Pulmonary Embolism Intervention: Call to Action 2.0

In 2008, the U.S. Surgeon General joined with National Heart, Lung, and Blood Institute to issue a national “Call to Action” proclaiming pulmonary embolism (PE) a major public health threat in the United States, and to encourage public awareness and increased research on its causes, prevention, and treatment. A decade later, gains have been made, but PE remains a growing public health problem that requires leadership by U.S. hospitals and health systems to mitigate.  

A Growing Imperative

Each year, PE afflicts an estimated 300,000 to 600,000 people and leads to the death of up to 200,000 people in the U.S., making PE the third most common cause of cardiovascular death behind myocardial infarction and stroke, according to U.S. Centers for Disease Control and Prevention. Its incidence is on the rise, triggered in part by aging baby boomers, since those older than 50 are at increased risk of PE. Other risk factors for PE include immobility, surgeries, obesity, cancer, and pulmonary disease. An expensive illness to diagnose and treat, PE places a heavy economic burden on healthcare systems.

Despite the broad impact of the disease, there is no existing consensus about the best practices for PE therapeutic treatment strategies. The current state of medical literature about PE management is limited, compared to the robust research base for stroke and myocardial infarction. As much as 70% of PE cases are initially misdiagnosed, with the disease often referred to as “The Great Masquerader”.  Nearly half of patients with PE have no apparent symptoms, and other patients have symptoms that mimic many other diseases, such as dizziness, chest pain, shortness of breath, coughing, swelling in a leg, and a fluctuating heartbeat, that often aren’t immediately recognized as PE by even the most experienced clinicians. PE patients present across multiple healthcare venues, from outpatient settings to emergency and operating rooms and within hospital wards, resulting in various specialists managing interventions — with each specialty applying its own treatment protocol, leading to inconsistent outcomes. 

Emerging Shift 

In recent years, however, new strategies and tools have emerged to improve the treatment paradigm for PE and facilitate improved patient outcomes. In 2011, for example, the American Heart Association published the first risk classification of PEs: high risk or “massive PE”, intermediate risk or “submassive PE”, and low risk, with treatment guided by severity. Most PE patients today are treated with anticoagulant medications alone, the standard medical protocol over the past half century. For the 40% of total PE patients who are categorized as low risk, anticoagulants have historically proven effective. For the 5 to 15% of patients with massive PE and 40 to 45% of patients with submassive PE, anticoagulation therapy alone is often ineffective, particularly when there is a large clot burden¹, leading to in-hospital mortality rates as high as 65% for the most extreme cases² and up to 20% for intermediate risk patients¹.

With the existing lack of clinical evidence, the management of massive and submassive PE remains controversial. There are now more treatment options beyond systemic thrombolysis, which itself carries a potential risk of excessive bleeding, including intracranial hemorrhage. Surgical thrombectomy techniques have advanced and there are a number of technologies being used, tested, and evaluated for PE therapy. In 2014, for example, the EkoSonic Endovascular System, an ultrasound-accelerated catheter-directed  thrombolysis treatment of PE (developed by BTG) was approved by the U.S. Food  and Drug Administration, and was the agency’s first clearance for a new endovascular treatment option specifically for the disease, in more than a decade. An array of novel treatment strategies including other catheter-based therapies, pharmacomechanical approaches, and aspiration or suction assist devices are also being developed and tested for PE, with randomized, controlled trials in early stages.  

Frontline Offense 

Some hospitals are meeting the challenge of improving PE outcomes head on by creating pulmonary embolism response programs, a model of care that builds upon the concept of rapidly activating and deploying a multidisciplinary team of specialists to care for critically ill patients, and currently in use for patients who have suffered heart attacks or strokes. A rapid response team is vital in treating PE, since half of all deaths occur within the first 72 hours of its presentation.³ Instead of relying on a single provider, PE teams convene multiple specialists in real time, often by phone or online, for a virtual meeting to review clinical data, discuss the risks and benefits of different treatment options, agree upon a specific intervention plan, and mobilize the required resources to care for PE patients. This model of coordinated and multidisciplinary care for time-sensitive illnesses has been shown to improve patient outcomes compared to the traditional and often randomized approach of gathering input from individual hospital specialists, particularly in urgent care situations. 

