Choosing Wisely internationally - helpful recommendations for antimicrobial stewardship!

PURPOSE: Antimicrobial resistance poses a major threat to human health globally and antibiotic overuse is a main driver of resistance. Antimicrobial stewardship (AMS) was developed to improve the rationale use of antibiotics. The Choosing Wisely campaign was initiated to ameliorate medical practice through avoidance of unnecessary diagnostic and therapeutic procedures. Our objective was to give an overview on the Choosing Wisely recommendations related to AMS practices from a selection of different countries in order to define future needs. METHODS: We evaluated the seven countries already analyzed for Choosing Wisely recommendations related to topics of infectious medicine before. Finally, we included five of the former countries (Australia/New Zealand, Canada, Italy, Switzerland, and USA) and Germany with easily accessible recommendations and selected those related to six categories of AMS as following: diagnostics, indication, choice of antiinfective drugs, dosing, application and duration of therapy. RESULTS: In total, 213 recommendations could be extracted related to AMS for the six countries and were matched to the chosen categories. Interestingly, no recommendations were found for the category "dosing." Topics related to indication and diagnostics were most frequently found with 85 and 78 recommendations, respectively. Perioperative prophylaxis was a frequently addressed issue - both related to application, indication and duration. Avoiding antibiotic treatment of asymptomatic bacteriuria and upper respiratory tract infections were central topics of all countries. CONCLUSION: AMS is an important strategy to fight increasing resistance and is frequently addressed by Choosing Wisely recommendations of different countries. Similar issues are considered important in the selected countries.

Comparison of risk assessment strategies incorporating coronary artery calcium score with estimation of pretest probability to defer cardiovascular testing in patients with stable chest pain.

BACKGROUND: The risk assessment of patients with stable chest pain (SCP) to defer further cardiovascular testing is crucial, but the most appropriate risk assessment strategy remains unknown. We aimed to compare current strategies to identify low risk SCP patients. METHODS: 5289 symptomatic patients who had undergone coronary artery calcium score (CACS) and coronary computed tomographic angiography scan were identified and followed. Pretest probability (PTP) of obstructive coronary artery disease (CAD) for every patient was estimated according to European Society of Cardiology (ESC)-PTP model and CACS-weighted clinical likelihood (CACS-CL) model, respectively. Based on the 2019 ESC guideline-determined risk assessment strategy (ESC strategy) and CACS-CL model-based risk assessment strategy (CACS-CL strategy), all patients were divided into low and high risk group, respectively. Area under receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) was used. RESULTS: CACS-CL model provided more robust estimation of PTP than ESC-PTP model did, with a larger AUC (0.838 versus 0.735, p < 0.0001), positive IDI (9%, p < 0.0001) and less discrepancy between observed and predicted probabilities. As a result, compared to ESC strategy which only applied CACS-CL model to patients with borderline ESC-PTP, CACS-CL strategy incorporating CACS with estimation of PTP to entire SCP patients indicated a positive NRI (19%, p < 0.0001) and a stronger association to major adverse cardiovascular events, with hazard ratios: 3.97 (95% confidence intervals: 2.75-5.72) versus 5.11 (95% confidence intervals: 3.40-7.69). CONCLUSION: The additional use of CACS for all SCP patients in CACS-CL strategy improved the risk assessment of SCP patients to identify individuals at low risk.

Comparison of two diagnostic strategies for patients with stable chest pain suggestive of chronic coronary syndrome: rationale and design of the double-blind, pragmatic, randomized and controlled OPERATE Trial.

