High 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.

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.

Cardiovascular magnetic resonance imaging in COVID-19 patients: An important tool in everyday clinical practice.

Myocarditis is a typical complication of many viral diseases1 and has also been described in other coronavirus diseases other than COVID-19.2, 3 However, it is only one possible complication of cardiac involvement in COVID-19 and requires an endomyocardial biopsy or a combination of suggestive clinical and imaging findings to reach a definitive diagnosis.4 Cardiovascular magnetic resonance (CMR) imaging is a cornerstone of the non-invasive diagnosis of myocarditis. Clinical studies have reported the diagnosis of myocarditis by CMR both in acute infections and in the post-acute phase.5 Cardiac involvement in COVID-19 was described early in the pandemic as a risk factor for poor outcomes.6 Inflammatory, thromboembolic and ischemic events are relevant complications of acute SARS-CoV-2 infection. However, even months after acute infection, many patients describe cardiopulmonary symptoms,7 and CMR indicates inflammatory processes,5 although their contribution to often complex clinical syndromes is questionable in some cases. Palmisano et al. investigated cardiac changes on CMR in 39 patients in the acute or post-acute phase of COVID-19 and found inflammatory changes in most patients.8 However, ischemic, valvular or other cardiomyopathies could also be diagnosed on the basis of CMR. The authors mention the heterogeneous patient population as a limitation of their study. On the contrary, this demonstrates the real additional impact of CMR since it has been shown that it can be used in a broad range of clinical scenarios. CMR can lead to a diagnosis independent of other accompanying factors and allows the exclusion or confirmation of possible differential diagnoses in the case of suspected virus-associated myocarditis. This is one of the most important tasks of cardiac imaging in the context of COVID-19. Especially potentially pre-existing but unknown cardiovascular diseases can be exacerbated in the context of SARS-CoV-2 infection and should therefore be excluded. Three major factors in Palmisano et al.'s study should be emphasized. First, the rate of diagnosed myocarditis (53%) appears to be very high. Although early studies on survivors of SARS-CoV-2 infection postulated high myocarditis rates, this could not be confirmed in actual autopsy studies,9 in which the use of histological criteria for the diagnosis of myocarditis showed a high degree of cardiac involvement but actual myocarditis in only 7.2% of the cases. In Palmisano et al.'s study, this can likely be explained by the good clinical pre-specification of the patients with a high clinical pre-test probability. This illustrates that CMR contributes to confirming the diagnosis, especially when it is well indicated. Second, the authors examined 17 patients with acute SARS-CoV-2 infection using CMR over a period of 5 months. Experience has shown that at several hospitals, this has not been done in fear of exposing staff to the risk of infection. This demonstrates the feasibility of CMR for infectious patients in a clinical setting. Third, with mostly normal biventricular function, non-invasive tissue characterization with an appropriate pre-test probability offers insights that goes far beyond pure functional or volumetric analyses. CMR diagnosis is not the first-line imaging method for diagnosis of myocarditis in mildly ill patients. However, in patients with a clinically justifiable diagnosis due to abnormal ECG and particularly echocardiographic findings and/or abnormal troponin levels accompanied with typical symptoms, CMR should be a diagnostic cornerstone in the acute and post-acute phase. The ongoing debate about short- and long-term cardiovascular consequences of COVID-19 needs to be put in a broader perspective than just the treatment of patients during pandemic. The great scientific effort and gained knowledge can potentially be used for other post-infectious syndromes, such as sequelae of Lyme disease, influenza and pneumococcal pneumonia. Moreover, this and similar studies showed that cardiovascular imaging in general and particularly advanced methods such as CMR and T1-derived parametric mapping should become a clinical routine that will serve not only for better understanding of cardiac involvement in COVID-19, but in overall better acceptance of CMR in everyday clinical practice in large spectrum of cardiovascular diseases. Open Access funding enabled and organized by Projekt DEAL.

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...

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.

Baseline use of angiotensin-converting enzyme inhibitor/AT1 blocker and outcomes in hospitalized coronavirus disease 2019 African-American patients.

