Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

Impact of atherosclerosis imaging-quantitative computed tomography on diagnostic certainty, downstream testing, coronary revascularization, and medical therapy: the CERTAIN study.

AIMS: The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. METHODS AND RESULTS: In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. CONCLUSION: The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy.

Rationale and design of the CONFIRM2 (Quantitative COroNary CT Angiography Evaluation For Evaluation of Clinical Outcomes: An InteRnational, Multicenter Registry) study.

BACKGROUND: In the last 15 years, large registries and several randomized clinical trials have demonstrated the diagnostic and prognostic value of coronary computed tomography angiography (CCTA). Advances in CT scanner technology and developments of analytic tools now enable accurate quantification of coronary artery disease (CAD), including total coronary plaque volume and low attenuation plaque volume. The primary aim of CONFIRM2, (Quantitative COroNary CT Angiography Evaluation For Evaluation of Clinical Outcomes: An InteRnational, Multicenter Registry) is to perform comprehensive quantification of CCTA findings, including coronary, non-coronary cardiac, non-cardiac vascular, non-cardiac findings, and relate them to clinical variables and cardiovascular clinical outcomes. DESIGN: CONFIRM2 is a multicenter, international observational cohort study designed to evaluate multidimensional associations between quantitative phenotype of cardiovascular disease and future adverse clinical outcomes in subjects undergoing clinically indicated CCTA. The targeted population is heterogenous and includes patients undergoing CCTA for atherosclerotic evaluation, valvular heart disease, congenital heart disease or pre-procedural evaluation. Automated software will be utilized for quantification of coronary plaque, stenosis, vascular morphology and cardiac structures for rapid and reproducible tissue characterization. Up to 30,000 patients will be included from up to 50 international multi-continental clinical CCTA sites and followed for 3-4 years. SUMMARY: CONFIRM2 is one of the largest CCTA studies to establish the clinical value of a multiparametric approach to quantify the phenotype of cardiovascular disease by CCTA using automated imaging solutions.

Distal-vessel fractional flow reserve by computed tomography to monitor epicardial coronary artery disease.

AIMS: Coronary computed tomography angiography (CTA) and fractional flow reserve by computed tomography (FFR-CT) are increasingly utilized to characterize coronary artery disease (CAD). We evaluated the feasibility of distal-vessel FFR-CT as an integrated measure of epicardial CAD that can be followed serially, assessed the CTA parameters that correlate with distal-vessel FFR-CT, and determined the combination of clinical and CTA parameters that best predict distal-vessel FFR-CT and distal-vessel FFR-CT changes. METHODS AND RESULTS: Patients (n = 71) who underwent serial CTA scans at ≥2 years interval (median = 5.2 years) over a 14-year period were included in this retrospective study. Coronary arteries were analysed blindly using artificial intelligence-enabled quantitative coronary CTA. Two investigators jointly determined the anatomic location and corresponding distal-vessel FFR-CT values at CT1 and CT2. A total of 45.3% had no significant change, 27.8% an improvement, and 26.9% a worsening in distal-vessel FFR-CT at CT2. Stepwise multiple logistic regression analysis identified a four-parameter model consisting of stenosis diameter ratio, lumen volume, low density plaque volume, and age, that best predicted distal-vessel FFR-CT ≤ 0.80 with an area under the curve (AUC) = 0.820 at CT1 and AUC = 0.799 at CT2. Improvement of distal-vessel FFR-CT was captured by a decrease in high-risk plaque and increases in lumen volume and remodelling index (AUC = 0.865), whereas increases in stenosis diameter ratio, medium density calcified plaque volume, and total cholesterol presaged worsening of distal-vessel FFR-CT (AUC = 0.707). CONCLUSION: Distal-vessel FFR-CT permits the integrative assessment of epicardial atherosclerotic plaque burden in a vessel-specific manner and can be followed serially to determine changes in global CAD.

Encapsulated Calcified Hematoma Mimicking a Cardiac Tumor, Diagnosed 25 Years Post-Traumatic Injury.

A 45-year-old man presented with nonspecific symptoms caused by a mass compressing the right ventricle. Cardiac computed tomography accurately predicted the operative and pathologic appearance of the mass, and the final diagnosis of an encapsulated cardiac hematoma was confirmed by pathologic examination. This condition is infrequent and mimics a cardiac tumor. (Level of Difficulty: Advanced.).

