Low Clinical Pretest Probability Research Articles

External validation of the CHEDDAR score for suspected pulmonary embolism in patients with SARS-CoV-2 infection in an independent cohort.

The accuracy of the classic scores that help stratify the pretest clinical probability of pulmonary embolism (PE) in SARS-CoV-2 infection (COVID-19) is low. Therefore, to estimate the risk of PE in these patients, a new set of guidelines must be established. The recently published CHEDDAR score proposes a new diagnostic strategy to reduce the use of computed tomography pulmonary angiography (CTPA) in non-critically ill SARS-COV-2 patients with suspected PE. According to the nomogram, patients are segregated intolow-risk (< 182points) or high-risk (≥ 182points) based on the best cut-off value to discard PE in the original cohort. We aimed to externally validate this diagnostic strategy in an independent cohort. We analyzed data from two retrospective cohorts of hospitalized non-critically ill COVID-19 patients who underwent a CTPA due to suspicion for PE. CHEDDAR score was applied. As per the CHEDDAR nomogram, patients were classified as having a low or high clinical pre-test probability. Of the 270 patients included, 69 (25.5%) had PE. Applying the CHEDDAR score, 182 (67.4%) patients could have had PE excluded without imaging. Among 58 patients classified as having high clinical pre-test probability, 39 (67.2%) had PE. Sensitivity, specificity, positive and negative predictive values, and AUC were 56%, 90%, 67%, 85%, and 0.783 (95% CI 0.71-0.85), respectively. We provide external validation of the CHEDDAR score in an independent cohort. Even though the CHEDDAR score showed good discrimination capacity, caution is required in patients classified as having low clinical pre-test probability with a D-dimer value > 3000ng/mL, and a RALE score ≥ 4.

Performance of the 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) in the diagnostic management of pulmonary embolism: An external validation study

BackgroundThe recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE). AimTo externally validate the performance of 4PEPS in an independent cohort. MethodsIn this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer <1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold. ResultsOf the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80–0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57–60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86–1.9). ConclusionIn this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study.

External validation of the PEGeD diagnostic algorithm for suspected pulmonary embolism in an independent cohort.

Sequential diagnostic algorithms are used in the case of suspected pulmonary embolism (PE). The PEGeD study proposed a new diagnostic strategy to reduce the use of computed tomography pulmonary angiography (CTPA). We aimed to externally validate this diagnostic strategy in an independent cohort. We analyzed data from 3 prospective studies of outpatients with suspected PE. As per the PEGeD algorithm, patients were classified as having a low, moderate, or high clinical pretest probability (C-PTP). PE was excluded with a D-dimer <1000 ng/mL in case of low C-PTP and <500 ng/mL in case of moderate C-PTP. We assessed the yield and safety of this approach and compared them with those of previously validated algorithms. Among the 3308 evaluated patients, 1615 (49%) patients could have had PE excluded according to the PEGeD algorithm, without the need for imaging. Of these patients, 38 (2.3%; 95% confidence interval [CI], 1.7-3.2) were diagnosed with a symptomatic PE at initial testing or during the 3-month follow-up. On further analysis, 36 patients out ofthese 38 patients had a positive age-adjusted D-dimer. The risk of venous thromboembolic events among the 414 patients with a D-dimer <1000 ng/mL but above the age-adjusted D-dimer cut-off was 36 of 414 (8.7%; 95% CI, 6.4-11.8). We provide external validation of the PEGeD algorithm in an independent cohort. Compared with standard algorithms, the PEGeD decreased the number of CTPA examinations. However, caution isrequired in patients with a low C-PTP and a D-dimer <1000 ng/mL but above their age-adjusted D-dimer cut-off.

