Pretest Probability Assessment Research Articles

Sex Differences in Clinical Presentation of Lower Extremity Deep Vein Thrombosis.

Background: Differences between men and women in the clinical features and extent of lower limb deep vein thrombosis (DVT) may influence DVT diagnostic algorithms involving pretest clinical probability (PTP) assessment, D-dimer, and compression ultrasonography (CUS). Aims: To assess differences in DVT clinical presentation between men and women and their effect on PTP and D-dimer. Methods: We conducted a retrospective study in outpatients referred for suspected DVT of the lower limbs to our vascular emergency department from January 2005 to December 2019. Patients underwent PTP assessment with the Wells score, D-dimer testing, and CUS. Results: More women were referred for suspected DVT than men (M/F: 1,785/2,821; F: 61.4%; p < 0.0001). Women were older than men (median age: 71 vs. 67 years; p = 0.0001), DVT was diagnosed in 436 patients (9.4%) but in more men than women (M: 210 [11.8%] vs. F: 226 [8%]; p = 0.0002), with more proximal DVT in men than women (M: 131 7.3% vs. F: 124 [4.4%]; p = 0.00021). PTP was more likely in men (355 [19.9%]) than women (455 [16.2%]) (p = 0.0011); more men had swelling in the entire limb, increased calf circumference by >3 cm compared with the contralateral limb, and pitting edema, than women. D-dimer levels (available in 65% of patients) were more frequently positive in women with DVT than in men (94.6% vs. 85.7%; p = 0.016). However, a positive D-dimer and/or likely PTP was similarly frequent in men (92%) and women (96%) with DVT. Conclusions: More women than men are referred for suspected DVT, and men have a higher prevalence of proximal DVT. However, current algorithms for DVT diagnosis perform similarly in men and in women.

Trends in the utilization of computed tomography chest for acute pulmonary embolism in the emergency department and the yield in treatment

Background: Acute pulmonary embolism (PE) is a life-threatening condition with high mortality rates. Prompt and accurate diagnosis is crucial to prevent morbidity and mortality. Overutilizing computed tomography pulmonary angiography (CTPA) in low-risk patients can lead to unnecessary health-care costs and radiation exposure. Proper pretest probability assessment is recommended to guide the use of CTPA. Aim: This study aimed to evaluate the utilization of CTPA in the diagnosis of acute PE in the emergency department, with a focus on the application of pretest probability assessment (modified Wells score [MWS] and D-dimer). The primary objectives were to assess the extent of CTPA usage in low-risk patients, determine the effectiveness of D-dimer levels and the MWS in predicting PE, and identify areas for potential improvement in CTPA utilization to reduce unnecessary imaging and enhance patient care. In addition, the study aimed to evaluate the appropriateness of anticoagulant treatment in patients diagnosed with acute PE, particularly in cases of segmental/subsegmental PE. Settings and Design: A retrospective analysis was done on all suspected PE patients in the emergency room at our facility who underwent CTPA over 5 years. Patient demographic information, presenting complaints, physical examination findings, laboratory test results, and imaging findings were all included in the data collection. Materials and Methods: A retrospective review of 758 patient records at a tertiary hospital was conducted over 5 years. Data included demographics, presenting symptoms, test results, and imaging findings. D-dimer levels and the MWS were used for pretest probability evaluation. Anticoagulant treatment and appropriateness were also assessed. Statistical Analysis: Statistical analysis was carried out using RStudio (R version 4.3.0). Numerical variables were expressed as median (interquartile range), and frequencies and percentages were used to present categorical variables. A Fisher’s exact test was applied to assess the differences between patients who received anticoagulants and those who did not, as well as patients with PE statuses across D-dimer levels, Wells score categories, and receiving anticoagulants. A Kruskal–Wallis test explored the time to read reports between PE categories. P &lt;0.05 indicated statistical significance. Results: Among 758 patients, 18.8% had acute PE, with 6.2% being segmental/subsegmental PE. The majority of cases (79.8%) were negative for PE. A high rate of CTPA utilization was observed, especially in low-risk patients. Sixty-eight percent of low-risk patients had negative PE results. Among patients with acute PE, lobar PE (36.4%) and segmental/subsegmental PE (32.9%) were the most common locations. D-dimer and MWS were underutilized. Conclusions: By identifying low-risk patients who might not need CTPA, compliance with pretest probability evaluation using the MWS and D-dimer levels can help minimize unnecessary imaging and its associated risks. The results showed that efforts should be made to adhere to guidelines and recommendations, especially if the patients were categorized as low risk based on MWS or normal D-dimer levels. This will eventually improve patient outcomes and lower health-care costs.

