Inpatient management strategy for pulmonary embolism: a narrative review

Introduction

Pulmonary embolism (PE) is a critical venous thromboembolic (VTE) disorder and ranks as the third most common cause of death among hospitalized patients. Although precise global prevalence figures for PE are challenging to ascertain, it is estimated that there are approximately 10 million cases worldwide. Notably, about 60% of VTE cases occur during or immediately after hospitalization with more than 95% of pulmonary emboli originating from thrombi in the lower extremities (1-5). PE symptoms can range from mild dyspnea to severe hemodynamic collapse, contributing to an estimated 100,000 annual deaths in the USA and 544,000 in Europe, closely linked to the patient’s hemodynamic stability and right ventricular (RV) dysfunction (3).

Historically, PE management followed a binary approach, categorizing patients as either low-risk (managed with anticoagulation) or high-risk (requiring thrombolysis or surgical intervention). However, a significant proportion of patients fall into an intermediate category, presented with stable hemodynamics yet exhibiting signs of RV strain or myocardial injury. This subgroup is clinically challenging: some recovered uneventfully with anticoagulation alone, while others deteriorated rapidly without aggressive intervention.

Management of low- and high-risk PE is well established, with anticoagulation recommended for low-risk cases and reperfusion therapies reserved for hemodynamically unstable patients. However, intermediate-risk PE—defined by RV dysfunction or myocardial injury in the absence of hypotension—remains a clinical gray zone. Recent guidelines and studies have proposed refined stratification strategies and emerging therapies, yet uncertainty persists regarding the use of systemic thrombolysis, catheter-directed interventions, and the role of imaging and biomarkers in guiding treatment decisions. This review critically examines the current evidence on risk assessment and therapeutic approaches, with a focus on inpatient management of intermediate- and intermediate-high-risk PE. We present this article in accordance with the Narrative Review reporting checklist (available at https://shc.amegroups.com/article/view/10.21037/shc-2024-35/rc).

Methods

This review summarizes the risk stratification and management of patients with PE. We searched PubMed, Medline, and Google Scholar databases for articles on PE. We used the MeSH terms “Pulmonary embolism”, “Risk stratification”, “Troponin”, “ProBNP”, “lactate”, “D-dimer”, “CTPA”, “lung scintigraphy”, “MRA”, “PESI”, “sPESI”, “BOVA”, “Mortality rate of pulmonary embolism”, “RV dysfunction”, “thrombolytics”, “Catheter directed therapy”, “surgical embolectomy”, “Vena cava filter”, and “PERT”. Studies reporting patient demographics, clinical presentations, and management of PE were included in this review. Publications, including clinical trials, cohort studies, and case-control studies published before September 2024, were included. In addition, the bibliography of selected articles was examined for further studies. We included only studies published in English and excluded articles that included opinions, letters, abstracts, and preprints yet to undergo peer reviews (Table 1).

Risk stratification

Once a diagnosis of PE is confirmed, immediate risk stratification (Table 2) is essential to guide appropriate management strategies. Risk stratification initially relies on assessing clinical symptoms and signs of hemodynamic instability, as these indicate a higher mortality risk.

Patients with PE who do not exhibit hemodynamic instability are typically classified into low or intermediate-risk categories. This classification is based on a combination of clinical, imaging, and laboratory findings, including evidence of RV dysfunction. Additional factors that may influence early prognosis, such as comorbid conditions, are also considered (6).

The following section will explore the tools and methods employed for effective risk stratification in PE management.

Biomarkers

Troponin

Cardiac troponin I and cardiac troponin T have been clinically available since 1995 and have been widely used in diagnosing myocardial infarction (7). Troponin is a structural protein found in myocardial cells, making it a specific biomarker for myocardial injury (8). Theoretically, an acute PE that impairs RV outflow can cause a sudden increase in RV pressure, leading to strain on the myocardium and resulting in the release of cardiac troponin into the bloodstream. Since 2000, elevated levels of cardiac troponin have been observed in patients with PE, particularly those with higher mortality rates (9-12), and it has been established as an independent predictor of 30-day mortality, even in patients who do not have hemodynamic instability (9,13,14). Furthermore, evidence suggests that mortality rates increase with higher concentrations of cardiac troponin in patients with PE. With the advent of high-sensitivity cardiac troponin assays, which can detect even minor elevations of cardiac troponin beyond the thresholds of conventional assays, there is potential for more sensitive risk stratification of PE in hemodynamically stable patients. However, current evidence suggests that modest elevations of cardiac troponin may not have significant clinical relevance (15). Notably, cardiac troponin levels can be falsely elevated in patients with conditions that increase cardiac demand or impair troponin clearance.

Pro brain-type natriuretic peptide (proBNP)

Plasma BNP and its precursor, N-terminal proBNP, are neurohormones secreted by the cardiac ventricles in response to myocardial stretch, analogous to the role of cardiac troponin. Elevated levels of proBNP have been associated with a sixfold increase in the risk of adverse events compared to individuals with normal plasma concentrations (16-18), underscoring its utility in assessing the severity and prognosis of PE. However, elevated proBNP levels can also occur in the context of left ventricular dysfunction associated with chronic congestive heart failure and are significantly influenced by underlying chronic kidney disease. This results in proBNP having high sensitivity but low specificity, thereby conferring a high negative predictive value.

Lactate

Lactate is produced during anaerobic metabolism as part of normal physiological respiration. However, when lactate production surpasses its clearance, hyperlactatemia can occur. This condition is commonly observed in cases of regional or global tissue hypoxia secondary to hypoperfusion such as in shock, sepsis, or severe heart failure (19). Historically, arterial lactate levels of 2 mmol/L and a venous lactate level of 3.3 mmol/L or higher in cases of PE have been associated with a nearly fivefold increase in PE-related mortality, regardless of the presence of hypotension or RV dysfunction at presentation (20-23). This elevated lactate level reflects not only the obstruction of the right ventricle but also the inflammatory response to sudden RV obstruction and acute circulatory failure. This explains why hypoperfusion can occur at a microcirculatory level even in the absence of significant hypotension (24-27). Hence, incorporating lactate levels into risk stratification is crucial, as most bedside scoring systems currently do not include lactate levels in their assessments (28).

