Pulmonary embolism response teams: Purpose, evidence for efficacy, and future research directions (2024)

Abstract

Pulmonary embolism (PE) is a major cause of morbidity and mortality in the United States. Although new therapeutic tools and strategies have recently been developed for the diagnosis and treatment of patients with PE, the outcomes for patients who present with massive or high‐risk PE remain dismal. To address this crisis, pulmonary embolism response teams (PERTs) are being created around the world in an effort to immediately and simultaneously engage multiple specialists to determine the best course of action and coordinate the clinical care for patients with acute PE. The scope of this review is to describe the PERT model and purpose, present the structure and organization, examine the available evidence for efficacy and usefulness, and propose future directions for research that is needed to demonstrate the value of PERT and determine if this multidisciplinary approach represents a new standard of care.

Keywords: advanced therapies, catheter‐directed thrombolysis, follow‐up care, multidisciplinary, pulmonary embolism, pulmonary embolism response team

1. INTRODUCTION

Pulmonary embolism (PE) is a major cause of morbidity and mortality.¹, ², ³ In the United States, there are approximately 900000 cases of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and PE, every year. Of those, 150000 to 250000 are PE‐related hospitalizations and 60000 to 100000 deaths, making it the third most common cause of cardiovascular death.⁴, ⁵ The diagnosis and treatment of acute PE can be challenging, as it has a heterogenous range of presentations, from an asymptomatic incidentally identified PE to one that causes hemodynamic instability or even sudden death. Over the past decade, there has been a surge of new therapeutic tools and strategies designed to treat PE patients. Despite these developments, the mortality rate for patients who present with massive or high‐risk PE remains high.⁶, ⁷ Additionally, there is a lack of robust evidence investigating or comparing each strategy as well as current standardized guidelines in the treatment of acute PE. Consequently, treatment decisions are often based on expert opinion, which can be inconsistent and variable. To address this need, multidisciplinary rapid response teams focused on PE have developed across the world. These pulmonary embolism response teams (PERTs) aim to expeditiously engage multiple experts simultaneously to generate a thoughtful, coordinated, and comprehensive treatment plan for each PE patient. Recently, these teams formed the PERT Consortium, an international nonprofit organization, whose goal is to guide and influence PE care. The purpose of this article is to define the PERT concept and purpose, describe the structure and operation, review the evidence for efficacy, and explore future directions for research that is needed to solidify the idea.

2. CASE PRESENTATION

A 64‐year‐old woman presented to the emergency department complaining of 1week of cough and increasing dyspnea on exertion. Her symptoms had progressively worsened in the 24hours before presentation, with associated scant hemoptysis and dull substernal chest pressure. She had a past medical history of hypertension, hypothyroidism, DVT, and PE 8years prior but had been off anticoagulation for the past 6months. On presentation, her vital signs were: temperature 37°C, blood pressure (BP) 109/56mmHg, heart rate 108bpm, respiratory rate 22, and oxygen saturation of 92% on room air. Electrocardiogram showed sinus tachycardia. Labs were remarkable for a troponin of 0.46ng/mL (normal <0.1ng/mL). A contrast‐enhanced chest computed tomography angiogram was ordered (Figure1) which showed a saddle PE with extensive extension into bilateral pulmonary arterial branches and segments, and an enlarged right ventricle. She was immediately started on unfractionated heparin infusion (UFH) and transferred to the intensive care unit (ICU) for closer observation. Although low‐molecular‐weight heparin with its rapid and reliable bioavailability and excellent safety profile was considered, her initial providers preferred UFH, as they believed it allowed for optimal management flexibility, especially since advanced therapies may be considered. On arrival at the ICU, the patient's vital signs were: temperature 36.1°C, BP 136/76mmHg, heart rate 140bpm, respiratory rate 34, and oxygen saturation of 96% on 4‐L nasal cannula. On examination, she appeared to be in mild distress, tachypneic, tachycardic, with clear lungs sounds, and without lower extremity edema. A transthoracic echocardiogram was done promptly on arrival at the ICU (Figure2). It showed severe right ventricular (RV) enlargement with hypokinesis, interventricular septal flattening, and McConnell's sign (RV free wall dysfunction with sparing of apex).