The primary objective of this study is to determine the effect of baseline use of angiotensin-converting enzyme inhibitor (ACE-i)/AT1 blocker (ARB) on mortality in hospitalized coronavirus disease 2019 (Covid-19) African-American patients. The secondary objectives are, to determine the effect of baseline use of ACE-i/ARB on the need for mechanical ventilation, new dialysis, ICU care, and on composite of above-mentioned outcomes in the same cohort. In this retrospective study, we analyzed data using electronic medical records from all hospitalized Covid-19 African-American patients, who either died in the hospital or survived to discharge between 2 March and 22 May 2020. Patients were divided into two groups, those on ACE-i/ARB at baseline and those not on them. We used Pearson chi-square test for categorical variables, and Student's t test for continuous variables. We performed multiple logistic regression to test the primary and secondary objectives using SAS 9.4. Out of 531 patients included in the analysis, 207 (39%) were on ACE-i/ARB at baseline. Patients in ACE-i/ARB group were older (64 vs. 57 years, P < 0.001), and had higher prevalence of hypertension (96.6 vs. 69.4%, P < 0.001) and diabetes mellitus (55.6 vs. 34.9%, P < 0.001). There was no difference in sex, BMI, other comorbidities, and presenting illness severity among the groups. After adjustment of multiple covariates, there was no difference in outcomes between the two groups including mortality, need for mechanical ventilation, new dialysis, ICU care, as well as composite outcomes. Baseline use of ACE-i/ARB does not worsen outcomes in hospitalized Covid-19 African-American patients.

Safety of multidetector computed tomography pulmonary angiography to exclude pulmonary embolism in patients with a likely pretest clinical probability

Background In patients with suspected pulmonary embolism (PE) classified as having a likely or high pretest clinical probability, the need to perform additional testing after a negative multidetector computed tomography pulmonary angiography (CTPA) finding remains a matter of debate. Objectives To assess the safety of excluding PE by CTPA without additional imaging in patients with a likely pretest probability of PE. Patients/Methods We retrospectively analyzed patients included in two multicenter management outcome studies that assessed diagnostic algorithms for PE diagnosis. Results Two thousand five hundred and twenty-two outpatients with suspected PE were available for analysis. Of these 2522 patients, 845 had a likely clinical probability as assessed by use of the simplified revised Geneva score. Of all of these patients, 314 had the diagnosis of PE excluded by a negative CTPA finding alone without additional testing, and were left without anticoagulant treatment and followed up for 3 months. Two patients presented with a venous thromboembolism (VTE) during follow-up. Therefore, the 3-month VTE risk in likely-probability patients after a negative CTPA finding alone was 2/314 (0.6%; 95% confidence interval [CI] 0.2-2.3%). Conclusions In outpatients with suspected PE and a likely clinical probability as assessed by use of the simplified revised Geneva score, CTPA alone seems to be able to safely exclude PE, with a low 3-month VTE rate, which is similar to the VTE rate following the gold standard, i.e. pulmonary angiography.

Multidetector computed tomographic pulmonary angiography in patients with a high clinical probability of pulmonary embolism

ESSENTIALS: When high probability of pulmonary embolism (PE), sensitivity of computed tomography (CT) is unclear. We investigated the sensitivity of multidetector CT among 134 patients with a high probability of PE. A normal CT alone may not safely exclude PE in patients with a high clinical pretest probability. In patients with no clear alternative diagnosis after CTPA, further testing should be strongly considered. Whether patients with a negative multidetector computed tomographic pulmonary angiography (CTPA) result and a high clinical pretest probability of pulmonary embolism (PE) should be further investigated is controversial. This was a prospective investigation of the sensitivity of multidetector CTPA among patients with a priori clinical assessment of a high probability of PE according to the Wells criteria. Among patients with a negative CTPA result, the diagnosis of PE required at least one of the following conditions: ventilation/perfusion lung scan showing a high probability of PE in a patient with no history of PE, abnormal findings on venous ultrasonography in a patient without previous deep vein thrombosis at that site, or the occurrence of venous thromboembolism (VTE) in a 3-month follow-up period after anticoagulation was withheld because of a negative multidetector CTPA result. We identified 498 patients with a priori clinical assessment of a high probability of PE and a completed CTPA study. CTPA excluded PE in 134 patients; in these patients, the pooled incidence of VTE was 5.2% (seven of 134 patients; 95% confidence interval [CI] 1.5-9.0). Five patients had VTEs that were confirmed by an additional imaging test despite a negative CTPA result (five of 48 patients; 10.4%; 95% CI 1.8-19.1), and two patients had objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months (two of 86 patients; 2.3%; 95% CI 0-5.5). None of the patients had a fatal PE during follow-up. A normal multidetector CTPA result alone may not safely exclude PE in patients with a high clinical pretest probability.