Imaging of RV size and function

An abrupt increase in RV afterload leads to acute RV dilation, which subsequently reduces left ventricular filling and can result in obstructive shock. Consequently, evidence of RV dysfunction and dilation is often linked to high mortality and adverse outcomes.

The RV size can be rapidly assessed using computed tomography (CT) (Figure 1). A meta-analysis by Meinel et al., which included 49 studies with 13,162 patients with acute PE, found that an increased RV/left ventricular (LV) diameter ratio, measured on transverse sections, was associated with a 2.5-fold increased risk of all-cause mortality and a 5-fold increased risk of PE-related mortality. Furthermore, the presence of contrast reflux in the inferior vena cava (Figure 1B) was also associated with a higher risk of all-cause mortality and the study indicated that thrombus load and location were not predictive of all-cause mortality (29,30). It is worth noting that these data might not be an accurate predictor in low-risk PE (31).

Figure 1 A 56-year-old woman without significant past medical history presented to us with sudden onset chest pain and shortness of breath 2 weeks after an open reduction and internal fixation surgery of her fractured right ankle. A CT pulmonary angiogram was performed and revealed bilateral pulmonary embolism. (A) Enlarged RV (green arrow) notable bilateral pulmonary embolism (red arrows). (B) Bilateral pulmonary embolism (red arrows) with inferior vena cava reflux (green arrow) on coronal view. CT, computed tomography; RV, right ventricle.

Echocardiography, in contrast to CT, is considered the gold standard for evaluating RV size and function due to its real-time feedback and dynamic measurements. Like CT, an elevated RV/LV ratio on echocardiogram (ECHO) has been associated with increased all-cause mortality. However, it is crucial to recognize that the RV/LV ratio reflects RV morphology and can be falsely elevated in patients with chronic pulmonary hypertension (32). Therefore, alternative echocardiographic parameters, such as tricuspid annulus plane systolic excursion (TAPSE), have been proposed for predicting clinical outcomes. Pruszczyk et al. found that TAPSE ≤15 mm identifies patients at higher risk for 30-day acute PE-related mortality, whereas TAPSE >20 mm is associated with very low-risk, with a negative predictive value approaching 100% (33).

It is important to note that while CT provides a quicker assessment of RV strain, its sensitivity and specificity are 67–88% and 39–60%, respectively (34-36), which are significantly lower compared to ECHO. The predictive value of RV strain on CT ranges from 59% to 78% when ECHO is used as the criterion standard (35,36). However, the predictive value improves if additional findings are present along with RV enlargements on CT, such as hepatic vein reflux, septal bowing, or right atrial enlargement. When these findings are combined with RV enlargement, they offer the highest predictive value for right heart strain, particularly when verified with ECHO (36).

Scoring system

Several bedside scoring systems (Tables 3-5), such as the pulmonary embolism severity index (PESI) and the simplified PESI (sPESI), can help predict mortality and morbidity in cases of PE and are very reliable in high-risk cases (37,38). However, their effectiveness in intermediate-risk patients is limited. In contrast, the Bova score (Tables 6,7) was specifically developed to identify the risk of PE-related complications in normotensive individuals by incorporating the presence of RV strain (39,40). While these scoring systems offer valuable insights, they also have limitations and should be used in conjunction with clinical judgment. Furthermore, despite the Bova score’s ability to identify intermediate- or high-risk PE in normotensive patients, evidence supporting advanced therapies for these patients remains scarce (40). Hence, a tailored treatment strategy should be based on an individual’s clinical gestalt.

Treatment

Systemic anticoagulation

Anticoagulation such as unfractionated heparin (UFH), low molecular weight heparin (LMWH), or fondaparinux remains the backbone of PE treatment in order to reduce mortality by prevention of thrombus extension and formation of new thrombi. Although direct oral anticoagulation (DOAC) is non-inferior to the above-mentioned anticoagulation, its many relative contraindications make it less likely to be initiated.

In the 1980s, LMWHs and fondaparinux, derivatives of UFH became the first line therapy for PE during the initial phase of treatment due to less bleeding risk and a more predictable pharmacokinetic profile (41-43). In addition, fondaparinux further distinguishes itself by having a longer half-life than UFH due to its reduced affinity for endothelial cells and macrophages.

The initial anticoagulation choice depends on the clinical gestalt of the patient. Direct comparisons between LMWHs and UFH were carried out in a large number of trials (44-46) which was concluded in a Cochrane systematic review in 2019, where they concluded 18 studies with 6,238 patients and found that patients who were treated with LMWHs have lower recurrent VTE event during initial treatment period, at 3 months follow-up after oral anticoagulation was started and at the end of the follow-up period (42). It was well established that one should be therapeutically anticoagulated within 24 hours in order to have a significant mortality rate reduction (47). Unfortunately, a retrospective study by Prucnal et al. revealed concerning findings: the majority of the 505 patients with PE spent most of the first 48 hours after UFH initiation outside the therapeutic activated partial thromboplastin time (aPTT) range, with more than half remaining subtherapeutic (48), which potentially increases the chances of adverse outcome due to delay in adequate treatment. However, the efficacy of LMWHs and fondaparinux are not well studied in patients with creatinine clearance of <30 mL/min, and severe obesity [body mass index (BMI) >40 kg/m²] (49,50). Although anti-factor Xa assays are increasingly used to dose LMWH in clinical practice, data regarding the correlation between anti-factor Xa activity and VTE events or bleeding complications remains limited (51), and the assays are not widely available in comparison to aPTT. Hence, intravenous UFH remains the drug of choice in this population.

