Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: State of the art

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complex chronic disease in which pulmonary artery stenosis or obstruction caused by organized thrombus can lead to increased pulmonary artery pressure and pulmonary vascular resistance, ultimately triggering progressive right heart failure and death. Currently, its exact mechanism is not fully understood. Pulmonary endarterectomy (PEA) has immediate effects with low perioperative mortality and satisfactory prognosis in experienced expert centers for CTEPH patients with proximal lesions. Nevertheless, 37% of patients are deemed unsuitable for PEA surgery due to comorbidities and other factors, and nearly half of the operated patients have residual or recurrent pulmonary hypertension. Riociguat is the only approved drug for CTEPH, although its effect is limited. Balloon pulmonary angioplasty (BPA) is a promising alternative treatment for patients with CTEPH. After more than 30 years of development and refinements, emerging evidence has confirmed its role in patients with inoperable CTEPH or residual/recurrent pulmonary hypertension, with acceptable complications and comparable long-term prognosis to PEA. This review summarizes the pathophysiology of CTEPH, BPA history and development, therapeutic principles, indications and contraindications, interventional procedures, imaging modalities, efficacy and prognosis, complications and management, bridging and hybrid therapies, ongoing clinical trials and future prospects.     

Computed tomography angiographic parameters of pulmonary artery as prognostic factors of residual pulmonary hypertension after pulmonary endarterectomy

ObjectivesThis study aimed to retrospectively assess using computed tomography pulmonary angiography (CTPA) for predicting residual pulmonary hypertension (RPH) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA).MethodsWe retrospectively analyzed data of 131 patients with CTEPH who underwent PEA in our center (2008–2015). We measured several diameters of the pulmonary artery and thoracic aorta preoperatively. We evaluated the relationship between these measurements (and their indices) and signs of RPH represented by pulmonary artery systolic pressure (PASP) estimated by echocardiography.ResultsSignificant correlations were observed between the aortopulmonary index and prediction of any residual hypertension and moderate/severe hypertension 1 year after PEA, and any residual hypertension and severe hypertension 2 years after PEA. The aortopulmonary index was significantly related to a reduction in PASP 1 year after the operation. A lower aortopulmonary index (≤0.88 for the ascending aorta and ≤0.64 for the descending aorta) predicted lower RPH.ConclusionsPreoperative CTPA parameters can be used to assess the risk of RPH after PEA. The aortopulmonary index has significant predictive value for RPH and a reduction in PASP after PEA. Lower values of the aortopulmonary index suggest a better outcome after PEA.     

Autopsy‐proven untreated previous pulmonary thromboembolism: frequency and distribution in the pulmonary artery and correlation with patients’ clinical characteristics

Summary. Background: This study aimed to evaluate untreated, previous pulmonary thromboembolism (PE) in patients with acute fatal PE. Patients and Methods: We studied 64 patients diagnosed as having died from acute PE by medico‐legal autopsy. Previous PE was histologically confirmed on the basis of organized thrombi (OT). The distributions of OT were analyzed in five different sizes of pulmonary artery branches in each of 18 pulmonary segmental arteries (90 in total). The frequency of OT in each patient was evaluated by determining the percentage of examined sections containing OT. Results: OT were confirmed in 59 of 64 (92%) patients. The mean frequency of OT per patient was 27% of the 90 branches. Among the segmental arteries, the right posterior basal lobe showed the highest frequency of OT; among the five artery branches examined, the subsegmental branch showed the highest frequency of OT. OT were not detected in arterioles. Patients with recent trauma or surgery and inpatients showed significantly lower frequencies of OT than those without these risk factors. The 26 patients with prolonged pre‐existing symptoms lasting more than a day showed a higher frequency of OT than the 12 patients who suffered for less than a day and the 26 without pre‐existing symptoms. Conclusions: Most patients with acute fatal PE have a subclinical history of recurrent PE. The frequency of their untreated PE is suspected to correlate with specific risk factors for venous thromboembolism and their clinical course.     

