Birth of PERT: Systematic Approach to Acute PE
Due to a lack of clarity and uniformity in how to proceed with vulnerable massive and submassive pulmonary embolism, one Boston provider is taking steps to standardize care across specialties in lieu of guidelines, as well as accrue data to develop a better evidence base for more informed decisions in the future.


Pulmonary embolism (PE)—the sudden blockage of an artery in the lung—and deep vein thrombosis (DVT)—a blood clot generally occurring in the legs—constitute the two categories of venous thromboembolism (VTE). Acute PE can occur rapidly and unpredictably. Approximately 150,000 U.S. patients per year are diagnosed with acute PE, resulting in thousands of deaths annually from massive PE (Arch Intern Med 2003;163:1213-1219). The estimated annual incidence of PE is 23 to 69 cases per 100,000 persons with hospitalizations resulting in 676,700 inpatient days (Vital Health Stat 13 2005;(158):1-199).

However, these patients first must be diagnosed before they can be treated, which is particularly important in a population that has a mortality rate as high as 25 to 30 percent if left untreated (Arch Intern Med 2001;161[1]:92-97). This rate has resulted in its reputation as a “silent killer,” causing more than 100,000 U.S. deaths each year, estimates the American College of Cardiology (ACC).

“PE is not immediately recognizable through a clear set of symptoms, so even experienced medical personnel don’t always identify it as the potential diagnosis,” says Kenneth Rosenfield, MD, section head for vascular medicine and intervention within the cardiology department at Massachusetts General Hospital (MGH) in Boston. “Also, the signs are subtle; thus, it is often referred to as ‘the great masquerader,’ since it may mimic many other illnesses.”

The most common symptoms are shortness of breath, chest pain and a cough (that may produce bloody sputum), sweating and lightheadedness or fainting. Other signs can include wheezing, leg swelling (typically in one leg only), clammy or bluish-colored skin, rapid or irregular heartbeat and weak pulse. These symptoms can easily be confused and diagnosed as another condition.

Another challenge to standardizing care for the appropriate diagnosis and treatment of acute PE is that no one specialty “owns” this disease state. What compounds this problem is that PE can present in a multitude of venues—intraoperatively, post-operatively or when the patient presents to the emergency room (ER). “There are multiple specialists, including in trauma, orthopedics, gynecology, surgery, cardiology and cardiac surgery, pulmonary, and hematology, who all approach this disease differently and see it from their own perspective,” says Rosenfield.  

Michael R. Jaff, DO, medical director of the vascular center at MGH, adds, “Internists like me who don’t perform procedures might consider medical therapy the appropriate first step, whereas cardiac surgeons who have been trained to perform acute pulmonary thromboendarterectomy or embolectomy might go with that first.” He adds that patients who present with submassive PE “don’t look so bad, particularly when they are lying down. It has a lot to do it with how patients present and how sick they actually look.”

One final challenge is the discrepancy of care depending on which specialist accepts responsibility for a patient because there is no defined algorithm to optimally treat him or her. “PE has been treated in an unstructured, disparate manner,” says Joshua N. Baker, MD, cardiac surgeon at MGH.

PERT Protocol: Pulmonary Embolism Response Team Activation (PERT)
1. Large Pulmonary Embolus?
For example:
- PE with abnormal vital signs (tachycardia or hypotension)
- Evidence of right heart strain (echo, EKG or positive biomarkers)
- Central or Saddle PE
2. Call x4-4 PERT (4-7378)
To activate the PERT
3. Please Order: (unless already done)
- Stat Echocardiogram
- CBC, PT/PTT, Creatinine
- Troponin, NT, and NT-proBNP
- Type and Screen
PERT: A multidisciplinary team to coordinate and expedite appropriate treatment of pulmonary embolus
Jaff chalks up some of the disparity in care delivery to the plethora of “very confusing” literature. For instance, he says it’s unclear whether intervention offers any real advantage over standard anticoagulation for submassive PE. He adds that the literature is lacking because of the paucity of controlled studies; furthermore, many published studies were sponsored by industry, with companies trying to get their drug or device approved, resulting in a limited scope in the studies.

Filling the gap

The biggest question lies in how to treat the moderate-risk patients with PE. “At the extremes, we know the answer. We know if a patient is dying from a massive PE and is a surgical candidate, then he or she should go to the operating room,” explains Rosenfield. “Likewise, if a patient has a very minor pulmonary embolus, you could treat him or her with heparin and convert to home-based systemic anticoagulation for six months.”

The confusion lies with the majority of PE patients who fall in the middle—those with moderately large or submassive PE. “In these patients, we don’t really have any evidence-based guidelines to say what is the optimal therapy,” Rosenfield adds. “And there are many options from which to choose, including heparin alone, systemic lysis, catheter-directed lysis, suction catheter or Vortex thrombectomy and open surgical removal of the clot.”

At the 2012 ACC annual meeting, there were two late-breaking clinical trials that addressed the ongoing debate for the medication management of PE patients. First, EINSTEIN-PE is one of a series of international phase III trials of the anticoagulant rivaroxaban (Xarelto, Bayer HealthCare/Janssen Pharmaceuticals) to treat VTE or prevent a recurrence in patients with acute PE or DVT. This study, conducted at 263 sites in 38 countries, randomized 2,419 patients to rivaroxaban and 2,414 to enoxaparin (Lovenox, Sanofi-Aventis). The researchers found that a first symptomatic recurrent VTE event occurred in 2.1 percent of patients on rivaroxaban compared with 1.8 percent on enoxaparin. Bleeding occurred in 10.3 percent of patients on rivaroxaban compared with 11.4 percent on enoxaparin. At the meeting, panelists noted the reduction in bleeding, despite the trial’s noninferior findings.