Once the patient has been clinically stable for 24–48 hours, oral anticoagulation can be considered. Historically, vitamin K antagonists (VKAs), such as warfarin, have been the mainstay of treatment. In recent years, DOACs such as factor Xa inhibitors—apixaban, rivaroxaban, and edoxaban—and the thrombin inhibitor dabigatran were found to be non-inferior compared to LMWH plus VKAs combination (52,53) and have since become increasingly preferred for outpatient management of low-risk PE, as well as post-hospitalization treatment due to significant shorter length of stay and lower hospital treatment costs versus heparin bridging to warfarin (54). Clinical trials and meta-analyses have shown that DOACs typically have a lower risk of fatal bleeding and reduced all-cause mortality compared to VKAs (53,55-58). They also require less frequent monitoring and have fewer drug-drug interactions, enhancing their appeal for long-term use.

However, VKAs continue to hold particular indications. They are preferred for patients with severe renal impairment (creatinine clearance <30 mL/min) due to the limited safety data for DOACs in this group. Warfarin is also the drug of choice for patients with VTE associated with antiphospholipid syndrome, as DOACs may not be as effective in these cases. Cost considerations also play a role, as warfarin is generally less expensive than DOACs, which might influence the choice of therapy in settings with financial constraints.

Systemic thrombolytics

Thrombolytic agents exert their therapeutic effect by activating plasminogen, which leads to fibrinolysis and the dissolution of blood clots. This process facilitates the revascularization of affected pulmonary arteries, alleviating pulmonary obstruction, reducing pulmonary arterial pressure, and decreasing pulmonary vascular resistance more rapidly. This was demonstrated in the PAIMS 2 trial (59) and a nonrandomized trial by Goldhaber et al. (1), where both were reported to have rapid improvement in RV function after alteplase administration. Another pivotal clinical trial conducted in 1995 (60) demonstrated a lower mortality rate compared to those treated with heparin alone. Although the trial only included eight patients with PE and were treated with streptokinase, this was the first trial that included patients who could be classified as high-risk based on the current definition and laid the foundation of thrombolytic use in high-risk PE per current guidelines.

A meta-analysis by Marti et al. has also demonstrated that thrombolytic therapy can significantly decrease both mortality and recurrence rates associated with PE (61). However, this potential benefit is accompanied by a notable increase in the risk of severe adverse events, including a 3.18-fold elevation in the likelihood of fatal or intracranial hemorrhage. Interestingly, the study conducted by Goldhaber et al. was designed where thrombolytics were not co-administered with anticoagulation and found no increase in bleeding risk (1). This raises the question of whether the risk of major bleeding decreases when thrombolytics are given exclusively to patients not receiving anticoagulation. More evidence is needed to clarify this relationship.

The role of thrombolytics in patients with intermediate-risk PE continues to provoke discussion within the medical community. The MAPETT 3 trial indicated that alteplase may improve clinical outcomes for patients classified as intermediate-risk or submissive PE (62). However, this trial was underpowered and did not provide sufficient evidence to assess its impact on mortality or adverse events. Similarly, Becattini et al. and the TOPCOAT trial by Kline et al. found that treating intermediate-risk PE patients with tenecteplase showed have significant reduction in RV dysfunction within 24 hours (63,64). However, these studies were ultimately limited by their underpowered design. In parallel, the PEITHO trial, one of the largest randomized controlled trials assessing systemic thrombolysis for PE, provided insights into the management of normotensive patients with intermediate-risk PE (65). This study found that a single intravenous bolus of tenecteplase was associated with a reduced composite primary outcome of early death or hemodynamic decompensation.

However, it is essential to interpret these findings with caution, as the primary outcome encompassed both mortality and hemodynamic decompensation, which are not necessarily interchangeable. The trial reported a 2.58% incidence of hemodynamic decompensation, with one-third of these patients not requiring catecholamines. This raises questions regarding the clinical relevance of the term “hemodynamic decompensation”, especially given the lack of data on resolution timelines or persistent organ dysfunction in the study cohort. Furthermore, the trial’s limitations in power hindered its ability to definitively assess the mortality benefits of thrombolytic therapy in this patient population (65).

While thrombolytics offer a promising strategy to improve outcomes in acute PE, their application in intermediate-risk patients requires careful consideration of the associated benefits and risks. To address concerns about bleeding complications associated with standard-dose thrombolysis, studies were conducted to evaluate the efficacy and safety of low-dose thrombolysis (50 mg of alteplase instead of 100 mg in standard dose). Wang et al. conducted a prospective study in 118 patients with massive PE or high clot burden and found that half-dose of alteplase provided the same efficacy as the standard dose (66). However, they also presented a trend where half-dose alteplase does not have statistical significance in reducing bleeding risk. The efficacy of low-dose alteplase was later demonstrated in the MOPETT trial (67). However, the trial was not adequately powered to ascertain differences in mortality outcomes, which limits the generalizability of its findings. Additionally, these studies utilized an older classification system for patient enrollment, which did not mandate the presence of RV enlargement or elevated cardiac biomarkers. Of note, current studies were conducted using alteplase as thrombolytics rather than tenectaplase, hence, it is uncertain if low-dose tenectaplase may be able to reproduce a similar effect as shown in the studies.

These discrepancies underscore the current lack of robust evidence supporting the routine use of half-dose thrombolysis in intermediate-risk PE patients. Further, well-designed studies are needed to clarify the role of low-dose thrombolysis and establish clear guidelines for its application in this population. Until then, clinicians must weigh the potential advantages of reduced bleeding risk against the uncertainties regarding efficacy and outcomes.