The Lung Cancer Prediction Model “Stress Test”: Assessment of Models’ Performance in a High-Risk Prospective Pulmonary Nodule Cohort

Pulmonary nodules represent a growing health care burden because of delayed diagnosis of malignant lesions and overtesting for benign processes. Clinical prediction models were developed to inform physician assessment of pretest probability of nodule malignancy but have not been validated in a high-risk cohort of nodules for which biopsy was ultimately performed. Do guideline-recommended prediction models sufficiently discriminate between benign and malignant nodules when applied to cases referred for biopsy by navigational bronchoscopy? We assembled a prospective cohort of 322 indeterminate pulmonary nodules in 282 patients referred to a tertiary medical center for diagnostic navigational bronchoscopy between 2017 and 2019. We calculated the probability of malignancy for each nodule using the Brock model, Mayo Clinic model, and Veterans Affairs (VA) model. On a subset of 168 patients who also had PET-CT scans before biopsy, we also calculated the probability of malignancy using the Herder model. The performance of the models was evaluated by calculating the area under the receiver operating characteristic curves (AUCs) for each model. The study cohort contained 185 malignant and 137 benign nodules (57% prevalence of malignancy). The malignant and benign cohorts were similar in terms of size, with a median longest diameter for benign and malignant nodules of 15 and 16 mm, respectively. The Brock model, Mayo Clinic model, and VA model showed similar performance in the entire cohort (Brock AUC, 0.70; 95% CI, 0.64-0.76; Mayo Clinic AUC, 0.70; 95% CI, 0.64-0.76; VA AUC, 0.67; 95% CI, 0.62-0.74). For 168 nodules with available PET-CT scans, the Herder model had an AUC of 0.77 (95% CI, 0.68-0.85). Currently available clinical models provide insufficient discrimination between benign and malignant nodules in the common clinical scenario in which a patient is being referred for biopsy, especially when PET-CT scan information is not available.

Artificial intelligence to improve ischemia prediction in Rubidium Positron Emission Tomography—a validation study