Frequent off-label use of fondaparinux in patients with suspected acute heparin-induced thrombocytopenia (HIT) – findings from the GerHIT multi-centre registry study

IntroductionIn life-threatening immune heparin-induced thrombocytopenia (HIT), treatment with an approved non-heparin anticoagulant is essential. However, off-label use with fondaparinux has been reported in the literature. The study aim was to collect data on “real-life” management of patients with suspected acute HIT regarding diagnostic and therapeutic strategies. Patients and MethodsIn a national multi-centre registry study, patients with a 4T’s HIT-probability score of ≥4 points and treatment with at least one dose of (A)rgatroban, (L)epirudin, (D)anaparoid, or (F)ondaparinux were retrospectively evaluated. ResultsOf 195 patients, the 4T’s scores were 4/5/6/7/8 points in 46 (23.6%)/50 (25.6%)/74 (38.0%)/13 (6.7%)/7 (3.6%) patients, respectively. During heparin therapy, 47 (24.1%) thromboembolic events, 5 (2.6%) skin lesions, 1 (0.5%) amputation, 24 (12.3%) Hb-relevant bleedings, and 2 (1.0%) fatalities occurred. A functional heparin-induced platelet activation assay was performed in 96.9%, a platelet factor 4/heparin-dependent enzyme immunoassay in 89.2%, a particle gel immunoassay in 12.3%, and a serotonin-release assay in none of the patients. Argatroban was used in 16.4%, lepirudin in 2.1%, danaparoid in 23.6%, fondaparinux in 40.0% of the patients; the sequential therapy strata were: AF (5.6%), DA (5.6%), DF (2.6%), DL (2.1%), ADF (1.5%), and DFL (0.5%). ConclusionsThe current diagnostic laboratory strategy for suspected HIT is mostly (>96%) based on the recommended 2-step strategy (immunoassay plus functional assay). However, there is a wide fondaparinux off-label use (up to 50.3%) for suspected HIT, even in those patients with a high clinical pretest probability. Efficacy and safety of fondaparinux for HIT-treatment require further evaluation.

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.

CT pulmonary angiography: an over-utilized imaging modality in hospitalized patients with suspected pulmonary embolism

AimsTo determine if computed tomographic pulmonary angiography (CTPA) was overemployed in the evaluation of hospitalized patients with suspected acute pulmonary embolism (PE).MethodsData were gathered retrospectively on hospitalized patients (n=185) who had CTPA for suspected PE between June and August 2009 at our institution.ResultsCTPA was done in 185 hospitalized patients to diagnose acute PE based on clinical suspicion. Of these, 30 (16.2%) patients were tested positive for acute PE on CTPA. The Well's pretest probability for PE was low, moderate, and high in 77 (41.6%), 83 (44.9%), and 25 (13.5%) patients, respectively. Out of the 30 PE-positive patients, pretest probability was low in 2 (6.6%), moderate in 20 (66.7%), and high in 8 (26.6%) (p=0.003). Modified Well's criteria applied to all patients in our study revealed 113 (61%) with low and 72 (39%) with high clinical pretest probability. When modified Well's criteria was applied to 30 PE-positive patients, 10 (33.3%) and 20 (66.6%) were found to have low and high pretest probability, respectively (p=0.006). D-dimer assay was done in 30 (16.2%) of the inpatients with suspected PE and all of them were found to have elevated levels. A lower extremity duplex ultrasound confirmed deep venous thrombosis in 17 (9.1%) of the patients with suspected PE, at least 1 week prior to having CTPA.ConclusionUnderstanding the recommended guidelines, evidence-based literature, and current concepts in evaluation of patients with suspected acute PE will reduce unnecessary CTPA examinations.

Positive Predictive Value of Progressively Elevated D-Dimer Levels in Patients with a Suspected First Deep Vein Thrombosis.

