The role of the PERT in the management and therapeutic decision-making in pulmonary embolism

Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality with comparatively limited research into advanced treatment modalities by contrast to stroke and acute myocardial infarction.1,2 Over recent years, numerous mechanical and pharmacomechanical approaches have become available in the PE management arsenal to offer rapid reperfusion while mitigating risks associated with systemic thrombolysis.1,3,4 Data exploring endovascular therapies are limited to small, generally single-arm studies focused on intermediate-risk PE with efficacy defined by surrogate endpoints.1,4 How best to select candidates for advanced therapeutic modalities remains elusive and often deferred to clinical judgement.5,6 An amalgam of the heart team and rapid response system concept, the PE response team (PERT) brings together a multidisciplinary group of clinicians with assorted expertise in PE care to collaborate surrounding risk stratification, rapid treatment, follow up, and quality improvement.7,8 The real-time cross-specialty collaboration is most applicable to intermediate-risk PE, a heterogenous group with select patients potentially deriving benefit from rapid reperfusion.1,6 As certain markers of risk are not captured in current stratification schemes, and paucity of data creates equipoise, a team approach allows for nuanced decision-making.2,8 With therapeutic options for high-risk PE expanding beyond systemic thrombolytics and surgical embolectomy, PERTs may be instrumental in navigating alternative approaches and mobilizing procedural services. The PERT model is endorsed by professional societies and is instrumental in the aforementioned settings as well as in scenarios of therapeutic uncertainty.5,6 The first PERT was formed in 2012 at the Massachusetts General Hospital with other centres subsequently adopting a similar model; 3 years later, the National PERT Consortium was established.8 Presently, there are over 150 institutions with PERTs worldwide.9 Team structure varies by site and involves an average of three to five specialists with pulmonary/critical care, interventional cardiology, and emergency medicine most often represented.8,9 When activated, a full multidisciplinary team commonly responds by contrast to a tiered approach with initial single physician consultation implemented at some hospitals.7 Beyond rapid risk assessment and therapeutic decision-making, PERT follow-up clinics can screen for long-term complications such as chronic thromboembolic pulmonary hypertension, and guide duration of anticoagulation therapy.10 The National PERT Consortium aims to influence PE management and research worldwide with multispecialty consensus documents providing a framework for PE care.6 In contrast to angioplasty for acute myocardial infarction, standard of care for decades, interventional therapies for PE are in their infancy.3 Studies have shown the increased use of catheter based, and other advanced therapies, with the implementation of PERTs.10 However, implications with respect to improved clinical outcomes are debated.8,10 Intermediate-risk PE represents 25–40% of all cases and carries a short-term mortality of under 5%.8 Yet PE severity falls on a continuum even within this category; approximately 10% of intermediate-risk patients will experience haemodynamic deterioration. Accordingly, endovascular therapies may be most appropriate for a subset of patients. Those with high-risk PE and contraindications to systemic fibrinolytics additionally represent a niche population most suited for percutaneous embolectomy. Interventional therapies for PE aim to rapidly decrease thrombus burden either via catheter-directed thrombolysis (CDT) or percutaneous embolectomy.1,4 Promptly reversing haemodynamic derangement, or mitigating the risk thereof, serves as the rationale behind such approaches. The theoretical advantage of CDT is the infusion of thrombolytics directly into the thrombus; thrombolytic doses administered are approximately a quarter of the usual systemic doses.1 The ULTrasound Accelerated ThrombolysIs of PulMonary Embolism (ULTIMA) trial was the first to compare anticoagulation alone to ultrasound-assisted CDT among intermediate-risk patients. At 24 h, those randomized to CDT had reduced right ventricular (RV) dilatation as the primary outcome.1,11 Subsequent studies evaluating CDT were single-arm trials demonstrating improvement in RV dilatation or pulmonary pressures with good safety profiles.1,4 Multiple devices allow for percutaneous embolectomy using manual suction or thrombus maceration obviating the need for any thrombolytic administration. Beyond risks associated with fibrinolytics, partially fibrotic thrombi characteristic in some patients may not be as amenable to lysis. Similar to CDT, studies involving percutaneous embolectomy have focused on surrogate outcomes.1,3,4 Currently, no study supports short-term