Artificial intelligence using a deep learning versus expert computed tomography human reading in calcium score and coronary artery calcium data and reporting system classification.

BACKGROUND: Artificial intelligence (AI) applied to cardiac imaging may provide improved processing, reading precision and advantages of automation. Coronary artery calcium (CAC) score testing is a standard stratification tool that is rapid and highly reproducible. We analyzed CAC results of 100 studies in order to determine the accuracy and correlation between the AI software (Coreline AVIEW, Seoul, South Korea) and expert level-3 computed tomography (CT) human CAC interpretation and its performance when coronary artery disease data and reporting system (coronary artery calcium data and reporting system) classification is applied. METHODS: A total of 100 non-contrast calcium score images were selected by blinded randomization and processed with the AI software versus human level-3 CT reading. The results were compared and the Pearson correlation index was calculated. The CAC-DRS classification system was applied, and the cause of category reclassification was determined using an anatomical qualitative description by the readers. RESULTS: The mean age was age 64.5 years, with 48% female. The absolute CAC scores between AI versus human reading demonstrated a highly significant correlation (Pearson coefficient R  = 0.996); however, despite these minimal CAC score differences, 14% of the patients had their CAC-DRS category reclassified. The main source of reclassification was observed in CAC-DRS 0-1, where 13 were recategorized, particularly between studies having a CAC Agatston score of 0 versus 1. Qualitative description of the errors showed that the main cause of misclassification was AI underestimation of right coronary calcium, AI overestimation of right ventricle densities and human underestimation of right coronary artery calcium. CONCLUSION: Correlation between AI and human values is excellent with absolute numbers. When the CAC-DRS classification system was adopted, there was a strong correlation in the respective categories. Misclassified were predominantly in the category of CAC = 0, most often with minimal values of calcium volume. Additional algorithm optimization with enhanced sensitivity and specificity for low values of calcium volume will be required to enhance AI CAC score utilization for minimal disease. Over a broad range of calcium scores, AI software for calcium scoring had an excellent correlation compared to human expert reading and in rare cases determined calcium missed by human interpretation.

Serial analysis of coronary artery disease progression by artificial intelligence assisted coronary computed tomography angiography: early clinical experience.

BACKGROUND: Studies have shown that quantitative evaluation of coronary artery plaque on Coronary Computed Tomography Angiography (CCTA) can identify patients at risk of cardiac events. Recent demonstration of artificial intelligence (AI) assisted CCTA shows that it allows for evaluation of CAD and plaque characteristics. Based on publications to date, we are the first group to perform AI augmented CCTA serial analysis of changes in coronary plaque characteristics over 13 years. We evaluated whether AI assisted CCTA can accurately assess changes in coronary plaque progression, which has potential clinical prognostic value in CAD management. CASE PRESENTATION: 51-year-old male with hypertension, hyperlipidemia and family history of myocardial infarction, underwent CCTA exams for anginal symptom evaluation and CAD assessment. 5 CCTAs were performed between 2008 and 2021. Quantitative atherosclerosis plaque characterization (APC) using an AI platform (Cleerly), was performed to assess CAD burden. Total plaque volume (TPV) change-over-time demonstrated decreasing low-density non-calcified plaque (LD-NCP) with increasing overall NCP and calcified-plaque (CP). Examination of individual segments revealed a proximal-LAD lesion with decreasing NCP over-time and increasing CP. In contrast, although the D2/D1/ramus lesions showed increasing stenosis, CP, and total plaque, there were no significant differences in NCP over-time, with stable NCP and increased CP. Remarkably, we also consistently visualized small plaques, which typically readers may interpret as false positives due to artifacts. But in this case, they reappeared each study in the same locations, generally progressing in size and demonstrating expected plaque transformation over-time. CONCLUSIONS: We performed the first AI augmented CCTA based serial analysis of changes in coronary plaque characteristics over 13 years. We were able to consistently assess progression of plaque volumes, stenosis, and APCs with this novel methodology. We found a significant increase in TPV composed of decreasing LD-NCP, and increasing NCP and CP, with variations in the evolution of APCs between vessels. Although the significance of evolving APCs needs to be investigated, this case demonstrates AI-based CCTA analysis can serve as valuable clinical tool to accurately define unique CAD characteristics over time. Prospective trails are needed to assess whether quantification of APCs provides prognostic capabilities to improve clinical care.

