Coalition of the Willing: PERTs Aim to Disentangle ‘Gordian Knot’ of Acute Pulmonary Embolism

An attorney in her mid-thirties, 26-weeks pregnant, collapsed in her kitchen due to a massive pulmonary embolism (PE). After having an emergency cesarean delivery at a local hospital she was transferred to a tertiary center outside of Boston for a lifesaving pulmonary embolectomy, then transferred again to Massachusetts General Hospital, which could handle long-term extracorporeal membrane oxygen (ECMO) support for her right ventricular dysfunction. The ECMO circuit failed to work, but following surgery for abdominal cavity bleeding, the ECMO began to function.

More than 100 units of blood and a multiweek hospital stay later, the patient’s right ventricle recovered and ECMO was discontinued. And now, several years after the fact, the patient—and her daughter born during the ordeal—are doing well.

That experience was the tipping point for Mass General interventional cardiologist Kenneth Rosenfield, MD. “It’s an amazing story of medicine, of coordinated care, and of working together amongst specialties to bring life back to a person who was clearly going to die,” he said. Rosenfield was brought in to help with the follow-up cardiovascular care of that patient. “The reason for the save was the fact that we did this working together in collaboration, and we really brought to this patient a much better result and outcome as a consequence of our collaboration as multiple specialties,” he explained.

That case—though an extreme example—served as the inspiration for the PE response team (PERT) concept, which aims to provide a rapid response to acute PE similar to those that are well established for MI and stroke. In 2012, Rosenfield and a handful of colleagues from various specialties involved in treating acute PE held a meeting at which Richard Channick, MD, a pulmonary/critical care physician at Mass General, coined the term PERT.

Now numbering about 40 people, the PERT team at Mass General—a “coalition of the willing” who do not get paid for their participation in the effort, according to Rosenfield—gets alerts 24/7 by email and pager when a PERT activation comes through. Available members then connect by video conference to review test results, discuss the case, and select the best treatment approach.

“While [the team members are] not getting paid for it, they get a great sense of satisfaction that we’re actually treating patients in the optimal way possible,” Rosenfield said.

The idea has taken hold across the United States and in some places abroad, where hospital systems are organizing teams to tackle acute PE, the third leading cause of cardiovascular mortality. The effort is seen as a way to reduce variability in care for this condition, improve the selection of therapies, and—it is hoped—improve patient outcomes.

Still, potential criticisms exist, as many of the interventions being administered by PERTs lack supporting clinical trial evidence and it remains unclear whether such a coordinated effort is warranted in many cases and will make a difference in overall outcomes.

‘Amazingly Underserved’

Although there are guidelines for treating patients with acute PE, there are major areas of uncertainty, particularly for the 40% to 45% of patients with intermediate-risk (submassive) PE. That uncertainty leads to a high degree of variation in how acute PE is treated. Although physicians from different specialties had already been collaborating to treat acute PE, PERTs make the arrangement more organized.

The teams are not the same at every center but contain a mix of specialists from cardiology, emergency medicine, hematology, pulmonary/critical care, surgery, radiology, and vascular medicine. A recently published research letter in CHEST showed that the most common specialties involved are pulmonary/critical care (in 84% of PERTs), interventional cardiology (79%), and emergency medicine (63%).

Wissam Jaber, MD (Emory Heart & Vascular Center, Atlanta, GA), a member of one of the earliest PERTs, said the teams mostly consist of physicians, although nurse practitioners will sometimes see patients and pharmacists will help with dosing of lytic medications.

Jay Giri, MD, MPH (Hospital of the University of Pennsylvania, Philadelphia), who helped set up the initial PERT at Mass General when he was a fellow, said the main benefits of the effort include the gathering of clinicians who are most interested in and knowledgeable about acute PE, the creation of protocols to establish best practices and diminish variability in care, and the ability to quickly mobilize more advanced therapies when needed.

Anecdotally, he said, there are probably more than 100 PERTs in the United States as of now, with some starting up internationally.

When asked by TCTMD whether the rapid spread of PERTs over about 5 years is justified, Josh Beckman, MD (Vanderbilt University, Nashville, TN), a vascular medicine specialist, said: “When you recognize that pulmonary embolism is the third most common cause of death from cardiovascular disease, it suddenly puts into perspective that we probably haven’t been paying quite enough attention.”