BackgroundPatients are referred to functional coronary artery disease (CAD) testing based on their pre-test probability (PTP) to search for myocardial ischemia. The recommended prediction tools incorporate three variables (symptoms, age, sex) and are easy to use, but have a limited diagnostic accuracy. Hence, a substantial proportion of non-invasive functional tests reveal no myocardial ischemia, leading to unnecessary radiation exposure and costs. Therefore, preselection of patients before ischemia testing needs to be improved using a more predictive and personalised approach.AimsUsing multiple variables (symptoms, vitals, ECG, biomarkers), artificial intelligence–based tools can provide a detailed and individualised profile of each patient. This could improve PTP assessment and provide a more personalised diagnostic approach in the framework of predictive, preventive and personalised medicine (PPPM).MethodsConsecutive patients (n = 2417) referred for Rubidium-82 positron emission tomography were evaluated. PTP was calculated using the ESC 2013/2019 and ACC 2012/2021 guidelines, and a memetic pattern–based algorithm (MPA) was applied incorporating symptoms, vitals, ECG and biomarkers. Five PTP categories from very low to very high PTP were defined (i.e., < 5%, 5–15%, 15–50%, 50–85%, > 85%). Ischemia was defined as summed difference score (SDS) ≥ 2.ResultsIschemia was present in 37.1%. The MPA model was most accurate to predict ischemia (AUC: 0.758, p < 0.001 compared to ESC 2013, 0.661; ESC 2019, 0.673; ACC 2012, 0.585; ACC 2021, 0.667). Using the < 5% threshold, the MPA’s sensitivity and negative predictive value to rule out ischemia were 99.1% and 96.4%, respectively. The model allocated patients more evenly across PTP categories, reduced the proportion of patients in the intermediate (15–85%) range by 29% (ACC 2012)–51% (ESC 2019), and was the only tool to correctly predict ischemia prevalence in the very low PTP category.ConclusionThe MPA model enhanced ischemia testing according to the PPPM framework:The MPA model improved individual prediction of ischemia significantly and could safely exclude ischemia based on readily available variables without advanced testing (“predictive”).It reduced the proportion of patients in the intermediate PTP range. Therefore, it could be used as a gatekeeper to prevent patients from further unnecessary downstream testing, radiation exposure and costs (“preventive”).Consequently, the MPA model could transform ischemia testing towards a more personalised diagnostic algorithm (“personalised”).

A study of modified Wells score for pulmonary embolism and age-adjusted D-dimer values in patients at risk for deep venous thrombosis.

Pulmonary embolism (PE) is the most severe complication of deep venous thrombosis (DVT). This study was designed to evaluate the usefulness of modified Wells score combined with age-adjusted D-dimer cut-off levels as a clinical pre-test probability assessment for predicting PE in patients 'at risk for DVT.' This was a cross-sectional study including 200 in-patients at risk for DVT. Patients were categorized as 'pulmonary embolism unlikely' or 'pulmonary embolism likely' using modified Wells score and underwent D-dimer testing. PE was considered excluded in patients classified as unlikely with normal D-dimer levels, whereas the rest of the patients underwent computed tomography pulmonary angiogram (CTPA). Out of 200 patients, 163 patients (81.50%) were 'pulmonary embolism unlikely,' whereas 37 patients (18.50%) were 'pulmonary embolism likely.' Of 163 patients categorized as 'pulmonary embolism unlikely,' 67 patients (41.5%) had normal D-dimer values and were excluded from CTPA. PE was detected in 24.2% of the patients who underwent CTPA. The combined strategy using modified Wells score and age-adjusted D-dimer cut-off value has 100% sensitivity and a negative predictive value and can be used to safely exclude PE in in-patients.

Artificial intelligence to improve ischemia prediction in rubidium positron emission tomography

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients are referred to coronary artery disease (CAD) testing based on their pre-test probability (PTP). The available, easy-to-use risk prediction tools use three variables only and their diagnostic accuracy is limited. Artificial intelligence-based tools incorporate multiple variables and could improve PTP assessment due to the resulting combinatorial power. The factors in the AI model are not seen as independent individual values, but are recognized as patterns derived by a combinatorial analysis of the individual metabolic profile of each patient. Purpose We aimed to compare the diagnostic accuracy of a novel, artificial intelligence-based tool with commonly used PTP tools to predict ischemia. Methods Consecutive patients (n = 2417) referred for Rubidium-Position Emission Tomography (PET) were evaluated. PTP was calculated using the ESC 2013/2019 and ACC 2012/2021 guidelines, and a memetic pattern-based algorithm (MPA) model incorporating symptoms, vitals, ECG and laboratory findings. Five risk categories (very low to very high risk) were defined (&amp;lt;5%, 5–15%, 15–50%, 50–85%, &amp;gt;85%). Ischemia was defined as summed difference score (SDS) ≥2 on PET. Receiver operator characteristics were calculated and compared using the DeLong method. Results Known CAD, ischemia and scar (detected on PET) were present in 46.3%, 37.1% and 24.6%, respectively. The MPA model was most accurate to assess PTP of ischemia (AUC: 0.758, ESC 2013: 0.661, ESC 2019: 0.673, ACC 2012: 0.585, ACC 2021: 0.667, p&amp;lt;0.0001 each) as depicted in figure 1. The MPA’s sensitivity and negative predictive value to rule-out ischemia were 99.1% and 96.4%, respectively. The model allocated patients more evenly across risk groups, reduced the proportion of patients in the 15–85% range by 29% (ACC 2012) to 51% (ESC 2013), and was the only risk tool to correctly estimate ischemia prevalence in the very low risk group (table 1). Conclusion The MPA model significantly improved PTP assessment of ischemia. The MPA model has originally been derived on the endpoint coronary stenosis &amp;gt;50% and validated in three clinical studies (1–3). This study now confirms that the MPA model applied to the endpoint ischemia outperforms the current risk assessment tools and is most accurate to assess PTP. It enables clinicians to safely exclude ischemia based on readily available variables without advanced testing. It could be used to improve risk stratification of patients and to significantly reduce unnecessary non-invasive functional tests.