BACKGROUND: To achieve potential financial savings and avoid exposing the patients to unnecessary risk, an optimal diagnostic strategy to identify low risk individual who may derive minimal benefit from further cardiac imaging testing (CIT) is important for patients with stable chest pain (SCP) suggestive of chronic coronary syndrome (CCS). Although several diagnostic strategies have been recommended by the most recent guidelines, few randomized controlled trials (RCTs) have prospectively investigated the actual effect of applying these strategies in clinical practice. METHODS: OPERATE (OPtimal Evaluation of stable chest pain to Reduce unnecessAry utilization of cardiac imaging TEsting) trial is an investigator-initiated, multicenter, coronary computed tomography angiography (CCTA)-based, 2-arm parallel-group, double-blind, pragmatic and confirmative RCT planning to include 800 subjects with SCP suggestive of CCS. After enrollment, all subjects will be randomized to two arms (2016 U.K. National Institute of Health and Care Excellence guideline-determined and 2019 European Society of Cardiology guideline-determined diagnostic strategy) on a 1:1 basis. According to each strategy, CCTA should be referred and deferred for a subject in high and low risk group, respectively. The primary (effectiveness) endpoint is CCTA without obstructive coronary artery disease. Safety of each strategy will be mainly assessed by 1-year major adverse cardiovascular event rates. DISCUSSION: The OPERATE trial will provide comparative effectiveness and safety evidences for two different diagnostic strategies for patients with SCP suggestive of CCS, with the intension of improving the diagnostic yield of CCTA at no expense of safety. CLINICAL TRIAL REGISTRATION: ClinicalTrial.org Identifier NCT05640752.

PECSS: Pulmonary Embolism Comprehensive Screening Score to safely rule out pulmonary embolism among suspected patients presenting to emergency department.

BACKGROUND: Pulmonary embolism is a severe cardiovascular disease and can be life-threatening if left untreated. However, the detection rate of pulmonary embolism using existing pretest probability scores remained relatively low and clinical rule out often relied on excessive use of computed tomographic pulmonary angiography. METHODS: We retrospectively collected data from pulmonary embolism suspected patients in Zhongshan Hospital from July 2018 to October 2022. Pulmonary embolism diagnosis and severity grades were confirmed by computed tomographic pulmonary angiography. Patients were randomly divided into derivation and validation set. To construct the Pulmonary Embolism Comprehensive Screening Score (PECSS), we first screened for candidate clinical predictors using univariate logistic regression models. These predictors were then included in a searching algorithm with indicators of Wells score, where a series of points were assigned to each predictor. Optimal D-Dimer cutoff values were investigated and incorporated with PECSS to rule out pulmonary embolism. RESULTS: In addition to Wells score, PECSS identified seven clinical predictors (anhelation, abnormal blood pressure, in critical condition when admitted, age > 65 years and high levels of pro-BNP, CRP and UA,) strongly associated with pulmonary embolism. Patients can be safely ruled out of pulmonary embolism if PECSS ≤ 4, or if 4 < PECSS ≤ 6 and D-Dimer ≤ 2.5 mg/L. Comparing with Wells approach, PECSS achieved lower failure rates across all pulmonary embolism severity grades. These findings were validated in the held-out validation set. CONCLUSIONS: Compared to Wells score, PECSS approaches achieved lower failure rates and better compromise between sensitivity and specificity. Calculation of PECSS is easy and all predictors are readily available upon emergency department admission, making it widely applicable in clinical settings. TRAIL REGISTRATION: The study was retrospectively registered (No. CJ0647) and approved by Human Genetic Resources in China in April 2022. Ethical approval was received from the Medical Ethics Committee of Zhongshan Hospital (NO.B2021-839R).

Comparison of NICE and ESC strategy for risk assessment in women with stable chest pain: a coronary computed tomography angiography study.

BACKGROUND: For women presenting with stable chest pain (SCP), the appropriate risk assessment strategy to identify individuals unlikely to benefit from further cardiovascular imaging testing (CIT) is debatable. Thus, the present study intended to compare two risk assessment strategies in these individuals. METHODS: 2592 women with SCP who underwent coronary computed tomography angiography (CCTA) were divided into low and high risk group according to 2016 National Institute of Health and Care Excellence guideline-determined strategy (NICE strategy) and 2019 European Society of Cardiology guideline-determined strategy (ESC strategy), respectively. The associations of coronary artery disease (CAD), major adverse cardiovascular event (MACE) and other subsequent clinical outcomes with risk groups and net reclassification improvement (NRI) were evaluated to compare different strategies. RESULTS: Both NICE strategy which focused on symptom evaluation and ESC strategy which was based on pretest probability (PTP) determined by ESC-PTP model and coronary artery calcium score-weighted clinical likelihood (CACS-CL) model classified a proportion (34.49% and 63.97%, respectively) of individuals into the low risk group. Compared to NICE strategy, ESC strategy indicated stronger associations between risk groups and obstructive CAD (odds ratio: 27.63 versus 3.57), MACE (hazard ratios: 4.24 versus 1.91), more intensive clinical management as well as a positive NRI (27.71%, p < 0.0001). CONCLUSION: Compared to NICE strategy, ESC strategy which sequentially incorporated ESC-PTP model with CACS-CL model seemed to be associated with greater effectiveness in identifying individuals who may derive maximum benefit from further CIT in women presenting with SCP.