Serial Changes in Troponin I in COVID-19 Vaccine-Associated Myocarditis.

A 63-year-old woman presented with atypical chest pain after a third dose of the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine. Serial cardiac troponin measurements were performed to evaluate the trajectory of her time-concentration curve which showed a typical myocarditis curve with rapid normalization. The diagnosis of myocarditis was confirmed by cardiac magnetic resonance imaging and follow-up imaging showed resolution. All symptoms resolved with weeks.

Interobserver variability among expert readers quantifying plaque volume and plaque characteristics on coronary CT angiography: a CLARIFY trial sub-study.

BACKGROUND: The difference between expert level (L3) reader and artificial intelligence (AI) performance for quantifying coronary plaque and plaque components is unknown. OBJECTIVE: This study evaluates the interobserver variability among expert readers for quantifying the volume of coronary plaque and plaque components on coronary computed tomographic angiography (CCTA) using an artificial intelligence enabled quantitative CCTA analysis software as a reference (AI-QCT). METHODS: This study uses CCTA imaging obtained from 232 patients enrolled in the CLARIFY (CT EvaLuation by ARtificial Intelligence For Atherosclerosis, Stenosis and Vascular MorphologY) study. Readers quantified overall plaque volume and the % breakdown of noncalcified plaque (NCP) and calcified plaque (CP) on a per vessel basis. Readers categorized high risk plaque (HRP) based on the presence of low-attenuation-noncalcified plaque (LA-NCP) and positive remodeling (PR; ≥1.10). All CCTAs were analyzed by an FDA-cleared software service that performs AI-driven plaque characterization and quantification (AI-QCT) for comparison to L3 readers. Reader generated analyses were compared among readers and to AI-QCT generated analyses. RESULTS: When evaluating plaque volume on a per vessel basis, expert readers achieved moderate to high interobserver consistency with an intra-class correlation coefficient of 0.78 for a single reader score and 0.91 for mean scores. There was a moderate trend between readers 1, 2, and 3 and AI with spearman coefficients of 0.70, 0.68 and 0.74, respectively. There was high discordance between readers and AI plaque component analyses. When quantifying %NCP v. %CP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.23, 0.34 and 0.24, respectively, compared to AI with a spearman coefficient of 0.38, 0.51, and 0.60, respectively. The intra-class correlation coefficient among readers for plaque composition assessment was 0.68. With respect to HRP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.22, 0.26, and 0.17, respectively, and a spearman coefficient of 0.36, 0.35, and 0.44, respectively. CONCLUSION: Expert readers performed moderately well quantifying total plaque volumes with high consistency. However, there was both significant interobserver variability and high discordance with AI-QCT when quantifying plaque composition.

Quantitative plaque analysis with A.I.-augmented CCTA in end-stage renal disease and complex CAD.

BACKGROUND: Adverse cardiovascular events are a significant cause of mortality in end-stage renal disease (ESRD) patients. High-risk plaque anatomy may be a significant contributor. However, their atherosclerotic phenotypes have not been described. We sought to define atherosclerotic plaque characteristics (APC) in dialysis patients using artificial-intelligence augmented CCTA. METHODS: We retrospectively analyzed ESRD patients referred for CCTA using an FDA approved artificial-intelligence augmented-CCTA program (Cleerly). Coronary lesions were evaluated for APCs by CCTA. APCs included percent atheroma volume(PAV), low-density non-calcified-plaque (LD-NCP), non-calcified-plaque (NCP), calcified-plaque (CP), length, and high-risk-plaque (HRP), defined by LD-NCP and positive arterial remodeling >1.10 (PR). RESULTS: 79 ESRD patients were enrolled, mean age 65.3 years, 32.9% female. Disease distribution was non-obstructive (65.8%), 1-vessel disease (21.5%), 2-vessel disease (7.6%), and 3-vessel disease (5.1%). Mean total plaque volume (TPV) was 810.0 mm3, LD-NCP 16.8 mm3, NCP 403.1 mm3, and CP 390.1 mm3. HRP was present in 81.0% patients. Patients with at least one >50% stenosis, or obstructive lesions, had significantly higher TPV, LD-NCP, NCP, and CP. Patients >65 years had more CP and higher PAV. CONCLUSION: Our study provides novel insight into ESRD plaque phenotypes and demonstrates that artificial-intelligence augmented CCTA analysis is feasible for CAD characterization despite severe calcification. We demonstrate elevated plaque burden and stenosis caused by predominantly non-calcified-plaque. Furthermore, the quantity of calcified-plaques increased with age, with men exhibiting increased number of 2-feature plaques and higher plaque volumes. Artificial-intelligence augmented CCTA analysis of APCs may be a promising metric for cardiac risk stratification and warrants further prospective investigation.