Pre-Test Probability Assessment and d-Dimer Based Evaluation in Patients with Previous Acute Aortic Syndrome.

Background and Objectives. Acute aortic syndromes (AASs) are emergencies burdened by high morbidity and mortality. Guideline-recommended diagnostic workup is based on pre-test probability assessment (PPA) and d-dimer testing. However, the performance of PPA and d-dimer has never been studied in individuals with previous AAS (pAAS), which represent a challenging population. Materials and Methods. We analyzed a registry of patients with pAAS evaluated in two Emergency Departments (EDs) for suspected novel AAS (nAAS). Enrolment criteria were history of pAAS and the presence of truncal pain, syncope or perfusion deficit. All patients underwent advanced imaging. Clinical data were registered prospectively and PPA was performed by applying the aortic dissection detection (ADD) and an aorta simplified (AORTAs) score. Results. A total of 128 patients were enrolled, including 77 patients with previous Stanford type A aortic dissection and 45 patients with previous Stanford type B aortic dissection. The final diagnosis was nAAS in 40 (31%) patients. Clinical variables associated with nAAS were: aortic valve disease, thoracic aortic aneurysm, severe pain, sudden pain, ripping/tearing pain and hypotension/shock. ADD score ≥ 2 had a sensitivity of 65% and a specificity of 83% for nAAS; AORTAs score ≥ 2 had a sensitivity of 48% and a specificity of 88%. d-dimer (cutoff ≥ 500 ng/mL or age-adjusted cutoff) had a sensitivity of 97% and a specificity of 13%/14.7%, for diagnosis of nAAS. Patients that were candidates for guideline-compliant PPA/d-dimer integrated rule-out were: 5 (4.9%) with ADD ≤ 1/d-dimer and 8 (7.8%) with AORTAs ≤ 1/d-dimer < age-adjusted cutoff. None of them had a nAAS. Conclusions. Patients with pAAS evaluated in the ED for red-flag symptoms showed intermediate-to-high pre-test probability of nAAS. The ADD score had lower sensitivity and specificity than in unselected patients. d-dimer, alone and integrated with PPA, was highly sensitive for nAAS, but very unspecific. PPA/d-dimer integrated strategies are unlikely to significantly reduce the number of patients with pAAS undergoing advanced imaging.

Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data

BackgroundFew studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. ObjectivesThe aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis. MethodsWe performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided. ResultsWe identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127). ConclusionThis study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis.

D-dimer Testing in Pulmonary Embolism with a Focus on Potential Pitfalls: A Narrative Review.