Comparison of the CAD consortium and updated Diamond-Forrester scores for predicting obstructive coronary artery disease.

OBJECTIVE: Current guidelines recommend the use of the updated Diamond-Forrester (DF) method and Coronary Artery Disease (CAD) Consortium models to assess the pretest probability of obstructive CAD. The present study aimed to compare the performance of these models among patients with chest pain evaluated in an emergency department (ED). METHODS: We compared three scores (DF, CAD consortium basic, and clinical) among 1247 consecutive patients with chest pain who underwent coronary computed tomographic angiography (CTA). Invasive angiography was performed to confirm the stenosis for those who showed obstructive CAD on CTA, if clinically indicated. Primary outcome was the presence of obstructive CAD (≧50% stenosis). RESULTS: Overall, 426 (34.2%) patients were diagnosed with obstructive CAD. The expected prevalence of CAD was underestimated by the CAD consortium clinical model (23.4%) and overestimated by the DF model (53.1%). For the prediction of obstructive CAD, the CAD consortium clinical model had superior area under the receiver-operating curve (0.754), followed by the CAD consortium basic (0.736), and finally, the DF model (0.718). Whereas the CAD consortium models more accurately classified patients without any CAD or nonobstructive CAD as low-risk patients, the DF model more accurately classified high-risk patients with obstructive CAD. The net reclassification improvement of CAD consortium basic and clinical models were 24.7% and 27.9%, respectively. CONCLUSIONS: Compared with the DF model, the CAD consortium clinical model appears to improve the prediction of low-risk patients with <15% probability of having obstructive CAD. However, this model needs caution when using in high-risk population.

Data sources and methods used to determine pretest probabilities in a cohort of Cochrane diagnostic test accuracy reviews.

BACKGROUND: A pretest probability must be selected to calculate data to help clinicians, guideline boards and policy makers interpret diagnostic accuracy parameters. When multiple analyses for the same target condition are compared, identical pretest probabilities might be selected to facilitate the comparison. Some pretest probabilities may lead to exaggerations of the patient harms or benefits, and guidance on how and why to select a specific pretest probability is minimally described. Therefore, the aim of this study was to assess the data sources and methods used in Cochrane diagnostic test accuracy (DTA) reviews for determining pretest probabilities to facilitate the interpretation of DTA parameters. A secondary aim was to assess the use of identical pretest probabilities to compare multiple meta-analyses within the same target condition. METHODS: Cochrane DTA reviews presenting at least one meta-analytic estimate of the sensitivity and/or specificity as a primary analysis published between 2008 and January 2018 were included. Study selection and data extraction were performed by one author and checked by other authors. Observed data sources (e.g. studies in the review, or external sources) and methods to select pretest probabilities (e.g. median) were categorized. RESULTS: Fifty-nine DTA reviews were included, comprising of 308 meta-analyses. A pretest probability was used in 148 analyses. Authors used included studies in the DTA review, external sources, and author consensus as data sources for the pretest probability. Measures of central tendency with or without a measure of dispersion were used to determine the pretest probabilities, with the median most commonly used. Thirty-two target conditions had at least one identical pretest probability for all of the meta-analyses within their target condition. About half of the used identical pretest probabilities were inside the prevalence ranges from all analyses within a target condition. CONCLUSIONS: Multiple sources and methods were used to determine (identical) pretest probabilities in Cochrane DTA reviews. Indirectness and severity of downstream consequences may influence the acceptability of the certainty in calculated data with pretest probabilities. Consider: whether to present normalized frequencies, the influence of pretest probabilities on normalized frequencies, and whether to use identical pretest probabilities for meta-analyses in a target condition.