Catheter-directed treatment (CDT)

Percutaneous CDT is an effective reperfusion strategy for PE and can be differentiated into catheter-directed thrombolysis and percutaneous catheter embolectomy.

Catheter-directed thrombolysis

This approach integrated ultrasound or mechanical fragmentation with a reduced dose of thrombolytics directly delivered to the thrombus. This targeted delivery minimizes systemic exposure and has the potential benefit of reducing the risk of major bleeding compared to traditional thrombolytic therapies. The procedure is typically performed by inserting a catheter into the pulmonary artery through either the internal jugular vein or the femoral vein, allowing for focused treatment of the embolism.

The ULTIMA trial, a phase II study utilizing ECHO-driven surrogate endpoints, enrolled 30 patients with submissive or intermediate-risk PE (68). The findings demonstrated that ultrasound-assisted CDT was superior to UFH alone, treating intermediate-risk PE with only 10–20% of a typical systemic thrombolytic dose (unilateral vs. bilateral PE, respectively). These results were further supported by the SEATTLE II study, a larger prospective, single-arm multicenter trial (69). However, this study was unable to compare the efficacy or safety of ultrasound-facilitated CDT against full-dose systemic fibrinolysis, as it lacked a comparator group.

Data from prospective cohort studies and registries support the use of ultrasound-assisted CDT in intermediate- or high-risk PE (69-71). However, due to the relatively small number of patients treated and the lack of comparative data with systemic thrombolytic therapy, these findings should be interpreted with caution. One of these cohorts reported cases of intracranial hemorrhage, underscoring that, despite the lower doses of thrombolytics administered, the risk of intracranial hemorrhage—although rare—persists (71).

It is also worth mentioning that current available trials are all funded by pharmaceutical companies and the catheters used were paired with ultrasound technology to increase fibrin breakdown. A retrospective study by Kuo et al. indicated that 64% of patients who received CDT did not have the ultrasound feature enabled during treatment, yet no difference in outcomes was observed (70). Another randomized trial by Engelberger et al. found that ultrasound technology did not enhance fibrinolysis in iliofemoral deep vein thrombosis (DVT) (72).

Furthermore, a small retrospective study by Gaba et al. found that more than half of their patient population achieved contralateral resolution of pulmonary thrombus without the need to reposition the catheter (73). This finding raises concerns about the relevance of proximal low-dose infusion. Additionally, case series by Guru et al. and Aykan et al. suggest that peripheral low-dose tissue plasminogen activator (tPA) (25 mg) infusion over 6–24 hours may achieve similar outcomes even in high-risk PE cases, prompting the question of whether a central catheter is essential to administer such low-dose tPA (74,75).

These findings suggest that while current clinical trials support the use of catheter-directed thrombolysis, they do not adequately address the fundamental question of its efficacy compared to systemic fibrinolysis, which remains the standard of care.

Percutaneous pulmonary embolectomy

Percutaneous pulmonary embolectomy, on the other hand, does not require thrombolytics and serves as an alternative for patients with contraindications to these agents. As of the date of this article, only the FlowTriever and Lightning 12 devices have been approved by the Food and Drug Administration (FDA) (76,77). The FLARE and EXTRACT-PE studies, both industry-sponsored, indicated that the FlowTriever and Lightning 12 devices appear safe and effective for patients with acute intermediate-risk PE, demonstrating significant improvements in the RV/LV ratio and minimal major bleeding (78,79). However, we still lack sufficient randomized controlled trial data with consistent parameters and outcome measures to support the routine use of these techniques in patients with contraindications to thrombolytics (80).

Additionally, there is a potential risk of worsening RV function, as the insertion of a large-bore catheter (20 French for the FlowTriever and 12 French for the Lightning 12) into an obstructed pulmonary artery could hypothetically increase RV afterload. Therefore, while these technologies offer promising options for managing PE, their use should be guided by careful consideration of individual patient risks and the existing evidence base. Further research is essential to clarify their efficacy, safety, and optimal application in clinical practice.

Surgical embolectomy

Surgical embolectomy, typically performed under cardiopulmonary bypass, involves incising the pulmonary arteries to remove fresh clots. Although advancements in surgical techniques have led to a reduction in in-hospital mortality (81-83), rates still range from 22.5% to 30.5% (84), indicating that the procedure remains highly invasive and is generally reserved for patients contraindicated for fibrinolytic.

Several earlier retrospective studies have examined outcomes for patients with intermediate-risk PE, indicating that those treated at experienced centers before hemodynamic collapse may achieve favorable outcomes (85,86). This suggests a potential role for surgical embolectomy in selected patient populations. However, more prospective data is needed to further validate these findings and optimize treatment strategies.

Of note, surgical embolectomy is considered the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), although this topic is beyond the scope of this review.

Inferior vena cava filters (IVCFs)

The primary goal of IVCFs in treating PE is to prevent venous clots from entering the pulmonary circulation. Current guidelines recommend against the routine use of IVCFs and should only be considered in patients with an absolute contraindication for anticoagulation and PE recurrence despite therapeutic anticoagulation (8). The initial PREPIC study (87), published in 1998, demonstrated that permanent IVCF placement reduced the rate of recurrent PE; however, it was also associated with significantly increased rates of DVT compared to anticoagulation alone, with no impact on overall survival.

Bikdeli et al. and Quezada et al. have supported the use of IVCFs in patients at high-risk for PE recurrence who have contraindications to anticoagulation (88,89). These studies have shown a short-term reduction in the risk of PE-related mortality. However, despite the protective effects against immediate PE, evidence indicates a higher rate of recurrent venous thromboembolism in the long-term for patients with IVCFs. Specifically, the risk-adjusted recurrence rate for PE was higher in filter recipients compared to those without filters. Additionally, patients in the filter group experienced a 1.8-fold increase in recurrent DVT compared to the no-filter group (87,88,90,91).