D-dimer is a multifaceted biomarker of concomitant activation of coagulation and fibrinolysis, which is routinely used for ruling out pulmonary embolism (PE) and/or deep vein thrombosis (DVT) combined with a clinical pretest probability assessment. The intended use of the tests depends largely on the assay used, and local guidance should be applied. D-dimer testing may suffer from diagnostic errors occurring throughout the pre-analytical, analytical, and post-analytical phases of the testing process. This review aims to provide an overview of D-dimer testing and its value in diagnosing PE and discusses the variables that may impact the quality of its laboratory assessment.

Risk of neonatal hypothyroidism in newborns from mothers exposed to CTPA during pregnancy: Ancillary data from a prospective outcome study

BackgroundNeonatal hypothyroidism is often raised as a potential concern for the use of computed tomography pulmonary angiography (CTPA) in pregnant women with suspected pulmonary embolism (PE). ObjectivesTo assess the incidence of neonatal hypothyroidism among newborns from mothers exposed to CTPA. Patients/MethodsPregnant women with clinically suspected PE were included in a multicenter, multinational prospective diagnostic management outcome study, based on pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb venous compression ultrasonography, and CTPA. Results of Guthrie tests were systematically collected for newborns of all women who required CTPA as part of the diagnostic strategy. A thyroid-stimulating hormone (TSH) level above 15 U/ml was used to define hypothyroidism. ResultsOut of the 166 women included in the Swiss participating centers, 149 underwent a CTPA including 14 with twin pregnancies. Eight women suffered a pregnancy loss and results of the Guthrie test could not be retrieved for four newborns. All TSH levels were reported as being below 15 U/ml. The incidence of neonatal hypothyroidism was 0/151 (0.0%, 95% confidence interval: 0.0%–2.5%). ConclusionsWe did not identify any cases of neonatal hypothyroidism in our cohort of 149 pregnant women investigated for suspected PE using a CTPA. Along with previous literature data, this provides further reassuring data regarding the use of CTPA in this indication.

Modified Haller index is inversely correlated with true positive exercise stress echocardiographic results.

The influence of chest wall shape on exercise stress echocardiography (ESE) results has been poorly investigated. We aimed at evaluating the main predictors of true positive (TP)-ESE in a population of subjects with suspected coronary artery disease (CAD), categorized according to chest wall conformation, assessed by modified Haller index (MHI, chest transverse diameter over the distance between sternum and spine). All consecutive patients with suspected CAD referred to our EchoLab for performing ESE between September 2011 and October 2021 were retrospectively enrolled. Preliminary assessment of both pretest probability (PTP) and MHI was performed. All patients with positive ESE underwent coronary angiography. Obstructive CAD was diagnosed by ≥70% stenosis in any epicardial coronary artery. Outcome was TP ESE result. One thousand two hundred and seventy-five consecutive patients (64.9 ± 13.0 years) entered the study. Subjects with concave-shaped chest wall (MHI > 2.5) (10.7%) and those with normal chest shape (MHI ≤ 2.5) (89.3%) were separately analyzed. PTP was similar in both groups (21.8 ± 13.2 vs. 23.5 ± 13.3%, P = 0.15). One hundred and seventy patients were diagnosed with positive ESE: 129 (75.9%) had obstructive CAD (TP), whereas the remaining 41 (24.1%) had no CAD. Only 2.3% of TP ESE was detected in subjects with MHI >2.5. PTP [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.04], dyslipidemia (OR 4.37, 95% CI 2.81-6.80), dyssynergy in the left anterior descending territory (OR 8.21, 95% CI 5.07-13.3) were linearly correlated with TP ESE, whereas MHI >2.5 (OR 0.25, 95% CI 0.14-0.67) was inversely associated with outcome. Subjects with MHI >2.5 have low prevalence of TP ESE, regardless of PTP. Preliminary MHI assessment may reduce overestimation of PTP of CAD.