[Myocardial perfusion single-photon emission computer tomography and coronary angiography results in patients with different pretest probability of ischemic heart disease].

AIM: To study the relationship between pretest probability (PTP) of ischemic heart disease (IHD), calculated according to the recommendations of the European Society of Cardiology (ESC) of 2013 and 2019, with the perfusion of the left ventricle of the myocardium according to the single-photon emission tomography (SPECT) and the results of the invasive coronary angiography (CAG). MATERIAL AND METHODS: The study included 220 patients with a preliminary diagnosis of ischemic heart disease and planned invasive CAG. All patients underwent rest-stress perfusion myocardial SPECT within 1 month prior to or after CAG, standard quantitative parameters of left ventricular perfusion were assessed. Retrospectively clinical data was analyzed and PTP of IHD was assessed according to ESC recommendations for 2013 and 2019. RESULTS: Invasive CAG revealed obstructive lesion of one or more coromary arteries in 204 of the 220 patients (92.7%). In a retrospective analysis, taking into account gender, age and nature of the complaints, as recommended by ESC in 2013, PTP was rated as low (15%) in 13 patients (5.9%), as intermediate (1585%) in 207 patients (94.1%). Following the comprehensive survey (SPECT and CAG) 8 patients with low PTP (61.5%) underwent coronary revascularization. Among patients with intermediate PTP significant transient ischemia according to SPECT was detected in 31 (15.0%), initial at 107 (51.7%). According CAG among patients with intermediate PTP obstructive lesion was found in 192 (92.7%), 113 patients (58.8%) underwent revascularization. According to ESC recommendations of 2019, PTP was rated as low (15%) in 117 patients (53.2%), including 514% in 98 (44.5%). According to a survey (SPECT and CAG) 68 of them (58.1%) underwent revascularization. CONCLUSION: PTP measurements proposed by ESC can not be applied to patients of the Russian population with suspected ischemic heart disease without significant corrections. 2013 ESC recommendations with higher PTP values for all categories of patients reflect Russian population better, while 2019 recommendations mistakenly attribute patients to low PTP in at least 58% of cases. These results are preliminary and will be expanded in subsequent studies with more detailed analysis of PTP in included patients with suspected IHD.

Imaging functional stress test for stable chest pain symptoms in patients at low pretest probability of coronary artery disease: Current practice and long-term outcome.

BACKGROUND: Stress testing in patients with low pretest probability (PTP) of coronary artery disease (CAD) has become an increasing practice, potentially leading to underestimation of its true clinical value. Our aim was to describe the current use of most employed imaging functional tests and their prognostic value. METHODS AND RESULTS: We selected patients with low PTP of CAD (CAD consortium clinical score < 15%) who underwent exercise or dipyridamole stress echocardiography or single photon emission computed tomography for suspected angina. Main exclusions were age < 45, known CAD, and abnormal rest wall motion. Of the 2279 subjects undergoing stress test, 883 (39%) had low PTP, and 91 (10.3%) had a positive test for ischemia. After a median follow-up of 5.8 years, 36 patients had events (21 died, 14 had nonfatal myocardial infarction). The percentage of events in the abnormal and normal stress test groups were similar (5 [5.5%] vs 31 [3.9%], P = ns), as the annualized event rate (0.87% vs 0.62%, P = ns). Age was the only variable associated with outcome in the regression analysis (hazard ratio 1.072, 95% CI 1.034-1.113, P < 0.001). An abnormal result was not associated with worse outcome in each of the subgroups of functional tests. CONCLUSIONS: In our geographical area, a considerable proportion of patients undergoing imaging functional tests for stable chest pain have a low estimated PTP of CAD. Of these, 1 in 10 resulted positive for inducible ischemia. However, none of the most common imaging functional tests, single photon emission computed tomography (SPECT), and stress echocardiography offer prognostic information in these patients.

