Diagnostic management of clinically suspected acute pulmonary embolism

Summary.  Current diagnostic management of hemodynamically stable patients with clinically suspected acute pulmonary embolism (PE) consists of the accurate and rapid distinction between the approximate 20–25% of patients who have acute PE and require anticoagulant treatment, and the overall majority of patients who do not have the disease in question. Clinical outcome studies have demonstrated that, using algorithms with sequential diagnostic tests, PE can be safely ruled out in patients with a clinical probability indicating PE to be unlikely and a normal D-dimer test result. This obviates the need for additional radiological imaging tests in 20–40% of patients. CT pulmonary angiography (CTPA) has become the first line tool to confirm or exclude the diagnosis of PE in patients with a likely probability of PE or an elevated D-dimer blood concentration. While single-row-detector technology CTPA has a low sensitivity for PE and bilateral compression ultrasound (CUS) of the lower limbs is considered necessary to rule out PE, multi-row-detector CTPA is safe to exclude PE without the confirmatory use of CUS.     

血浆D-二聚体对疑似肺栓塞患者诊断价值的研究

目的：探讨血浆 D-二聚体对对疑似肺栓塞患者的诊断价值。方法采用自动化免疫比浊法测定患者血浆D-二聚体水平。统计分析血浆D-二聚体诊断肺栓塞的敏感性、特异性、阴性及阳性预测值,并绘制ROC曲线以评价其诊断价值并对D-二聚体阴性排除肺栓塞价值进行分析。结果在317例疑似肺栓塞患者中D-二聚体＜500μg/L的患者73例,其中6例被诊断为肺栓塞。D-二聚体对肺栓塞的诊断的敏感性为95.86%（95%CI：91.27%～98.08%）,特异性为38.95%（95%CI：31.98%～41.41%）,阴性预测值为91.78%（95%CI：83.21%～96.18%）,阳性预测值为56.97%（95%CI：50.69%～63.02%）,诊断准确性为64.98%（95%CI：59.58%～70.03%）。ROC曲线下面积为0.674（95%CI：0.615～0.733）。结论 D-二聚体对肺栓塞的诊断具有较高的敏感性,阴性排除肺栓塞的准确性较高,但仍可受患者年龄、测试方法等的影响。     

Complete venous ultrasound in outpatients with suspected pulmonary embolism

Summary.  Background: Compression ultrasonography (US) confined to the proximal veins is usually performed to detect deep vein thrombosis (DVT) in patients with suspected pulmonary embolism (PE). Recent studies suggested a limited yield of proximal US when multislice computed tomography (MSCT) was used. Objectives: To assess whether performing an additional distal vein US would increase the diagnostic yield of the test. Patients and methods: Data of 855 consecutive outpatients included in a multicenter randomized controlled trial were analyzed. Patients were investigated by a sequential diagnostic strategy including clinical probability assessment, D-dimer measurement, proximal US and MSCT. Proximal US was completed by an examination of the distal veins, the result of which was not disclosed to the physician in charge of the patient. Results: US was positive in 21% of patients, of whom 10% (53/541) had proximal DVT and 11% (59/541) isolated distal DVT. Of the 59 patients with distal DVT, 21 (36%) had no PE on MSCT. Twenty of those 21 patients were not given anticoagulant therapy and had an uneventful follow-up. The diagnostic performance of distal US for the diagnosis of PE was as follows: sensitivity 22% [95% confidence interval (CI) 17–29]; specificity 94% (95% CI  91–96); positive likelihood ratio 3.9 (95% CI  2.4–6.4). Conclusions: In patients with suspected PE, distal US has limited diagnostic performance, and its additional use only modestly increases the yield of US. Moreover, it carries a high false-positive rate, impeding the use of distal US as a confirmatory test for PE.     

The use of D-dimer testing and Wells score in patients with high probability for acute pulmonary embolism

Rationale, aims and objective  To investigate if a combination of Wells pre-test probability score and D-dimer testing could be used as a safe base for making clinical decisions on further investigations for patients with intermediate to high risks of pulmonary embolism (PE).
Methods  One hundred and twenty patients with signs or symptoms of acute PE were investigated with pulmonary angiography (PA) or contrast enhanced computed tomography of the pulmonary arteries (CTPA), D-dimer testing (Tinaquant^®) and clinical scoring using the Wells pre-test probability score during their first 48 hours at the hospital. Patients were recruited consecutively from emergency departments at two teaching hospitals.
Results  The cut-off value of 0.5 mg L⁻¹ in D-dimer analysis is proved adequate with a negative predictive value (NPV) of 92% in this group of patients with intermediate to high risks. The combination of D-dimer testing and Wells score increases the NPV to 94%. The specificities of both tests were low.
Conclusion  D-dimer and Wells pre-test probability scores are safe to rule out acute PE even in patients with at least an intermediate risk of PE, but the specificity is low. D-dimer testing had a higher NPV than Wells score and the combination improved the algorithm further. The cut-off level for a high risk of PE measured with the Wells score was four and it seems reasonable to use that cut-off level in future algorithms. In addition, both PA and CTPA can present false positive and negative results difficult to interpret.     