The pulmonary and critical care fellow and attending physician evaluated the patient at the bedside and activated their PERT. After careful review of the patient's presenting history, comorbidities, bleeding risks, imaging, and labs, a multidisciplinary PERT meeting took place via telephone call, via a secure hospital call center. The meeting included members from PERT (fellow and attending), pulmonary and critical care team (fellow and attending), and interventional cardiology (attending) and had a duration of approximately 10minutes. The patient was risk stratified as intermediate–high‐risk (submassive) PE, as she had signs of RV dilation on imaging and positive cardiac biomarkers. A detailed discussion ensued where each member of the team opined on various treatment options, reviewing the risks and benefits for this patient, and proposed a recommendation. Ultimately, a consensus decision was made to perform catheter‐directed thrombolysis (CDT). This plan was decided on and urgently executed given that the patient had an intermediate–high‐risk PE and signs of impending hemodynamic decompensation, based on clinical appearance, increasing heart rate (HR, 108‐140bpm) and escalating supplemental oxygen requirements (O₂ increased from room air to 4‐L nasal cannula), despite a few hours on therapeutic anticoagulation, adequate fluid resuscitation, and no contraindications to thrombolysis. An initial bolus of 1mg of tissue plasminogen activator was given, followed by an infusion at 1mg/h for 12hours via bilateral catheters. UFH infusion was also continued with a low‐intensity protocol targeting an anti‐Xa range of 0.2 to 0.5units/mL. The next morning, her vitals were: temperature 36.5°C, BP 142/82mmHg, heart rate 98bpm, respiratory rate 18, oxygen saturation of 95% on 1‐L nasal canula. She appeared more comfortable and reported feeling better. The catheters were removed, hemoglobin remained stable, and she was transitioned to oral anticoagulation and discharged home on day 4.

3. DEFINITION AND PURPOSE OF PERT

This case illustrates the complexity with which PE patients can present and the urgency with which treatment decisions must be made. Recently, many promising and novel strategies have emerged to treat patients with acute PE. These treatments are wide ranging and include anticoagulation, systemic thrombolysis, CDT, catheter embolectomy, surgical embolectomy, and/or mechanical circulatory support devices. Deciding which therapy is most appropriate for each patient can be challenging. As demonstrated in this case, PERTs can bring together a multidisciplinary group of clinicians with expertise in the diagnosis and management of acute PE who collaborate to improve patient care. PERTs are often called to treat patients who present with submassive or massive PE; however, PERTs may also be helpful in determining the best course of treatment in low‐risk PE patients who have significant comorbidities such as intracranial hemorrhage where anticoagulation may be contraindicated. In the first 30months at Massachusetts General Hospital (MGH), for example, the number of PERT activations for low‐risk PE patients increased over time, which may reflect the value of a multidisciplinary team approach in low‐risk but ill PE patients for whom management decisions are complex.⁸ It is important to emphasize that the initiation of anticoagulation is paramount in the treatment of PE and must not be delayed unless contraindicated. With the emergence of this new approach to treating PE, concurrent management recommendations need to be implemented simultaneously with PERT activations and discussions.

The optimal structure of a PERT remains unknown, and its members vary by institution.⁹, ¹⁰ It may involve critical care, pulmonary medicine, vascular medicine, emergency medicine, interventional and noninterventional cardiology, interventional radiology, vascular surgery, cardiac surgery, hematology, and pharmacy (Figure3). Each member has a crucial role in PERT. The initial steps in acute PE care, such as diagnosis and risk stratification, are often managed by emergency medicine specialists, although acute PE may also be diagnosed after a patient has been admitted. Then, either critical care, pulmonary medicine, vascular medicine, or cardiology provide an initial PERT consultation and gather relevant patient information. Endovascular procedures, such as CDT or catheter embolectomy, if warranted, are usually provided by interventional cardiology or radiology or vascular surgery. If a surgical thrombectomy is indicated, this is done by cardiac surgery. The hematologist on the team can provide expertise in anticoagulation selection and, if appropriate and feasible, duration as well as thrombophilia evaluation, if indicated. Finally, a clinical pharmacist is usually overseeing to ensure that dosing of different drugs, such as thrombolytics and anticoagulants, are appropriate and adequate. Importantly, these roles may vary by sites and country.

The first PERT was created in 2012 at MGH.¹¹ Thereafter, other hospitals formed their own PERTs. Given this rising interest, an inaugural meeting of over 30 institutions, convened on May 21, 2015, in Boston, Massachusetts, and the National PERT Consortium was established; the definition of a PERT was crafted and adopted (Table1).¹² Since this time, the Consortium has become international, with members from Europe, Asia, South America, and Australia. The vision of the PERT Consortium is to guide and influence PE care worldwide. With the goal of multicenter collaboration in education, research, and clinical guidelines, PERT created a framework of committees: Governance, Research, Education, Clinical Practice and Protocols, Development, and Communication. Each committee collaborates to create the infrastructure for advancement of PE care.