Pulmonary flow profile and distensibility following acute pulmonary embolism

Objective

Proof of concept study evaluating CMR as screening tool for chronic thromboembolic pulmonary hypertension (CTEPH) in patients treated for acute pulmonary embolism (PE).

Materials and methods

Right and left ventricular function of 15 consecutive patients treated for PE and 10 consecutive patients in whom PE was excluded was estimated at baseline by cardiac CT and at 6 months follow-up by CMR. Additionally, during the follow-up visit, pulmonary artery (PA) hemodynamics were studied by CMR and the presence of pulmonary hypertension by echocardiography.

Results

CT measured right ventricular ejection fraction (RVEF) was lower in patients with PE compared to patients without PE at time of diagnosis (median 47%, interquartile range 39-53 vs. 55%, 52-58; p = 0.014). After 6 months follow up, the RVEF between patients treated for PE and patients without PE were not statistically significant different (55%, 52-60 versus 54%, 51-57; p = 0.57), as were distensibility index (0.18 ± 0.18 versus 0.25 ± 0.18, p = 0.20), mean velocity (14.1 ± 3.9 cm/s versus 14.0 ± 2.5 cm/s, p = 0.81), peak velocity (86.5 ± 22 cm/s versus 89.6 ± 13 cm/s, p = 0.43) and time to peak PA blood flow velocity (142 ± 49 ms versus 161 ± 29 ms, p = 0.14). One patient was diagnosed with CTEPH and CMR revealed poor right systolic function, decreased PA distensibility and flow velocity, and a systolic notch in the PA flow profile consistent with persistent PA obstruction.

Conclusion

In this small series, right ventricular performance and PA flow profiles of patients treated for 6 months after PE are equivalent to those parameters in normal patients.     

Metabolomic analysis of 92 pulmonary embolism patients from a nested case–control study identifies metabolites associated with adverse clinical outcomes

Essentials

• Risk‐stratification often fails to predict clinical deterioration in pulmonary embolism (PE).
• First‐ever high‐throughput metabolomics analysis of risk‐stratified PE patients.
• Changes in circulating metabolites reflect a compromised energy metabolism in PE.
• Metabolites play a key role in the pathophysiology and risk stratification of PE.

Summary

Background

Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low‐risk and high‐risk PE is limited, so current risk‐stratification efforts often fail to predict clinical deterioration and are insufficient to guide management.

Objectives

To improve our understanding of the physiology differentiating low‐risk from high‐risk PE, we conducted the first‐ever high‐throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case–control study.

Patients/methods

We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk‐strata.

Results

When we compared 46 low‐risk with 46 intermediate/high‐risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high‐risk PE patients. When we compared 28 intermediate‐risk with 18 high‐risk PE patients, 41 metabolites differed at a nominal P‐value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism.

Conclusion

Our results suggest that high‐throughput metabolomics can provide insight into the pathophysiology of PE. Specifically, changes in circulating metabolites reflect compromised energy metabolism in intermediate/high‐risk PE patients. These findings demonstrate the important role metabolites play in the pathophysiology of PE and highlight metabolomics as a potential tool for risk stratification of PE.

     

Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) results from non‐resolving pulmonary thromboemboli that are resistant to plasmatic anticoagulation. Because of a secondary pulmonary arteriopathy accompanying major vessel obstruction, the disorder may be a target for vasodilator therapy. Objectives: In an open‐label uncontrolled study, we investigated the prostacyclin analog treprostinil given s.c. in patients with severe inoperable CTEPH. Methods: Between September 1999 and September 2005, 25 patients were included if their World Health Organization (WHO) functional class was III or IV, if their six‐minute walking distance (6‐MWD) ≤ 380 m, and if they had undergone at least one hospitalization for right heart decompensation within the prior six months, albeit not within one month before treatment start. Right heart catheterization was performed at baseline and after a minimum of 12 months (range: 12–33 months) of treatment. Treprostinil plasma concentrations were determined after at least six months of treatment. A historical group of 31 patients at our center with inoperable CTEPH matched for disease severity was used for comparative analyses. Results: Treprostinil‐treated patients demonstrated significant improvements in 6‐MWD (P = 0.01), WHO functional class (P = 0.001), B‐type brain natriuretic peptide plasma levels (P = 0.02), cardiac outputs (P = 0.007) and pulmonary vascular resistances (P = 0.01) after 19 ± 6.3 months. Treprostinil plasma concentrations correlated with drug dose (P < 0.001), indicating stable absorption over time. Long‐term survival was significantly better than in controls. Conclusions: Treprostinil improves exercise capacity, hemodynamics and survival in patients with severe inoperable CTEPH. We speculate that the effects may be explained by a combined vasodilatatory, platelet‐antagonistic and potential antiproliferative action of the drug.     

Endovascular treatment for chronic pulmonary hypertension: a focus on angioplasty for chronic thromboembolic pulmonary hypertension

Introduction: Percutaneous transluminal pulmonary angioplasty (PTPA) was introduced for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) in the late 20^th century, and first attempts in collective patients were made in 2001 with beneficial effects but a moderate amount of complications. It was refined around 2010, and has been recently established as an effective and safe treatment.

Areas covered: The indication was originally inoperable CTEPH with peripheral lesions, but has now widened to symptomatic or hypoxic patients. The lesion is typically a meshwork-like structure of organized thrombi and is sometimes not seen as a stenosis angiographically, necessitating other means of investigation such as measurement of distal pressure. The technique to treat lesions is the same as for coronary angioplasty except in several ways.

Expert commentary: The effects of PTPA are comparable to those of surgical endarterectomy, and the complications of reperfusion pulmonary edema and vascular injury are now controlled by several strategies and based on experience.     

Perfusion defects after pulmonary embolism: risk factors and clinical significance

Summary. Background: Little is known about residual abnormalities after pulmonary embolism (PE). Objectives: To assess risk factors and the clinical significance of perfusion defects in patients with PE. Patients/Methods: Consecutive patients receiving at least 3 months of anticoagulant for an acute PE were included in a prospective cohort study. Ventilation/perfusion lung scan, echocardiography, 6‐min walk test, thrombophilia and hemostatic variables were performed 6–12 months after PE. Perfusion defect was defined as a perfusion defect in at least two segments. Results: Seventy‐three out of 254 patients (29%) had perfusion defects during follow‐up (median 12 months) and were more likely to have dyspnea, had a higher systolic pulmonary arterial pressure [39 mmHg (SD) (12) vs. 31 mmHg (8); P < 0.001] and walked a shorter distance during the 6‐min walk test [374 m (122) vs. 427 m (99); P = 0.004]. Age [odds ratio (OR) 1.35; 95% confidence interval (CI), 1.11–1.63], the time interval between symptom onset and diagnosis (OR, 1.17; 95% CI, 1.04–1.31), pulmonary vascular obstruction at the onset of PE (OR, 1.34; 95% CI, 1.16–1.55) and previous venous thromboembolism (OR 2.06; 95% CI, 1.03–4.11) were independent predictors of perfusion defect after treatment of acute PE. Total tissue factor pathway inhibitor concentration was associated with perfusion defects. Conclusions: Perfusion defects are associated with an increase in pulmonary artery pressure (PAP) and functional limitation. Age, longer times between symptom onset and diagnosis, initial pulmonary vascular obstruction and previous venous thromboembolism were associated with perfusion defects.     

