Massive Embolism: Knife versus PCI

Abstract

Pulmonary embolism is the third most common cardiovascular syndrome with an estimated up to 25% of patients presenting with sudden death. For those who survive, a mainstay of management for patients with hemodynamic stability is anticoagulation; however, recommendations and options are rapidly changing for patients with submassive or massive pulmonary embolism with hemodynamic instability. Catheter-based and surgical approaches offer efficacious management options for unstable patients or patients with contraindications to anticoagulation; however, both approaches have inherent benefits and risk. This article seeks to offer a brief review on the recommendations and options for management of pulmonary embolism from both surgical and catheter-based perspectives.

Pulmonary embolism (PE) is a relatively common and often lethal pathology that is internationally the third most common cardiovascular syndrome. ^{1 2} PE is frequently found as a sequalae of venous thromboembolic disease, which is estimated to have an occurrence rate of 71 to 117 per 100,000 with PE having an incidence of approximately 53 to 162 per 100,000. It is estimated that up to 25% of patients with a PE present with sudden death. ^{1 3 4 5 6} For over 100 years, surgical management has been pursued as a strategy to treat PE with Trendelenburg attempting surgical pulmonary embolectomy (SPE) as early as 1872, and Kirshner (a student of Trendelenburg) and colleagues performing the earliest known successful SPE in 1924, almost 40 years before the suggestion of cardiopulmonary bypass (CPB). ^{7 8}

The American Heart Association (AHA) and European Society of Cardiology (ESC) have traditionally categorized PE into three categories:

1. Stable or low risk without evidence of right ventricular (RV) dysfunction and can undergo optimal medical therapy (OMT).

2. Submassive PE (intermediate risk) or those that preserve hemodynamic stability but have evidence of RV dysfunction.

3. Massive PE (high risk), or those with hemodynamic instability, hypoxemia, and evidence of end-organ malperfusion. Frequently, these patients have failed OMT and require invasive intervention. ^{1 9}

Further guiding early management/intervention, in 2005 Aujesky et al devised the Pulmonary Embolism Severity Index (PESI), a prognostic model that was simplified by Jiménez et al in 2010. These models help identify those patients that are at high risk for mortality and require more aggressive and earlier intervention. ^{10 11} With the 2019 revisions, ESC released an updated algorithm to assist in identification and management of patients with acute PE. When focusing on hemodynamically unstable (submassive and massive PE) patients after anticoagulation is initiated, the recommendation is progression to computed tomography with pulmonary artery protocol (CTPA) if available. If CTPA is not available or if it confirms the diagnosis, management can proceed with treatment as suggested by ESC guidelines and depicted in Fig. 1 . ¹

Fig. 1.

Summarized European Society of Cardiology 2019 risk adjusted management strategy for acute pulmonary embolism. ¹

First-line approaches for hemodynamically stable patients remain systemic anticoagulation. For patients with intermediate or high probability of PE, it is recommended systemic anticoagulation is started immediately, even if that is prior to diagnostic radiographic studies (Class I Level of Evidence [LOE] C). ^{1 12} Furthermore, when hypoxemia or RV failure occur, thrombolytic therapy has been shown to result in faster improvement than anticoagulation alone. ^{13 14}

SPE traditionally was reserved for patients with massive hemodynamically unstable PE and either contraindications to or failure of OMT. As catheter-based and surgical therapies advance, their recommendations and implementation in management for PE continue to change, which has been demonstrated by Mullan et al who sampled the National Inpatient Sample (NIS) database and showed a trend toward increased extracorporeal membrane oxygenation (ECMO) and catheter-directed therapies in recent years. ¹⁵

Given the rapidly changing environment of catheter and surgical options for managing acute PE, we hereby provide a brief review of these various management approaches.

Review of Catheter-Directed Management of Massive Pulmonary Embolism

Catheter-directed therapies are indicated for patients with submassive or massive PE in which OMT is contraindicated or unsuccessful. Catheter-directed therapies utilize both pharmacologic and mechanical techniques to decrease thrombus burden. ⁹ The AHA defines two main categories of catheter-directed therapies: catheter-directed thrombolysis (CDT) and catheter-based embolectomy (CBE). ⁹ These categories vary in their methods and goals. However, CDT and CBE have both demonstrated clinical success in early studies.