Bringing together these multidisciplinary teams and putting the spotlight on the issue is important in defining the best ways to treat these patients and laying the groundwork for clinical trials to address areas of uncertainty, he said.

Doctors are coming to realize that it’s not appropriate anymore to be a single-person shop. Josh Beckman

The PERT movement is a good example of what’s happening more generally in complicated disease, Beckman added. “If you take a look around medicine now, as we’re trying to figure out how to provide value-based care in general, doctors are coming to realize that it’s not appropriate anymore to be a single-person shop, that really the best care for patients occurs when physicians, particularly those who have different backgrounds and different perspectives, come together to try and provide care to an individual,” he said.

PERT programs have some similarities to the systems set up around ACS or stroke in that they are designed to speed the delivery of effective treatments, but there are major differences, Rosenfield said.

First, there are relatively few specialties involved in treating acute MI or stroke and the systems set up to handle them are well defined and evidence based, he said. With acute PE, however, “it’s a lot messier,” Rosenfield said, pointing out that patients can present in numerous different settings—various parts of the hospital in about half and outside of the hospital in the other half—and receive treatment from physicians of many disparate specialties.

Second, identification of acute PE can be tricky, he said, with often subtle symptoms including tiredness, shortness of breath, and tachycardia; chest pain may or may not be present.

“It’s often called the ‘great masquerader,’ because it masquerades as many other entities,” Rosenfield noted.

Third, and perhaps most importantly, the evidence base for acute PE therapies is not as strong as for ACS or stroke, with ill-defined treatment algorithms, he said.

“In spite of its prevalence and impact on patients, it’s really amazingly underserved right now,” Rosenfield said.

Uncertainty in Intermediate-Risk Patients

Soophia Naydenov, MD (Saint Louis University, MO), a critical care pulmonologist, told TCTMD that even though there are guidelines for treating acute PE, they are vague, leading to a high degree of variability in treatment depending on where patients are in the hospital and who is treating them. That’s why it’s useful to have a team approach when selecting the right strategy, particularly in the intermediate-risk patients, she said.

Roughly half of patients with acute PE are at low risk and typically receive anticoagulation, Naydenov said. Another 5% present with massive PE, which carries a very high risk of mortality. Guidelines recommend treating those patients with systemic thrombolysis, but in the presence of contraindications, endovascular approaches can be considered, she advised.

It’s often called the ‘great masquerader,’ because it masquerades as many other entities. Kenneth Rosenfield

The remaining patients with submassive PE have an intermediate level of risk, and the appropriate treatment in this group remains uncertain and an area of active investigation. Various approaches can be considered, ranging from anticoagulation, systemic thrombolysis, and surgical embolectomy to newer catheter-based techniques. One of the most commonly used endovascular therapies is ultrasound-assisted catheter-directed thrombolysis, but there still has not been a definitive study proving its benefit compared with anticoagulation or systemic thrombolysis.

Other interventions currently being evaluated for acute PE include pharmacomechanical lysis and thrombectomy with various devices, including AngioVac (AngioDynamics), FlowTriever (Inari Medical), AngioJet (Boston Scientific), and Indigo (Penumbra). Use of those devices for acute PE is in various stages of evaluation, but there is a renewed enthusiasm for looking at these therapies, said Rosenfield, who is co-chair of the FLARE trial evaluating the FlowTriever.

Criticisms of PERTs

One of the potential criticisms of PERTs is that there is no proof that many of the interventions being deployed are improving outcomes, said Jaber, who recently published a paper highlighting the “paucity of data to support widespread adoption of such techniques.”

But he likened the situation to the early days of interventional cardiology when there wasn’t solid evidence to support the new procedures being done at that time for coronary disease. By doing them in the absence of definitive data, the field was able to develop expertise that allowed for the conduct of randomized trials to confirm or refute early signs of benefit, he said, and something similar can occur with acute PE.

Another potential criticism, according to Giri, is that all acute PEs are eventually to be treated like acute MI or stroke when such an effort is not needed in all cases. His response to that concern is that the teams have been designed to ensure that that does not happen and that all patients receive only the treatment that is required based on the severity of their condition. Not every patient will be rushed to receive a procedure, he said, “but if you have this structure in place, when the patients are really in need of these advanced therapies, they can be rapidly mobilized.”