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

OBJECTIVES: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Exploring the Negative Likelihood Ratio and How It Can Be Used to Minimize False-Positives in Breast Imaging.

OBJECTIVE: This article describes the definition and proposed utilization of negative likelihood ratios (NLRs) as statistical parameters in breast imaging. Examples with calculations are provided using BI-RADS category 4 subcategories. CONCLUSION: By auditing individual performance early and often against American College of Radiology benchmark positive predictive value ranges for the BI-RADS category 4 subcategories, and by fully understanding NLRs and their application in breast imaging, radiologists can minimize false-positive findings and unnecessary biopsies.

Coronary calcium score improves the estimation for pretest probability of obstructive coronary artery disease and avoids unnecessary testing in individuals at low extreme of traditional risk factor burden: validation and comparison of CONFIRM score and genders extended model.

BACKGROUND: Reliability of models for estimating pretest probability (PTP) of obstructive coronary artery disease (CAD) has not been investigated in individuals at low extreme of traditional risk factor (RF) burden. Thus, we sought to validate and compare CONFIRM score and Genders extended model (GEM) among these individuals. METHODS: We identified symptomatic individuals with 0 or 1 RF who underwent coronary calcium scan and coronary computed tomographic angiography (CCTA). Follow-up clinical data were also recorded. PTP of obstructive CAD for every individual was estimated according to CONFIRM score and GEM, respectively. Area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI) and Hosmer-Lemeshow (H-L) test were used to assess the performance of models. RESULTS: There were 1201 individuals with 0 RF and 2415 with 1 RF. The AUC for GEM was significantly larger than that for CONFIRM score, no matter in individuals with 0 (0.843 v.s. 0.762, p < 0.0001) or 1 (0.823 v.s. 0.752, p < 0.0001) RF. Compared to CONFIRM score, GEM demonstrated positive IDI (5% in individuals with 0 RF and 8% in individuals with 1 RF), positive NRI (41.50% in individuals with 0 RF and 40.19% in individuals with 1 RF), better prediction of clinical events and less discrepancy between observed and predicted probabilities, resulting in a significant decrease of unnecessary testing, especially in negative individuals. CONCLUSION: In individuals at low extreme of traditional RF burden of CAD, the addition of coronary calcium score provided a more accurate estimation for PTP and application of GEM instead of CONFIRM score could avoid unnecessary testing.

Compliance to clinical pathways in the management of suspected pulmonary embolus: are there cost implications?

This study investigated the cost implications of poor compliance to established guidelines for management of suspected pulmonary embolism (PE) in two NSW public hospitals. A retrospective audit showed that the prevalence of PE overall was 9.9% (4.3% in the low-risk groups) in 436 patients. An estimated total of $32 454 (14%) was spent on unnecessary tests.

The unlikely presence of deep vein thrombosis in a patient with low pretest probability and a negative D-dimer: a case report.

BACKGROUND: Deep vein thrombosis (DVT) is commonly encountered in the emergency department. Clinical models, such as the Wells criteria, allow physicians to estimate the probability of DVT in a patient. Current literature suggests a low pretest probability combined with a negative D-dimer laboratory study rules out DVT approximately 99% of the time. CASE REPORT: This case discusses a 37-year-old male patient who had a low pretest probability and a negative D-dimer, but was found to have a DVT on Doppler ultrasound. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The astute emergency physician must not discount clinical suspicion in order to decide when radiographic imaging is warranted for a possible venous thromboembolism. New adjuncts, such as bedside ultrasonography, can also be implemented to further risk stratify patients, potentially decreasing morbidity and mortality associated with DVT.

A Diagnostic Approach to Fungal Pneumonia: An Infectious Diseases Perspective.