Prevalence of pulmonary embolism among patients with recent onset of dyspnea on exertion. A cross-sectional study

BackgroundExertional dyspnea is a frequently encountered complaint in clinical practice. However, the prevalence of pulmonary embolism (PE) among patients with dyspnea on exertion has not been reported. ObjectiveThe objective of this study was to assess the prevalence of objectively confirmed PE among consecutive patients visiting an emergency department because of recent onset of exertional dyspnea. MethodsPatients aged ≤75 years with recent (<1 month) marked exertional dyspnea had a systematic workup for PE, irrespective of concomitant signs or symptoms of venous thromboembolism and alternative explanations for dyspnea. PE was excluded on the basis of a low pretest clinical probability and normal age-adjusted D-dimer. All other patients had computed tomography pulmonary angiography. An interim analysis after inclusion of 400 patients would stop recruitment if the 95% confidence interval (CI) of the PE prevalence had a lower limit exceeding 20%. ResultsThe study was prematurely terminated after the inclusion of 417 patients. In 134 patients (32.1%), PE was excluded based on low clinical probability and normal D-dimer. PE was found in 134 (47.3%) of the remaining 283 patients, for an overall prevalence of 32.1% (95% CI, 27.8-36.8). PE was present in 40 of 204 (19.6%) patients without other findings suspicious for PE and in 94 of 213 patients (44.1%) with such findings. PE involved a main pulmonary artery in 37% and multiple lobes in 87% of the patients. ConclusionThe angiographic demonstration of PE is common in patients presenting with recent onset of marked exertional dyspnea, including 20% without other findings suggesting pulmonary embolism.

Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: prospective diagnostic management study

ObjectiveTo evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT.DesignProspective diagnostic management study.SettingUniversity based...

Pragmatic Evaluation of an Algorithm Using D-Dimer Adjusted to Clinical Probability in the Diagnosis of Pulmonary Embolism

BACKGROUNDDiagnosis of pulmonary embolism (PE) using clinical decision rules in combination with D-dimer (DD) values is a standard practice. The Wells score is the most commonly used rule, either in its original (3-category) or modified (2-category) versions, and in conjunction with a (DD) <500 ng/mL allows to exclude a PE in approximately 30% of patients. The recent PEGeD study (Kearon et al. 2019) concluded that a PE can be safely excluded by using a DD threshold adjusted to the clinical pre-test probability (C-PTP). In that study PE was excluded in patients with low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL In the present study we aimed to evaluate the performance of the PEGeD algorithm in daily practice. METHODSWe conducted a retrospective cohort study involving all adult patients who presented at London Health Sciences Centre or St. Joseph's Health Care Emergency Departments in London, Ontario, Canada between November 1, 2018 and December 31, 2020 with signs or symptoms suggestive of a pulmonary embolism and for whom a DD was ordered electronically. They were excluded if they did not have complete follow-up information for at least 90 days from the initial visit, they were pregnant, they were on long term anticoagulation for other indications, or had chest imaging prior to DD order. Using the electronic hospital chart, we extracted demographics, imaging results, and the Wells score with all its individual components. In our center, information about the Wells score and its components is routinely and prospectively collected when ordering DD. Since the PEGeD algorithm is not routinely used in our hospital, data of the C-PTP was utilized to determine which DD cut-off should be applied to the patient. Decision to perform imaging studies was taken by the ED physician at the time of assessment. The outcome of interest was the proportion of a PE or DVT at 90 days after the visit to the ED in patients with a low or intermediate C-PTP and who did not receive an initial diagnosis of PE and 99% confidence intervals (CI) were estimated using the Wilson's score method. RESULTSA total of 2769 patient charts were reviewed and 1070 were included (Table 1, Figure 1). Of the 1070 patients, 71 (7%) of patients had a pulmonary embolism on initial presentation to the emergency department. At 90 days of follow up none (99% CI 0, 0.84) of the 787 patients who had a low C-PTP or a moderate C-PTP score and a DD <1000 ng/mL or <500 ng/mL, respectively, were positive for a PE . This included 194 patients who had a low C-PTP and a DD level of 500-999 ng/mL and 26 patients who had an intermediate C-PTP and a DD level of <500 ng/mL. Notably, 8 (1.02%, 99% CI 0.42-2.43) PEs would have been missed using the PEGeD protocol when using DD cut-off levels of <1000 ng/mL in the low C-PTP group, or <500 ng/mL in the intermediate C-PTP. CONCLUSIONSIn this cohort we found that if the PEGeD algorithm had been used, it would have resulted in a low risk of VTE during follow up in patients without an initial diagnosis of PE and who had either a low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL. We also found it would have been associated with 194 (48%) less diagnostic imaging studies in the low C-PTP range and 2 (6%) less studies in the intermediate C-PTP range. Despite this, 1% of patients with PE (99% upper confidence limit 2.43%) would have been missed. This study is limited by its retrospective nature with an inherent risk of misclassification. Further studies are needed before recommending the use of this algorithm in clinical practice.Work CitedKearon, C., de Wit, K., Parpia, S., Schulman, S., Afilalo, M., Hirsch, A., Spencer, F. A., Sharma, S., D'Aragon, F., Deshaies, J.-F., Le Gal, G., Lazo-Langner, A., Wu, C., Rudd-Scott, L., Bates, S. M., & Julian, J. A. (2019). Diagnosis of Pulmonary Embolism with d -Dimer Adjusted to Clinical Probability. New England Journal of Medicine, 381(22), 2125-2134. https://doi.org/10.1056/NEJMoa1909159 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A simplified decision rule to rule out deep vein thrombosis using clinical assessment and D‐dimer