Furthermore, mortality rates between filter and no-filter groups have shown no significant difference, suggesting that the overall impact of IVCFs on all-cause mortality remains unclear (88). Therefore, while IVCFs can be beneficial in preventing acute PE, careful consideration of their long-term implications and potential complications is essential.

Mechanical circulatory support and oxygenation

Extracorporeal membrane oxygenation (ECMO) is mainly employed in cases of PE to address cardiogenic shock or cardiac arrest resulting from acute PE. Venous-arterial ECMO (VA-ECMO) delivers comprehensive support for both pulmonary and cardiac functions, effectively decreasing RV afterload and enhancing tissue oxygenation. On the other hand, venous-venous ECMO (VV-ECMO) is designed specifically to provide respiratory support for patients who do not respond sufficiently to mechanical ventilation.

Three key strategies exist for the use of ECMO in treating PE. The first serves as a bridge to definitive therapy, providing pre-operative and peri-operative support for patients undergoing surgical embolectomy or percutaneous thrombectomy. The second strategy employs ECMO as the sole treatment modality, assisting patients receiving anticoagulation or systemic thrombolysis, although this approach remains controversial (89,92). Finally, ECMO can be employed to facilitate recovery after treatment, to help restore end-organ function once the thrombus has been removed.

Despite these applications, no randomized controlled trials have been conducted to assess the efficacy and safety of ECMO in high-risk PE cases. Additionally, the use of ECMO is associated with a significant risk of complications, even over short durations. Outcomes can vary based on the expertise of the treating center and the careful selection of patients. Furthermore, the potential for increased bleeding related to the need for vascular access must be taken into account, particularly for patients undergoing thrombolysis.

Treatment for intermediate-risk PE

Intermediate-risk PE patients are at increased risk for clinical deterioration despite preserved systemic blood pressure. Whether additional therapy beyond systemic anticoagulation improves outcomes in this group remains uncertain. Given the current evidence as described above, no single treatment strategy is appropriate for all patients. While CDT has emerged as a promising alternative to low-dose systemic thrombolytics in this subset of patients, long-term outcome data are still lacking. Therefore, a multidisciplinary, individualized approach should guide the management of intermediate-risk PE as further evidence evolves.

Pulmonary Embolism Response Team (PERT)

PERT is a multidisciplinary group designed to facilitate real-time consensus and provide treatment recommendations for patients with acute PE. A meta-analysis by Fleitas Sosa et al. found that PERT patients predominantly consisted of intermediate- and high-risk individuals, who received more advanced therapies and experienced a decrease in the insertion of IVCFs (93). While a trend toward reduced mortality was observed, it did not reach statistical significance. PERTs offer a platform for rapid discussions among experts in challenging situations, such as managing intermediate-risk PE with stable hemodynamics. However, randomized controlled trials evaluating the impact of PERT implementation are needed to better elucidate its effects on mortality and other outcomes, including financial implications. These studies could provide valuable insights into the overall benefits of PERTs in clinical practice.

Conclusions

In conclusion, the management of PE necessitates a nuanced approach to risk stratification, which is vital for optimizing patient outcomes. While we have made strides in understanding high- and low-risk cases, there remains a significant knowledge gap regarding intermediate-risk PE. All above mentioned clinical trials are summarized in Table 8. Current prognostication tools for hemodynamically stable patients require enhancement to facilitate more accurate risk assessments.

In our center, we adopt a comprehensive approach to managing PE that aligns with, yet also builds upon, the ERS guidelines (6) (Figure 2). We prioritize individualized risk assessments that integrate the latest prognostic tools and clinical data, enabling us to better identify patients who may benefit from advanced treatment strategies. This approach not only emphasizes the importance of timely intervention for high-risk patients but also places significant focus on the intermediate-risk group, where our protocols aim to bridge existing gaps in management. By actively engaging in multidisciplinary collaboration and utilizing a robust database for ongoing patient evaluation, we strive to enhance our clinical practices and align with evolving evidence-based recommendations.

Figure 2 Approach to pulmonary embolism in our institution (A) in comparison with 2019 European Respiratory Society pulmonary embolism guideline (B). BNP, brain-type natriuretic peptide; BP, blood pressure; CTA, computed tomography angiography; DVT, deep vein thrombosis; ECHO, echocardiogram; HR, heart rate; hsTnT, high-sensitivity cardiac troponin T; ICU, intensive care unit; IV, intravenous; IVCF, inferior vena cava filter; LMWH, low molecular weight heparin; LV, left ventricle; NT-pro-BNP, N-terminal fragment of BNP; PE, pulmonary embolism; PERT, pulmonary embolism response team; PESI, pulmonary embolism severity index; POCUS, point of care ultrasound; RIETE, Registro Informatizado de Enfermedad TromboEmbolica; RV, right ventricle; TTE, transthoracic echocardiography; UFH, unfractionated heparin; VA-ECMO, venous-arterial extracorporeal membrane oxygenation.

Moreover, the treatment strategies for intermediate-risk PE warrant further investigation to establish evidence-based protocols. Although CDT shows promise as a therapeutic option, the existing data are limited and necessitate additional research to clarify its efficacy and safety.