Catheter-Directed Thrombolysis

CDT uses pharmacologic methods to treat submassive and massive PE. The goal of CDT is to downstage acute PE from high to intermediate risk while using lower doses of thrombolytic medication to decrease the risk of bleeding sequalae with maintenance of similar or greater effectiveness when compared with systemic thrombolysis. ⁹ CDT does not attempt to completely remove the occlusive thrombus.

The two main types of CDT are standard thrombolysis and ultrasound-assisted thrombolysis (USAT). Standard CDT delivers a thrombolytic agent directly into the pulmonary arterial circulation. Although the clinical implication remains uncertain, a theoretical significant advantage of CDT is that only 25% of the dose of thrombolytic agent is required when compared with systemic administration. Additionally, the directed delivery of thrombolytics can allow avoidance of the risk of the thrombolytic agent being shunted to an unobstructed pulmonary artery, as can occur with systemic administration. ⁹

USAT combines standard CDT with ultrasound transducers in the head of the catheter, which can aid in the dissociation of fibrin strands within the thrombus and permit deeper penetration of delivered thrombolytic agent in a shorter amount of time. ⁹ USAT has demonstrated trends toward better recovery when compared with standard CDT; however, conclusive data remains limited. ¹⁶ Furthermore, a 2019 retrospective study showed that CDT had a lower rate of significant bleeding events and a higher survival-to-discharge rate when compared with USAT. ¹⁷ Given the greater equipment cost of USAT when compared with standard CDT, further trials are needed to elucidate the potential benefits of USAT. ¹⁷

Catheter-Based Embolectomy

The goal of CBE is to completely remove the thrombotic burden from the pulmonary circulation. This approach can be used in conjunction with or after failed CDT, as many CBE catheters allow for delivery of thrombolytic agents at the time of embolectomy. Carrying up to a 90% success rate, CDT and CBE are indicated in patients with high-risk PE in whom thrombolysis is contraindicated or has failed (Class IIa). ¹ However, because of the associated complications they are usually used only in those patients with massive PE and hemodynamic instability. ¹⁸ Various approaches exist for CBE, and the choice of approach is dependent on institutional ability and availability.

Suction embolectomy, or manual aspiration embolectomy, involves thrombus removal through direct aspiration. Suction embolectomy has seen mixed success, as submassive and massive PEs are often too large to be completely removed through simple aspiration. ⁹ Furthermore, suction embolectomy has been shown to have worse outcomes for patients that have experienced hemodynamic compromise greater than 48 hours prior to procedural intervention. ¹⁹

Rheolytic thrombectomy uses saline jets to create a vacuum within the occluded vessel based on the Venturi principle. The negative pressures from this vacuum break down the occlusive thrombus, which is then aspirated. This approach is recommended in patients who have failed fibrinolytic therapy and remain unstable (Class IIa, LOE C). ²⁰ A commonly used device for rheolytic thrombectomy is the AngioJet (Boston Scientific, Marlborough, MA), which allows for delivery of thrombolytic agent while offering rheolytic embolectomy. It is important to note that this device has seen in-hospital mortality rates of 14 to 16%. ^{21 22} As such, the procedure-related complications and mortalities have resulted in a black-box warning for its use in PE. ^{9 20}

Rotational thrombectomy, or mechanical aspiration thrombectomy, uses a catheter with a helix at its head. This helix rotates at high speeds to create a negative pressure at the site of occlusion that then pulls the thrombus into the catheter. Similar to other approaches, studies (although some smaller) have seen rotational thrombectomy result in clot clearances up to 90%, but outcome largely depends on thrombus age and size. ^{23 24 25}