BackgroundCurrent clinical decision rules to exclude deep vein thrombosis (DVT) are underused partly because of their complexity. A simplified rule that can be easily applied would be more appealing to use in clinical practice. MethodsWe used individual patient data from prospective diagnostic studies of patients suspected of DVT to develop a new clinical decision rule. The primary outcome was presence of DVT either at initial testing or during follow‐up. DVT was considered safely excluded if the upper 95% confidence interval (CI) of DVT prevalence was <2%. ResultsFour studies and 3368 patients were eligible for this analysis. Overall prevalence of DVT was 17%. In addition to D‐dimer, two variables, calf swelling and DVT as the most likely diagnosis, are included in the new rule. Based on these two variables, two clinical pretest probability (CPTP) groups were defined; low (none of the two items present) and high (at least one of the items present). DVT can be safely excluded in patients with low CPTP with a D‐dimer <500 ng/mL (prevalence = 0.1%; 95% CI, 0.0‐0.8), low CPTP with a D‐dimer between 500 ng/ml and 1000 ng/ml (prevalence = 0.3%; 95% CI, 0.0‐1.7), and D‐dimer <500 ng/ml in patients with high CPTP (prevalence = 0.3%; 95% CI, 0.0‐1.0). ConclusionsThe combination of D‐dimer and Wells items resulted in a simple clinical decision rule with 3 items. The results suggest that the rule can safely exclude DVT. Prospective validation is required.

Deep Vein Thrombosis Diagnosis with D-Dimer Adjusted to Clinical Probability

Introduction Diagnostic testing for deep vein thrombosis (DVT) is a multi-step and time-consuming process. Testing starts with clinical pretest probability (C-PTP) assessment. A negative D-dimer in combination with low C-PTP is widely used to exclude DVT; otherwise ultrasound imaging is required. When proximal vein ultrasound is used, a repeat ultrasound after a week is usually required to exclude DVT in moderate or high C-PTP patients. Ultrasound imaging is costly and can introduce delays. The goal of this study was to evaluate the safety and efficiency of a diagnostic algorithm for DVT that was designed to minimize the need for ultrasound imaging by using C-PTP-based D-dimer thresholds to exclude DVT (the 4D algorithm), rather than a standard fixed D-dimer cut-off value. Methods Consenting patients were enrolled in a Canadian prospective multicentre management study. Outpatients with symptoms or signs of DVT were eligible to be included in this study. Physicians used the 9-item Wells score to categorize the patient's C-PTP as low (Wells score, -2 to 0), moderate (1 or 2), or high (≥3). Patients with low C-PTP and a D-dimer &amp;lt;1,000 ng/mL or with a moderate C-PTP and a D-dimer &amp;lt;500 ng/mL underwent no further diagnostic testing for DVT and did not receive anticoagulant therapy. All other patients underwent proximal vein ultrasound. Patients with a single negative ultrasound but very high D-dimer (low or moderate C-PTP with D-dimer ≥3000 ng/mL, high C-PTP with D-dimer ≥1500 ng/mL) had a second proximal venous ultrasound one week later. The primary outcome was symptomatic, objectively verified, venous thromboembolism (VTE), which included proximal DVT or pulmonary embolism. All patients were followed for 90 days. A sample size of 1500 was required to establish 4D algorithm safety (90-day post-test probability of VTE &amp;lt;2%). Results From April 2014 through March 2020, a total of 1512 patients were enrolled and analyzed. The mean age was 60 years and 58% were female. Overall, 173 (11%) had DVT on initial or serial diagnostic testing (168 had DVT on ultrasound imaging on the day of presentation and 5 had DVT on repeat ultrasound imaging at one week). Of all 1298 patients (86% of total) who did not have DVT (at either initial presentation or at scheduled repeat ultrasound imaging) and who did not receive anticoagulant therapy, 7 had VTE during follow-up (0.5%, 95% confidence interval (CI): 0.3 to 1.1%). In the 579 patients who had low (378 patients) or moderate (201 patients) C-PTP and negative D-dimer results (i.e. &amp;lt;1000 or &amp;lt;500 ng/mL respectively) and who did not receive anticoagulant therapy, 2 had VTE during follow-up (0.4%, 95% CI: 0.1 to 1.3%). In the 572 patients with a single negative ultrasound who were low or moderate C-PTP with D-dimer &amp;lt;3000 ng/mL (423 patients), or high C-PTP with D-dimer &amp;lt;1500 ng/mL (149 patients) and who did not receive anticoagulant therapy, 3 had VTE during follow-up (0.5%, 95% CI: 0.2 to 1.5%). The difference in the mean number of ultrasound examinations with the 4D algorithm (0.72) compared with the conventional algorithm (1.36) was -0.64 (95% CI, -0.68 to -0.61), corresponding to a 47% relative reduction (1083 ultrasound scans performed with the 4D algorithm compared with 2053 ultrasound scans required for the conventional algorithm). Conclusions The 4D diagnostic algorithm ruled out DVT safely while substantially reducing the requirement for ultrasound imaging. Disclosures Wu: BMS-pfizer: Honoraria, Other: advisory board; leo pharma: Other: advisory board; Pfizer: Honoraria; Servier: Other: advisory board.