Deep vein thrombosis and pulmonary embolism : Diagnosis and treatment

This review summarizes current evidence and guideline recommendations concerning diagnosis and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). For the diagnostic pathway, evidence-based algorithms should be employed, based on the assessment of pretest clinical probability. D‑dimer tests may reduce the need for subsequent diagnostic procedures. Clinical management of PE is guided by risk stratification according to early mortality. Lactate levels may be helpful for further risk stratification. The acute treatment of venous thromboembolism (VTE) is commenced with intensified anticoagulation (AC), either with parenteral AC or higher initial doses of apixaban or rivaroxaban. All patients with VTE should receive the anticoagulation maintenance therapy for 3-6months, while the duration of the subsequent secondary prophylaxis depends on the presumed risk of VTE recurrence and bleeding. Compression therapy is used to prevent postthrombotic syndrome. Acute revascularization procedures are limited to rare special cases. In obese patients up to 150 kg, standard doses of rivaroxaban and apixaban are appropriate. In cancer-associated thromboembolism (CAT), the previous guideline recommendation to use low molecular weight heparin (LMWH) for 3-6months is now broadened with the recommendation for factor Xa inhibitors, with the caveat for gastrointestinal and urothelial cancer or expected drug-drug interactions with the anticancer treatment. Here, and in unstable clinical situations, LMWH is preferred.

Thoracic non-traumatic cardiovascular diseases: current perspective and multi-detectors Computed Tomography protocols optimization in the emergency setting.

Cardiovascular diseases (CVDs) are among the most common causes of access to the Emergency Department and among the leading causes of death worldwide. Accurate diagnostic algorithms are mandatory to ensure a rapid life-saving treatment. However, non-specific clinical presentation and unnecessary referrals to other subspecialties may lead to misinterpretation of the diagnosis and delays. In recent years, the development of imaging technologies has allowed Computed Tomography (CT) to play a prominent role in the concepts of CVD rule-in and rule-out. An optimization strategy for CT protocols is needed to reduce variability and improve image quality. A correct diagnostic suspicion is crucial, as different districts (i.e., heart, aorta and pulmonary circulation) may require different investigation techniques. Additionally, the CVD pre-test probability assessment is highly correlated with CT accuracy. The purpose of this narrative review is to analyze the current role of CT in the approach to the CVDs in the ED, and to analyze the main strategies of CT optimization.

Are risk factors necessary for pretest probability assessment of coronary artery disease? A patient similarity network analysis of the PROMISE trial

BackgroundPretest probability (PTP) calculators utilize epidemiological-level findings to provide patient-level risk assessment of obstructive coronary artery disease (CAD). However, their limited accuracies question whether dissimilarities in risk factors necessarily result in differences in CAD. Using patient similarity network (PSN) analyses, we wished to assess the accuracy of risk factors and imaging markers to identify ≥50% luminal narrowing on coronary CT angiography (CCTA) in stable chest-pain patients. MethodsWe created four PSNs representing: patient characteristics, risk factors, non-coronary imaging markers and calcium score. We used spectral clustering to group individuals with similar risk profiles. We compared PSNs to a contemporary PTP score incorporating calcium score and risk factors to identify ≥50% luminal narrowing on CCTA in the CT-arm of the PROMISE trial. We also conducted subanalyses in different age and sex groups. ResultsIn 3556 individuals, the calcium score PSN significantly outperformed patient characteristic, risk factor, and non-coronary imaging marker PSNs (AUC: 0.81 vs. 0.57, 0.55, 0.54; respectively, p ​< ​0.001 for all). The calcium score PSN significantly outperformed the contemporary PTP score (AUC: 0.81 vs. 0.78, p ​< ​0.001), and using 0, 1–100 and ​> ​100 cut-offs provided comparable results (AUC: 0.81 vs. 0.81, p ​= ​0.06). Similar results were found in all subanalyses. ConclusionCalcium score on its own provides better individualized obstructive CAD prediction than contemporary PTP scores incorporating calcium score and risk factors. Risk factors may not be able to improve the diagnostic accuracy of calcium score to predict ≥50% luminal narrowing on CCTA.