AbstractAbstract 2258 BackgroundD-dimer is nearly always increased in patients with acute venous thromboembolism (VTE) and, therefore, a low value (i.e., negative test) has high negative predictive value. A positive result indicates the need for further diagnostic testing (e.g. ultrasound imaging if deep vein thrombosis is suspected), but it is generally believed that the predictive value of a positive result is of no clinical value. While this is true if D-dimer values are dichotomized as positive or negative, D-dimer may have diagnostically useful positive predictive value when levels are markedly elevated (i.e., positive results are not considered as a single category). ObjectiveTo determine the prevalence of, and likelihood ratios for, deep vein thrombosis (DVT) associated with progressively elevated D-dimer levels in patients with a suspected first DVT. MethodsWe performed a retrospective analysis of D-dimer level from 1224 banked peripheral blood samples from participants enrolled at 4 of the 5 participating clinical centres in the recently competed SELECT study, which compared two diagnostic strategies in patients with a suspected first DVT. D-dimer levels were measured using the Triage® D-dimer assay. The clinical pretest probability (CPTP) was determined in all patients using the 9 point Wells score and categorized as low, moderate or high. Patients were categorized as DVT positive if DVT was diagnosed by lower limb ultrasound (US) at initial presentation or VTE was diagnosed during three months of follow-up. Patients were categorized as DVT negative if DVT was not diagnosed at initial assessment (patients with low CPTP and negative D-dimer results did not undergo US) and there was no VTE during three months of follow-up. The diagnosis or exclusion of DVT was made independently of the Triage® D-dimer measurements (a different D-dimer assay was used at presentation in the SELECT study, and D-dimer was not used to evaluate suspected VTE during the 3 month follow-up).The prevalence of DVT and likelihood ratios (LHR) for all patients, and according to CPTP (low, moderate or high), was determined for the following intervals of D-dimer level: <500ug/L, 500–1000ug/L, 1001–1500ug/L, 1501–2000ug/L, 2001–3000 ug/L, 3001–4000ug/L, 4001ug/L-5000ug/L and >5000ug/L. ResultsThe prevalence of DVT, and associated LHR, among all patients increased steadily with rising D-dimer levels (Table 1). At values of less than 1000ug/L, the prevalence of DVT among all patients was low (0.15% for D-dimer <500ug/L and 1.2% for 500–1000ug/L). However, at levels above 1500ug/L there was a progressive increase in the prevalence from 14.3% for 1500–2000ug/L to 64.0% at levels >5000ug/L. The associated likelihood ratios for DVT also increased according to D-dimer level from 2.6 for levels of 1500–2000ug/L to 28.0 for values >5000ug/L.The prevalence of DVT was 2.6% for patients with low CPTP, 6.0% among those with moderate CPTP and 22.0% among patients with high CPTP. The increase in prevalence and associated LHR for DVT with increasing D-dimer levels was consistent across all three CPTP groups. ConclusionIncreasing D-dimer levels are associated with a progressive increase in prevalence and LHR for DVT across all clinical pretest probability strata. The positive predictive value of markedly elevated D-dimer levels was high and may help to identify the subgroup of patients with an abnormal D-dimer level who require more intensive investigation after a normal imaging test.Table 1-Prevalence and Likelihood Ratio associated with different D-dimer levelsD-dimer (ug/L)All patientsLow CPTPModerate CPTPHigh CPTPPrev (%)LHRPrev (%)LHRPrev (%)LHRPrev (%)LHR<5000.150.02000.40.0600500-10001.20.20000.90.15110.441001-15005.00.824.61.74.40.738.30.321501-2000142.6145.6173.2002001-3000193.7156.2203.2251.23001-4000286.12311265.5503.44001-5000306.9209275.9432.7>50006428432756208928Prev, prevalence; LHR, likelihood ratio; CPTP, clinical pretest probability Disclosures:Bates:Trinity Biotech: Consultancy, consultation fees and in-kind support (D-dimer kits) Other. Kearon:Alere: Consultancy.