Although bacteria significantly exceed fungi as the most common cause of lower respiratory tract infection, the incidence of fungal pneumonia is increasing because of a growing at-risk population of immunocompromised individuals as well as anthropogenic global heating and environmental disruption. When a patient presents with a clinical syndrome of pneumonia, a constellation of factors must be considered to determine the probability of a fungal pneumonia, including host factors, epidemiologic exposures, suggestive radiographic patterns, and the presence of a non-resolving pneumonia. In addition, knowledge of clinically important fungal pathogens, their epidemiology, and associated clinical syndromes are key in guiding appropriate diagnostic testing and result interpretation, and ultimately rendering a correct diagnosis of a fungal pneumonia. This article aims to provide a framework for the evaluation and appropriate diagnostic testing of patients with suspected fungal pneumonia.

[Screening, risk stratification and CT imaging for assessment of coronary artery disease]. / Screening, Risikostratifizierung und CT-Bildgebung zur Abklärung der koronaren Herzkrankheit.

BACKGROUND: Early treatment of cardiovascular risk factors and characterization of coronary plaques is essential to collect prognostic information about coronary artery disease (CAD) and prevent cardiovascular events. OBJECTIVES: Discussion of the most important risk factors of CAD, basic diagnostic of CAD, prevention, and prognostic factors of CAD with focus on cardiac computed tomography (CT). MATERIALS AND METHODS: Prevalence and prognostic impact of CAD risk factors; description of specific assessment of risk profiles; estimation of pretest probability; conventional prevention of CAD; prognostic assessment of CAD using the Calcium Scoring and coronary CT angiography. RESULTS: Assessment of risk profiles and estimation of pretest probability for obstructive coronary stenosis necessitates a thorough evaluation of medical history and laboratory values. The composition and extent of calcified and noncalcified plaques in CT exams based on the criteria of the Coronary Artery Disease-Reporting and Data System give important prognostic information about the risk of cardiovascular events, which increases with high plaque burden and vice versa. Initial imaging with CT for evaluation of CAD leads to a reduction of invasive coronary angiographies and catheter-associated complications. CONCLUSIONS: Besides early detection of cardiovascular risk factors, the additional assessment of plaque burden and significant stenosis in CT gives further prognostic information to facilitate effective therapies to prevent cardiovascular events and in the case of low plaque burden avoid invasive coronary angiography. However, systmatic screening using Calcium Scoring is not established yet due to insufficient data, although it could potentially be used for an early risk stratification in patients with multiple risk factors.

Clinical Likelihood Prediction of Hemodynamically Obstructive Coronary Artery Disease in Patients With Stable Chest Pain.

BACKGROUND: Selection for invasive angiography is recommended to be based on pretest probabilities (PTPs), and physiological measures of hemodynamical impairment by, for example, fractional flow reserve (FFR) should guide revascularization. The risk factor-weighted clinical likelihood (RF-CL) and coronary artery calcium score-weighted clinical likelihood (CACS-CL) models show superior discrimination of patients with suspected obstructive coronary artery disease (CAD), but validation against hemodynamic impairment is warranted. OBJECTIVES: The aim of this study was to validate the RF-CL and CACS-CL models against hemodynamically obstructive CAD. METHODS: Stable de novo chest pain patients (N = 4,371) underwent coronary computed tomography angiography and subsequently invasive coronary angiography with FFR measurements. Hemodynamically obstructive CAD was defined as invasive FFR ≤0.80 or high-grade stenosis by visual assessment (>90% diameter stenosis). For comparison, a guideline-endorsed basic PTP model was calculated based on age, sex, and symptom typicality. The RF-CL model additionally included the number of risk factors, and the CACS-CL model incorporated the coronary artery calcium score into the RF-CL. RESULTS: In total, 447 of 4,371 (10.9%) patients had hemodynamically obstructive CAD. Both the RF-CL and CACS-CL models classified more patients with a very low clinical likelihood (≤5%) of obstructive CAD compared to the basic PTP model (33.0% and 53.7% vs 12.0%; P < 0.001) with a preserved low prevalence of hemodynamically obstructive CAD (<5% for all models). Against hemodynamically obstructive CAD, calibration and discrimination of the RF-CL and CACS-CL models were superior to the basic PTP model. CONCLUSIONS: The RF-CL and CACS-CL models are well calibrated and superior to a currently recommended basic PTP model to predict hemodynamically obstructive CAD. (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease [Dan-NICAD]; NCT02264717; Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 [Dan-NICAD 2]; NCT03481712, Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 3 [Dan-NICAD 3]; NCT04707859).

