Targeted prophylactic anticoagulation based on the TRiP(cast) score in patients with lower limb immobilisation: a multicentre, stepped wedge, randomised implementation trial.

BACKGROUND: Prophylactic anticoagulation in emergency department patients with lower limb trauma requiring immobilisation is controversial. The Thrombosis Risk Prediction for Patients with Cast Immobilisation-TRiP(cast)-score could identify a large subgroup of patients at low risk of venous thromboembolism for whom prophylactic anticoagulation can be safely withheld. We aimed to prospectively assess the safety of withholding anticoagulation for patients with lower limb trauma at low risk of venous thromboembolism, defined by a TRiP(cast) score of less than 7. METHODS: CASTING was a stepped-wedge, multicentre, cluster-randomised trial with blinded outcome assessment. 15 emergency departments in France and Belgium were selected and randomly assigned staggered start dates for switching from the control phase (ie, anticoagulation prescription according to the physician's usual practice) to the intervention phase (ie, targeted anticoagulation according to TRiP(cast) score: no prescription if score <7 and anticoagulation if score was ≥7). Patients were included if they presented to a participating emergency department with lower limb trauma requiring immobilisation for at least 7 days and were aged 18 years or older. The primary outcome was the 3-month cumulative rate of symptomatic venous thromboembolism during the intervention phase in patients with a TRiP(cast) score of less than 7. The targeted strategy was considered safe if this rate was less than 1% with an upper 95% CI of less than 2%. The primary analysis was performed in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT04064489). FINDINGS: Between June 16, 2020, and Sept 15, 2021, 15 clusters and 2120 patients were included. Of the 1505 patients analysed in the intervention phase, 1159 (77·0%) had a TRiP(cast) score of less than 7 and did not receive anticoagulant treatment. The symptomatic venous thromboembolism rate was 0·7% (95% CI 0·3-1·4, n=8/1159). There was no difference between the control and the intervention phases in the cumulative rate of symptomatic venous thromboembolism or in bleeding rates. INTERPRETATION: Patients with a TRiP(cast) score of less than 7 who are not receiving anticoagulation have a very low risk of venous thromboembolism. A large proportion of patients with lower limb trauma and immobilisation could safely avoid thromboprophylaxis. FUNDING: French Ministry of Health.

Derivation and validation of a risk-stratification model for patients with probable or proven COVID-19 in EDs: the revised HOME-CoV score.

BACKGROUND: The HOME-CoV (Hospitalisation or Outpatient ManagEment of patients with SARS-CoV-2 infection) score is a validated list of uniquely clinical criteria indicating which patients with probable or proven COVID-19 can be treated at home. The aim of this study was to optimise the score to improve its ability to discriminate between patients who do and do not need admission. METHODS: A revised HOME-CoV score was derived using data from a previous prospective multicentre study which evaluated the original Home-CoV score. Patients with proven or probable COVID-19 attending 34 EDs in France, Monaco and Belgium between April and May 2020 were included. The population was split into a derivation and validation sample corresponding to the observational and interventional phases of the original study. The main outcome was non-invasive or invasive ventilation or all-cause death within 7 days following inclusion. Two threshold values were defined using a sensitivity of >0.9 and a specificity of >0.9 to identify low-risk and high-risk patients, respectively. The revised HOME-CoV score was then validated by retrospectively applying it to patients in the same EDs with proven or probable COVID-19 during the interventional phase. The revised HOME-CoV score was also tested against original HOME-CoV, qCSI, qSOFA, CRB65 and SMART-COP in this validation cohort. RESULTS: There were 1696 patients in the derivation cohort, of whom 65 (3.8%) required non-invasive ventilation or mechanical ventilation or died within 7 days and 1304 patients in the validation cohort, of whom 22 (1.7%) had a progression of illness. The revised score included seven clinical criteria. The area under the curve (AUC) was 87.6 (95% CI 84.7 to 90.6). The cut-offs to define low-risk and high-risk patients were <2 and >3, respectively. In the validation cohort, the AUC was 85.8 (95% CI 80.6 to 91.0). A score of <2 qualified 73% of patients as low risk with a sensitivity of 0.77 (0.55-0.92) and a negative predictive value of 0.99 (0.99-1.00). CONCLUSION: The revised HOME-CoV score, which does not require laboratory testing, may allow accurate risk stratification and safely qualify a significant proportion of patients with probable or proven COVID-19 for home treatment.