Computed tomography pulmonary angiography in the diagnosis of acute pulmonary embolism in the emergency department

This study was undertaken to evaluate the use of computed tomography pulmonary angiography (CTPA) in patients with pulmonary embolism (PE) who were followed in the emergency department (ED). The files and computer records of 850 patients older than 16 years of age who were seen in the Hacettepe University Hospital ED between April 10, 2001, and December 1, 2005, and who required CTPA for PE prediagnosis and/or another diagnosis, were studied retrospectively. PE was identified by CTPA in 9.4% of 416 women and in 5.8% of 434 men. A significant difference (P< .05) was noted in the women and men in whom PE was detected. The mean age of the patients was 58.13±17.88 y (range, 16–100 y). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for clinical susceptibility to PE among patients who underwent CTPA were assessed at 95.3%, 48.2%, 13%, and 99.2%, respectively. CTPA was done for different reasons: aortic aneurysm dissection (n=1), cough distinctive diagnosis (n=1), dyspnea distinctive diagnosis (n=6), chest pain distinctive diagnosis (n=3), PE prediagnosis (n=51), and other reasons (n=2). Also, sensitivity, specificity, PPV, and NPV were found to be 95.4%, 16.2%, 14.4%, and 96%, respectively, for D-dimer. CTPA, which is accessible on a 24-h basis in the ED, is a valuable tool for the diagnosis of PE.     

Clinical probability and alveolar dead space measurement for suspected pulmonary embolism in patients with an abnormal D-dimer test result

BACKGROUND: Most patients with suspected pulmonary embolism (PE) have a positive D-dimer test and undergo diagnostic imaging. Additional non-invasive bedside tests are required to reduce the need for further diagnostic tests. OBJECTIVES: We aimed to determine whether a combination of clinical probability assessment and alveolar dead space fraction measurement can confirm or exclude PE in patients with an abnormal D-dimer test. METHODS: We assessed clinical probability of PE and alveolar dead space fraction in 270 consecutive in- and outpatients with suspected PE and positive D-dimer. An alveolar dead space fraction < 0.15 was considered normal. PE was subsequently excluded or confirmed by venous compression ultrasonography, spiral computed tomography and a 3-month follow-up. Radiologists were unaware of the results of clinical probability and capnography. RESULTS: PE was confirmed in 108 patients (40%). Capnography had a sensitivity of 68.5% (95% confidence interval [CI]: 58.9-77.1%) and a specificity of 81.5% (95% CI: 74.6-87.1%) for PE. Forty-five patients (16.6%) had both a low clinical probability and normal capnography (sensitivity: 99.1%, 95% CI: 94.9-100%) and 34 patients (12.6%) had both a high clinical probability and abnormal capnography (specificity: 100%, 95% CI: 97.7-100%). CONCLUSION: Capnography alone does not exclude PE accurately. The combination of clinical probability and capnography accurately excludes or confirms PE and avoids further testing in up to 30% of patients.     

Wells评分联合D-dimer在急性肺栓塞诊断的临床预测价值

目的 评价Wells评分联合D-dimer在急性肺栓塞诊断的临床预测价值.方法 收集2008年至2011年就诊北京朝阳医院急诊科疑似肺栓塞患者540例,以CTPA检查阳性为确诊肺栓塞的依据,分为肺栓塞(PE)组与非肺栓塞(Non-PE)组,对两组患者在人口学特征、基础疾病、主诉、体征、静脉血栓危险因素、相关实验室检查、Wells评分等进行比较和统计学分析.结果 最终入选患者502例,PE组246例,Non-PE组256例,近期术后或卧床、近期骨盆或下肢骨折、咯血、一过性意识障碍、单侧下肢肿胀、低氧低碳酸血症、D-dimer升高、高危Wells评分等在PE组出现的频率显著高于Non-PE组,P＜0.05,其他参数在两组中差异无统计学意义.Wells评分、D-dimer值及二者联合的ROC曲线下面积分别是0.775 (95％CI:0.719～0.831),0.802(95％CI:0.751～0.853),0.899 (95％ CI:0.834～0.964),二者联合ROC曲线下面积大于二者单独应用,P ＜0.05.截点值Wells评分5分,D-dimer 1 724.00 μg/L为敏感度与特异度加权最大值,超过截点值时,诊断PE的可靠性明显提高;低于截点值时,排除PE的可靠性也明显升高.结论 Wells评分联合D-Dimer检查比单独应用在急性肺栓塞预测中更具备临床价值.     