European and American suspected and confirmed pulmonary embolism populations: comparison and analysis

If the prevalence of pulmonary embolism (PE) differs significantly between the US and Europe, this observation could reduce the generalizability of diagnostic protocols for PE derived in either location. To determine possible causes and potential clinical consequences of these PE prevalence differences. Secondary analysis of three prospectively collected multicenter samples (two French and one from the US) including 3174 European and 7940 American PE-suspected patients in Emergency departments (ED) (117 for Europe and 12 for US). Comparison of clinical features, resource use and outcomes of European- and US-suspected PE populations in ED. European patients evaluated for PE were significantly older and had a higher clinical pretest probability (CPP) for PE. The final PE prevalence was significantly higher in Europe, in the overall sample (26.5% vs. 7.6%) and in each level of CPP. Suspected European patients categorized as low CPP had a higher posttest probability than US low CPP patients. Suspected US patients categorized as high CPP had a much lower posttest probability of PE than in Europe. The mean number of tests performed for one PE diagnosis was lower in Europe (7.4 vs. 21.6). Among patients diagnosed with PE, European patients had a higher mean severity of illness score and a higher PE-mortality rate (3.4% vs. 0.7%). Among patients suspected of a PE and those ultimately diagnosed with a PE, European patients had higher acuity, a higher pretest probability and worse outcome than US patients. The present study underscores the importance of disease prevalence for pretest probability scoring approaches and for significance interpretation of imaging tests.

Incidence of Deep Venous Thrombosis in Patients with Erysipelas of the Leg: Prospective Study of 30 Cases in an Emergency Department

The treatment of lower limb erysipelas is based on anti-streptococcal antibiotherapy. The indication of adjuvant anticoagulant therapy is not clear because of the lack of data about the incidence of deep venous thrombosis (DVT) in these patients. We performed a prospective study using a colour Doppler vein exploration combined with ultrasonography within the first 48 h, with evaluation of clinical probability of DVT according to the Wells score to assess the incidence of DVT in patients with erysipelas of the lower limb. Of 30 patients studied, 3 DVT were diagnosed: 2 distal DVT (posterior tibial vein) and 1 proximal DVT (superficial femoral vein) in patients having a clinical score ≥3. Pulmonary embolism was diagnosed in 2 cases. The incidence of DVTin our study was 10%.DVT should be considered in patients with erysipelas of the lower limb having a high pretest clinical probability.

A multicenter evaluation of a new quantitative highly sensitive D-dimer assay for exclusion of venous thromboembolism

D-dimer testing is widely applied for exclusion of deep-vein thrombosis (DVT) and pulmonary embolism (PE). We report on a multicenter performance evaluation of a new particle-enhanced immunoassay, Innovance D-Dimer. Innovance D-Dimer assay was performed in 1,543 frozen samples from outpatients suspected of DVT and/or PE enrolled in three management studies as well as in a routine clinical practice. Samples were assayed on BCS/BCS XP, BCT as well as Sysmex CA-7000, CA-1500 and CA-560 analyzers (cut-off on all analyzers: 0.5 mg/l). Stratus CS D-Dimer and Vidas D-Dimer Exclusion were used for comparison. The precision study indicated total coefficients of variation ranging from 2.1% to 8.4% depending on the analyzer and on the sample. Sensitivity and negative predictive values were above 99% and their lower 95% confidence interval were equal or above 97.4% and 98.6%, respectively. Specificity ranged from 38.2% to 40.4% and the respective lower 95% confidence intervals from 35.5% to 37.7%. Area under the curve was 0.90 for all assay systems except for Innovance D-Dimer with BCT (0.89). Two samples from patients with distal DVT tested negative with all assay systems. One patient with high pre-test clinical probability and proximal DVT tested negative with Vidas D-Dimer Exclusion. Our data indicate that the performances of Innovance D-Dimer, regardless of the analyzer, are similar to the reference methods, and that this assay can be used for the exclusion of venous thromboembolic disease.

Clinical applicability of D-dimer assay in the diagnosis of pulmonary embolism reduces with aging

Despite modern algorithms have been proposed for diagnosis of pulmonary embolism (PE), it remains understimed and often missed in clinical practice, especially in elderly patients, resulting in high morbidity and mortality when early and correctly untreated. One of the main controversial issue is represented by the role and applicability of D-dimer in the diagnostic work up of geriatric patients. Most recent guidelines in young-adult patients suggest to perform D-dimer assay by ELISA or immunoturbidimetric methods only in non high pre-test clinical probability (PTP) patients; in these patients negative D-dimer can safely rule out the diagnosis of PE. This strategy is safe also in elderly patients; however the percentage of patients with non high PTP and negative D-dimer reduces progressively with age, making difficult its clinical applicability. The Authors, starting from two case reports, up date the diagnostic management of PE underling the limitations of D-dimer assay in elderly patients.