How to Combat Over-Testing for Patients Suspected of Pulmonary Embolism: A Narrative Review.

The diagnosis of PE remains difficult in 2023 because the signs and symptoms are not sensible nor specific. The consequences of potential diagnostic errors can be dramatic, whether by default or by excess. Furthermore, the achievement of a simple diagnostic strategy, based on clinical probability assessment, D-dimer measurement and computed tomography pulmonary angiography (CTPA) leads to a new challenge for PE diagnosis: over-testing. Indeed, since the 2000s, the wide availability of CTPA resulted in a major increase in investigations with a mod I confirm erate increase in PE diagnosis, without any notable improvement in patient outcomes. Quite the contrary, the complications of anticoagulation for PE increased significantly, and the long-term consequences of imaging diagnostic radiation is an important concern, especially the risk of breast cancer for young women. As a result, several strategies have been proposed to fight over-testing. They are mostly based on defining a subgroup of patients for whom no specific exam should be required to rule-out PE and adjusting the D-dimer cutoff to allow the exclusion of PE without performing CTPA. This narrative review presents the advantages and limitations of these different strategies as well as the perspective in PE diagnosis.

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

BACKGROUND: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. OBJECTIVES: The 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. METHODS: We 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. RESULTS: We 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). CONCLUSION: This 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.

Diagnostic Strategy for Suspected Pulmonary Embolism in Emergency Departments Based on the 4-Level Pulmonary Embolism Clinical Probability Score: Study Protocol of SPEED&PEPS Trial.

Introduction: Several strategies have been devised to safely limit the use of thoracic imaging in patients suspected of pulmonary embolism (PE). However, they are based on different rules for clinical probability (CP) assessment, rendering their combination difficult. The four-level pulmonary embolism probability score (4PEPS) allows the combination of all other strategies using a single CP assessment. Methods and analysis: Pragmatic cluster-randomized trial in 20 EDs. Patients with suspected PE will be included and followed for 90 days (number of patients to be included: 2560, 1280 in each arm). Ten centers will be allocated to the control group where physicians will be free to do as they see fit but they will be given the recommendation to apply a validated strategy. Ten centers will be allocated to the interventional group where the physicians will be given the recommendation to apply the 4PEPS strategy. The primary objective will be to demonstrate that the application of the 4PEPS strategy by the emergency physicians, in comparison to current practices, (i) does not increase the risk of serious events related to diagnostic strategies and (ii) significantly reduces the use of thoracic imaging. Ethics and dissemination: The study will be submitted for approval to an institutional ethics review board for all participating centers. If successful, the SPEED&PEPS trial will have an important impact for patients suspected of PE limiting their irradiation and for public health in substantial savings in terms of the direct cost of diagnostic investigations and the indirect cost of hospitalizations due to waiting times or delayed harmful effects. Funding: This work is funded by a French Public Health grant (PREPS-N 2019). The funding source plays no role in the study design, data collection, analysis, interpretation or the writing of the manuscript. Trial registration: ongoing. Trial status: not started.

Comparison of the safety and efficacy of YEARS, PEGeD, 4PEPS or the sole item "PE is the most likely diagnosis" strategies for the diagnosis of pulmonary embolism in the emergency department: post-hoc analysis of two European cohort studies.

BACKGROUND: The optimal strategy for the diagnosis of pulmonary embolism (PE) in the emergency department (ED) remains debated. To reduce the need of imaging testing, several rules have been recently validated using an elevated D-dimer threshold. OBJECTIVE: To validate the safety of different diagnostic strategies and compare the efficacy in terms of chest imaging testing. DESIGN AND PATIENTS: Post-hoc analysis of individual data of 3330 adult patients without a high clinical probability of PE in the ED followed-up at 3 months in France and Spain (1916 from the PROPER cohort, 1414 from the MODIGLIANI cohort). EXPOSURE: Four diagnostic strategies with an elevated D-dimer threshold if PE is unlikely. The YEARS combined with Pulmonary Embolism Rule-out Criteria (PERC) the pulmonary embolism graduated D-dimer (PEGeD) combined with PERC and the 4-level pulmonary embolism probability score (4PEPS) rules were assessed. A modified simplified (MODS) rule with a simplified YEARS reduced to the sole item of "Is PE the most likely diagnosis" combined with PERC was also tested. OUTCOME MEASURE AND ANALYSIS: The primary outcome was the proportion of diagnosed PE or deep venous thrombosis at 3 months in patients in whom PE could have been excluded without chest imaging according to the tested strategy. The safety of a strategy was confirmed if the failure rate was less than 1.85%. The secondary outcome was the use of imaging testing according to each rule. RESULTS: Among 3330 analyzed patients, 150 (4.5%) had a PE. The number of missed PEs were 25, 29, 30 and 26 for the PERC+YEARS, PERC+PEGeD, 4PEPS and MODS rules respectively, with a failure rate of 0.75% (95% CI 0.51% to 1.10%), 0.87% (0.61% to 1.25%), 0.90% (0.63% to 1.28%) and 0.78% (0.53% to 1.14%) respectively. There was no significant difference in the failure rate between rules. Except for a significant lower use of chest imaging for 4PEPS compared to YEARS (14.9% vs 16.3%, difference -1.4% [95%CI -2.1% to -0.8%]), there was no difference in the proportion of imaging testing. CONCLUSION: In this post-hoc analysis of patients with suspicion of PE, YEARS and PEGeD combined with PERC, and 4PEPS were safe to exclude PE. The safety of the modified simplified MODS strategy was also confirmed. There was no significant difference of the failure rate between strategies.