4. STRUCTURE AND OPERATION OF PERT

There are many ways to create a PERT and the organization and structure of each one largely depends on the resources of the institution, the interests of its members, and the clinical demands of the community. Because the definition of PERT includes the ability to exercise a full range of medical, surgical, and endovascular therapies, several specialists are often involved in the system. A recent survey of 31 PERT programs found that pulmonary/critical care, interventional cardiology, and emergency medicine are the most commonly involved specialists, followed by cardiac surgery, interventional radiology, noninterventional cardiology, hematology, and vascular medicine.⁹, ¹⁰ Most PERTs have 3 to 5 specialists involved in their program, with 1 having 10 specialists. This survey also demonstrated that the institutional setting and organizational structure of each PERT varies. Although the majority of PERTs surveyed are in academic hospitals (71%), one quarter of the programs are in community hospitals. The size and management of teams also differ and range from a small intimate group to a large inclusive group and from 1 physician in charge of running the team to a steering committee overseeing the entire enterprise, respectively.

Similar to the diverse composition and organization of PERTs, the operation of each PERT differs across programs. Each PERT has an infrastructure that can rapidly identify appropriate patients, activate the team, and assemble necessary resources if advanced interventions are warranted. Often, teams will also arrange for comprehensive follow‐up care. Most programs have the entire multidisciplinary team respond to the initial PERT activation, and a tiered approach whereby a single physician consults on the initial response followed by a multidisciplinary team discussion for complex cases is less often practiced. The way teams communicate also vary. PERT‐specific or individual clinicians’ pagers and telephone alerts are used to notify the point person on the team of a potential patient. Teams then use phone calls, conference calls, or virtual meetings to discuss the case. Occasionally, and if feasible, the patient or a family member is included in those conversations. To date, there are 32 published descriptions or reviews of how various PERTs establish, organize, operate, and/or manage their programs (Table2).⁹, ¹⁰, ¹¹, ¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹, ²², ²³, ²⁴, ²⁵, ²⁶, ²⁷, ²⁸, ²⁹, ³⁰, ³¹, ³², ³³, ³⁴, ³⁵, ³⁶, ³⁷, ³⁸, ³⁹, ⁴⁰ To identify published studies on PERT, we conducted a systematic search of the literature for publications in MEDLINE and EMBASE from inception to November 2018 using the following search strategy: (pulmonary) and (embolism) and (response) and (team or teams) or (PERT) or (PERTs). Articles were eligible for inclusion if the primary focus of the report was a description or review of PERTs. In total, we reviewed 68 published papers, and 32 were selected for inclusion.

As an example, to activate the PERT at MGH, any referring medical provider from either inside the hospital or an outside institution can call a 24‐hour/7‐days‐a‐week telephone number with the last 4 digits being PERT (7378). This call is then sent to the PERT fellow, who gathers pertinent information about the patient to help determine the severity of the PE (Figure4). The fellow and attending physician of record will decide if the case warrants activation of the entire multidisciplinary team. If the whole team is needed, a page and email are sent to each specialist with a link to a web‐based virtual electronic meeting. During that meeting, the fellow outlines the patient's clinical course, and the team discusses various available diagnostic and treatment options. During that discourse, the team generates recommendations and then assembles the appropriate resources to carry out those recommendations, especially if advanced therapies are felt to be warranted. On discharge, patients are scheduled in a multidisciplinary follow‐up clinic to help bridge the gap between the patient's in‐hospital stay and their outpatient follow‐up care. During the follow‐up clinic visit, many issues can be addressed, including further inquiry into the cause of the PE, thrombophilia testing if appropriate, age‐appropriate cancer screening, anticoagulation management, scheduling removal of an inferior vena cava (IVC) filter if placed, and screening for long‐term PE complications such as pulmonary hypertension, post‐PE syndrome, and chronic thromboembolic pulmonary hypertension. An essential feature of each PERT is the ability to include nontraditional PERT members when necessary, such as an obstetrician for pregnant patients or a neurosurgeon for patients with intracranial hemorrhage. Creating an infrastructure that can accommodate all the various aspects of each PERT is critical for its success.

