tissue imaging biomarkers are currently under investigation for cardiovascular risk stratification. However, a specific compartment of the epicardial adipose tissue (EAT), lipomatous hypertrophy of the interatrial septum (LHIS), is included in the pericardial fat volume (PCFV) quantification software. Our aim was to evaluate LHIS by computed tomography angiography (CTA), to elaborate differences to other pericardial adipose tissue components (EAT) and paracardial adipose tissue (PAT), and to compare CT with [18F]FDG-PET. MATERIALS AND METHODS: Of 6983 patients screened who underwent coronary CTA for clinical indications, 190 patients with LHIS were finally included (age 62.8 years ± 9.6, 31.6% females, BMI 28.5 kg/cm2 ± 4.7) in our retrospective cohort study. CT images were quantified for LHIS, EAT, and PAT density (HU), and total PCFV, with and without LHIS, was calculated. CT was compared with [18F]FDG-PET if available. RESULTS: CT-density of LHIS was higher (- 22.4 HU ± 22.8) than all other pericardial adipose tissue components: EAT right and left (97.4 HU ± 13 and - 95.1 HU ± 13) PAT right and left (- 107.5 HU ± 13.4 and - 106.3 HU ± 14.5) and PCFV density -83.3 HU ± 5.6 (p < 0.001). There was a mild association between LHIS and PAT right (Beta 0.338, p = 0.006, 95% CI: 0.098-577) and PAT left (Beta 0.249, p = 0.030; 95% CI: 0.024-0.474) but not EAT right (p = 0.325) and left (p = 0.351), and not with total PCFV density (p = 0.164). The segmented LHIS volume comprised 3.01% of the total PCFV, and 4.3% (range, 2.16-11.7%) in those with LHIS > 9 mm. [18F]FDG-PET: LHIS was tracer uptake positive in 83.3% (37.5%: mild and 45.8%: minimal) of 24 patients. CONCLUSIONS: LHIS is a distinct compartment of PCFV with higher density suggesting brown fat and has no consistent association with EAT, but rather with PAT. CLINICAL RELEVANCE STATEMENT: LHIS should be recognized as a distinct compartment of the EAT, when using EAT for cardiovascular risk stratification. KEY POINTS: LHIS is currently included in EAT quantification software. LHIS density is relatively high, it is not associated with EAT, and has a high [18F]FDG-PET positive rate suggesting brown fat. LHIS is a distinct compartment of the EAT, and it may act differently as an imaging biomarker for cardiovascular risk stratification.

Review: The Role of Dual-Energy Computed Tomography in Detecting Monosodium Urate Deposits in Vascular Tissues.

PURPOSE OF REVIEW: To highlight novel findings in the detection of monosodium urate deposits in vessels using dual energy computed tomography, and to discuss the potential clinical implications for gout and hyperuricemia patients. RECENT FINDINGS: Gout is an independent risk factor for cardiovascular disease. However, classical risk calculators do not take into account these hazards, and parameters to identify patients at risk are lacking. Monosodium urate measured by dual energy computed tomography is a well-established technology for the detection and quantification of monosodium urate deposits in peripheral joints and tendons. Recent findings also suggest its applicability to identify vascular urate deposits. Dual energy computed tomography is a promising tool for detection of cardiovascular monosodium urate deposits in gout patients, to better delineate individuals at increased risk for cardiovascular disease.

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.

Chest CT of Lung Injury 1 Year after COVID-19 Pneumonia: The CovILD Study.