Diagnosis of Pulmonary Embolism during Pregnancy.

Although rare, pulmonary embolism (PE) remains one of the most common causes of severe maternal morbidity and mortality during pregnancy. Among pregnant women with suspected PE, the prevalence of confirmed disease is far lower than in the general population, reflecting the fear of missing the diagnosis and a low threshold to suspect PE in this setting. Two prospective management outcome trials have recently assessed two different diagnostic algorithms based on the assessment of clinical probability, D-dimer, venous compression ultrasonography of the lower limbs (CUS), and computed tomography pulmonary angiography (CTPA). Both demonstrated the safety of such strategies to exclude PE, with a very low failure rate defined as the rate of subsequent 3-month venous thromboembolism in women left untreated after a negative work-up. These studies were also the first to prospectively demonstrate the safety of negative D-dimer associated with a clinical prediction rule to exclude PE without any chest imaging. Pregnant women are known to be a subgroup at particularly high risk of inappropriate diagnostic management, so the implementation of such validated diagnostic strategies in clinical practice should represent a high priority goal.

Prevalence and characterization of forgoing care: comparison of two prospective multicentre cohorts between pre-COVID-19 era and a lockdown period.

BACKGROUND: Little is known about patients who forego healthcare, although it is an important provider of unfavorable health-related outcomes. Forgoing healthcare characterizes situations in which people do not initiate or interrupt a care process, even though they perceive the need for it, whether or not this need is medically proven. The aims of this study were to assess the prevalence and the determinants of patients who forego healthcare. The second aim was to compare the characteristics of patients who gave up healthcare during the French lockdown due to COVID-19. METHODS: We conducted two multicenter cross-sectional studies in 2017 and 2020 carried out in French patients presenting to the emergency departments. Patients who gave their consent to participate were interviewed with a standardized questionnaire. It consisted of two parts: epidemiological characteristics and health care refusal. A third part concerning the renunciation of care during the COVID-19 period was added to the second study period. RESULTS: A total of 1878 patients had completed the questionnaire during the interview with the physicians, 900 during the first period in 2017 (47.9%) and 978 (52.1%) during the second period. A total of 401/1878 patients reported not seeking care in the last 12 months (21.4% [95%CI: 19.5-23.3%]). In 2020, patients forewent care more during the confinement period than outside with different characteristics of the foregoing care populations. CONCLUSION: Forgoing care is common in a universal health care system such as France's and increased during the pandemic. Key public health messages targeted at the reasons for not seeking care must now be disseminated in order to combat this.

Efficacy of HEAR and HEART score to rule out major adverse cardiac events in patients presenting to the emergency department with chest pain: study protocol of the eCARE stepped-wedge randomised control trial.