5. EVIDENCE FOR EFFICACY OF PERT

Most patients with PE are successfully treated with anticoagulation alone, and many will have no lasting consequences.⁴¹ However, there is a subset of patients at increased risk of rapid hemodynamic decompensation. Guidelines have been developed to help identify patients at risk for short‐term mortality and clinical deterioration. The American College of Chest Physicians,⁴² American Heart Association (AHA),⁴³ and the European Society of Cardiology (ESC)⁴⁴ recommend advanced therapy (other than anticoagulation alone) for patients with acute PE and sustained hypotension, classifying them as having massive PE (AHA) or at high risk (ESC); massive PE patients represent 5% of the PE population and have a 58% mortality risk.⁴⁵ However, the appropriate management is less clear for normotensive patients with evidence of RV dysfunction and/or elevated cardiac biomarkers. These patients are classified as having submassive PE (AHA) or at intermediate risk (ESC); submassive PE patients represent 25% to 40% of the PE population with a mortality risk ranging from 2% to 3% to 21% at 3months.⁴⁵, ⁴⁶ Both the AHA and ESC defer management to clinical judgment in patients with a submassive/intermediate‐risk PE, a decision that is not straightforward given patient complexity and potential risks of advanced therapy. To this end, PERTs may provide the necessary clinical expertise.

Survivors of acute PE are also at risk for lasting adverse effects.⁴⁷, ⁴⁸ In a recent prospective cohort study, almost half of PE patients have exercise limitation at 1year, defined by percent‐predicted VO_2max <80% on cardiopulmonary exercise testing, which influences their quality of life and degree of dyspnea.⁴⁹, ⁵⁰ Other cohort studies evaluating the degree of functional impairment following acute PE found that 45% to 52% of surviving patients exhibit a New York Heart Association heart failure score of ≥2 at 6months to 3years of follow‐up.⁵¹, ⁵², ⁵³ It is believed that the elevated RV and pulmonary arterial pressures caused by occlusive thrombus cause cardiovascular damage and subsequent maladaptive remodeling, decreasing the ability to adapt to exercise. It has been postulated that the rapid unloading of the right ventricle and increased thrombus clearance through advanced therapy may help prevent such remodeling. The limited evidence has so far been inconsistent. Data from the MOPETT (Moderate Pulmonary Embolism Treated With Thrombolysis) trial showed significant immediate reduction in pulmonary arterial pressure that was maintained at 28months’ follow‐up in PE patients receiving thrombolytic therapy vs. anticoagulation only.⁵⁴ However, data from the PEITHO (Pulmonary Embolism International Thrombolysis Study) trial showed that thrombolytic treatment did not affect long‐term mortality rates, residual dyspnea, or RV dysfunction vs. anticoagulation alone.⁴¹

Data from a recent multicenter registry indicate that management of acute PE remains poorly standardized, and advanced therapy (other than anticoagulation alone) is underutilized. Only 2% of all patients with PE and 9% of patients with massive PE are treated with thrombolysis.³ The PERT model aims to streamline the care of patients with PE and, in particular, expeditiously identify patients with massive (high‐risk) or submassive (intermediate‐risk) PE who may benefit from advanced therapies and initiate and coordinate appropriate treatment.

It remains to be determined whether the PERT approach leads to improved survival, reduces long‐term complications, or is cost‐effective. PERT is still a novel concept. As such, there are no randomized controlled trial data or robust clinical evidence evaluating the PERT approach, though efforts are under way to bridge this gap.⁵⁵ Current available data from 12 prospective and retrospective studies are summarized in Table3.⁸, ⁵⁶, ⁵⁷, ⁵⁸, ⁵⁹, ⁶⁰, ⁶¹, ⁶², ⁶³, ⁶⁴, ⁶⁵, ⁶⁶ To identify these published studies on PERT, we conducted a similar systematic search of the literature as we did for Table2. Articles were eligible for inclusion if the primary focus of the report was a prospective or retrospective study involving PERTs. In total, we reviewed 68 published papers, and 12 were selected for inclusion.