Thrombus fragmentation, or thrombus maceration, uses either rotational methods or balloon angioplasty to mechanically displace the thrombus. ²⁶ Once displaced, the previously occluded vessel is recanalized and the thrombus is naturally or artificially lysed. This is the only CBE approach that does not remove the PE from circulation but rather macerates it, and as such carries a risk of postoperative embolization. ^{9 18}

Outcomes of Catheter-Directed Management

There has been an increasing amount of research in the last decade to determine the efficacy and safety of catheter-based interventions in the setting of submassive and massive PE, with many studies demonstrating catheter-based intervention is noninferior or superior to alternative treatment modalities. Supporting this, a 2018 meta-analysis, found that CDT and USAT clinical success (defined as improvement of hemodynamic decompensation) rates were 70.8 and 83.1%, respectively. ¹⁶ However, that is not to say that catheter-based interventions are risk free as this same analysis found that although CDT is efficacious, major bleeding and stroke occurred up to 6.7 and 6.3% of the time in certain studies, resepectively. ¹⁶ Following this, a 2019 retrospective review found no significant difference in major bleeding events or clinical success between CDT and CBE; however, there remains very limited data comparing CBT to CBE as well as among the various CBE techniques. ²⁷

Catheter-Directed Management versus Medical Management

Studies have shown that catheter-directed interventions are associated with similar or lower mortality rates than OMT when used in intermediate to high-risk acute PE. Geller et al demonstrated in a recent meta-analysis of 1,915 patients with high-risk PE that CDT had a statistically significantly lower short- and intermediate-term mortality rate than systemic thrombolysis. Similar all-cause bleeding rates were observed but CDT cohort carried a higher rate of intracranial hemorrhage when compared with systemic thrombolysis, though the authors acknowledge it is unclear if this is because intracranial hemorrhage was preprocedural and a contraindication to systemic thrombolysis. ²⁸ Supporting the assertion that CDT reduces the risk of intracranial hemorrhage compared with systemic thrombolytics, indirect comparisons made from multiple meta-analyses by the AHA in 2019 suggest that CDT may be associated with half the risk of intra- and nonintracranial bleeding when compared with systemic thrombolytic administration. ⁹

A recent retrospective review demonstrated that there is no statistically significant difference in mortality rate, bleeding sequalae, or length of stay. However, recurrent PE was less likely in the catheter-based therapy group when compared with OMT (0% vs. 6.4%). ²⁹ A brief summary of the risks and benefits of each approach above can be found in Table 1 .

Table 1. Brief review of risks and benefits of specific catheter-directed approaches.

	Benefits	Risks
Catheter-directed thrombolytic	Possibility of as much as 50% reduction in bleeding complications compared with systemic thrombolytics	Risk of arrhythmia or cardiac perforation from wires and catheters in heart (less than CBE)
	Reduced dose (25%) of thrombolytic required	Major bleeding risk associated with thrombolytic
	Thrombolytic delivered direct to thrombus	Does not remove thrombus from PA system
	Compared with OMT, reduced rate of recurrence	Pulmonary hemorrhage
	Lower prolonged ventilation rates than with SPE	Contrast if pulmonary angiogram is used
	Avoid theoretical shunt of systemic thrombolytic to unobstructed PAs
USAT	Fibrin dissociation and deeper penetration of thrombolytic into thrombus in shorter time	Theoretical increased bleeding risk compared with standard CDT
Catheter-based embolectomy	Removes partial thrombus burden from PA	In intermediate risk patients, may cause shower emboli and increase PA pressures
	Can allow CDT depending on device	Contrast if pulmonary angiogram is used
		Requires stiff wires with increased risk of traumatic cardiac or pulmonary injury compared with CDT
Suction embolectomy		Large PE cannot be frequently removed
		Inferior outcomes compared with SPE if patients have had hemodynamic compromise for > 48 h
Rheolytic therapy		Elevated in-hospital mortality compared with CDT and SPE
		Elevated periprocedural bleeding compared with suction embolectomy
		Known association with severe bradyarrhythmia and hypotension
		Larger access site requirements increase risk of access site complications
Rotational thrombectomy	In small studies may offer clot clearance up to 90%	Decreased success rates with larger or more chronic thrombus
		Limited data with utilization in pulmonary system
Thrombus fragmentation		Fragmented thrombus is not removed from system
		High risk of embolization

Abbreviations: CBE, catheter-based embolectomy; CDT, catheter-directed thrombolysis; OMT, optimal medical therapy; PA, pulmonary artery; PE, pulmonary embolism; SPE, surgical pulmonary embolectomy; USAT, ultrasound-assisted thrombolysis.