Additionally, the PERT has demonstrated potential benefits in managing PE, but their effectiveness is yet to be validated in larger cohorts. As the field evolves, continued exploration of these areas is essential to refine our understanding and improve the clinical management of PE.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://shc.amegroups.com/article/view/10.21037/shc-2024-35/rc

Peer Review File: Available at https://shc.amegroups.com/article/view/10.21037/shc-2024-35/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://shc.amegroups.com/article/view/10.21037/shc-2024-35/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Goldhaber SZ, Haire WD, Feldstein ML, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993;341:507-11. [Crossref] [PubMed]
2. Ansab H, Joshua G. National Trends in Pulmonary Embolism Management and Outcomes: Shifting Paradigms [Internet]. [cited 2024 Sep 13]. Available online: https://touroscholar.touro.edu/nymc_fac_abstracts/254/
3. Weinberg AS, Jaff MR, Tapson VF. Pulmonary Embolism: An International Crisis. [cited 2024 Sep 13]. Available online: https://evtoday.com/articles/2019-july-supplement/pulmonary-embolism-an-international-crisis
4. Horlander KT, Mannino DM, Leeper KV. Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. Arch Intern Med 2003;163:1711-7. [Crossref] [PubMed]
5. Jha AK, Larizgoitia I, Audera-Lopez C, et al. The global burden of unsafe medical care: analytic modelling of observational studies. BMJ Qual Saf 2013;22:809-15. [Crossref] [PubMed]
6. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020;41:543-603. [Crossref] [PubMed]
7. Xu RY, Zhu XF, Yang Y, et al. High-sensitive cardiac troponin T. J Geriatr Cardiol 2013;10:102-9. [Crossref] [PubMed]
8. Potter JM, Hickman PE, Cullen L. Troponins in myocardial infarction and injury. Aust Prescr 2022;45:53-7. [Crossref] [PubMed]
9. Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007;116:427-33. [Crossref] [PubMed]
10. Douketis JD, Crowther MA, Stanton EB, et al. Elevated cardiac troponin levels in patients with submassive pulmonary embolism. Arch Intern Med 2002;162:79-81. [Crossref] [PubMed]
11. Giannitsis E, Müller-Bardorff M, Kurowski V, et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation 2000;102:211-7. [Crossref] [PubMed]
12. Konstantinides S, Geibel A, Olschewski M, et al. Importance of cardiac troponins I and T in risk stratification of patients with acute pulmonary embolism. Circulation 2002;106:1263-8. [Crossref] [PubMed]
13. Sonne-Holm E, Winther-Jensen M, Bang LE, et al. Troponin dependent 30-day mortality in patients with acute pulmonary embolism. J Thromb Thrombolysis 2023;56:485-94. [Crossref] [PubMed]
14. Bangalore S, Horowitz JM, Beam D, et al. Prevalence and Predictors of Cardiogenic Shock in Intermediate-Risk Pulmonary Embolism: Insights From the FLASH Registry. JACC Cardiovasc Interv 2023;16:958-72. [Crossref] [PubMed]
15. Bikdeli B, Muriel A, Rodríguez C, et al. High-Sensitivity vs Conventional Troponin Cutoffs for Risk Stratification in Patients With Acute Pulmonary Embolism. JAMA Cardiol 2024;9:64-70. [Crossref] [PubMed]
16. Coutance G, Le Page O, Lo T, et al. Prognostic value of brain natriuretic peptide in acute pulmonary embolism. Crit Care 2008;12:R109. [Crossref] [PubMed]
17. Pruszczyk P, Kostrubiec M, Bochowicz A, et al. N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism. Eur Respir J 2003;22:649-53. [Crossref] [PubMed]
18. Klok FA, Mos IC, Huisman MV. Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis. Am J Respir Crit Care Med 2008;178:425-30. [Crossref] [PubMed]
19. Kraut JA, Madias NE. Lactic acidosis. N Engl J Med 2014;371:2309-19. [Crossref] [PubMed]
20. Ebner M, Pagel CF, Sentler C, et al. Venous lactate improves the prediction of in-hospital adverse outcomes in normotensive pulmonary embolism. Eur J Intern Med 2021;86:25-31. [Crossref] [PubMed]
21. Vanni S, Socci F, Pepe G, et al. High plasma lactate levels are associated with increased risk of in-hospital mortality in patients with pulmonary embolism. Acad Emerg Med 2011;18:830-5. [Crossref] [PubMed]
22. Vanni S, Viviani G, Baioni M, et al. Prognostic value of plasma lactate levels among patients with acute pulmonary embolism: the thrombo-embolism lactate outcome study. Ann Emerg Med 2013;61:330-8. [Crossref] [PubMed]
23. Wang Y, Feng Y, Yang X, et al. Prognostic role of elevated lactate in acute pulmonary embolism: A systematic review and meta-analysis. Phlebology 2022;37:338-47. [Crossref] [PubMed]
24. Urbina T, Bigé N, Nguyen Y, et al. Tissue perfusion alterations correlate with mortality in patients admitted to the intensive care unit for acute pulmonary embolism: An observational study. Medicine (Baltimore) 2018;97:e11993. [Crossref] [PubMed]
25. Watts JA, Gellar MA, Obraztsova M, et al. Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats. Int J Exp Pathol 2008;89:389-99. [Crossref] [PubMed]
26. Kurtipek E, Büyükterzi Z, Büyükterzi M, et al. Endothelial dysfunction in patients with pulmonary thromboembolism: neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. Clin Respir J 2017;11:78-82. [Crossref] [PubMed]
27. De Backer D, Orbegozo Cortes D, Donadello K, et al. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence 2014;5:73-9. [Crossref] [PubMed]
28. Galić K, Pravdić D, Prskalo Z, et al. Prognostic value of lactates in relation to gas analysis and acid-base status in patients with pulmonary embolism. Croat Med J 2018;59:149-55. [Crossref] [PubMed]