Assessment of Pre-test and Clinical Probability in the Diagnosis of Chronic Coronary Syndrome — What's New?

In the 2019 European Society of Cardiology (ESC) guidelines, the diagnostic algorithm for chronic coronary syndrome (CCS) was significantly changed, a significant revision of the pretest probability assessment scale (PTP) was made, an assessment of the clinical probability of obstructive coronary artery disease was proposed, the recommendations on the use of diagnostic tests in various groups of patients were updated. Such a radical change in approaches to the diagnosis of CCS raised many questions that had to be answered by further studies conducted in the past two years. The review provides data on the validation of the new PTP scale and the proposed assessment of the clinical probability of obstructive coronary artery disease, taking into account risk factors and with the additional inclusion of information on the calcium index of coronary arteries. The proposals of experts on new algorithms for the choice of non-invasive / invasive examination of this category of patients were also considered. Overall, the new PTV rating scale (ECS 2019) has been validated and validated in retrospective analyzes of cohort studies. The scale for assessing the clinical likelihood of obstructive coronary artery disease makes it possible to classify 3.8-5 times more patients as a low probability of coronary artery disease compared to the assessment of PTP alone. Assessment of the post-test probability of coronary artery disease does not allow to confirm the presence of obstructive lesion and was not used. The experts proposed new modifications of the diagnostic algorithm (with a detailed assessment of the clinical probability, as well as without taking it into account), which require verification in further studies. Therefore, it is advisable to conduct prospective studies to confirm the possibility of reducing the total number of non-invasive and invasive studies in patients with suspected coronary heart disease, as well as the safety of such a decrease in diagnostic procedures.

Contemporary Management of Stable Coronary Artery Disease.

Coronary artery disease (CAD) continues to be the leading cause of mortality and morbidity in developed countries. Assessment of pre-test probability (PTP) based on patient’s characteristics, gender and symptoms, help to identify more accurate patient's clinical likelihood of coronary artery disease. Consequently, non-invasive imaging tests are performed more appropriately to rule in or rule out CAD rather than invasive coronary angiography (ICA). Coronary computed tomography angiography (CCTA) is the first-line non-invasive imaging technique in patients with suspected CAD and could be used to plan and guide coronary intervention. Invasive coronary angiography remains the gold-standard method for the identification and characterization of coronary artery stenosis. However, it is recommended in patients where the imaging tests are non-conclusive, and the clinical likelihood is very high, remembering that in clinical practice, approximately 30 to 70% of patients with symptoms and/or signs of ischemia, referred to coronary angiography, have non obstructive coronary artery disease (INOCA). In this contest, physiology and imaging-guided revascularization represent the cornerstone of contemporary management of chronic coronary syndromes (CCS) patients allowing us to focus specifically on ischemia-inducing stenoses. Finally, we also discuss contemporary medical therapeutic approach for secondary prevention. The aim of this review is to provide an updated diagnostic and therapeutic approach for the management of patients with stable coronary artery disease.

D-dimer Thresholds to Exclude Pulmonary Embolism among COVID-19 Patients in the Emergency Department: Derivation with Independent Validation

ObjectiveTo derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED).MethodsA retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data.ResultsAmong 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 μ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%−98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 μ/mL was associated with a NPV of 99.5% (95% CI = 99.3%−99.7%).ConclusionA D-dimer cutoff of <2 μ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.