Catheter-Directed Management versus Surgical Management

SPE, discussed at length below, is a traditional treatment for submassive and massive centrally located acute PE. Supporting the Mullan et al finding that catheter-directed therapy is being used with increasing frequency, Cires-Drouet et al demonstrated catheter-directed therapies are associated with a shorter length of stay. ¹⁵ Loyalka et al found in a systemic review of over 2,500 patients that catheter-directed therapies resulted in a 8.4% lower in-hospital mortality rate when compared with SPE. ³⁰

Further supporting catheter-directed therapies as an efficacious alternative to SPE, a 2019 study found that CDT and SPE had no significant difference in their in-hospital mortality rates (3% vs. 3.3%) and that patients receiving CDT were 13.5% less likely to receive prolonged ventilation. ³¹ These results hint that modern CDT may be associated with similar efficacy and improved safety when compared with SPE.

Although some studies offer promising results, Cires-Drouet et al also illustrate the variability in outcomes for CDT therapies showing that catheter-directed therapies were associated with a 17% greater mortality rate than SPE. ²⁹ It is important to note that operator skillset and institutional resources will play a large role in dictating if and when catheter-directed intervention is applied. While multiple retrospective studies have compared CBT to OMT and SPE, prospective randomized data remains limited. Further research into these devices is required, but with the U.S. Food and Drug Administration classifying the devices as moderate risk to patients, high-level research will likely be slow and require investment and conduction by charitable organizations, professional societies, industry, and public funding. ⁹

Review of Surgical Management for Massive Pulmonary Embolism

SPE was once approached as an option of last resort in a series of interventions aimed at reducing clot burden and alleviating the RV overload that would lead to cardiac collapse. Among several studies, indication for surgical intervention included predicted risk of 30-day mortality greater than or equal to 5% based on the Bova score and the PESI. ^{10 32 33 34} While variation exists, most procedures employed CPB and normothermia.

Outcomes associated with SPE have improved over the past several decades paralleling improvements in CPB, with some groups demonstrating mortality rates less than 5%. ³⁵ In a review by Kilic et al, mortality rates for SPE approached 27.2% between 1999 and 2008, with more recent data from Choi et demonstrating in-hospital mortality rates of 16% in the past decade. ^{36 37} As mortality rates improve, SPE can be transitioned from a salvage operation to a first-line alternative to OMT. Importantly, utilizing SPE as a salvage operation remains superior to repeated OMT as demonstrated by Meneveau et al with mortality rates approaching 38% with repeat thrombolysis compared with 7% for SPE after failed OMT. ³⁸ Compared with CDT and CBE, SPE is definitive treatment for massive PE and reduces the risk of clot recurrence or incomplete clot removal ( Fig. 2 ), which yields improvement in pulmonary perfusion pressures and can prevent circulatory collapse from residual or distally embolized clot burden. ^{36 38}

Fig. 2.

Demonstration of complete saddle embolus extraction that extended into the bilateral pulmonary arterial trees during surgical pulmonary embolectomy (SPE).