A Retrospective Review of the Appropriateness of D-Dimer Ordering and Interpretation Using Wells' Clinical Probability Criteria

Introduction The D-dimer has been validated in diagnostic venous thromboembolism (VTE) algorithms. The high sensitivity of the assay allows for safe exclusion of VTE in patients with low clinical pre-test probability and a negative D-dimer. The Wells score for Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) are validated pre-test probability tools which help guide physicians on when to order a D-dimer in patients with suspected VTE. However, we suspect these scoring tools are often under-utilized by physicians leading to inappropriate D-dimer ordering and subsequent interventions. We sought to explore the landscape of D-dimer ordering at our institution. Methods We conducted a retrospective chart review of 482 patients in whom a D-dimer had been ordered over a 3-month period at the University of Alberta Hospital, a tertiary care teaching hospital in Edmonton, Canada. Charts were reviewed for patient demographics, specialty of ordering physician, apparent indication for ordering, patient risk factors for VTE and evidence of a pre-test probability (PTP) calculation. WIf no PTP score was documented, we retrospectively calculated Wells DVT or PE scores. VTE was deemed likely with a calculated Wells score for DVT ≧2 or Wells score for PE &amp;gt;4. In the case of high PTP for PE, patients should go directly to imaging and a D-dimer should not be performed. A cut off of ≥ 0.50 mg/L was deemed a positive D-dimer (STA-LIATEST). We also reviewed subsequent investigations thought to be influenced by interpretation of the D-dimer including: ventilation/perfusion (V/Q) and pulmonary angiography (CTPA) scans, and upper and lower extremity doppler ultrasound studies. We then used multivariable logistic regression analysis to evaluate the proportion of patients who received imaging despite a low PTP and negative D-dimer. Results Seventy eight percent of D-dimers were ordered by Emergency physicians while 15.3% were drawn on admitted patients, and 5.8% in the outpatient setting. The indication for ordering was unknown in 87 (17.5%) of cases. Pre-test probability scores were documented in only 8 (1.6%) of cases. All of those documented were the Wells PE score. When Wells DVT and PE scores were calculated retrospectively, 30.0% and 17.1% (87 cases) were deemed 'likely' for VTE, respectively. However, imaging was performed in 172 cases (34.6%), including in 36 cases despite a negative D-dimer result and low PTP. In contrast, 68 cases (17.2%) had a D-dimer performed with a high Wells PTP for PE despite the recommendation to proceed directly to imaging. VTE (either DVT or PE) was confirmed by imaging in 32 (18.6%) of cases, the majority (53.1%) had a high retrospective PTP. Conclusions Inappropriate ordering and interpretation of D-dimers remains a significant problem despite the implementation of clinical guidelines and pre-test probability algorithms, namely the Wells score for DVT and PE meant to guide physicians. This leads to unnecessary cost, radiation exposure, and prolonged contact with the health care system for patients. This suggests the need for quality improvement initiatives which draw physician's attention to pre-test probability tools which can curbing subsequent inappropriate investigations and improve patient care. Disclosures Wu: Servier: Other: advisory board; BMS-pfizer: Honoraria, Other: advisory board; leo pharma: Other: advisory board; Pfizer: Honoraria.