INTRODUCTION: Current guidelines for patients presenting to the emergency department (ED) with chest pain without ST-segment elevation myocardial infarction (STEMI) on ECG are based on serial troponin measurements. A clinical tool able to identify very low-risk patients who could forgo a troponin test and low-risk patients requiring only one troponin measurement would be of great interest. To do so, the HEAR and HEART score, standing for history, ECG, age, risk factors±troponin were prospectively assessed, but not combined and implemented in clinical practice. The objective of the eCARE study is to assess the impact of implementing a diagnostic strategy based on a HEAR score <2 or a HEART score <4 (HEAR-T strategy) to rule out non-STEMI without or with a single troponin measurement in patients presenting to the ED with chest pain without obvious diagnosis after physical examination and an ECG. METHODS AND ANALYSIS: Stepped-wedge cluster-randomised control trial in 10 EDs. Patients with non-traumatic chest pain and no formal diagnosis were included and followed for 30 days. In the interventional phase, the doctor will be asked not to perform a troponin test to look for an acute coronary if the HEAR score is <2 and not to perform an additional troponin test if the HEAR score is ≥2 and HEART score is <4. The main endpoint is the non-inferiority of the rates of major adverse cardiac events occurring between a patient's discharge and the 30-day follow-up against current recommended guidelines. ETHICS AND DISSEMINATION: The study was approved by an institutional review board for all participating centres. If successful, the eCARE study will cover a gap in the evidence, proving that it is safe and efficient to rule out the hypothesis of an acute myocardial infarction in some selected very low-risk patients or based on a single troponin measurement in some low-risk patients. TRIAL REGISTRATION NUMBER: NCT04157790.

Risk of symptomatic venous thromboembolism in mild and moderate COVID-19: A comparison of two prospective European cohorts.

BACKGROUND: Severely ill patients with SARS-CoV-2 have an increased risk of venous thromboembolism (VTE) i.e., deep vein thrombosis and pulmonary embolism. However, the VTE risk in patients with mild and moderate COVID-19, hospitalized or managed at home, remain uncertain. The aims of this study were to assess the rate and the risk factors symptomatic VTE, in patients with mild and moderate COVID-19 and to compare them to a cohort of similar patients without COVID-19. METHODS: Patients presenting to the emergency department (ED) of participating centers for confirmed or probable mild or moderate COVID-19 and not having acute VTE were included. This COVID-19 cohort was retrospectively compared to a prospective cohort of similar ED patients using propensity score matching. The main outcome was the rate of symptomatic VTE within the 28 days after ED presentation. RESULTS: A total of 2292 patients were included in the COVID-19 cohort. The 28-day incidence of symptomatic VTE was 1.3% (n = 29/2292, 95%CI: 0.9 to 1.8), 2.3% (n = 20/866, 95%CI: 1.5 to 3.5) in moderate COVID-19 patients and 0.6% (n = 9/1426; 95%CI: 0.3 to 1.2) in mild COVID-19 patients managed as outpatients. An age over 65 years and hospitalization were independent risk factors of VTE. After adjustment, patients in the COVID-19 cohort had an absolute increase in over symptomatic VTE risk of +1.69% (95%CI, 0.88 to 2.51) versus patients in the comparison cohort (n = 1539). CONCLUSIONS: Patients with moderate COVID-19 presenting to the ED had a high risk of subsequent VTE. TRIAL REGISTRATION: Ethics committee of the CHU of Angers (N°2020/87).

Assessing the clinical probability of pulmonary embolism during pregnancy: The Pregnancy-Adapted Geneva (PAG) score.

BACKGROUND: The diagnosis of pulmonary embolism (PE) in pregnant women represents an ongoing challenge. As in the general population, the first step in pregnant women with suspected PE consists of assessing clinical pre-test probability (PTP). However, no dedicated clinical decision rule has been developed in this population. OBJECTIVE: To propose a new version of the Geneva score adapted to pregnant women with suspected PE. METHODS: Data from a multicenter, prospective management outcome study including 395 women with suspected PE, in whom PTP was assessed using the Geneva score, were used. We first removed items which were present in none of the patients (cancer, age >65 years). Receiver operating characteristic (ROC) curve analysis was then performed for quantitative variables and the optimal threshold defined. The obtained Pregnancy-Adapted Geneva Score (PAG Score) comprised seven items, including an age 40 years or older and a heart rate >110 beats per minute. RESULTS: The PAG Score showed a high discriminative power to identify patients with a low, intermediate, or high PTP, associated with increasing prevalence of PE, 2.3%, 11.6%, and 61.5%, respectively. The ROC curves showed an area under the curve of 0.795 for the PAG Score compared to 0.684 for the Geneva score. CONCLUSION: In pregnant women with suspected PE, the PAG Score shows a high discriminative power to identify patients at low, intermediate, or high PTP. It has the strength of being a fully objective decision rule, is clinically relevant, easy to compute, and should now be tested in a prospective outcome study.

Adaptation of ED design layout during the COVID-19 pandemic: a national cross-sectional survey.