Background The long-term pulmonary sequelae of COVID-19 is not well known. Purpose To characterize patterns and rates of improvement of chest CT abnormalities 1 year after COVID-19 pneumonia. Materials and Methods This was a secondary analysis of a prospective, multicenter observational cohort study conducted from April 29 to August 12, 2020, to assess pulmonary abnormalities at chest CT approximately 2, 3, and 6 months and 1 year after onset of COVID-19 symptoms. Pulmonary findings were graded for each lung lobe using a qualitative CT severity score (CTSS) ranging from 0 (normal) to 25 (all lobes involved). The association of demographic and clinical factors with CT abnormalities after 1 year was assessed with logistic regression. The rate of change of the CTSS at follow-up CT was investigated by using the Friedmann test. Results Of 142 enrolled participants, 91 underwent a 1-year follow-up CT examination and were included in the analysis (mean age, 59 years ± 13 [SD]; 35 women [38%]). In 49 of 91 (54%) participants, CT abnormalities were observed: 31 of 91 (34%) participants showed subtle subpleural reticulation, ground-glass opacities, or both, and 18 of 91 (20%) participants had extensive ground-glass opacities, reticulations, bronchial dilation, microcystic changes, or a combination thereof. At multivariable analysis, age of more than 60 years (odds ratio [OR], 5.8; 95% CI: 1.7, 24; P = .009), critical COVID-19 severity (OR, 29; 95% CI: 4.8, 280; P < .001), and male sex (OR, 8.9; 95% CI: 2.6, 36; P < .001) were associated with persistent CT abnormalities at 1-year follow-up. Reduction of CTSS was observed in participants at subsequent follow-up CT (P < .001); during the study period, 49% (69 of 142) of participants had complete resolution of CT abnormalities. Thirty-one of 49 (63%) participants with CT abnormalities showed no further improvement after 6 months. Conclusion Long-term CT abnormalities were common 1 year after COVID-19 pneumonia. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leung in this issue.

Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial.

BACKGROUND: After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking. METHODS: In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT). RESULTS: Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time. CONCLUSION: A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities >100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.

Coronary atherosclerosis profile in patients with end-stage liver disease prior to liver transplantation due to alcoholic fatty liver: a coronary CTA study.

OBJECTIVES: To assess the coronary atherosclerosis profile by coronary computed tomography angiography (CTA) in patients with end-stage liver disease (ESLD) due to alcohol-related liver disease (ARLD) evaluated for liver transplantation (LT), in a retrospective matched case-controlled cohort study. METHODS: One hundred forty patients (age 60.6 years ± 9.8, 20.7% females) who underwent coronary CTA were included. Seventy patients with ESLD due to ARLD (ESLD-alc) were propensity score (1:1) matched for age, gender, and the major 5 cardiovascular risk factors with healthy controls. CTA analysis included the following: stenosis severity according to CAD-RADS as (0) = no, (1) minimal < 25%, (2) mild 25-50%, (3) moderate 50-70%, and (4) severe > 70% stenosis, total mixed plaque burden weighted for non-calcified component (G-score) and high-risk plaque criteria (Napkin-Ring, low attenuation plaque, spotty calcification, positive remodeling). RESULTS: Prevalence of coronary artery disease (CAD) was high (84.4%) in the ESLD-alc group but similar to controls. Stenosis severity was similar (CAD-RADS, 1.9 vs. 2.2, p = 0.289). High-grade stenosis (> 70%) was observed in 12.5% of ESLD-alc patients. High-risk plaques were less frequent in the ESLD-alc cohort as compared to controls (4.5% vs. 37.5%, p < 0.001), and total mixed plaque burden was lower (G-score, 4.9 versus 7.4, p = 0.001). Plaque density was lower in controls (56.6HU ± 3.2 vs. 91.3HU ± 4.5, p = 0.007) indicating more lipid-rich in controls, but higher mixed fibro-calcific plaque component in those with alcohol-related ESLD. CONCLUSION: Patients with alcohol-related ESLD exhibit more mixed fibro-calcified plaques but less plaque with high-risk features and less fibro-fatty plaque burden, while total CAD prevalence is high. KEY POINTS: • Patients with ESLD prior to LT have a high total prevalence of CAD and stenosis severity, which is similar to those of healthy controls with an identical cardiovascular risk profile. • Patients with ESLD prior to LT due to alcohol abuse have more calcific but less fibro-fatty plaque and less high-risk plaque. • CTA seems to be a useful imaging technique for risk stratification prior to LT.