Performance of the Quantitative Latex Immunoturbidimetric D-dimer Assay for the Diagnosis of Acute Pulmonary Embolism at Rafik Hariri University Hospital

Background and aims: The diagnostic workup for pulmonary embolism (PE) includes D-dimer assay and computed tomographic angiography. Several D-dimer assays have been approved for PE diagnosis with different sensitivity and specificity. We aimed to study the sensitivity and specificity of the quantitative latex agglutination D-dimer assay used in a referral teaching hospital in Lebanon for the diagnosis of acute PE. Methods: Using a retrospective chart review, we studied 300 patients who had D-dimer test at Rafik Hariri University Hospital in the period between January 1, 2012 and December 31, 2013. Accordingly, 93 patients had a CT angiography after being suspected to have acute PE. A statistical table 2*2 was used to compare the results of CT angiography and D-dimer test. Results: Thirteen patients (13.97%) had PE and 60 patients (64.51%) had positive D-dimer test. Quantitative latex agglutination D-dimer assay had a sensitivity of 69%, specificity of 36%, and negative predictive value of 88%. False positive ratio was also 64%. Moreover, the receiver operating characteristic (ROC) curve was obtained with an area under the curve measuring 0.527. Conclusion: Quantitative latex agglutination D-dimer assay has a high negative predictive value; thus, it can exclude a PE diagnosis if it is associated with low clinical pretest probability.

LO55: Comparison of the age-adjusted D-dimer, clinical probability-adjusted D-dimer, and Wells rule with D-dimer for diagnosing deep vein thrombosis in the emergency department.

Introduction: Diagnosing deep vein thrombosis (DVT) is of critical importance because of its associated morbidity and mortality. Diagnosing DVT can be challenging in the Emergency Department (ED) due to inconsistent adherence to, and utilization of the Wells rule. Both the age-adjusted and clinical probability adjusted D-dimer have been shown to decrease ultrasound (US) utilization rates. We aimed to compare the safety and efficacy of the Wells score with D-dimer to the age-adjusted and clinical probability-adjusted D-dimer in Canadian ED patients tested for DVT. Methods: This was a health records review of ED patients investigated for DVT at two EDs over a two-year period. Inclusion criteria were ED physician ordered duplex ultrasonography or D-dimer for investigation of lower limb DVT. Patients under the age of 18 were excluded. DVT was considered to be present during the ED visit if DVT was diagnosed on duplex ultrasonography and was treated for acute DVT, or if the patient was subsequently diagnosed with pulmonary embolism (PE) or DVT during the next 30 days. Trained researchers extracted anonymized data. The Wells D-dimer, age-adjusted D-dimer, and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of duplex ultrasonography imaging and the false negative rate was calculated for each rule. Results: Between April 1st 2013 and March 31st 2015, there were 1,198 patients tested for DVT. Of the low and moderate clinical pretest probability patients (Wells score ≤ 2), only 436 had a D-Dimer test and were eligible for our analysis. The average age of the patients was 59, 56% were female, and 4% had a malignancy. 207/436 patients (47.4%, 95%CI 42.8-52.2%) would have had US imaging for DVT if the age-adjusted D-dimer rule was used. 214/436 patients (49.1%, 95%CI 44.4-53.8%) would have had imaging for DVT if the clinical probability-adjusted D-dimer was used. If the Wells rule was used with the standard D-dimer cutoff of 500, 241/436 patients (55.2%, 95%CI 50.6-59.9%) would have had imaging for DVT. The false-negative rate for the Wells rule was 1.5% (95%CI 0.5-4.4%). The false-negative rate for the age-adjusted D-dimer rule was 1.3% (95%CI 0.4-3.8%). The false-negative rate for the clinical-probability adjusted D-Dimer was 1.8% (95%CI 0.7-4.5%). Conclusion: In comparison with the approach of the Wells score and D-dimer, both the age-adjusted and clinical probability-adjusted D-dimer diagnostic strategies could reduce the proportion of patients who require US imaging.