Surgical Embolectomy with Cardiogenic Shock

Patients who present in cardiogenic shock requiring cardiopulmonary resuscitation (CPR) are most likely to require emergent SPE. Furthermore, these patients carry the highest mortality rate of patients undergoing SPE, with Kon et al demonstrating mortality rates approaching 44% when compared with 16% for acute PE without cardiogenic shock and CPR. ³⁹ As discussed below, frequently this group of patients requires a temporary assist device such as ECMO. ³⁶ As has been observed with other high-risk procedures, experience matters. High-volume SPE centers have demonstrated superior short- and mid-term mortality rates; however, even in these specialized centers, cardiogenic shock was associated with increased mortality with hemodynamic instability acting as an independent risk factor. ^{32 40 41}

Outcomes of Nonsurgical versus Surgical Interventions for Massive PE

Directly comparing surgical versus nonsurgical interventions for patients with acute massive PE remains challenging given the variations in preoperative status. Loyalka et al demonstrated that under 4% of patients undergoing catheter-based intervention required CPR compared with 21.4% of patients undergoing SPE, a finding likely resultant from SPE being recommended by multiple societies as a salvage operation. ³⁰ To attempt to compensate for the different preoperative characteristics, Mullan et al performed a retrospective analysis of the NIS with propensity matched cohorts. When looking at saddle PE with shock, both catheter-directed intervention (odds ratio [OR] 0.68; p  = 0.028) and SPE (OR 0.30; p  < 0.001) were found to independently be associated with decreased in-hospital mortality when compared with OMT. Perhaps not surprising given the society recommendations, even among patients having PE associated with shock, catheter-directed interventions and SPE were utilized in a minority of presentations (3.9 and 2.4%, respectively). ¹⁵

Extracorporeal Membrane Oxygenation—Is There a Role in Massive Pulmonary Embolism?

Indication for ECMO Initiation in Massive PE

In 2019, the ESC revised their management guidelines, making a Class IIb recommendation (LOE C) that ECMO is considered in combination with SPE or catheter intervention for patients with refractory circulatory collapse or cardiac arrest. ¹ Patients who present with cardiogenic shock secondary to massive PE may undergo ECMO as either a delay to definitive therapy or to offer time for organ restitution and clot dissolution.

Continuing, the Extracorporeal Life Support Organization (ELSO) recommends that ECMO be considered as a bridge to recovery or while other interventions are being pursued, has failed conventional therapies, and without ECMO would have an otherwise high mortality risk. Although ECMO offers a support option for the most critically ill patients, when considering ECMO in patients with PE and shock, it is important to remember that ELSO also recommends against institution of ECMO support with conditions incompatible with normal life if the acute insult resolves, preexisting conditions, advanced age/size, and last but not least, medical futility. ⁴²

Outcomes of Patient with Massive PE on ECMO

Literature devoted to the use of ECMO in patients with massive PE is growing but generally presents overall survival at 47%, with an in-hospital mortality rate of 47.6%. Like other interventions, cardiac arrest prior to ECMO cannulation is a significant predictor of in-hospital mortality. Of those patients that survived to discharge, most were discharged without sequalae from a PE, including resolution of any RV dysfunction. ⁴³ Looking further into the impact of precannulation CPR, Sertic et al demonstrated that those patients that had return of spontaneous circulation prior to cannulation had superior short- and mid-term outcomes as well as a lower rate of cerebrovascular accidents when compared with those who were placed on ECMO while actively undergoing CPR. ⁴³

In another study by George et al, looking at patients who required ECMO for massive PE, 65.5% survived until decannulation and 53.1% survived to discharge. In this study, the most common causes of death were unrecoverable hemodynamic collapse, gastrointestinal bleeding, ischemic colitis, and hemorrhagic stroke. ⁴⁴

ECMO appears to be an effective salvage adjunct for patients with life-threatening PE, with excellent outcomes possible if patients are cannulated prior to the onset of circulatory collapse and cardiac arrest. This is significant as it is estimated that approximately 70% of patients with massive PE will die within 1 hour of developing symptoms and ECMO may offer an evolving modality to support these patients and allow for more definitive management.