29. Meinel FG, Nance JW Jr, Schoepf UJ, et al. Predictive Value of Computed Tomography in Acute Pulmonary Embolism: Systematic Review and Meta-analysis. Am J Med 2015;128:747-59.e2. [Crossref] [PubMed]
30. Bach AG, Nansalmaa B, Kranz J, et al. CT pulmonary angiography findings that predict 30-day mortality in patients with acute pulmonary embolism. Eur J Radiol 2015;84:332-7. [Crossref] [PubMed]
31. Côté B, Jiménez D, Planquette B, et al. Prognostic value of right ventricular dilatation in patients with low-risk pulmonary embolism. Eur Respir J 2017;50:1701611. [Crossref] [PubMed]
32. Alerhand S, Adrian RJ. What echocardiographic findings differentiate acute pulmonary embolism and chronic pulmonary hypertension? Am J Emerg Med 2023;72:72-84. [Crossref] [PubMed]
33. Pruszczyk P, Goliszek S, Lichodziejewska B, et al. Prognostic value of echocardiography in normotensive patients with acute pulmonary embolism. JACC Cardiovasc Imaging 2014;7:553-60. [Crossref] [PubMed]
34. Wisa D, Zapata D, Walczyszyn M, et al. 1018: Comparing CT scan and echocardiography for evaluation of right heart strain in submassive PE. Critical Care Medicine 2016;44:330.
35. Shams A, Hung J, Bahl A. Ability of computed tomography to predict right heart strain on an echocardiogram in patients with acute pulmonary embolus. J Biol Regul Homeost Agents 2018;32:365-70.
36. Dudzinski DM, Hariharan P, Parry BA, et al. Assessment of Right Ventricular Strain by Computed Tomography Versus Echocardiography in Acute Pulmonary Embolism. Acad Emerg Med 2017;24:337-43. [Crossref] [PubMed]
37. Aujesky D, Roy PM, Le Manach CP, et al. Validation of a model to predict adverse outcomes in patients with pulmonary embolism. Eur Heart J 2006;27:476-81. [Crossref] [PubMed]
38. Donzé J, Le Gal G, Fine MJ, et al. Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism. Thromb Haemost 2008;100:943-8. [Crossref] [PubMed]
39. Fernández C, Bova C, Sanchez O, et al. Validation of a Model for Identification of Patients at Intermediate to High Risk for Complications Associated With Acute Symptomatic Pulmonary Embolism. Chest 2015;148:211-8. [Crossref] [PubMed]
40. Bova C, Sanchez O, Prandoni P, et al. Identification of intermediate-risk patients with acute symptomatic pulmonary embolism. Eur Respir J 2014;44:694-703. [Crossref] [PubMed]
41. Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992;79:1-17.
42. Robertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev 2017;2:CD001100. [Crossref] [PubMed]
43. Roy PM, Douillet D, Penaloza A. Contemporary management of acute pulmonary embolism. Trends Cardiovasc Med 2022;32:259-68. [Crossref] [PubMed]
44. Dolovich LR, Ginsberg JS, Douketis JD, et al. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med 2000;160:181-8. [Crossref] [PubMed]
45. McRae SJ, Ginsberg JS. Initial treatment of venous thromboembolism. Circulation 2004;110:I3-9. [Crossref] [PubMed]
46. Senturk A, Ucar EY, Berk S, et al. Should Low-Molecular-Weight Heparin be Preferred Over Unfractionated Heparin After Thrombolysis for Severity Pulmonary Embolism? Clin Appl Thromb Hemost 2016;22:395-9. [Crossref] [PubMed]
47. Smith SB, Geske JB, Maguire JM, et al. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism. Chest 2010;137:1382-90. [Crossref] [PubMed]
48. Prucnal CK, Jansson PS, Deadmon E, et al. Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin. Acad Emerg Med 2020;27:117-27. [Crossref] [PubMed]
49. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e24S-43S.
50. Patel JP, Roberts LN, Arya R. Anticoagulating obese patients in the modern era. Br J Haematol 2011;155:137-49. [Crossref] [PubMed]
51. Leentjens J, Peters M, Esselink AC, et al. Initial anticoagulation in patients with pulmonary embolism: thrombolysis, unfractionated heparin, LMWH, fondaparinux, or DOACs? Br J Clin Pharmacol 2017;83:2356-66. [Crossref] [PubMed]
52. Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510. [Crossref] [PubMed]
53. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013;369:799-808. [Crossref] [PubMed]
54. Weeda ER, Kohn CG, Peacock WF, et al. Rivaroxaban versus Heparin Bridging to Warfarin Therapy: Impact on Hospital Length of Stay and Treatment Costs for Low-Risk Patients with Pulmonary Embolism. Pharmacotherapy 2016;36:1109-15. [Crossref] [PubMed]
55. Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013;369:1406-15. [Crossref] [PubMed]
56. van der Hulle T, Kooiman J, den Exter PL, et al. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 2014;12:320-8. [Crossref] [PubMed]
57. Chai-Adisaksopha C, Hillis C, Isayama T, et al. Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost 2015;13:2012-20. [Crossref] [PubMed]
58. Dubinski D, Won SY, Voss M, et al. Direct oral anticoagulants vs. low-molecular-weight heparin for pulmonary embolism in patients with glioblastoma. Neurosurg Rev 2022;45:451-7. [Crossref] [PubMed]
59. Dalla-Volta S, Palla A, Santolicandro A, et al. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. J Am Coll Cardiol 1992;20:520-6. [Crossref] [PubMed]
60. Jerjes-Sanchez C, Ramírez-Rivera A, de Lourdes García M, et al. Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism: A Randomized Controlled Trial. J Thromb Thrombolysis 1995;2:227-9. [Crossref] [PubMed]
61. Marti C, John G, Konstantinides S, et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J 2015;36:605-14. [Crossref] [PubMed]