Accuracy of clinical decision rule, D-dimer and spiral computed tomography in patients with malignancy, previous venous thromboembolism, COPD or heart failure and in older patients with suspected pulmonary embolism

BACKGROUND: The diagnostic work-up of patients with suspected pulmonary embolism (PE) has been optimized and simplified by the use of clinical decision rules (CDR), D-dimer (DD) testing and spiral computed tomography (s-CT). Whether this strategy is equally safe and efficient in specific subgroups of patients is evaluated in this study. METHODS: A diagnostic strategy including a CDR, DD test and s-CT was evaluated in patients with malignancy, previous venous thromboembolism (VTE), chronic obstructive pulmonary disease or heart failure and in older patients. PE was ruled out by either an unlikely CDR and a normal DD or a s-CT negative for PE. The safety of these tests was assessed by the 3-month incidence rate of symptomatic VTE in those without PE at baseline. The efficiency was evaluated by calculating the numbers needed to test for the different subgroups. RESULTS: The venous thromboembolic incidence rate after the combination of an unlikely CDR and a normal DD varied from 0% (95% CI: 0-7.9%) in the 482 patients older than 75 years of age to 2% (95% CI: 0.05-10.9%) in the 474 patients with a malignancy. For s-CT these incidences varied from 0.3% to 1.8%. The number needed to test in order to rule out one patient from PE with the studied strategy was highest in cancer patients and in the elderly patients (approximately 10). CONCLUSION: It appears to be safe to rule out PE by either the combination of an unlikely CDR and a normal DD or by a negative s-CT in various subgroups of patients with suspected PE. However, the clinical usefulness of the CDR in combination with the DD as the initial step in the diagnostic process varied among these patient groups.     

D-Dimer and thrombus burden in acute pulmonary embolism

Background

Thrombus burden in pulmonary embolism (PE) is associated with higher D-Dimer-levels and poorer prognosis. We aimed to investigate i) the influence of right ventricular dysfunction (RVD), deep venous thrombosis (DVT), and high-risk PE-status on D-Dimer-levels and ii) effectiveness of D-Dimer to predict RVD in normotensive PE patients.

肺癌患者发生肺栓塞的相关危险因素及对预后的影响

目的探讨肺癌患者发生肺栓塞(PTE)的危险因素,并分析其对患者预后的影响。方法 46例肺癌合并PTE患者为观察组,46例无PTE的单纯肺癌患者为对照组。对比2组患者性别、年龄、体质量指数(BMI)、病理类型、TNM分期、手术史、中心静脉置管、血红蛋白(Hb)、D-二聚体、吸烟史、饮酒史、放化疗史、COPD史、糖尿病病史、心脑血管疾病史,并进行Logistic回归分析,探讨肺癌发生PTE的危险因素,并对比2组患者3、6、12个月生存率与中位生存时间。结果 2组患者在性别、年龄、手术史、吸烟史、饮酒史、放疗史、糖尿病病史、心脑血管病史方面比较无显著差异(P0.05),而在BMI、病理类型、TNM分期、Hb、D-Dimer、化疗史、中心静脉置管、COPD病史方面具有显著差异(P0.05或P0.01)。Logistic回归分析发现,病理类型为腺癌、TNM分期高、D-Dimer浓度高、有化疗史均为肺癌患者发生PTE的独立危险因素(P0.05或P0.01)。观察组3、6、12个月生存率均显著低于对照组(P0.05或P0.01),观察组中位生存时间显著短于对照组(P0.01)。结论PTE将严重缩短肺癌患者生存期,降低生存率。对病理类型为腺癌、TNM分期较高、D-Dimer浓度较高、有化疗史的肺癌患者,应早期给予抗凝治疗,以降低PTE风险,延长患者生存期,提高患者生活质量。     

氨基末端B型利钠肽前体与D-二聚体和肌钙蛋白I在急性肺栓塞患者中的应用价值

目的 探讨氨基末端B型利钠肽前体(NT-proBNP)与D-二聚体(D-Dimer)和肌钙蛋白I(cTnI)在急性肺栓塞(APE)患者中的应用价值.方法 回顾性分析145例经肺动脉CT血管造影确诊的APE患者,同时行超声心动图、NT-proBNP、cTnI、D-Dimer检查,排除可能影响NT-proBNP、cTnI、...     