BACKGROUND: The aim was to describe the organisational changes in French EDs in response to the COVID-19 pandemic with regard to architectural constraints and compare with the recommendations of the various bodies concerning the structural adjustments to be made in this context. METHODS: As part of this cross-sectional study, all heads of emergency services or their deputies were contacted to complete an electronic survey. This was a standardised online questionnaire consisting of four parts: characteristics of the responding centre, creation of the COVID-19 zone and activation of the hospital's emergency operations plan, flow and circulation of patients and, finally, staff management. Each centre was classified according to its workload related to COVID-19 and its size (university hospital centre, high-capacity hospital centre and low-capacity hospital centre). The main endpoint was the frequency of implementation of international guidelines for ED organisation. RESULTS: Between 11 May and 20 June 2020, 57 French EDs completed the online questionnaire and were included in the analysis. Twenty-eight EDs were able to separate patient flows into two zones: high and low viral density (n=28/57, 49.1%). Of the centres included, 52.6% set up a specific triage area for patients with suspected COVID-19 (n=30/57). Whereas, in 15 of the EDs (26.3%), the architecture made it impossible to increase the surface area of the ED. CONCLUSION: All EDs have adapted, but many of the changes recommended for the organisation of ED could not be implemented. ED architecture constrains adaptive capacities in the context of COVID-19.

Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial.

AIMS: The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment. METHODS AND RESULTS: Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm. CONCLUSIONS: For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications.

Kneeling-induced calf ischemia: a pilot study in apparently healthy European young subjects.

PURPOSE: Many tasks, sports or leisure activities require maximal knee flexion. We hypothesized that this position could result in reduced calf perfusion, in young European subjects. METHODS: We quantified calf ischemia resulting from the knee flexion with transcutaneous oxygen pressure (TcpO2) sensors by assessing the decrease from rest of TcpO2 (DROP) defined as limb changes minus chest changes. A minimal DROP (DROPm) <-15 mmHg defines the presence of ischemia. From the crawling position, participants kneeled for 3 min while bending as in prostration/prayer position (P). Thirty-five participants repeated this maneuver a second time, while 7 participants were also required to sit on their heels with the torso in the vertical position to attain knee flexion without significant groin flexion (S). RESULT: In 41 healthy young volunteers (30 males), 25 [20-31] years old, 37 patients showed a DROPm < -15 mmHg from "R" to "P" in one (n = 4) or both (n = 33) calves (90.2%; 95% CI 76.9-97.3). After backward regression of the DROPm, there was no significant association with side, body weight of systolic blood pressure. However, age was strongly associated with DROPm (OR 5.34 [2.45-8.69]) so that DROPm was significantly higher in older, with a correlation ρ = 0.31 (p = 0.003). CONCLUSION: Kneeling dramatically reduces calf perfusion, likely through popliteal artery kinking, possibly through muscle crushing. Eastern lifestyle includes routine flexed position since childhood. Whether or not such a chronic training reduces the risk of kneeling-induced ischemia in adults is unknown to date.

Thromboembolic risk stratification by TRiP(cast) score to rationalise thromboprophylaxis in patients with lower leg trauma requiring immobilisation: a study protocol of the casting stepped-wedge cluster randomised trial.

INTRODUCTION: Patients with lower limb trauma requiring orthopaedic immobilisation may be at risk of venous thromboembolism but opinions differ about who may benefit from thromboprophylactic anticoagulant treatment.The aim of this CASTING study is to demonstrate the safety of thromboprophylaxis based on the Thrombosis Risk Prediction for patients with cast immobilisation (TRiP(cast) score with regards to the 3-month incidence of symptomatic venous thromboembolism events in low-risk patients not receiving thromboprophylaxis, as well as the usefulness of this strategy on the rate of patients receiving anticoagulant treatment in comparison to current practice. METHODS AND ANALYSIS: CASTING will be a stepped-wedge cluster randomised controlled clinical trial, performed in 15 emergency departments in France and Belgium. With their informed consent, outpatients admitted to one of the participating emergency departments for a lower limb trauma requiring orthopaedic immobilisation without surgery will be included. All centres will begin the trial with the 'observational period' and, every 2 weeks, 1 centre will be randomly assigned to switch to the 'interventional period' and to apply the TRiP(cast) score, in which only patients with a score ≥7 will receive thromboprophylactic anticoagulant treatment. The primary endpoint is the rate of clinical thromboembolic events within 90 days following the inclusion of low-risk patients not receiving thromboprophylaxis. ETHICS AND DISSEMINATION: The protocol has been approved by the Comité de Protection des Personnes Sud I (Ethics Review ID-RCB: 2019-A01829-48) for France and the Comité d'éthique hôpital-facultaire Saint Luc (N° B403201941338) for Belgium. It is carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The findings of this study will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04064489.