The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism

Summary. Background: Although previous studies have provided evidence that the majority of deaths following an acute pulmonary embolism (PE) directly relate to the PE, more recent registries and cohort studies suggest otherwise. Methods: We assessed the cause of death during the first 30 days after the diagnosis of acute symptomatic PE in a consecutive series of patients. We also assessed the prognostic characteristics of the simplified Pulmonary Embolism Severity Index (sPESI) and cardiac troponin I (cTnI) obtained at the time of PE diagnosis. Results: During the first 30 days after diagnosis, 127 of the 1291 patients died (9.8%; 95% confidence interval [CI], 8.2–11.5). Sixty patients (4.6%; 95% CI, 3.5–5.8) died from definite or possible PE, and 67 (5.2%; 95% CI, 4.0–6.4) died from other causes (cancer 25, infection 18, hemorrhage 7, heart failure 7, chronic obstructive pulmonary disease 5, renal failure 1, seizures 1, unknown 3). The sPESI predicted all‐cause (odds ratio [OR], 5.97; 95% CI, 1.74–20.54; P < 0.01) and PE‐associated mortality (OR, 8.79; 95% CI, 1.12–68.79; P = 0.04). cTnI only predicted PE‐associated mortality (adjusted OR, 2.39; 95% CI, 1.25–4.57; P < 0.01). For all‐cause mortality, the sPESI low‐risk strata had a negative predictive value of 98.8% (95% CI, 97.4–100) in comparison with 91.3% (95% CI, 88.9–93.6) for the cTnI. Conclusions: Within the first 30 days after the diagnosis of acute symptomatic PE, death due to PE and death due to other causes occur in a similar proportion of patients. As cTnI only predicted PE‐associated mortality, low‐risk sPESI had a higher negative predictive value for all‐cause mortality compared with cTnI.     

Pulmonary embolism

The underlying disorder of pulmonary embolism (PE) is venous thromboembolism (VTE), comprising deep vein thrombosis, thrombus in transit, acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH). PE may recur and cause serious long-term complications, such as post-thrombotic syndrome and CTEPH. This short overview summarizes current concepts on pathophysiology, epidemiology, diagnosis and treatment of this common disorder.     

Bosentan for chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and underdiagnosed disease characterized by progressive hypertension secondary to organized thrombi in pulmonary vessels. The arteriolar lesions of CTEPH are similar to those seen in idiopathic pulmonary arterial hypertension (PAH). Surgical disobliteration of the vessels by pulmonary endarterectomy is the therapy of choice but this is not suitable for all cases. To date, there is no licensed specific drug for CTEPH. Endothelin-1, a vasoconstrictor and promoter of cell proliferation, is involved in the pathogenesis of both CTEPH and PAH. Bosentan, the first oral dual endothelin receptor antagonist, has been shown to be effective in PAH. Preliminary uncontrolled and/or unblinded studies reported efficacy of bosentan in CTEPH, and the only randomized, controlled trials showed a positive hemodynamic effect but failed its other co-primary end point, namely the improvement of 6-min walking distance. Nevertheless, bosentan has been shown to be safe and the data from most literature encourage its use for inoperable CTEPH. However, further randomized controlled trials are needed to definitively establish bosentan as a standard drug for CTEPH.     

Clinical features of patients inappropriately undiagnosed of pulmonary embolism

PurposesThe objective of this study was to identify clinical factors associated with delayed diagnosis of acute pulmonary embolism (PE) in the emergency department (ED).Basic proceduresA retrospective observational study was performed at three University affiliated Hospitals; 436 consecutive patients who presented to the ED with an acute PE confirmed by chest computed tomography from 2008 to 2011 were included. Patients were divided into 3 groups: group 1, PE was diagnosed while the patient was still in the ED; group 2, PE was diagnosed during hospitalization; group 3, patients who were sent home with a wrong alternative diagnosis and returned to the ED and were diagnosed of PE.Main findingsOne hundred forty-six patients (33.5%) had a delayed diagnosis of PE—21.5% belong to group 2 and 11.9% to Group 3. Chronic coexisting medical conditions like asthma or chronic obstructive pulmonary disease were independent predictors of a delayed diagnosis in patients who were admitted to hospital whereas non-specific and less severe symptoms like the presence of pleuro-mechanic thoracic pain, fever, hemoptysis, or the presence of a pulmonary infiltrate in chest x-ray were independent predictors of a delayed diagnosis in patients who were sent home.Principal conclusionsDelay in diagnosis of acute PE is frequent despite current diagnostic strategies. Patients are sent home or admitted to hospital with a wrong diagnosis depending on clinical presentation or coexisting medical conditions.     

Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta‐analysis of the management outcome studies

Summary. Background: Multiple‐detectors computed tomographic pulmonary angiography (CTPA) has a higher sensitivity for pulmonary embolism (PE) within the subsegmental pulmonary arteries as compared with single‐detector CTPA. Multiple‐detectors CTPA might increase the rate of subsegmental PE diagnosis. The clinical significance of subsegmental PE is unknown. We sought to summarize the proportion of subsegmental PE diagnosed with single‐ and multiple‐detectors CTPA and assess the safety of diagnostic strategies based on single‐ or multiple‐detectors CTPA to exclude PE. Patients and methods: A systematic literature search strategy was conducted using MEDLINE, EMBASE and the Cochrane Register of Controlled Trials. We selected 22 articles (20 prospective cohort studies and two randomized controlled trials) that included patients with suspected PE who underwent a CTPA and reported the rate of subsegmental PE. Two reviewers independently extracted data onto standardized forms. Results: The rate of subsegmental PE diagnosis was 4.7% [95% confidence interval (CI): 2.5–7.6] and 9.4 (95% CI: 5.5–14.2) in patients that underwent a single‐ and multiple‐detectors CTPA, respectively. The 3‐month thromboembolic risks in patients with suspected PE and who were left untreated based on a diagnostic algorithm including a negative CTPA was 0.9% (95% CI: 0.4–1.4) and 1.1% (95% CI: 0.7–1.4) for single‐ and multiple‐detectors CTPA, respectively. Conclusion: Multiple‐detectors CTPA seems to increase the proportion of patients diagnosed with subsegmental PE without lowering the 3‐month risk of thromboembolism suggesting that subsegmental PE may not be clinically relevant.     

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.     

Is atrial fibrillation associated with pulmonary embolism?

Summary. Background: A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data. Objectives: To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF. Patients/methods: We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model. Results: The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42–1.11). However, when PE suspicion was based on new‐onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26–0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97–6.07). Conclusions: Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new‐onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.     

B-type natriuretic peptide as an indicator of right ventricular dysfunction in acute pulmonary embolism

Objective: B‐type natriuretic peptide (BNP) is a neurohormone secreted from cardiac ventricles in response to ventricular strain. The aim of present study was to evaluate the role of BNP in the diagnosis of the right ventricular (RV) dysfunction in acute pulmonary embolism (PE). Methods: BNP levels were measured in patients with acute PE as diagnosed by high probability lung scan or positive spiral computed tomography. All patients underwent standard echocardiography and blood tests during the second hour of the diagnosis. Results: Forty patients diagnosed as acute PE (mean age, 60.4 ± 13.2 years; 62.5% women) were enrolled in this study. Patients with RV dysfunction had significantly higher BNP levels than patients without RV dysfunction (426 ± 299.42 pg/ml vs. 39.09 ± 25.22 pg/ml, p < 0.001). BNP‐discriminated patients with or without RV dysfunction (area under the receiver operating characteristic curve, 0.943; 95% CI, 0.863–1.022). BNP > 90 pg/ml was associated with a risk ratio of 165 (95% CI, 13.7–1987.2) for the diagnosis of RV dysfunction. There was a significant correlation between RV end‐diastolic diameter and BNP (r = 0.89, p < 0.001). Sixteen patients (40%) were diagnosed as having low‐risk PE, 19 patients (47.5%) with submassive PE and five patients (12.5%) with massive PE. The mean BNP was 39.09 ± 25.2, 378.4 ± 288.4 and 609.2 ± 279.2 pg/ml in each group respectively. Conclusion: Measurement of BNP levels may be a useful approach in diagnosis of RV dysfunction in patients with acute PE. The possibility of RV dysfunction in patients with plasma BNP levels > 90 pg/ml should be strongly considered.     