Some of the new direct factor Xa inhibitors and oral antiplatelet agents may have an impact on smaller pulmonary emboli that don’t result in hemodynamic effects or echocardiographic, biomarker impacts, according to Jaff. “For smaller pulmonary emboli, some of these new agents might actually make a difference, but for submassive and massive PE, decisions will still largely be made in the hospital for these sick patients who either need observation or aggressive treatment.”

Second, MOPPET, a study of 121 randomized patients indicated that a half-dose of thrombolytic—about half the standard dose of tissue plasminogen activator (tPA) conventionally used—showed promise as an acute treatment for moderate PE. Lead author Seyed Mohsen Sharifi, MD, of Arizona Cardiovascular Consultants in Mesa, Ariz., said that “80 percent, or more, of pulmonary embolism patients would benefit from this treatment.” At the trial’s presentation, Sharifi also defended the lower dose over the usual doses of thrombolytic tPA for those patients with large but stable PE who present to the ER.

“Most clinicians will likely rely upon tPA unless it’s a very small PE,” says Jaff. “For those people who are sick enough to require more than standard anticoagulation, but not large enough to go to the cath lab or operating room, then tPA is going to be fairly standard.”

There also are a host of device options that do not have clear utilization strategies. For instance, data from cohort studies have suggested catheter thrombectomy appears to be particularly useful if surgical embolectomy is not available or the patient has contraindications to surgery (CHEST 2007;132[2]:657-663). However, no data from controlled clinical trials are available.

Likewise, no prospective observational or randomized trial has examined inferior vena cava (IVC) filter placement as a single therapy (without anticoagulation) in acute DVT, but the 2011 American College of Chest Physicians guidelines recommended that IVC filters generally should be placed in patients with acute PE or DVT who have a contraindication to anticoagulation, but not in patients with PE or DVT who are being treated with anticoagulants (CHEST 2012;141[suppl 2]:e419-e494S).

As a result, individual providers are left to make decisions on a case-by-case basis, due to the vacuum of guidelines or clear-cut data from randomized, controlled trials. “There is a definite need to collect more evidence, but in the absence of that evidence, there’s a need to have the input of a team of smart physicians who take care of these patients, in order to create a consensus as to what is the best thing for each individual,” says Rosenfield.  

PERT dawns

Recognizing the disparity of care, an MGH multispecialist team, including cardiologists and cardiac surgeons, interventionalists, pulmonologists as well as emergency medicine, critical care, vascular and stroke specialists, has decided to work together to draw on the varied expertise of the group to create a consensus on the optimal treatment plan for each of these patients.  

Rosenfield, who serves as MGH’s chairman of the STEMI & Acute MI Quality Improvement Committee, took his experience of applying a systematic process of treating STEMI patients, and collaborated with his colleagues to design Pulmonary Embolism Response Team (PERT) Activation. The program, which is scheduled to officially launch on Oct. 1, currently is being designed for patients with submassive or massive PE.  

Under the PERT protocol, “once a large or severe pulmonary embolus is identified, a single phone number is available that anyone within MGH or outside the institution can call to have the patient urgently evaluated by a multidisciplinary MGH team,” explains Rosenfield.

There will be a rapid response and intervention, says Baker, based on the input of multiple specialists who are aware of pulmonary emboli and its varied treatment options. “The collaboration between the specialties has been so integral to starting this process,” he adds. “If I accepted a patient diagnosed with massive or submassive PE, I now call one of my vascular medicine partners to consult about if we should proceed with a catheter-based or surgical intervention or with medical therapy.” The PERT team is taking a card from the transcatheter aortic valve replacement team, which requires collaboration between surgeons and interventionalists.

Also, because these patients are acute, this collaborative decision-making needs to be made rapidly. “You need all hands on deck very quickly to get the right therapy going as rapidly as you can because massive PE patients are really dying in front of your eyes,” Jaff notes. The team currently is using GoToMeeting for real-time collaboration.

Under the new program, the vascular medicine and the critical care pulmonary fellows will be the first responders, with the backup of their attendings. The fellow will examine the patient and assimilate the data. If the patient fits within a series of criteria, then it will trigger the threshold to initiate a PERT response and put together a GoToMeeting. “That threshold will be quite low initially,” says Rosenfield, “because we’re trying to capture everybody who might possibly need the input of the team.” The current timeframe for this process is approximately 20 minutes.

In extreme cases of massive and submassive PE, patients become hypoxic, but most deaths from PE result from right heart failure, Baker explains. “When a patient is hypoxic and has right heart failure, then the best support that can be implemented quickly is ECMO [extracorporeal membrane oxygenation].” He recommends that these PE patients with significant compromise should be placed on ECMO, and he foresees the PERT team using this strategy going forward; if time doesn’t permit, then the patient should receive systemic tPA.

In terms of challenges for the program, Jaff foresees identifying where these aggressive ECMO cases fit as one of those hurdles. “Some of us believe that ECMO buys a lot of time in the decision-making process for how to manage a patient, but we have to see how that plays out over a larger patient population and certainly a longer time period,” he says.  

Also, when advocating to start such a program, administrators may appreciate the fact that this could increase referrals and patient volume, as community hospitals are looking for centers of excellence to transfer these acute or submassive PE patients.

The PERT team acknowledges that their work is far from done. “We are just getting going with this, so we are going to learn a lot as time goes on. The way we have started is very smart, in that specialties from different domains get all notified at the same time as quickly as we get consulted. Because we are all able to hear about the case at the same time, look at the images at the same time no matter where we are, and give an opinion in real time, we’re headed in the right direction,” Rosenfield concludes.

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