Acute pulmonary embolism (PE), together with deep vein thrombosis are the entities of venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, right after myocardial infarction and stroke.1 VTE incidence significantly increases with age, and it is increasing over time.2 The aging of populations and the increasing diagnostic capacity suggest that VTE will continue to play an important role in health care systems in the future.

In Portugal, the incidence of PE follows this trend and has also increased in recent years. Its estimated prevalence is 35 per 100,000 inhabitants, with women being more affected than men.3 Despite this increase in incidence, the in-hospital mortality has shown a positive evolution. This may be explained by two main factors: first, and the most important one, the improvement and greater effectiveness of hospital health care; secondly, the increase in diagnostic capacity, with an increasing amount of diagnosis of minor PE with low risk of mortality, and more accurate and early diagnosis allowing more efficient treatment.3

The diagnosis, risk assessment and treatment of patients with PE have been reviewed according to the latest studies and scientific evidence. The last European Society of Cardiology (ESC) guidelines focusing on the diagnosis and management of acute pulmonary embolism were published in 2019 and some concepts have been updated.4

Acute phase treatment includes hemodynamic and respiratory support, initial anticoagulation, and reperfusion treatment.4 Initial anticoagulation and reperfusion treatment are decided based on the assessment of pulmonary embolism severity.

Reperfusion therapy with systemic thrombolysis is the treatment of choice in patients with high-risk PE and the rescue therapy in patients who evolve to hemodynamic deterioration under anticoagulation treatment. Surgical embolectomy and percutaneous catheter-directed treatment (CDT) are recommended in patients whom thrombolysis is contraindicated or has failed. 4,5

The aim of this study is to analyze the main clinical characteristics of patients presenting to the emergency department with pulmonary embolism, acute treatment decisions and the main outcomes in-hospital mortality and incidence of long-term sequelae of pulmonary embolism.

A single-center retrospective observational study was conducted considering data from patients with the diagnosis of PE at the emergency department over a period of three years (from January 2016 to December 2018). Data regarding sociodemographic characteristics, medical background, clinical presentation, and therapeutic decisions were collected. Additionally, one-year follow-up was performed to evaluate long term outcomes. The research was carried out in accordance with internationally accepted recommendations for clinical investigation. According to SAGER guidelines, sex was defined as binary, designating the sex assigned at birth.

Despite the current recommendations, only 25.7% of high-risk PE patients were managed with systemic thrombolytic therapy in our center. Among the 35 patients with intermediate-high risk PE, all were on anticoagulation with no further therapeutic interventions, even those with clinical deterioration and death. When analyzing the reasons for these therapeutic decisions, 2 of the patients had suffered an ischemic stroke in previous 6 months (an absolute contraindication for systemic thrombolysis; 1 patient had advanced liver disease and 2 patients were on oral anticoagulation) relative contraindications. The remaining patients had no formal contraindication to the procedure.

The reluctance to use thrombolytic therapy even in the absence of contraindications might be explained by a perceived increased risk of bleeding in patients with active malignancies, advanced age, or multiple comorbidities.6 Although we found no predictors of non-revascularization in our population, this may be explained by the small number of patients undergoing systemic thrombolytic.

Some recent studies have proposed the percutaneous CDT as an alternative to thrombolysis in patients with a perceived increased risk of bleeding, showing minimal major bleeding and improvement in right ventricular function by relieving the thromboembolic obstruction.7–11

The high mortality rate among patients with in intermediate-high risk PE shows how the management of these patients can be challenging since they present normal hemodynamics at initial evaluation. After initial treatment, it might be difficult to identify signs of treatment failure and redefine a new strategy. Studies have shown that even patients with no signs of RV disfunction and normotensive at first evaluation may deteriorate after the beginning of the treatment.11–14 This enhances the need to properly evaluate patients in this category of risk and early select those who might benefit from fibrinolytic therapy preventing hemodynamic deterioration without an increase in the risk of major hemorrhagic event.15

The definition of the best management strategy in patients with several comorbidities or with clinical deterioration may be challenging and must be individualized. Furthermore, it is not completely clear how to define a “treatment failure” and when to move on to another therapeutic approach. Since no evidence alone is enough to support these decisions, current guidelines recommend deciding based on the expert knowledge of a multidisciplinary team, in the form of Pulmonary Embolism Response Team (PERT), especially the management of high and intermediate-high risk PE when uncertainties remain regarding the best approach.13,16 This multidisciplinary team might help to define the best strategy based on individual characteristics of the patient and local expertise (Fig. 1).

Fig. 1.

Central illustration. Underuse of reperfusion treatment in high-risk pulmonary embolism. PE, pulmonary embolism; PERT, pulmonary embolism response teams.

Defining the optimal approach enhances the likelihood of success in the acute phase and reduces the risk of long-term sequelae, being the most clinically relevant being the chronic thromboembolic pulmonary disease with or without pulmonary hypertension, resulting from vascular remodeling and/or incomplete resolution of pulmonary thrombi. In our study, the cumulative prevalence of chronic thromboembolic pulmonary disease over four years was 34.8%, as expected by the literature, with values of chronic thromboembolic pulmonary hypertension of 12.8%, a noteworthy number.17–19 Although this could stem from the limited use of more aggressive therapies within high or intermediate-high risk subgroups of patients, most of these patients cluster within the intermediate-low risk category. When analyzing these patients, it was observed that three of them had previously experienced thromboembolic events, suggesting the plausibility of an acute-on-chronic event instead of isolated acute event. Furthermore, seven patients presented with chronic heart failure, and four with active cancer, both conditions predisposing to VTE, often with subclinical manifestations.

Patients with chronic thromboembolic pulmonary hypertension were seldom referred for specialized centers, remaining without proper treatment. Of the few who were referred, 2 underwent balloon pulmonary angioplasty, yielding favorable outcomes in symptom management. Unfortunately, additional data is not available as these patients are subsequently followed up at another institution to which we lack access. To our knowledge, none of the patients underwent pulmonary endarterectomy.

Patients who survived the first 30 days after PE seem to present higher mortality than expected in the general population, being the active cancer at the time of PE the most important predictor of mortality.17,20

Although data regarding the causes of death during the follow-up period are not available, 12 (41.4%) of these patients had active neoplasms and 7 of them (24.1%) had dementia at the time of PE, comorbidities that significantly increase the patient's frailty and risk ok death.

Acute treatment of pulmonary embolism is imperative to reduce mortality and prevent long-term sequelae. Systemic thrombolysis is the first line therapy in high-risk patients, but it is underused by medical population even in the absence of formal contraindications.

This data suggests that is necessary a new national-level model of actuation, implementing alternative strategies such as interventional ones to improve outcomes.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The work was approved by the Ethics Committee of the Hospital of Braga. Patient's informed consented does not apply to this work. We confirm that the possible variables of sex and gender have been taken into account in accordance with the SAGER guidelines.

Artificial intelligence was not used in the development of this work.

M. Dias was responsible for the conception of the work, as well as the acquisition, analysis, and interpretation of data, and drafting the work. R. Silva, F. Ribeiro Mané, I. Conde, and S. Fernandes were responsible for the acquisition and analysis of data, as well as drafting the work. C. Ferreira, F. Vilela, and O. Pires acquired and analyzed data for the work and drafted the manuscript. Ferreira, F. Vilela, and O. Pires acquired and analyzed data for the work and drafted the manuscript. N. Salomé analyzed and interpreted the data and revised the manuscript for important intellectual content. All authors meet all the characteristics defined by the International Committee of Medical Journal Editors in the criteria for authorship of scientific articles.

None declared.