Therapeutic approaches

In order to determine the appropriate therapeutic strategy, it is essential to stratify risk based on PE severity. Patients are first divided into those with hemodynamic instability and those without hemodynamic instability. Patients without hemodynamic instability are then further stratified based on clinical, imaging and laboratory findings indicative of PE severity and comorbidities that may contribute to an adverse prognosis [3].

Acute RV failure, defined as a rapidly progressive syndrome with systemic congestion resulting from impaired RV filling and/or reduced RV flow output, is a critical determinant of outcome in acute PE. Tachycardia, low systolic BP, respiratory insufficiency (tachypnea and/or low oxygen saturation), and syncope, alone or in combination, have been associated with an unfavorable short-term prognosis in acute PE [3].

Treatment modalities

American College of Cardiology current treatment guidelines currently recommend systemic thrombolytic therapy when there is high suspicion for imminent cardiopulmonary decline.

Anticoagulation in the form of subcutaneous, weight adjusted low molecular weight heparin, fondaparinux, intravenous unfractionated heparin (UFH) or non-vitamin K antagonist oral anticoagulant (NOAC), should be initiated in patients with high or intermediate clinical probability of PE [8].

However, it has been shown that thrombolytic therapy leads to accelerated improvement compared to UFH alone with improvements in RV dilatation. Thrombolysis must be initiated within 48 h of symptoms onset but may be effective up to 6–14 days after symptom onset [9]. This benefit was proven through a meta-analysis of trials of thrombolysis for PE showing a significant reduction in the combined outcome of mortality and recurrent PE [10]. To note, this benefit was achieved with a 9.9% rate of severe bleeding and a 1.7% rate of intracranial hemorrhage [11]. Intravenous administration of recombinant tissue-type plasminogen activator (rtPA) is superior to streptokinase and urokinase, first generations thrombolytic agents [12].

Absolute contraindications to the use of thrombolytics include active bleeding, recent cerebrovascular accident or transient ischemic attack, recent neurosurgical procedure, or recent intracranial trauma [1]. Thrombolytic therapy is also contraindicated in patients in whom anticoagulation is contraindicated for any reason. Relative contraindications include recent requirement for cardiopulmonary resuscitation, abdominal, ophthalmic, or obstetric surgery, extracranial trauma, intracranial tumor or vascular abnormality, systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg, or recent gastrointestinal bleed. A comprehensive list of relative contraindications is provided in the table below (Table 1).

Another point to consider is that a large segment of patients with acute deep venous tomography (DVT) or PE go on to develop disabling sequelae such as post thrombotic syndrome, recurrent venous thromboembolism, or chronic thromboembolic pulmonary hypertension (CTEPH) [6].

Full dose systemic thrombolysis is not recommended for intermediate risk PE due to the high risk of life threatening bleeding in comparison to the expected benefits of thrombolysis [12].

Limitations of both anticoagulation and systemic thrombolysis and the complexity and risk associated with open surgical embolectomy in some patients with PE have led to the development of percutaneous catheter based thrombectomy techniques.

Catheter-based mechanical thrombectomy

The indications of the use of catheter based thrombectomy are driven by the severity of the PE as well by specific patient related factors such risk for bleeding and other comorbidities [1]. Systemic thrombolysis has a reduction in both mortality as well as improvement in hemodynamic function but carries an increased risk of severe intracranial and extracranial bleeding as was demonstrated in the PEITHO (Pulmonary Embolism Thrombolysis) trial. Due to bleeding related adverse events as well as treatment failure in certain subsets of patients, catheter-based thrombus removal have emerged as a therapeutic option.

Given these limitations, endovascular therapy has been gaining momentum over the past 20 years. In general, catheter based thrombectomy for PE is considered when there are significant contraindications to thrombolytic therapy or when there are risk factors indicating an increased likelihood for mortality.

The American College of Cardiology/American Heart Association guidelines suggest that catheter thrombectomy can be considered when there is suspicion of cardiopulmonary worsening in sub-massive PE or evident cardiopulmonary deterioration [6].