D-dimer - origin and clinical significance

Introduction. D-dimer is formed during plasmin-mediated proteolysis of cross-linked fibrin; hence it serves as a biomarker of activated coagulation and fibrinolysis. Clinical significance. Measurement of D-dimer is most commonly used to exclude venous thromboembolism, and in the diagnosis of disseminated intravascular coagulation. For the diagnosis of venous thromboembolism D-dimer is part of the validated algorithm, which includes an assessment of clinical pre-test probability to guide further investigation. Due to very high negative predictive values, average levels of D-dimer are sufficient for ruling out venous thromboembolism in patients with low-medium pre-test clinical probability. However, in patients with high pre-test probability, the measurement of D-dimer is of limited value. Similarly, normal values of D-dimer reliably exclude disseminated intravascular coagulation. On the other hand, elevated values of D-dimer have low specificity for this condition and should be evaluated in a validated scoring system developed for the diagnosis of disseminated intravascular coagulation. Recently, measurement of D-dimer has been increasingly applied to assess the risk of venous thrombosis recurrence in women and to decide on the duration of anticoagulant therapy after the first unprovoked venous thrombosis. Elevated D-dimer level is an essential characteristic of COVID-19 - associated coagulopathy. The degree of coagulopathy and D-dimer levels correlate with the clinical severity of the disease and higher mortality, most likely reflecting increased activation of the coagulation system in the microcirculation of various organs, primarily the lungs. Conclusion. D-dimer is one of the most often used hemostasis test, validated so far for diagnosis of venous thromboembolism and disseminated intravascular coagulation.

Heparin‐induced thrombocytopenia: Construction of a pretest diagnostic score derived from the analysis of a prospective multinational database, with internal validation

BackgroundDiagnosis of heparin‐induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays. ObjectiveTo develop a pretest score for HIT. DesignObservational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839). SettingThirty‐one tertiary hospitals in France, Switzerland, and Belgium. PatientsPatients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts. MeasurementsIndependent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results. ResultsHeparin‐induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic‐dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5‐ to 21‐day interval from anticoagulation initiation to suspicion of HIT (4); ≥40% decrease in platelet count over ≤6 days (3); thrombotic event, arterial (3) or venous (3). The C‐statistic was 0.79 (95% CI, 0.76–0.82). In the validation cohort, the area under the receiver operating characteristic curve was 0.77 (95% CI, 0.74–0.80). Three groups of scores were defined; HIT prevalence reached almost 30% in the high‐probability group. LimitationThe performance of the score may depend on settings and practices. ConclusionThe objective, easy‐to‐collect, clinical features of HIT we evidenced were incorporated into a pretest score, which may guide clinical decisions regarding diagnostic testing and anticoagulation.

Electronic pulmonary embolism clinical decision support and effect on yield of computerized tomographic pulmonary angiography: ePE-A pragmatic prospective cohort study.

ObjectiveMultiple professional societies recommend pre‐test probability (PTP) assessment prior to imaging in the evaluation of patients with suspected pulmonary embolism (PE), however, PTP testing remains uncommon, with imaging occurring frequently and rates of confirmed PE remaining low. The goal of this study was to assess the impact of a clinical decision support tool embedded into the electronic health record to improve the diagnostic yield of computerized tomography pulmonary angiography (CTPA) in suspected patients with PE in the emergency department (ED).MethodsBetween July 24, 2014 and December 31, 2016, 4 hospitals from a healthcare system embedded an optional electronic clinical decision support system to assist in the diagnosis of pulmonary embolism (ePE). This system employs the Pulmonary Embolism Rule‐out Criteria (PERC) and revised Geneva Score (RGS) in series prior to CT imaging. We compared the diagnostic yield of CTPA) among patients for whom the physician opted to use ePE versus the diagnostic yield of CTPA when ePE was not used.ResultsDuring the 2.5‐year study period, 37,288 adult patients were eligible and included for study evaluation. Of eligible patients, 1949 of 37,288 (5.2%) were enrolled by activation of the tool. A total of 16,526 CTPAs were performed system‐wide. When ePE was not engaged, CTPA was positive for PE in 1556 of 15,546 scans for a positive yield of 10.0%. When ePE was used, CTPA identified PE in 211 of 980 scans (21.5% yield) (P < 0.001).ConclusionsePE significantly increased the diagnostic yield of CTPA without missing 30‐day clinically overt PE.