In outpatients, low or moderate clinical pretest probability with probability-defined D-dimer cut points ruled out PE.

Source Citation Kearon C, de Wit K, Parpia S, et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med. 2019;381:2125-34. 31774957

Coronary Computed Tomographic Angiography Imaging as a Prognostic Indicator for Coronary Artery Disease: Data from a Lebanese Tertiary Center.

Background:Coronary artery disease (CAD) is a major cause of death and disability worldwide. Coronary computed tomographic angiography (CCTA) is a noninvasive imaging technique with a high negative predictive value (NPV). Most studies were done in developed countries, where the prevalence of CAD does not reflect the actual disease burden in developing countries, such as Lebanon.Methods:We retrospectively evaluated the prognostic value of CCTA in predicting acute myocardial events (AMEs) in 200 Lebanese patients. We determined if specific medical and radiological characteristics are linked with AME and looked for any association between the patient's medical risk factors and the type/location of detected atheromatous plaques. Patients' records were reviewed, and the follow-up period of 5–8 years ensued. Chi-square/Fisher test and Student's t-test were used, in addition to multinomial logistic regression to adjust for the confounding variables. P <0.05 was considered statistically significant.Results:Our study showed that CCTA had a NPV that reaches 97.9% in asymptomatic patients, a positive predictive value (PPV) of 76.4% for symptomatic patients, a sensitivity of 88.9%, and a specificity of 52.5%. AMEs were significantly increased in patients with a mixed plaque type and/or a moderate-to-severe lumen reduction on CCTA.Conclusions:CCTA is a sensitive modality for plaque detection and is found to have a remarkably high NPV for asymptomatic patients. A CCTA, along with a low pretest clinical probability of CAD, can be sufficient to rule out an AME for up to 8 years.

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability

BackgroundRetrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP.MethodsWe performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism.ResultsA total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, −17.6 percentage points; 95% CI, −19.2 to −15.9).ConclusionsA combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.)

Diagnostic imaging in the management of patients with possible cerebral venous thrombosis: a cost-effectiveness analysis.

Imaging is crucial for management of patients with possible cerebral venous thrombosis (CVT). To evaluate the cost-effectiveness of different noninvasive imaging strategies in patients with possible CVT. A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALY) associated with the following imaging strategies: non-contrast CT (NCCT), NCCT plus CT venography (CTV), routine MRI without vascular imaging (R-MRI), and MRI with venography (MRV). The analysis was performed from a US healthcare perspective. Model input was based on best available and most recent evidence, including outcome data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Starting age was 37years; both high and low pre-test probabilities of CVT were evaluated. Probabilistic sensitivity analyses (PSA) estimated model uncertainty. In the base-case analysis, NCCT and CTV were dominant over R-MRI and MRV. CTV led to incremental lifetime QALYs compared with NCCT (23.385 QALYs vs. 23.374 QALYs) at slightly higher lifetime costs ($5210 vs. $5057). In PSA, CTV was the strategy with the highest percentage of cost-effective iterations if willingness-to-pay (WTP) thresholds were higher than $13,750/QALY. Complying with contemporary WTP thresholds, CTV was thus identified as the most cost-effective strategy. When the pre-test probability was set to 50%, CTV was also preferred. In patients at the peak age of CVT incidence yet low clinical pre-test probability, diagnostic imaging with CTV is the most cost-effective strategy.

Prospective Study of Pulmonary Embolism Presenting as Syncope.