Preliminary results from early adopters suggest that PERT facilitates access to advanced therapies. An interrupted time series analysis demonstrates an increase in the proportion of PE patients undergoing any advanced therapy, from 9% to 19%, after the introduction of PERT.⁶⁵ This increase is largely attributed to greater utilization of CDT, which grew from 1% to 14%, and reports from other PERT institutions show similar use of CDT.⁸, ⁵⁸, ⁶³, ⁶⁶ Possible reasons for the increase in CDT cases include (1) greater awareness and recognition of severe PE, (2) inclusion of interventional specialties in the management of PE, (3) evidence from the PEITHO trial that systemic thrombolysis prevents hemodynamic decompensation in intermediate‐risk PE,⁴⁶ and (4) the perception that CDT causes less bleeding than systemic thrombolysis.⁶⁷ The increased use of advanced therapies did not seem to result in increased major bleeding or mortality in these series.⁶⁵, ⁶⁶ This may be due to continued improvements in catheter technology and technique, more stringent monitoring of patients receiving thrombolytic therapy, or improved protocols. However, the sample sizes in these studies may not have been large enough to accurately describe CDT's bleeding risk.

As a consult service, PERT has been well received by adopting institutions. Several institutions report increasing numbers of PERT activations over time after implementation,⁸, ⁵⁸, ⁶⁵, ⁶⁶ which may be an indirect measure of success. PERTs are readily activated and respond rapidly irrespective of the time of day; an analysis of 457 PERT activations comparing daytime vs. nighttime activations showed no significant difference in the median time to intervention, rate of intervention within 24hours after activation, or 30‐day mortality.⁶⁴ Providers value the expedited and individually tailored treatment plans formed by the consensus of expert opinion. The majority (89%) of surveyed trainee physicians at a large PERT institution believe that a multidisciplinary team improves the care of patients with high‐risk PE, and 71% favor broad implementation of PERT.⁶⁰

6. FUTURE DIRECTIONS FOR RESEARCH

While the growth of the PERT model has been exponential, and numerous manuscripts have been published describing the development of similar teams (Tables2 and ​and3),3), objective evidence confirming the effectiveness of the approach is still limited. Most of the research studies published to date are descriptive in nature.⁸, ⁶³, ⁶⁶ While these studies have been helpful in describing the PERT model and expected effect of implementation, several key questions remain to be answered. The most important of these are (1) do advanced therapies provided by PERTs improve clinical outcomes? and (2) does the multidisciplinary decision‐making process integral to the PERT approach change clinical care in a positive way? Future research should be directed toward answering these questions. In addition, work is required to show that the PERT approach is cost‐effective and consistent across centers.

7. CONCLUSION

The PERT is a novel team‐approach program with the purpose of providing better and more coordinated care to acute PE patients by facilitating rapid consultation and expert consensus with a multitude of experienced specialists. PERT streamlines interdisciplinary communication, obtains consensus in patient care, and organizes and mobilizes resources to execute the agreed‐upon plan. Thus far, numerous descriptive and retrospective studies demonstrate that it is feasible to create such a multidisciplinary team and that there are many ways to establish a PERT. The formation of the PERT Consortium is a venue through which these teams together can collect data that can help inform treatment decisions, influence guidelines and algorithms, guide hospital policy, and shape future research in PE care. This additional evidence will help evaluate the value of this innovative model and determine if this collaborative approach improves PE outcomes, changes clinical care in a positive way, is cost‐effective, enriches patients’ quality of life, and advances the science of PE treatment.

RELATIONSHIP DISCLOSURE

RR is an institutional research grant recipient from Janssen Pharmaceuticals and Bristol Meyer Squibb and is a consultant to Portola and Bristol Meyer Squibb and Janssen. BRL is an institutional grant recipient from Actelion and a consultant to Bayer and Gilead. CK is an institutional grant recipient from Diagnostica Stago, Siemens Healthcare, and Janssen Pharmaceuticals and is a consultant to Bristol Meyer Squibb. KZ and AS report nothing to disclose.

AUTHOR CONTRIBUTIONS

All authors contributed to the writing and editing of the manuscript. RR takes responsibility for the integrity and accuracy of the data. Concept and design: RR; acquisition, analysis, or interpretation of data: RR, KZ, AS, BRL, and CK; drafting of the manuscript: RR, KZ, AS, BRL, and CK; critical revision of the manuscript for important intellectual content: RR, KZ, AS, BRL, and CK; final approval of the manuscript: RR, KZ, AS, BRL, and CK.

ACKNOWLEDGMENTS

Notes

Rosovsky R, Zhao K, Sista A, Rivera‐Lebron B, Kabrhel C. Pulmonary embolism response teams: Purpose, evidence for efficacy, and future research directions. Res Pract Thromb Haemost. 2019;3:315–330. 10.1002/rth2.12216 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

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