Evaluating the American Heart Association/American College of Cardiology Guideline-Recommended and Contemporary Pretest Probability Models in a Mixed Asian Cohort: The Contribution of Coronary Artery Calcium.

BACKGROUND: Most pretest probability (PTP) tools for obstructive coronary artery disease (CAD) were Western -developed. The most appropriate PTP models and the contribution of coronary artery calcium score (CACS) in Asian populations remain unknown. In a mixed Asian cohort, we compare 5 PTP models: local assessment of the heart (LAH), CAD Consortium (CAD2), risk factor-weighted clinical likelihood, the American Heart Association/American College of Cardiology and the European Society of Cardiology PTP and 3 extended versions of these models that incorporated CACS: LAH(CACS), CAD2(CACS), and the CACS-clinical likelihood. METHODS AND RESULTS: The study cohort included 771 patients referred for stable chest pain. Obstructive CAD prevalence was 27.5%. Calibration, area under the receiver-operating characteristic curves (AUC) and net reclassification index were evaluated. LAH clinical had the best calibration (χ2 5.8; P=0.12). For CACS models, LAH(CACS) showed least deviation between observed and expected cases (χ2 37.5; P<0.001). There was no difference in AUCs between the LAH clinical (AUC, 0.73 [95% CI, 0.69-0.77]), CAD2 clinical (AUC, 0.72 [95% CI, 0.68-0.76]), risk factor-weighted clinical likelihood (AUC, 0.73 [95% CI: 0.69-0.76) and European Society of Cardiology PTP (AUC, 0.71 [95% CI, 0.67-0.75]). CACS improved discrimination and reclassification of the LAH(CACS) (AUC, 0.88; net reclassification index, 0.46), CAD2(CACS) (AUC, 0.87; net reclassification index, 0.29) and CACS-CL (AUC, 0.87; net reclassification index, 0.25). CONCLUSIONS: In a mixed Asian cohort, Asian-derived LAH models had similar discriminatory performance but better calibration and risk categorization for clinically relevant PTP cutoffs. Incorporating CACS improved discrimination and reclassification. These results support the use of population-matched, CACS-inclusive PTP tools for the prediction of obstructive CAD.

Comparison of the RF-CL and CACS-CL models to estimate the pretest probability of obstructive coronary artery disease and predict prognosis in patients with stable chest pain and diabetes mellitus.

Background: The most appropriate tool for estimating the pretest probability (PTP) of obstructive coronary artery disease (CAD) in patients with diabetes mellitus (DM) and stable chest pain (SCP) remains unknown. Therefore, we aimed to validate and compare two recent models, namely, the risk factor-weighted clinical likelihood (RF-CL) model and coronary artery calcium score (CACS)-weighted clinical likelihood (CACS-CL) model, in these patient populations. Methods: A total of 1,245 symptomatic patients with DM, who underwent CACS and coronary computed tomographic angiography (CCTA) scan, were identified and followed up. PTP of obstructive CAD for each patient was estimated using the RF-CL model and CACS-CL model, respectively. Area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess the performance of models. The associations of major adverse cardiovascular events (MACE) with risk groups were evaluated using Cox proportional hazards regression. Results: Compared with the RF-CL model, the CACS-CL model revealed a larger AUC (0.856 vs. 0.782, p = 0.0016), positive IDI (12%, p < 0.0001) and NRI (34%, p < 0.0001), stronger association to MACE (hazard ratio: 0.26 vs. 0.38) and less discrepancy between observed and predicted probabilities, resulting in a more effective risk assessment to optimize downstream clinical management. Conclusion: Among patients with DM and SCP, the incorporation of CACS into the CACS-CL model resulted in a more accurate estimation for PTP and prediction of MACE. Utilizing the CACS-CL model, instead of the RF-CL model, might have greater potential to avoid unnecessary and omissive cardiovascular imaging testing with minimal cost.