Influence of age on the cost-effectiveness of diagnostic strategies for suspected pulmonary embolism

BACKGROUND: Age has a marked effect on the diagnostic yield of D-dimer measurement and lower limb compression ultrasonography (CUS) in patients with suspected pulmonary embolism (PE), suggesting that specific diagnostic strategies may be needed in elderly patients. OBJECTIVE: To evaluate the cost-effectiveness of including D-dimer and CUS in the workup of PE, with particular attention to patient age. SUBJECTS AND METHODS: We analyzed data from two recent outcome studies that enrolled 1721 consecutive outpatients with suspected PE. Both studies used a sequential diagnostic strategy that included assessment of clinical probability, D-dimer measurement, CUS, and helical computed tomography (hCT). A decision analysis model was created for analyzing cost-effectiveness according to six classes of age. The main outcome measures were 3-month quality-adjusted expected survival and costs per patient managed. RESULTS: All strategies were equally safe, with variations in the 3-month survival never exceeding 0.5% as compared to the most effective strategy. D-dimer measurement was highly cost-saving under the age of 80 years. Above 80 years, the cost-sparing effect of D-dimer was diminished, but not completely abolished. Inclusion of CUS increased the costs of diagnostic strategies irrespective of age. Results were unchanged over a wide range of the variables of interest (costs, sensitivity, and specificity of the tests). CONCLUSIONS: Diagnostic strategies using D-dimer are less expensive. The cost-sparing effect of D-dimer is reduced but not abolished above 80 years, suggesting that adapting specific diagnostic strategies in elderly outpatients is not mandatory. CUS is costly, and only marginally improves the safety of diagnostic strategies for PE.     

Comorbidity burden conditions the prognostic performance of D-dimer in elderly patients with acute pulmonary embolism

Introduction

The prognostic accuracy of D-dimer for risk assessment in acute Pulmonary Embolism (APE) patients may be hampered by comorbidities. We investigated the impact of comorbidity burden (CB) by using the Charlson Comorbidity Index (CCI), on the prognostic ability of D-dimer to predict 30 and 90-day mortality in hemodynamically stable elderly patients with APE.

老年人群发生急性肺栓塞的相关危险因素

目的：探讨老年人群发生急性肺栓塞(APE)的相关危险因素。方法回顾我院收治的105例 APE 患者临床资料,按年龄分为老年组55例和非老年组50例,比较两组临床表现,分析老年人 APE 危险因素。结果非老年组和老年组的呼吸困难、咳嗽、胸闷的发生率分别为82.0%(41/50)vs 85.5%(47/55)、70.0%(35/50)vs 78.5%(43/55)、62.0%(31/50)vs 52.7%(29/55)(均 P >0.05)。老年组的危险因素有慢性阻塞性肺疾病病史、心脑血管病史、糖尿病病史;非老年组的危险因素有深静脉血栓史、外伤及手术史。结论老年组 APE 患者的临床表现多不典型,与非老年组相似,老年组发生 APE 的危险因素与非老年组不同,临床上应密切注意。     

Thrombolytic therapy and outcome of patients with an acute symptomatic pulmonary embolism

Background:  While the primary therapy for most patients with a pulmonary embolism (PE) consists of anticoagulation, the efficacy of thrombolysis relative to standard therapy remains unclear. Methods:  In this retrospective cohort study of 15 944 patients with an objectively confirmed symptomatic acute PE, identified from the multicenter, international, prospective, Registro Informatizado de la Enfermedad TromboEmbólica (RIETE registry), we aimed to assess the association between thrombolytic therapy and all‐cause mortality during the first 3 months after the diagnosis of a PE. After creating two subgroups, stratified by systolic blood pressure (SBP) (< 100 mm Hg vs. other), we used propensity score‐matching for a comparison of patients who received thrombolysis to those who did not in each subgroup. Results:  Patients who received thrombolysis were younger, had fewer comorbid diseases and more signs of clinical severity compared with those who did not receive it. In the subgroup with systolic hypotension, analysis of propensity score‐matched pairs (n = 94 pairs) showed a non‐statistically significant but clinically relevant lower risk of death for thrombolysis compared with no thrombolysis (odds ratio [OR] 0.72; 95% confidence interval [CI], 0.36–1.46; P = 0.37). In the normotensive subgroup, analysis of propensity score‐matched pairs (n = 217 pairs) showed a statistically significant and clinically meaningful increased risk of death for thrombolysis compared with no thrombolysis (OR 2.32; 95% CI, 1.15–4.68; P = 0.018). When we imputed data for missing values for echocardiography and troponin tests in the group of normotensive patients, we no longer detected the increased risk of death associated with thrombolytic therapy. Conclusions:  In normotensive patients with acute symptomatic PE, thrombolytic therapy is associated with a higher risk of death than no thrombolytic therapy. In hemodynamically unstable patients, thrombolytic therapy is possibly associated with a lower risk of death than no thrombolytic therapy. However, study design limitations do not imply a causal relationship between thrombolytics and outcome.     