ECMO as Adjunctive Therapy in Massive PE

Systemic thrombolysis has long been the standard treatment for managing massive PE and its use in patients with out of hospital cardiac arrest has been associated with improved survival. Continuing, anticoagulation alone has also been shown to provide similar physiologic benefits in PE management albeit with a delay in onset of effect. ECMO is frequently utilized with systemic anticoagulation; however, systemic or CDT carry an increased risk of bleeding for patients on ECMO. Clinicians have to continuously weigh the risks and benefits of initiating these concomitant therapies. As ECMO technology continues to progress, cannulation can be undertaken in a percutaneous fashion, which can lower the risk of bleeding and allow safe administration of thrombolytic therapy. ⁴⁵ While ECMO may not necessarily be definitive management in and of itself, it provides a way to temporize patients at risk of ongoing or imminent hemodynamic collapse and allow for delayed intervention via either systemic anticoagulation, catheter intervention, or SPE.

When used concomitantly, adjunctive interventional therapies such as SPE and catheter-based interventions for ECMO patients with massive PE have been shown to have improved mortality outcomes than when only OMT is used with ECMO support. ^{38 43}

Limitations in Use of ECMO for Massive PE

Despite the promising benefit of ECMO in massive PE survival, there are important clinical presentations that limit its use in hemodynamically unstable patients. It has been seen that patients with a history of malignancy tend to have significantly higher mortality rates, with some studies demonstrating a sixfold increase in mortality compared with those patients without malignancy. This reduced survival in a disease with a high mortality rate at baseline brings into question if this resource should be employed in this critically ill group of patients. In addition, patients with a serum lactate of greater than 6 mmol/L at presentation should be carefully evaluated prior to consideration of ECMO initiation. Often these patients are at an extreme of the disease presentation and considered nonsalvageable. ⁴⁶

It is important to consider and plan for the utilization of adjunctive therapies. As previously mentioned, ECMO support may temporize critical patients and allow for systemic anticoagulation to be administered, but unlike invasive therapies (e.g., catheter-directed, SPE), ECMO does not remove the underlying clot burden. Therefore, it is important to remember if an adjunctive therapy is not employed these patients remain at risk for prolonged RV dysfunction and potential long-term development of chronic thromboembolic pulmonary hypertension. ⁴⁶

Pulmonary Embolism Response Team

PE has the potential to be a catastrophic disease pathology if diagnosis is not rapid and treatment expeditious. It is estimated that between 3 and 4.5% of patients with a PE are hypotensive at the time of presentation with a minority progressing to systemic thrombolytic, catheter-directed intervention or SPE. ^{1 15} It is presumed a contributing factor to such a small minority progressing to advanced therapies is from differing knowledge levels regarding risks, benefits, and availability of these therapeutics. ¹

A Pulmonary Embolism Response Team (PERT) is a multidisciplinary team designed to facilitate the diagnosis and expeditious management of patients presenting with submassive and massive acute PE. Similar to the heart team model, it ensures that the expertise of multiple specialties are considered. ⁴⁷ Although the model originated in the United States, it continues to gain acceptance globally. ¹ The specifics of a PERT differs by institution but is a response team that can be activated after the diagnosis of submassive or massive PE and frequently includes providers from: critical care, cardiac surgery, anesthesiology, interventional cardiology/radiology, and hematology. Although a tiered response can be employed, most institutions utilizing a PERT employ a full team response model for each activation. ⁴⁸ Given the rapidly evolving milieu of PE interventions and guidelines, it is thought that the availability of a multidisciplinary approach is of the utmost importance to prevent a sole clinician determining management of these critical patients and potentially not offering a new or alternative approach. ¹ In addition to mobilizing a multidisciplinary team, the PERT activation can allow rapid readying of institutional resources (e.g., catheterization suite, operating room) that may be required.

Although the theoretical benefits of the PERT approach are significant, there remains limited data supporting the anecdotal experiences. This data limitation is likely caused by the challenge of distinguishing if different outcomes are secondary to the PERT approach or the individual therapy employed. ¹ Solomon et al conducted a large systemic review demonstrating that a rapid response team is associated with a decrease in in-hospital mortality and nonintensive care unit cardiac arrest, which although not a direct assessment of PERT does hint toward the impact a PERT may have as the rapid response team model was the basis for the PERT. ⁴⁹

Society Recommendations in the Management of Acute PE

In 2011, the AHA released recommendations for management of submassive and massive PE, with more recent guidelines released by the ESC in 2019. ^{1 50} In line with improving outcomes from both interventional and surgical procedures, the more recent guidelines released by the ESC demonstrate an increase in the recommendation for catheter-based or surgical intervention. Though catheter-directed therapies are gaining favor, the most recent guidelines only Class I recommendation for invasive management in high-risk (massive) acute PE is that, “SPE is recommended for patients with high-risk PE, in whom thrombolysis is contraindicated or has failed (Ic).” ¹ A summary of recommendations between the two organizations can be found in Table 2 .