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 ).     

A potential diagnostic pitfall in acute chest pain: Massive pulmonary embolism mimicking acute STEMI

Background

Pulmonary embolism (PE) represents a clinical challenge for clinicians because of nonspecific presentations, including dyspnea, chest pain, and tachycardia. The immediate 12-lead electrocardiogram (ECG) is commonly used to facilitate differential diagnosis of acute chest pain. Although relative rare, massive pulmonary embolism could induce ST segment elevation and mimic acute myocardial infarction.

Emergency department focused bedside echocardiography in massive pulmonary embolism

Background

Massive pulmonary embolism (PE) is a common consideration in unstable patients presenting to the emergency department (ED) with chest pain, dyspnea, or cardiac arrest. It is a potentially lethal condition necessitating prompt recognition and aggressive management. Conventional diagnostic modalities in the ED, including chest computed tomography angiography and ventilation-perfusion scanning, require the unstable patient to leave the department, and raise concerns over renal injury. Several case reports document findings of massive PE on echocardiography performed in the ED; however, none was performed, interpreted, and acted upon in the form of thrombolytic therapy by an emergency physician without the additional benefit of a cardiologist’s interpretation or a confirmatory imaging study.

Objective

We present a case that illustrates the utility of ED focused bedside echocardiography in suspected massive PE and briefly review direct and indirect ultrasound findings of acute PE.

Case Report

A case of massive PE in a 61-year-old woman is reported. In this patient with marked dyspnea, progressive hemodynamic instability, and contraindications to definitive imaging, ED focused bedside echocardiography provided valuable information that strongly suggested the diagnosis and led to alteplase administration. To our knowledge, this case represents the first report of thrombolytic therapy administration for acute massive PE based solely on clinical presentation and an emergency physician-performed bedside echocardiogram.

Conclusion

In the hands of an experienced emergency physician ultrasonographer, ED focused bedside echocardiography provides a safe, rapid, and non-invasive diagnostic adjunct for evaluation of the patient suspected of having massive PE.     

Risk Factors Associated with Delayed Diagnosis of Acute Pulmonary Embolism

Background

Prompt diagnosis and treatment of acute pulmonary embolism (PE) is essential to reduce mortality. Risk factors for PE are well known, but factors associated with delayed diagnosis are less clear.

Objective

Our objective was to identify clinical factors associated with delayed diagnosis of patients with acute PE presenting to a tertiary-care emergency department (ED).

Methods

We studied 400 consecutive adults who presented to our ED with acute, symptomatic PE. All patients were diagnosed by computed tomography (CT) angiography. Early diagnosis was defined as CT diagnosis < 12 h from ED arrival, and delayed diagnosis as CT diagnosis > 12 h. Univariate and multiple logistic regression models were used to identify factors associated with delayed diagnosis. Odds ratios with 95% confidence intervals are reported.

Results

The median time from arrival to diagnosis was 2.4 h (interquartile range 1.4–7.6), and 73 (18.3%) patients had delayed diagnosis. Patients aged > 65 years and those with coronary artery disease or congestive heart failure had longer times from ED arrival to CT diagnosis, whereas patients with recent immobility had shorter times. Patients diagnosed > 12 h were older and had higher rates of morbid obesity and coronary artery disease, whereas patients diagnosed < 12 h had higher rates of tachycardia. In multiple regression modeling, tachycardia and recent immobility remained associated with early diagnosis, whereas morbid obesity remained associated with delayed diagnosis.

Conclusions

Older patients with cardiovascular comorbidities had longer times from ED arrival to CT diagnosis. Our data suggest that these patients represent more of a diagnostic challenge than those presenting with traditional risk factors for PE, such as tachycardia and recent immobilization. Physicians should consider these factors to diagnosis acute PE promptly in the ED.