Monosodium Urate Crystal Deposition in Coronary Artery Plaque by 128-Slice Dual-Energy Computed Tomography: An Ex Vivo Phantom and In Vivo Study.

OBJECTIVE: Monosodium uric acid (MSU) crystals may accumulate in the coronary plaque. The objective was to assess whether dual-energy computed tomography (DECT) allows for detection of MSU in coronary plaque. METHODS: Patients were examined with 128-slice DECT applying a cardiac electrocardiogram-gated and peripheral extremity protocol. Patients were divided into 3 groups: gout (tophi >1 cm in peripheral joints), hyperuricemia (>6.5 mg/dL serum uric acid), and controls. The groups were matched for cardiovascular risk factors. Monosodium uric acid-positive (+) and calcified plaque were distinguished, and the coronary artery calcium score was calculated. Ex vivo phantom: MSU solutions were diluted in different NaCL solutions (5%/10%/15%/20%/25%). Coronary artery models with 2 different plaque types (MSU+ and calcified) were created. RESULTS: A total of 96 patients were included (37 with gout, 33 with hyperuricemia, and 26 controls). Monosodium uric acid-positive plaques were found more often in patients with gout as compared with controls (91.9% vs 0.38%; P < 0.0001), and the number of plaques was higher (P < 0.0001). Of 102 MSU+ plaques, 26.7% were only MSU+ and 74.2% were mixed MSU+/calcified. Monosodium uric acid-positive plaque had mean 232.3 Hounsfield units (range, 213-264). Coronary artery calcium score was higher in patients with gout as compared with controls (659.1 vs 112.4 Agatston score; P < 0.001). Patients with gout had more MSU+ plaques as compared with patients with hyperuricemia (91.6% vs 2.9%; P < 0.0001), and coronary artery calcium score was higher (659.1 vs 254 Agatston score; P < 0.001), but there was no difference between patients with hyperuricemia and controls. Ex vivo phantom study: MSU crystals were detected by DECT in solutions with a concentration of 15% or greater MSU and could be distinguished from calcified. CONCLUSIONS: Coronary MSU+ plaques can be detected by DECT in patients with gout.

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.

Correction to: Pilot study of the multicentre DISCHARGE trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography.

The original version of this article, published on 16 December 2019, unfortunately contained two mistakes.

Pilot study of the multicentre DISCHARGE Trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography.

OBJECTIVE: To implement detailed EU cardiac computed tomography angiography (CCTA) quality criteria in the multicentre DISCHARGE trial (FP72007-2013, EC-GA 603266), we reviewed image quality and adherence to CCTA protocol and to the recommendations of invasive coronary angiography (ICA) in a pilot study. MATERIALS AND METHODS: From every clinical centre, imaging datasets of three patients per arm were assessed for adherence to the inclusion/exclusion criteria of the pilot study, predefined standards for the CCTA protocol and ICA recommendations, image quality and non-diagnostic (NDX) rate. These parameters were compared via multinomial regression and ANOVA. If a site did not reach the minimum quality level, additional datasets had to be sent before entering into the final accepted database (FADB). RESULTS: We analysed 226 cases (150 CCTA/76 ICA). The inclusion/exclusion criteria were not met by 6 of the 226 (2.7%) datasets. The predefined standard was not met by 13 of 76 ICA datasets (17.1%). This percentage decreased between the initial CCTA database and the FADB (multinomial regression, 53 of 70 vs 17 of 75 [76%] vs [23%]). The signal-to-noise ratio and contrast-to-noise ratio of the FADB did not improve significantly (ANOVA, p = 0.20; p = 0.09). The CTA NDX rate was reduced, but not significantly (initial CCTA database 15 of 70 [21.4%]) and FADB 9 of 75 [12%]; p = 0.13). CONCLUSION: We were able to increase conformity to the inclusion/exclusion criteria and CCTA protocol, improve image quality and decrease the CCTA NDX rate by implementing EU CCTA quality criteria and ICA recommendations. KEY POINTS: • Failure to meet protocol adherence in cardiac CTA was high in the pilot study (77.6%). • Image quality varies between sites and can be improved by feedback given by the core lab. • Conformance with new EU cardiac CT quality criteria might render cardiac CTA findings more consistent and comparable.