62. Konstantinides S, Geibel A, Heusel G, et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002;347:1143-50. [Crossref] [PubMed]
63. Kline JA, Nordenholz KE, Courtney DM, et al. Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial. J Thromb Haemost 2014;12:459-68. [Crossref] [PubMed]
64. Becattini C, Agnelli G, Salvi A, et al. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thromb Res 2010;125:e82-6. [Crossref] [PubMed]
65. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370:1402-11. [Crossref] [PubMed]
66. Wang C, Zhai Z, Yang Y, et al. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest 2010;137:254-62. [Crossref] [PubMed]
67. Sharifi M, Bay C, Skrocki L, et al. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol 2013;111:273-7. [Crossref] [PubMed]
68. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014;129:479-86. [Crossref] [PubMed]
69. Piazza G, Hohlfelder B, Jaff MR, et al. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv 2015;8:1382-92. [Crossref] [PubMed]
70. Kuo WT, Banerjee A, Kim PS, et al. Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry. Chest 2015;148:667-73. [Crossref] [PubMed]
71. Tapson VF, Sterling K, Jones N, et al. A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial. JACC Cardiovasc Interv 2018;11:1401-10. [Crossref] [PubMed]
72. Engelberger RP, Spirk D, Willenberg T, et al. Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis. Circ Cardiovasc Interv 2015;8:e002027. [Crossref] [PubMed]
73. Gaba RC, Gundavaram MS, Parvinian A, et al. Efficacy and safety of flow-directed pulmonary artery catheter thrombolysis for treatment of submassive pulmonary embolism. AJR Am J Roentgenol 2014;202:1355-60. [Crossref] [PubMed]
74. Guru PK, Giri AR, Sanghavi DK, et al. Ultra-Low-Dose Systemic Tissue Plasminogen Activator in High-Risk Submassive Pulmonary Embolism. Mayo Clin Proc 2022;97:1158-63. [Crossref] [PubMed]
75. Aykan AÇ, Gökdeniz T, Gül İ, et al. Reduced-Dose Systemic Fibrinolysis in Massive Pulmonary Embolism: A Pilot Study. Clin Exp Emerg Med 2023;10:280-6. [Crossref] [PubMed]
76. Lightning 12 | Penumbra Inc [Internet]. [cited 2024 Oct 23]. Available online: https://www.penumbrainc.com/products/lightning-12/
77. FlowTriever® system for the treatment of pulmonary embolism (PE)-Inari Medical-Patients First. Always. [Internet]. [cited 2024 Oct 23]. Available online: https://www.inarimedical.com/flowtriever-system
78. Tu T, Toma C, Tapson VF, et al. A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study. JACC Cardiovasc Interv 2019;12:859-69. [Crossref] [PubMed]
79. Sista AK, Horowitz JM, Tapson VF, et al. Indigo Aspiration System for Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial. JACC Cardiovasc Interv 2021;14:319-29. [Crossref] [PubMed]
80. Chandra VM, Khaja MS, Kryger MC, et al. Mechanical aspiration thrombectomy for the treatment of pulmonary embolism: A systematic review and meta-analysis. Vasc Med 2022;27:574-84. [Crossref] [PubMed]
81. Leacche M, Unic D, Goldhaber SZ, et al. Modern surgical treatment of massive pulmonary embolism: results in 47 consecutive patients after rapid diagnosis and aggressive surgical approach. J Thorac Cardiovasc Surg 2005;129:1018-23. [Crossref] [PubMed]
82. Yavuz S, Toktas F, Goncu T, et al. Surgical embolectomy for acute massive pulmonary embolism. Int J Clin Exp Med 2014;7:5362-75.
83. Iaccarino A, Frati G, Schirone L, et al. Surgical embolectomy for acute massive pulmonary embolism: state of the art. J Thorac Dis 2018;10:5154-61. [Crossref] [PubMed]
84. Kalra R, Bajaj NS, Arora P, et al. Surgical Embolectomy for Acute Pulmonary Embolism: Systematic Review and Comprehensive Meta-Analyses. Ann Thorac Surg 2017;103:982-90. [Crossref] [PubMed]
85. Keeling WB, Sundt T, Leacche M, et al. Outcomes After Surgical Pulmonary Embolectomy for Acute Pulmonary Embolus: A Multi-Institutional Study. Ann Thorac Surg 2016;102:1498-502. [Crossref] [PubMed]
86. Pasrija C, Kronfli A, Rouse M, et al. Outcomes after surgical pulmonary embolectomy for acute submassive and massive pulmonary embolism: A single-center experience. J Thorac Cardiovasc Surg 2018;155:1095-1106.e2. [Crossref] [PubMed]
87. Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med 1998;338:409-15. [Crossref] [PubMed]
88. Bikdeli B, Chatterjee S, Desai NR, et al. Inferior Vena Cava Filters to Prevent Pulmonary Embolism: Systematic Review and Meta-Analysis. J Am Coll Cardiol 2017;70:1587-97. [Crossref] [PubMed]
89. Quezada A, Jiménez D, Bikdeli B, et al. Outcomes after Vena Cava Filter Use in Patients with Cancer-Associated Venous Thromboembolism and Contraindications to Anticoagulation. Thromb Haemost 2020;120:1035-44. [Crossref] [PubMed]
90. PREPIC Study Group. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study. Circulation 2005;112:416-22. [Crossref] [PubMed]
91. Mismetti P, Laporte S, Pellerin O, et al. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial. JAMA 2015;313:1627-35. [Crossref] [PubMed]
92. Corsi F, Lebreton G, Bréchot N, et al. Life-threatening massive pulmonary embolism rescued by venoarterial-extracorporeal membrane oxygenation. Crit Care 2017;21:76. [Crossref] [PubMed]
93. Fleitas Sosa D, Lehr AL, Zhao H, et al. Impact of pulmonary embolism response teams on acute pulmonary embolism: a systematic review and meta-analysis. Eur Respir Rev 2022;31:220023. [Crossref] [PubMed]