Syncope represents a common condition among the general population. It is also a frequent complaint of patients in the emergency department (ED). Pulmonary embolism (PE) considers a differential diagnosis, particularly in a case of syncope without chest pain. What is the prevalence of PE among patients who presented an episode of syncope to the ED and among those hospitalized for syncope in a tertiary care hospital? From January 2012 to December 2017, we conducted a prospective observational study among adult patients presenting themselves to the ED consecutively or admitted for syncope. Syncope and PE were defined by professional guidelines. PE was ruled out in patients who had a low pretest clinical probability, as per Wells score and a negative D-dimer assay. In other patients, computed tomography pulmonary angiography was performed. Seventeen thousand eight-two patients (mean age 71.3 ± 13.24 years) visited the ED for syncope. PE was detected in 45 patients (mean age 65.75 ± 9.45 years): 4 with low risk, 26 with intermediate risk, and 15 with high risk. The prevalence of PE in those hospitalized with syncope was 11.47%, which is 45 of 392 (confidence interval 95% 8.48-15.04), and was 2.52%, 45 of 1782 (confidence interval 95% 1.8-3.3), in patients presenting with syncope to the ED. The location of the embolus was bilateral in 24 patients (53.33%), in a main pulmonary artery in 10 (22.22%), in a lobar artery in 10 (22.22%), and in a segmental artery in 1 (2.22%). The occurrence of syncope, if not explained otherwise, should alert one to consider PE as a differential diagnosis. PE rate, presenting as syncope, is the highest in patients with large thrombi, which is responsible for bilateral or proximal obstruction in a main or lobar pulmonary artery.

Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope

BackgroundThe prevalence of pulmonary embolism among patients hospitalized for syncope is not well documented, and current guidelines pay little attention to a diagnostic workup for pulmonary embolism in these patients.MethodsWe performed a systematic workup for pulmonary embolism in patients admitted to 11 hospitals in Italy for a first episode of syncope, regardless of whether there were alternative explanations for the syncope. The diagnosis of pulmonary embolism was ruled out in patients who had a low pretest clinical probability, which was defined according to the Wells score, in combination with a negative d-dimer assay. In all other patients, computed tomographic pulmonary angiography or ventilation–perfusion lung scanning was performed.ResultsA total of 560 patients (mean age, 76 years) were included in the study. A diagnosis of pulmonary embolism was ruled out in 330 of the 560 patients (58.9%) on the basis of the combination of a low pretest clinical probability of pulmonary embolism and negative d-dimer assay. Among the remaining 230 patients, pulmonary embolism was identified in 97 (42.2%). In the entire cohort, the prevalence of pulmonary embolism was 17.3% (95% confidence interval, 14.2 to 20.5). Evidence of an embolus in a main pulmonary or lobar artery or evidence of perfusion defects larger than 25% of the total area of both lungs was found in 61 patients. Pulmonary embolism was identified in 45 of the 355 patients (12.7%) who had an alternative explanation for syncope and in 52 of the 205 patients (25.4%) who did not.ConclusionsPulmonary embolism was identified in nearly one of every six patients hospitalized for a first episode of syncope. (Funded by the University of Padua; PESIT ClinicalTrials.gov number, NCT01797289.)

P136: A quality improvement initiative to optimize appropriate testing for venous thromboembolism in the emergency department

Introduction: Venous thromboembolism (VTE) is a common diagnostic consideration among patients presenting to the emergency department (ED) and often requires the use of diagnostic testing. A normal d-dimer (DD) blood test can exclude VTE and eliminate the need for costly imaging and the associated contrast medium and radiation exposure. The purpose of this quality improvement initiative was to increase the use of DD testing for patients with a low and intermediate clinical pretest probability of VTE, increase the use of ventilation perfusion scans (VQ) as an alternative to CT pulmonary angiogram (CTPA) and decrease the use of CTPA and venous doppler ultrasound (VDUS) at St. Michael’s hospital. Methods: A multispecialty team developed an ED specific algorithm set for appropriate VTE testing that were posted on the ED online portal along with a poster in each zone of the ED after an ED launch campaign with request for feedback. A run chart was used to track DD, CTPA, VQ and VDUS utilization. Two-sided T-test comparison was conducted to compare pre- and post-implementation utilization. Results: Physician feedback was positive regarding the use of: DD in VTE intermediate risk patients and the VTE algorithm set. Feedback was negative for DD turnaround time. We found a significant increase in DD use (77 tests per month to 93; p=0.013), but no significant change in the use of CTPA (27.3 per month to 30; p=0.38), VDUS, or VQ. Number of monthly ED visits remained constant. Conclusion: This intervention increased DD utilization, but measuring appropriateness will require prospective collection of clinical pre-test probability. Integrated risk stratification and decision aids into computer physician order entry may be necessary to track and improve appropriateness.