Table 2. Summary of guidelines surrounding surgical or interventional management of acute PE by the American Heart Association (2011) ⁵⁰ and the European Society of Cardiology (2019) ¹ .

	AHA Guidelines (2011)50	ESC Guidelines (2019)1
Ic		Surgical pulmonary embolectomy is recommended for patients with high-risk PE, in whom thrombolysis is contraindicated or has failed
IIa	Depending on local expertise, either catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE and contraindications to fibrinolysis	Percutaneous catheter-directed treatment should be considered for patients with high-risk PE, in whom thrombolysis is contraindicated or has failed
	For patients with massive PE who cannot receive fibrinolysis or who remain unstable after fibrinolysis, it is reasonable to consider transfer to an institution experienced in either catheter embolectomy or surgical embolectomy if these procedures are not available locally and safe transfer can be achieved	As an alternative to rescue thrombolytic therapy, surgical embolectomy or percutaneous catheter-directed treatment should be considered for patients with hemodynamic deterioration on anticoagulation treatment
	Catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE who remain unstable after receiving fibrinolysis	Thrombolysis or surgical embolectomy should be considered for pregnant women with high-risk PE
		Set-up of multidisciplinary teams for management of high-risk and selected cases of intermediate-risk PE should be considered, depending on the resources and expertise available in each hospital
		Set-up of a multidisciplinary team and a program for the management of high- and (in selected cases) intermediate-risk PE should be considered, depending on the resources and expertise available in each hospital
IIb	Either catheter embolectomy or surgical embolectomy may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory failure, severe RV dysfunction, or major myocardial necrosis)	Surgical embolectomy or catheter-directed treatment should be considered as alternatives to rescue thrombolytic therapy for patients who deteriorate hemodynamically
		ECMO may be considered, in combination with surgical embolectomy or catheter-directed treatment, in refractory circulatory collapse or cardiac arrest
III	Catheter embolectomy and surgical thrombectomy are not recommended for patients with low-risk PE or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening

Abbreviations: AHA, American Heart Association; ECMO, extracorporeal membrane oxygenation; ESC, European Society of Cardiology; PE, pulmonary embolism; RV, right ventricular.

Conclusion

PE remains a relatively common cardiovascular syndrome worldwide, with massive PE conferring a poor prognosis and an extremely morbid natural history if left untreated. Although exact medication implementation has changed over time, evidence-based guidelines have remained relatively congruous in that stable and to some degree submassive PE should be managed with OMT.

For those patients that present with submassive or massive PE and hemodynamic instability, there is a growing armamentarium of therapeutic options available. Traditionally, systemic thrombolytic therapy has been a first-line intervention, but as demonstrated above, catheter-based interventions and SPE have rapidly improving outcomes. Implementation of the therapies described in this review should be guided based on facility availability and user familiarity with the technology available. Additionally, given the multitude of interventions available, a PERT may offer a multidisciplinary model to ensure optimal and rapid intervention for critical patients. With the inclusion of ECMO in both the AHA and ESC guidelines for management of refractive cardiovascular collapse, definitive management can be achieved at a greater interval from symptom onset than in the past thereby allowing for interfacility transport to achieve a higher level of definitive care if needed.

We have sought to briefly review the different interventions available for patients with massive PE. With catheter-directed therapies and SPE both demonstrating improving morbidity and mortality profiles, the decision of exact intervention implementation should be based on a multidisciplinary approach at an institution-specific level. Importantly, SPE should no longer be considered an intervention of last resort.