Correction to: Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

An amendment to this paper has been published and can be accessed via the original article.

Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

BACKGROUND: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. METHODS: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. RESULTS: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type. CONCLUSIONS: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02400229.

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.

Gout of hand and wrist: the value of US as compared with DECT.

OBJECTIVES: The purpose of this study was to compare findings of ultrasound (US) with dual-energy CT (DECT) in patients presenting with suspected gouty hand and wrist arthritis. METHODS: This prospective study included 180 patients (136 men and 44 women, age range, 31- 94 years; mean age, 65.9 years) with an initial clinical diagnosis of acute gouty arthritis who underwent DECT and US examination. Intra- and extra-articular findings of each modality were tabulated and calculated with DECT as gold standard. RESULTS: The final diagnosis of gout was positive in 97/180 patients (53.9%) by DECT, an alternative diagnosis confirmed in 83 patients. US showed a sensitivity of 70.1% (extra-articular: 42.5%, p < 0.0001; intra-articular: 80.3%, p = 0.14) and specificity of 51%. The double contour sign (DCS) was present in 58/61 patients with a positive US study for intra-articular gout (95.1%). CONCLUSIONS: Sensitivity of US for diagnosis of gouty arthritis in hand and wrist is limited, particularly with respect to extra-articular urate deposition. The DCS is the most sensitive sign for the assessment of gouty hand and wrist arthritis by US. KEY POINTS: • Sensitivity of US for diagnosis of gouty arthritis in hand and wrist is limited, particularly with respect to extra-articular gouty deposits. • The double contour sign is the most sensitive finding for the assessment of gouty hand and wrist arthritis by US. • Although the sensitivity of US for diagnosis of gouty hand and wrist arthritis is limited, it can be used as a first-line imaging modality in the presence of the DCS.

Is MRI equivalent to CT in the guidance of TAVR? A pilot study.

OBJECTIVES: To compare a comprehensive cardiovascular magnetic resonance imaging (MRI) protocol with contrast-enhanced computed tomography angiography (CTA) for guidance in transcatheter aortic valve replacement (TAVR) evaluation. METHODS AND RESULTS: Non-contrast three-dimensional (3D) 'whole heart' MRI imaging for aortic annulus sizing and measurements of coronary ostia heights, contrast-enhanced MRI angiography (MRA) for evaluation of transfemoral routes as well as aortoiliofemoral-CTA were performed in 16 patients referred for evaluation of TAVR. Aortic annulus measurements by MRI and CTA showed a very strong correlation (r=0.956, p<0.0001; effective annulus area for MRI 430±74 vs. 428±78 mm2 for CTA, p=0.629). Regarding decision for valve size there was complete consistency between MRI and CTA. Moreover, vessel luminal diameters and angulations of aortoiliofemoral access as measured by MRA and CTA showed overall very strong correlations (r= 0.819 to 0.996, all p<0.001), the agreement of minimal vessel diameter between the two modalities revealed a bias of 0.02 mm (upper and lower limit of agreement: 1.02 mm and -0.98 mm). CONCLUSIONS: In patients referred for TAVR, MRI measurements of aortic annulus and minimal aortoiliofemoral diameters showed good to excellent agreement. Decisions based on MRI measurements regrading prosthesis sizing and transfemoral access would not have modified TAVR-strategy as compared to a CTA-based choice. KEY POINTS: • 'Whole heart' MRI and CTA measurements of aortic annulus correlate very strongly. • MRI- and CTA-based prostheses sizing are in excellent agreement. • MRA and CTA equally guide TAVR access strategy.