Terminological clarification of Brugada Phenocopy, Brugada Syndrome, and the Brugada ECG pattern: Re. Early repolarization pattern in patients with provocable Brugada Phenocopy: A marker of additional arrhythmogenic cardiomyopathy

We read the recent paper by Dr. Peters [1] with great interest and noted that the term Brugada Phenocopy (BrP) was used in the title; however, the discussion focuses on early repolarization pattern (ERP) in the context of arrhythmogenic right ventricular cardiomyopathy and provocable Brugada ECG pattern with sodium channel blockers. We have been publishing extensively on the subject of BrP [2–9] and would like to suggest a clarification on terminology so as to facilitate future research on BrP and avoid confusion with other forms of ERP. As previously described, Bayes de Luna et al. articulated the ECG criteria for type 1 and type 2 Brugada ECG patterns in the most recent consensus report [10]. In our recent publications [2–9], we have established the diagnostic criteria for BrP and would like to identify salient features that differentiate BrP from true congenital Brugada Syndrome (BrS). First, patients with BrP and BrS both have identical type 1 or type 2 ECG patterns in precordial leads V1–V3. Second, patients with BrP have an identifiable underlying condition that elicits the Brugada ECG pattern and once this underlying condition resolves, the ECG normalizes. Additionally, patients with BrS have a high clinical pretest probability of true congenital BrS, while patients with BrP have a low clinical pretest probability of true congenital BrS suggested by lack of symptoms, medical history, or family history. Most importantly, patients with BrP have a negative provocative challenge with sodium channel blockers such as procainamide, flecainide, or ajmaline while patients with true congenital BrS have a positive provocative challenge. As such, right ventricular outflow tract sodium channel dysfunction in patients with BrS may have a different pathophysiological basis compared to patients with BrP; however, the underlying mechanisms have yet to be elucidated. We thank Dr. Peters for incorporating the relatively new term Brugada Phenocopy into his literature but we would like to emphasize that this term should not be used for cases where the Brugada ECG pattern is provoked by the use of sodium channel blockers [2]. We are developing an international online registry at www.brugadaphenocopy.com and encourage all investigators working on BrP to submit their cases online in order to provide long-term follow-up and insight into the clinical evolution of this emerging phenomenon. The authors of this manuscript certify that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

Selectived-Dimer Testing for Diagnosis of a First Suspected Episode of Deep Venous Thrombosis

D-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis (DVT). Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing. To determine whether using a selective D-dimer testing strategy based on clinical pretest probability (C-PTP) for DVT is safe and reduces diagnostic testing compared with using a single D-dimer threshold for all patients. Randomized, multicenter, controlled trial. Patients were allocated using a central automated system. Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation. (ClinicalTrials.gov: NCT00157677) 5 Canadian hospitals. Consecutive symptomatic patients with a first episode of suspected DVT. Selective testing (n = 860), defined as D-dimer testing for outpatients with low or moderate C-PTP (DVT excluded at D-dimer levels <1.0 µg/mL [low C-PTP] or <0.5 µg/mL [moderate C-PTP]) and venous ultrasonography without D-dimer testing for outpatients with high C-PTP and inpatients, or uniform testing (n = 863), defined as D-dimer testing for all participants (DVT excluded at D-dimer levels <0.5 µg/mL). The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing D-dimer testing and ultrasonography. The incidence of symptomatic venous thromboembolism at 3 months was 0.5% in both study groups (difference, 0.0 percentage point [95% CI, -0.8 to 0.8 percentage points]). Selective testing reduced the proportion of patients who required D-dimer testing by 21.8 percentage points (CI, 19.1 to 24.8 percentage points). It reduced the proportion who required ultrasonography by 7.6 percentage points (CI, 2.9 to 12.2 percentage points) overall and by 21.0 percentage points (CI, 14.2 to 27.6 percentage points) in outpatients with low C-PTP. Results may not be generalizable to all D-dimer assays or patients with previous DVT, study personnel were not blinded, and the trial was stopped prematurely. A selective D-dimer testing strategy seems as safe as and more efficient than having everyone undergo D-dimer testing when diagnosing a first episode of suspected DVT. Heart and Stroke Foundation of Ontario.