Another issue that has been raised, Giri said, is whether PERTs, in general, are going to improve outcomes for patients. “Are they really going to do that, or are they really just serving as a way to increase business and procedural volume?” he asked, noting that proceduralists—typically cardiologists but sometimes radiologists—seem to be driving the development of PERTs.

The counter to that potential concern is that PERTs are designed to have heavy involvement from noninvasive physicians, who likely do not have the same incentives to push for a procedure, Giri said. He pointed to the fact that the most common specialty represented on PERTs is pulmonary/critical care medicine.

Beckman said that it is logical and reasonable for interventionalists to want to identify patients in whom their procedures can have a benefit.

“I think that the most important part of PERT is creating a pathway for the care of these patients where experts who do not do interventions generally figure out whether or not someone needs intervention,” he said. “And I think it actually works a lot better in that when you put people of all different stripes on a team, you get much broader decision-making rather than having an interventionalist come see the patient and decide to do their intervention.”

He said the PERT structure might actually limit the number of procedures done in patients with acute PE. “The more that something is organized and tracked, the more self-censoring occurs to avoid the appearance of bad outcomes,” he said.

Rosenfield said that interventional cardiologists are not pushing to use procedures when they’re not warranted, saying that most patients still receive anticoagulation alone. A report on the initial 30-month experience with Mass General’s PERT showed that anticoagulation alone was used in 69% of patients, with systemic or catheter-directed thrombolysis used in 11%.

“We don’t aggressively pursue things unless we think it’s the right thing to do,” Rosenfield said, adding that interventionalists bring more than just catheter skills to the discussion.

“It’s not just a matter of being able to do procedures,” Rosenfield explained. “It’s a matter of understanding what you can accomplish with those procedures, what the outcomes to expect are, when to do them and when not to do them, when to stop, and how to measure the outcomes. All of those things are critically important for the interventionalist who wishes to become a player in PE.”

Beckman, who is not an interventionalist, noted that “in the absence of large clinical trials we do what we’ve always done, which is try and understand the physiology, apply our understanding to the patient, and give the lowest-risk therapies that we think are necessary to get the best outcome.” He added that catheter-based therapies probably represent the next advance for the field, though that remains to be proven.

Endovascular treatment “has its role, but you have to be careful and keep a balance and pick the patients very carefully to receive a benefit,” Naydenov commented.

National PERT Consortium

In part because of the need to answer some questions about the effectiveness of various therapies in acute PE—and the PERT concept more generally—and in part because of the overwhelming interest generated by the PERTs at Mass General and other early adopters, Rosenfield and his colleagues decided to create the National PERT Consortium.

“We recognized that this was an opportunity to finally unravel the Gordian knot of pulmonary embolism and try to figure it out,” Rosenfield said.

The consortium consists of centers that will collect data as part of a registry that can be mined for information to guide better treatment decisions, and it represents an opportunity to create a research agenda to explore new and existing therapies in a prospective fashion and fill in knowledge gaps about acute PE, including the potential long-term consequences even after successful treatment, he said. Currently, nearly 70 centers are participating.

It will be essential, Beckman noted, to first identify the most important outcomes to collect in patients with acute PE and standardize collection of those data. Once that is worked out, then researchers can focus on conducting studies that will provide information to improve patient outcomes, he said.

Rosenfield and other leaders of the consortium organized an initial meeting in Boston in May 2015, when more than 80 people representing about 40 centers showed up. At that meeting, committees were organized in five areas: research, education, clinical practice and protocols, communications, and governance. The second annual meeting in June 2016 drew more than 140 people from nearly 80 centers, and the third such meeting is scheduled for June 2017.

Rosenfield said that centers interested in joining the consortium—who can contact him or the acting executive director, Michelle Lanno, directly—must meet certain requirements. The PERT needs to have physicians from at least two different disciplines making active decisions about patients with acute PE in a rapid response-type fashion, and the center must have an interest in collecting data and working with the consortium. There are also dues that must be paid and entitle professional members to attend the consortium’s meeting and participate in its activities.

“I want the world to know that this initiative has been enormously successful,” Rosenfield said. “What’s really fun about this entity is working together with colleagues from other disciplines. That has been really fun and really inspiring.”