Performance and Integration of Smartphone Wireless ECG Monitoring into the Enterprise Electronic Health Record: First Clinical Experience.

INTRODUCTION: Patient initiated, remote cardiac monitoring has proved to be a significant advance in the diagnosis and management of arrhythmias. Further improvements in ease of use and access to results will further improve health outcomes and cost-effectiveness. Here we describe a proof-of-concept evaluation to assess the feasibility of successfully implementing a cloud-based management system using KardiaPro (KP) for remote electrocardiogram (ECG) monitoring to interface into EPIC, an enterprise electronic health record (EHR) system. METHODS: The KP management system was embedded using hypertext markup language (HTML) code directly into the EHR. Encrypted credentials and patient data were bundled with an application programming interface key allowing linkage of remote monitoring from patients' smartphones. During the time of implementation, a total of 322 patients and 32 179 ECGs were recorded. RESULTS: The KP-EHR interface provided full functionality, allowing detection, interpretation and documentation of atrial fibrillation (AF), flutter events, ventricular tachycardia, and complete heart block. Our study focused on KP's detection of AF, and 16.7% of tracings were classified as probable AF with only 2.3% of tracings not analyzed by the KP algorithm because of tracings that were too noisy or truncated. Enhanced management was facilitated with clinical information immediately accessible. Blinded physician ECG review validated the KP proprietary algorithm interpretation and ECGs. CONCLUSIONS: Direct integration of KP into EHR was successful and practical. It allows for historical, point of care and immediate retrieval of remote ambulatory monitoring data and documentation into the electronic health record. KP EHR integration warrants further study as it has the potential to improve cost-effectiveness and clinical diagnostic value, leading to improvements in delivery of patient care.

CT ​Evaluation ​by ​Artificial ​Intelligence ​for ​Atherosclerosis, Stenosis and Vascular ​Morphology ​(CLARIFY): ​A ​Multi-center, international study.

BACKGROUND: Atherosclerosis evaluation by coronary computed tomography angiography (CCTA) is promising for coronary artery disease (CAD) risk stratification, but time consuming and requires high expertise. Artificial Intelligence (AI) applied to CCTA for comprehensive CAD assessment may overcome these limitations. We hypothesized AI aided analysis allows for rapid, accurate evaluation of vessel morphology and stenosis. METHODS: This was a multi-site study of 232 patients undergoing CCTA. Studies were analyzed by FDA-cleared software service that performs AI-driven coronary artery segmentation and labeling, lumen and vessel wall determination, plaque quantification and characterization with comparison to ground truth of consensus by three L3 readers. CCTAs were analyzed for: % maximal diameter stenosis, plaque volume and composition, presence of high-risk plaque and Coronary Artery Disease Reporting & Data System (CAD-RADS) category. RESULTS: AI performance was excellent for accuracy, sensitivity, specificity, positive predictive value and negative predictive value as follows: >70% stenosis: 99.7%, 90.9%, 99.8%, 93.3%, 99.9%, respectively; >50% stenosis: 94.8%, 80.0%, 97.0, 80.0%, 97.0%, respectively. Bland-Altman plots depict agreement between expert reader and AI determined maximal diameter stenosis for per-vessel (mean difference -0.8%; 95% CI 13.8% to -15.3%) and per-patient (mean difference -2.3%; 95% CI 15.8% to -20.4%). L3 and AI agreed within one CAD-RADS category in 228/232 (98.3%) exams per-patient and 923/924 (99.9%) vessels on a per-vessel basis. There was a wide range of atherosclerosis in the coronary artery territories assessed by AI when stratified by CAD-RADS distribution. CONCLUSIONS: AI-aided approach to CCTA interpretation determines coronary stenosis and CAD-RADS category in close agreement with consensus of L3 expert readers. There was a wide range of atherosclerosis identified through AI.

Low Wall Shear Stress Is Associated with Saphenous Vein Graft Stenosis in Patients with Coronary Artery Bypass Grafting.