Catheter based thrombectomy is indicated for patient with a high bleeding risk, failed thrombolysis or chock, as per current guidelines [13]. Patients who have low risk PE are generally not candidates for endovascular therapy—the exception being those with a saddle embolus without hemodynamic change or effect on the RV [14].

Patient selection and risk stratification

In clinical practice, patient should be carefully selected for an individualized endovascular strategy. There are three main considerations when selecting a patient for endovascular therapy: disease severity and acuity, risk of major bleeding, and patient specific factors. Thrombectomy techniques that have been developed include: thrombus fragmentation, thrombectomy with clot aspiration, hemolytic thrombectomy, and suction thrombectomy. With improper patient positioning, there is always a risk of distal embolization of thrombus and potential catastrophic vessel injury. Therefore, it is always advised to perform the procedure in conjunction with CT imaging.

Despite this, there are still multiple technical difficulties that users have encountered, many of which are due to catheter size. The newer devices, such as the FlowTriever System (Inari Medical, Irvine, CA) and the Indigo System (Penumbra Inc., Alameda, CA) have developed for patients with absolute contraindications to thrombolytic therapy.

The FlowTriever system is a large bore catheter system which received U.S. Food and Drug Administration clearance for use in PE in May 2018. A 20-French catheter is advanced over a guide wire to the level of the right or left pulmonary artery proximal to the location of the occlusive thrombus. The FlowTriever Catheter is then advanced through the over the guidewire. The clot is aspirated through the 20-French catheter initially placed and removed. This catheter, also known as the aspiration guide catheter, can be removed and reinserted. This whole procedure can be repeated multiple times as needed. The FlowTriever Pulmonary Embolectomy Clinical Study (FLARE) was a prospective, single-arm, multicenter investigational device exemption trial in which patients with acute intermediate-risk PE were treated with the FlowTriever Retrieval/Aspiration System. The results of this trial demonstrated a reduction in RV/LV ratio of 25% [15], with a 0.9% major bleeding rate (with no intracranial hemorrhages), which suggests an excellent safety profile. In addition, there were no major vascular complications or device related cardiac injury events that were noted [16].

The benefits of percutaneous mechanical thrombectomy can be summarized into the following points—rapid hemodynamic stabilization, use in patient cohort who are at high risk for bleeding and its potential to improve hospital costs, given the reduced need for intensive care unit (ICU) stay and short hospital stay, as illustrated in the FLARE study [16].

Current guidelines recommend anticoagulation alone, with catheter intervention reserved for patients who fail to respond to conservative therapy. Currently known complications of catheter thrombectomy for PE include perforation or dissection or cardiovascular structures, pericardial tamponade, distal thrombus embolization, and can also potentially lead to arrhythmias and vascular access complications. Thrombectomy should be performed only in the main and lobar pulmonary arteries, not in the segmental pulmonary arteries to minimize some of these risks. Once hemodynamic improvement has resulted, the procedure should be terminated [17].

A rapid, accurate risk stratification to determine an appropriate treatment plan is the first step in treating acute PE. Thrombolysis, catheter intervention, and ongoing collaboration with cardiac surgeons are strategies that can maximize the likelihood of complete recovery for these devastatingly ill patients.

Conclusion

Acute PE remains a significant cause of morbidity and requires prompt diagnosis and management. Patients with a life-threatening PE require additional treatment beyond anticoagulation. Percutaneous thrombectomy using the FlowTriever system with a large bore design has shown promising results in terms of reducing clot burden and improving hemodynamics. As it is technically more demanding to navigate through RV and pulmonary vasculature, there is risk of pulmonary artery perforation which can lead to pericardial tamponade and is frequently catastrophic. There are very few resources that compile all known complications of percutaneous mechanical thrombectomy for the treatment of PE, which is the need of the hour, and should be based upon large, multi-center settings. Attention must be paid to life threatening complications such as cardiac tamponade which can be precipitated by the use of these devices. With this case report and review of literature, we also hope to spur specialized operator training to minimize these adverse outcomes.