Evaluation of HEAR score to rule-out major adverse cardiac events without troponin test in patients presenting to the emergency department with chest pain.

BACKGROUND AND IMPORTANCE: Current guidelines for patients presenting to the emergency department with chest pain without ST-segment elevation myocardial infarction (non-STEMI) on electrocardiogram are based on troponin measurement. The HEART score is reportedly a reliable work-up strategy that combines clinical evaluation with troponin value. A clinical rule that could select very low-risk patients without the need for a blood test (HEAR score, being the HEART score without the troponin item) would be of great interest. OBJECTIVES: To prospectively assess the safety of a HEAR score <2 to rule-out non-STEMI without troponin measurement. Secondary objective was to assess the safety of a sequential strategy that combines HEAR score and HEART (defined as two-step HEART strategy). DESIGN, SETTINGS AND PARTICIPANTS: Prospective observational study in six emergency departments. Patients with nontraumatic chest pain and no alternative diagnosis were included and followed up for 45 day. Patients were considered at low-risk if the HEAR score was <2 or, for the two-step HEART strategy, if the HEART score was <4. OUTCOMES MEASURE AND ANALYSIS: The primary endpoint was the 45-day rate of major adverse cardiac events (MACE) in patients with a HEAR score <2. A HEAR score based strategy was consider safe if the rate of the primary endpoint was below 1%, with an upper margin of the 95% confidence interval (CI) below 3%. RESULTS: Among 1452 patients included, 1402 were analyzed and 97 (7%) had a MACE during the follow-up period. The HEAR score was <2 in 279 (20%) patients and one presented a MACE [0.4% (95% CI: 0.01-1.98)]. The two-step HEART strategy classified low-risk an additional 476 patients (34%) and one of these 476 patients had a MACE [0.3% (95% CI: 0.03-0.95)]. The two-step HEART strategy would have theoretically avoided 360 troponin measurements (19%). CONCLUSIONS: In our prospective multicenter study, a HEAR based work-up strategy was safe, with a very low risk of MACE at 45 day. We also report that a two-step HEART-based strategy may safely allow significant reduction of troponin measurements in patients presenting to the emergency department with chest pain.

Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing.

Importance: In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern. Objective: To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE. Design, Setting, and Participants: This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019. Main Outcomes and Measures: The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing. Results: Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from -2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 µg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were -22% (95% CI, -26 to -19) and -19% (95% CI, -22 to -16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing. Conclusions and Relevance: The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.

Identifying Patients with Low Risk of Acute Coronary Syndrome Without Troponin Testing: Validation of the HEAR Score.

BACKGROUND: Current guidelines for patients with suspected acute myocardial infarction are mainly based on troponin testing, commonly requiring an emergency department visit. HEAR score (History, Electrocardiogram, Age, and Risk factors) is a risk stratification tool validated in Europe, deduced from the HEART score (History, Electrocardiogram, Age, Risk factors, and Troponin), already implemented in clinical practice. We aimed to validate the HEAR score to rule out an acute myocardial infarction without needing biomarker testing. METHODS: Retrospective cohort study at 15 emergency departments between May 2016 and December 2017. All adult encounters evaluated for possible acute myocardial infarction with a physician-documented HEART score for health plan members of Kaiser Permanente Southern California were included. Patients with an ST-segment elevation myocardial infarction, those under hospice care, or with a "do not resuscitate" status were excluded. HEAR scores from 0-8 were calculated for each encounter and used to report 30-day acute myocardial infarction or all-cause mortality for each score. RESULTS: There were 22,109 patient encounters included in the study. Overall, 30-day acute myocardial infarction or death occurred in 1.1% of patients. Among the 4106 patients (19%) with a HEAR score <2, 3 died and 2 experienced an acute myocardial infarction within 30 days (0.1%; 95% confidence interval, 0.1-0.3). Sensitivity and specificity were 97.9% and 18.8%, respectively. CONCLUSIONS: A low HEAR score may accurately identify patients with a very low risk of 30-day acute myocardial infarction or death, representing a cohort of patients who might appropriately forego biomarker testing. Future research is warranted to assess the impact of implementing the HEAR score into routine clinical practice.