Safety of outpatient treatment in acute pulmonary embolism

See also Baglin T. Fifty per cent of patients with pulmonary embolism can be treated as outpatients. This issue, pp 2404–5; Kovacs MJ, Hawel JD, Rekman JF, Lazo‐Langner A. Ambulatory management of pulmonary embolism: a pragmatic evaluation. This issue, pp 2406–11. Summary. Introduction: Data regarding outpatient treatment of pulmonary embolism (PE) is scarce. This study evaluates the safety of outpatient management of acute PE. Methods: This is a retrospective cohort study of consecutive patients presenting at the Ottawa Hospital with acute PE diagnosed between 1 January 2007 and 31 December 2008. PE was defined as an arterial filling defect on CTPA or a high probability V/Q scan. Patients were managed as outpatients if they were hemodynamically stable, did not require supplemental oxygenation and did not have contraindications to low‐molecular‐weight heparin therapy. Results: In this cohort of 473 patients with acute PE, 260 (55.0%) were treated as outpatients and 213 (45.0%) were admitted to the hospital. The majority of the patients were admitted because of severe comorbidities (45.5%) or hypoxia (22.1%). No outpatient died of fatal PE during the 3‐month follow‐up period. At the end of follow‐up, the overall mortality was 5.0% (95% CI, 2.7–8.4%). The rates of recurrent venous thromboembolism (VTE) in outpatients were 0.4% (95% CI, 0.0–2.1%) and 3.8% (95% CI, 1.9–7.0%) within 14 days and 3 months, respectively. The rates of major bleeding episodes were 0% (95% CI, 0–1.4%) and 1.5% (95% CI, 0.4–3.9%) within 14 days and 3 months, respectively. Four (1.5%) outpatients were admitted to the hospital within 14 days. Conclusions: A majority of patients with acute PE can be managed as outpatients with a low risk of mortality, recurrent VTE and major bleeding episodes.     

Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study

Summary. Background: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non‐randomized studies suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. Objective: To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. Patients and Methods: A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow‐up. Results: Of 297 included patients, who all completed the follow‐up, six (2.0%; 95% confidence interval [CI] 0.8–4.3) had recurrent VTE (five PE [1.7%] and one DVT [0.3%]). Three patients (1.0%, 95% CI 0.2–2.9) died during the 3 months of follow‐up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08–2.4). Conclusion: Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp ).     

Circulatory failure in acute pulmonary embolism

Circulatory failure occurs in about 10% of patients with pulmonary embolism, resulting from a massive obstruction of the pulmonary arterial bed. Hemodynamic and respiratory features are well established; they involve precapillary pulmonary hypertension, low cardiac output state, elevated filling pressure for the right ventricle, and venous admixture. More recently, two-dimensional echocardiography permitted the visualization of pulmonary artery and right heart enlargement, reduced right ventricular ejection fraction, and tricuspid regurgitation. Evaluated by this latter means, left ventricular systolic function appeared unchanged, but diastolic function might be reduced by septal bulging.     

阿替普酶治疗急性肺栓塞高危患者29例疗效观察

目的探讨阿替普酶溶栓治疗急性肺栓塞高危患者的效果及安全性。方法 29例急性肺栓塞患者均应用阿替普酶进行溶栓治疗,溶栓后24h行CT肺动脉造影评定疗效,行超声心动图检查观察溶栓前、后右心室舒张末期前后径（anterior-posterior diameter,APD）、右心室舒张末期横径（transverse diameter,TD）、肺动脉压（pulmonary arterial pressure,PAP）、三尖瓣反流压差（tricuspid valve pressure gradient,TRPG）、右心室壁运动幅度（right ventricular wall motion amplitude,RVAWM）,检测溶栓前、后D-二聚体、B型脑钠肽（（brain natriuretic peptide,BNP）水平,记录溶栓后不良反应发生情况。结果本组有效率为93.1%;溶栓后APD、TD、PAP、TRPG较溶栓前下降,RVAWM较溶栓前增加（P〈0.05）;D-二聚体、BNP水平较治疗前下降（P〈0.05）;溶栓后出血4例,死亡1例。结论阿替普酶适用于急性肺栓塞高危患者的快速溶栓治疗。