mortality benefit nor reduction in long-term consequences with the use of interventional therapies. Navigating the available evidence and matching the patient to the best treatment is well suited for a multispecialty forum that may reduce individual biases and potential conflicts of interest.1,8 In the absence of robust data, cumulative experience and expertise are integral to patient care. This issue of the European Heart Journal: Acute Cardiovascular Care features two manuscripts focused on interventional therapies in PE—one addresses procedural approaches while the other, systems of care. Fengler et al.12 retrospectively compared 10 patients undergoing isolated catheter-directed therapy with 11 treated with combined catheter-directed fibrinolysis and thrombectomy (CCDT). The authors demonstrated significantly greater relative reduction in RV/LV ratio among those undergoing CCDT. The theoretical advantage of catheter embolectomy addressing partially fibrotic proximal clots with fibrinolysis targeting thrombotic material in smaller vessels may serve as the explanation behind the observed results. While limited by sample size and imbalanced groups, the study is hypothesis generating. Plausibly, CDT may follow percutaneous embolectomy if desired haemodynamic, or gas exchange goals are not met. Given the paucity of high-quality data on interventional therapies in PE, it is unlikely that these two approaches will be compared in a large randomized trial with respect to important clinical outcomes in the near future. Accordingly, the PERT can navigate the risk–benefit profile of this sequential approach determining optimal haemodynamic endpoints for the individual patient. Using the Nationwide Readmission Database, Sedhom et al.13 identified approximately 1.4 million PE admissions over a 3-year span with 2.6% undergoing catheter-based interventions. The authors found an inverse relationship between hospital procedural volume and in-hospital mortality, length of stay, and cost among patients undergoing interventional therapies. These results are in accord with studies demonstrating a similar relationship between procedural volume and outcomes in different arenas. The authors suggest that the implementation of PERT at high-volume centres may partially account for this relationship. Specifically, the PERT may allow for rapid risk stratification and selection of individuals most appropriate for interventional therapies. Prior reports have demonstrated a relationship between PERT implementation and improved mortality, though inconsistently.2,8 How best to manage patients at low-volume centres with limited experience in endovascular therapies may be the subject of future guidelines. Taken together, both manuscripts in this issue highlight meaningful roles of the PERT; selection of specific interventional approaches; as well as the patients most likely to benefit from a procedure. The future of PE care rests on high-quality data informing refined risk stratification and assessment of treatment modalities. Novel markers of risk, such as the echocardiographic stroke distance, have been described and may be added to current clinical criteria.14 With respect to randomized data, the HI-PEITHO trial is underway to compare an approach of ultrasound-assisted CDT plus anticoagulation, vs. anticoagulation alone among patients with intermediate-risk PE and additional criteria indicating elevated risk for haemodynamic collapse.15 While the primary outcomes of HI-PEITHO are centreed around short-term events, a recently NIH/NHLBI-funded trial, PE-TRACT, is powered to detect differences in long-term outcomes of this disease among patients randomized to a similar approach. Additionally, PE-TRACT seeks to define novel risk factors for the development of long-term disability and to refine our approach to risk stratification. As the aforementioned studies aim to compare interventional approaches to anticoagulation, the recently launched PEERLESS trial is designed to compare two different interventional strategies. In this study sponsored by Inari Medical Inc. (Irvine, CA, USA), intermediate high-risk patients with PE will be randomized to treatment with CDT vs. percutaneous embolectomy with the FlowTriever device (Inari Medical, Irvine, CA, USA). Over the next few years, we are excited to gain further clarity into this disease and to better justify our therapeutic approaches. In parallel to the randomized trials, the National PERT Consortium houses a database to explore contemporary practices in PE care with over 4000 patients enrolled. In addition to research, the database serves as a feedback mechanism to institutions informing quality and metrics. Since its inception in 2012, the PERT model has become the mainstay of PE care at many centres. Contemporaneously, advanced treatment options have evolved at an exceptional pace. While we gather experience with endovascular therapies, we eagerly await Level I evidence to inform our practices.