Biomechanical forces may play a key role in saphenous vein graft (SVG) disease after coronary artery bypass graft (CABG) surgery. Computed tomography angiography (CTA) of 430 post-CABG patients were evaluated and 15 patients were identified with both stenosed and healthy SVGs for paired analysis. The stenosis was virtually removed, and detailed 3D models were reconstructed to perform patient-specific computational fluid dynamic (CFD) simulations. Models were processed to compute anatomic parameters, and hemodynamic parameters such as local and vessel-averaged wall shear stress (WSS), normalized WSS (WSS*), low shear area (LSA), oscillatory shear index (OSI), and flow rate. WSS* was significantly lower in pre-diseased SVG segments compared to corresponding control segments without disease (1.22 vs. 1.73, p = 0.012) and the area under the ROC curve was 0.71. No differences were observed in vessel-averaged anatomic or hemodynamic parameters between pre-stenosed and control whole SVGs. There are currently no clinically available tools to predict SVG failure post-CABG. CFD modeling has the potential to identify high-risk CABG patients who may benefit from more aggressive medical therapy and closer surveillance. Graphical Abstract.

Left Main Coronary Artery Thrombus Diagnosed and Managed With Coronary Computed Tomography Angiography and Fractional Flow Reserve Derived From Computed Tomography.

Left main coronary artery thrombus (LMCA-T) is a rare disease state and diagnosed with invasive coronary angiography (ICA). We present a case of LMCA-T diagnosed with coronary computed tomography angiography (CTA) and treated without ICA in a patient who presented to a hospital in the middle of war zone in Erbil, Iraqi Kurdistan. Coronary CTA performed 1 month later demonstrated resolution of the thrombus. Fractional flow reserve computed from computed tomography (FFR-CT; HeartFlow, Redwood City, CA) performed retrospectively confirmed that the clot was not hemodynamically significant at the time of diagnosis. This case demonstrates the diagnostic capabilities of coronary CTA and FFR-CT when ICA is not readily available.

Fractional flow reserve by computerized tomography and subsequent coronary revascularization.

AIMS: Fractional flow reserve by computerized tomography (FFR-CT) provides non-invasive functional assessment of the hemodynamic significance of coronary artery stenosis. We determined the FFR-CT values, receiver operator characteristic (ROC) curves, and predictive ability of FFR-CT for actual standard of care guided coronary revascularization. METHODS AND RESULTS: Consecutive outpatients who underwent coronary CT angiography (coronary CTA) followed by invasive angiography over a 24-month period from 2012 to 2014 were identified. Studies that fit inclusion criteria (n = 75 patients, mean age 66, 75% males) were sent for FFR-CT analysis, and results stratified by coronary artery calcium (CAC) scores. Coronary CTA studies were re-interpreted in a blinded manner, and baseline FFR-CT values were obtained retrospectively. Therefore, results did not interfere with clinical decision-making. Median FFR-CT values were 0.70 in revascularized (n = 69) and 0.86 in not revascularized (n = 138) coronary arteries (P < 0.001). Using clinically established significance cut-offs of FFR-CT ≤0.80 and coronary CTA ≥70% stenosis for the prediction of clinical decision-making and subsequent coronary revascularization, the positive predictive values were 74 and 88% and negative predictive values were 96 and 84%, respectively. The area under the curve (AUC) for all studied territories was 0.904 for coronary CTA, 0.920 for FFR-CT, and 0.941 for coronary CTA combined with FFR-CT (P = 0.001). With increasing CAC scores, the AUC decreased for coronary CTA but remained higher for FFR-CT (P < 0.05). CONCLUSION: The addition of FFR-CT provides a complementary role to coronary CTA and increases the ability of a CT-based approach to identify subsequent standard of care guided coronary revascularization.

A clinical model to identify patients with high-risk coronary artery disease.

OBJECTIVES: This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). BACKGROUND: Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy. METHODS: Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort. RESULTS: The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (<0.1), whereas patients who scored ≥18 points had a high specificity of 99.3% and a positive likelihood ratio (8.48). In the validation group, the prevalence of high-risk CAD was 1% in patients with ≤7 points and 16.7% in those with ≥18 points. CONCLUSIONS: We propose a scoring system, based on clinical variables, that can be used to identify patients at high and low pre-test probability of having high-risk CAD. Identification of these populations may detect those who may benefit from a trial of medical therapy and those who may benefit most from an invasive strategy.

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.