Pulmonary Embolism Management – The New Frontier for Interventional Therapies?

Pulmonary embolism (PE) remains the third most frequent cause of cardiovascular death after stroke and myocardial infarction.¹ While each of the latter clinical disease states have developed significant advances in catheter based therapeutic approaches over the last several decades, invasive percutaneous therapies have only recently been approved for use in pulmonary embolism patients.

The majority of pulmonary embolism patients present with low risk features and can be treated with systemic anticoagulation alone. In fact, many of these patients do not need hospitalization in the modern era.^2,3 However, a small percentage of patients (5-10%) present with hemodynamically significant PE characterized mainly by hemodynamic instability and classified as high risk. Another 40-50% present with evidence of right heart strain, characterized either by imaging or biomarker evidence of impact on the right heart classified as intermediate risk.⁴ Traditionally, appropriate high risk patients with evidence of shock have been treated with systemic thrombolysis based on a small eight patient study over 20 years ago.⁵ The intermediate risk group has been treated with anticoagulation alone based on the PEITHO trial which suggested no difference in long term outcomes but an increased risk of intracranial hemorrhage for those receiving thrombolysis versus those receiving anticoagulation alone.⁶ However, the thrombolytic group did have a decreased risk in hemodynamic decompensation and improved recovery, hence providing some of the impetus to develop technologies that may provide the same benefits with less bleeding risk.

In this AHA scientific statement, Giri et al⁷ provide a comprehensive review of the nascent field of interventional therapies used in acute pulmonary embolism management. The technologies currently being used fall into two rough categories, those based on thrombolysis strategies using lower doses of thrombolytic locally delivered and those based on mechanical thrombus extraction strategies. Only one device in each class has been FDA approved at present – BTG EkoSonic catheter (Bothell, WA) which allows for catheter-based ultrasound assisted thrombolysis (USAT) and the INARI Flowtriever (Irvine, Calif.) catheter that is designed to mechanically remove thrombus. There are several other catheters in both classes seeking FDA approval or being used ‘off label’ in the pulmonary arteries.

The data supporting the use of these devices is sparse. Both FDA approved devices and other devices seeking FDA approval are obtaining clearance based on small randomized or single arm trials with surrogate endpoints. The surrogate endpoint of choice is right ventricle/left ventricle ratio (RV/LV) as observational data suggests that an RV/LV ratio >0.9 portends a worse prognosis. Both FDA approved devices demonstrated a significant reduction in RV/LV ratio at 48 hours.^8,9 However, there is no data to suggest that rapid reduction of RV/LV ratio reduces mortality. While these technologies may serve as valuable tools in downstaging disease in the intermediate risk population group, prospective data is needed to demonstrate significant improvement in hard outcomes before widespread adoption is possible. Furthermore, there are proposed theoretical benefits such as prevention of recurrent pulmonary embolism or prevention of chronic thromboembolic pulmonary hypertension, but there is no substantive data to prove these possibilities.

Given the challenges in patient recruitment and the number needed to treat to demonstrate significant mortality reductions, novel mechanisms may be necessary (embedding in large registries, etc.) to generate this data. FDA clearance through minimal data focused on surrogate outcomes may cause a proliferation of devices cleared with equally sparse data. It is incumbent upon the societies, foundations, industry partners, individual physicians, and the government to demand higher quality evidence and fund trials upon which we can advance the clinical science supporting these novel and often expensive therapies. Continued usage of existing and approval of new devices without rigorous data, may lead to harmful and unintended consequences across the spectrum of patients.

This AHA scientific statement is primarily focused on catheter-based strategies to debulk, lyse, or remove thrombus in the pulmonary arteries. However, the acute life limiting threat in pulmonary embolism stems from severe right heart failure leading to an underfilled left ventricle and a subsequent decrease in cardiac output. As such, strategies to improve right ventricular performance are of vital importance in the highest risk patients. This statement does not address the hemodynamic manifestations of severe PE or the possible interventional strategies employed to compensate for the hemodynamic disturbance. Some centers have been using ECMO (extracorporeal membrane oxygenation) with increased frequency in high risk PE patients.¹⁰ Right sided hemodynamic support devices may have limited use as well. We need prospective data and society consensus to guide the use of these technologies in these very high-risk patients. Moreover, all practitioners who participate in the care of high-risk PE patients need to become more facile with the acquisition, interpretation and response to hemodynamic information.

In the meantime, hospitals have organized pulmonary embolism response teams (PERT) to streamline decision making for these difficult patients. It is as yet unknown whether these teams will improve outcomes and decrease costs, but multidisciplinary team-based decision making has been effective in other such high morbidity high mortality illnesses such as myocardial infarction, complex coronary disease, stroke, and aortic stenosis. Certainly, as technologies proliferate, having interventional, surgical, and non-procedural specialists and patient’s role in shared decision making would theoretically yield outcomes that are in the best interests of the patient.

The possibilities to reduce the mortality of pulmonary embolism while minimizing risk using emerging technologies is certainly tantalizing. However, much more data is needed to elucidate the circumstances in which to use the correct technology for the right patient.