Uses of different D-dimer levels can reduce the need for venous duplex scanning to rule out deep vein thrombosis in patients with symptomatic pulmonary embolism

This study investigated the prevalence and distribution of deep vein thrombosis (DVT) in patients with symptomatic pulmonary embolism (PE) to establish a screening protocol to reduce unnecessary venous duplex scanning using different D-dimer level rather than single cutoff point of 0.5 microg/mL in patients with low and moderate pretest clinical probability (PTP). The PTP score and D-dimer testing were used to evaluate 85 consecutive patients with symptomatically proven PE before venous duplex scanning. After calculating the PTP score, patients were divided into low (<or=0 points), moderate (1 to 2 points), and high (>or=3 points) PTP groups. The receiver operating characteristic (ROC) curves analysis was used to determine the appropriate D-dimer cutoff point in low and moderate PTP, with a negative predictive value of >98%. The study enrolled 81 patients. The prevalence of DVT was 63%, with 27 patients (33%) classified as low, 38 (47%) as moderate, and 16 (20%) as high PTP. DVT was detected in nine patients (33%) in the low PTP group, in 27 (71%) in the moderate group, and in 15 (94%) in the high group. In the low PTP patients, the difference in the value of D-dimer assay between positive-scan and negative-scan patients was statistically significant (9.99 +/- 7.33 vs 3.46 +/- 4.20, respectively; P = .008). Conversely, no significant difference in the D-dimer assay value between positive and negative scan results was found in the moderate PTP patients. ROC curves analysis were used to select D-dimer cutoff points of 2.0 microg/mL for the low PTP group and 0.7 microg/mL for the moderate PTP groups. For both groups, D-dimer testing provided 100% sensitivity and 100% negative predictive value in the diagnosis of DVT. In the low PTP group, specificity increased from 33% to 67% (P = .046). In the moderate PTP group, however, the determined D-dimer level did not improve the specificity. Overall, venous duplex scanning could have been reduced by 17% (14/81) by using different D-dimer cutoff points. A combination of specific D-dimer level and clinical probability score is most effective in the low PTP patients in excluding DVT. In the moderate PTP group, however, the recommended cutoff point of 0.5 microg/mL may be preferable. These results show that a different D-dimer level is more useful than single cutoff point of 0.5 microg/mL in excluding DVT in established PE patients.

The role of fibrin monomers in optimizing the diagnostic work-up of deep vein thrombosis

Despite the use of a clinical score and D-dimers to exclude deep vein thrombosis (DVT), the majority of patients still need repeated ultrasound (US). The aim of the study was to investigate whether fibrin monomers (FMs), as markers of thrombin generation, have additional value in the diagnosis of DVT. This is a posthoc analysis of 464 outpatients, participants in a management study using D-dimers (Tina-Quant and a clinical score in the exclusion of DVT. Two new FM assays (Auto LIA-FM and IATRO SF, Japan) were performed. Overall sensitivity, negative predictive value (NPV) and specificity of the D-dimer test were 98%, 98% and 42%. The optimal cut-off point for the Auto LIA-FM test was <or=3 microg/ml with values of 88%, 88% and 59%, respectively. The IATRO SF test had an optimal cut-off point of <or=2 microg/ml with values of 92%, 81 and 22%, respectively. The NPV of a non-high clinical score and a normal D-dimer (n=97) was 100%. In patients with a high clinical score (n=160), the NPV of the D-dimer was 88%. In these patients, a single US combined with a normal D-dimer or FM test had an equal NPV as serial US (100 versus 98%, respectively) and lead to a reduction in the need for US by 36-53%, respectively. In patients with abnormal D-dimer concentrations (n=343), a normal US combined with a normal Auto LIA-FM test had a NPV of 97%, which was also true for serial US. This could lead to a reduction in the need for US by 45%. The present studied FMs are inferior to the Tina-Quant D-dimer test when used as primary screening tool to exclude DVT. Adding these FMs to patients with a normal Tina-Quant D-dimer has no benefit. In patients with a high pretest clinical probability score, a single US in combination with a normal D-dimer or FM test might be as safe as serial US. In patients with abnormal D-dimer concentrations and a normal US, a normal FM test might be able to replace the second US.