Since the first PE team was implemented in Massachusetts General Hospital in 2011, PE teams have been rapidly developing across the country, with an estimated 150 teams at some stage of formation. A national consortium was launched in 2015, currently comprised of several dozen healthcare institutions with PE teams, working to guide and influence PE care and research. Existing PE team programs are as diverse as the institutions that house them, with both small and large community and academic hospital systems participating, according to the consortium. Specialties commonly involved in PE teams include pulmonary and critical care (84%), interventional cardiology (79%), and emergency medicine (63%), with all programs involving at least two specialties, according to National PE Response Team (PERT) Consortium data. The majority of programs reported 6 to 20 monthly PE team activations, originating primarily in the emergency department, on a medical or cardiac intensive care unit, or a medical floor. In most institutions, a full multidisciplinary team responds to the initial PE team activation, although about one-third of hospitals reserve the multidisciplinary team for more complex cases.

During these early days of PE teams, their successes are hard to systematically measure. There are, however, a growing number of published articles describing how single-center PE programs and teams have been implemented and function. These teams hold the potential of benefiting patients in situations when coordinating care is opportune, by forming collaborative relationships among practitioners and facilitating multicenter, collaborative, and translational PE research in the future. 

Answering the Call

At Massachusetts General Hospital⁴, for example, the PE team was activated nearly 400 times over a 30-month period, according to a recent study, with about two-thirds of calls originating from emergency department, 20% from the intensive care unit (ICU), and the remaining from hospital floors. Only about 80% of patients for whom PE consultation was requested were proven to have PE, with nearly a majority of those diagnosed as submassive PE. Over two-thirds of total PE patients received anticoagulation treatment alone and 11% received systemic or catheter-directed thrombolysis. Hemorrhagic complications were rare, and the all-cause, 30-day mortality of PE patients with confirmed PE was 12%.  

The Cleveland Clinic⁵, which established a PE team in 2014, has released some favorable preliminary data. Based on 134 activations over a 23-month period ending August 2016, the hospital said a majority of patients were found to have PE, and of that number, 68% had submassive PE, 19% had massive PE, and the remaining number were categorized as low risk. Just over half of PE patients were treated with anticoagulation therapy alone, with about another third receiving systemic thrombolysis or catheter-directed thrombolysis. The 30-day all-cause mortality rate was 9%, with only 3% related to PE. Bleeding complications occurred in 12.7% of patients, most of whom were treated by anticoagulation alone, and with no major bleeding complications in those treated with systemic thrombolysis. Before establishing a PERT, the hospital says the major bleeding rate in its patients treated with systemic thrombolysis for PE was as high as 45%.

Both institutions reported that PE teams contributed to better decision making in treating PE patients. Despite this promise, the implementation and efficacy of operationalizing a PE program doesn’t come without challenges, particularly given the lack of outcome, cost-effectiveness, and quality data. Although frontline practitioners may advocate starting such a program, hospital administrators must fulfill the vital steps of creating the appropriate infrastructure — including both management and technology — to implement, support, and publicize a viable PE team. Creating teams that operate collaboratively can also be a major hurdle; one clinician likened the potential of PE teams to act as a team of rivals, with competing specialists attempting to dominate decision-making or generate volume for particular PE interventions. Operational challenges also include practitioner and patient education, quality measure development, outpatient follow-up, and involvement in registries or clinical trials. Currently most PE program participants provide their services without additional compensation, although evolving payment models may provide a solution. 

What’s certain is that healthcare innovation always requires transformational leadership to accomplish change. Knowledgeable advocates of PE team programs assure that over the next 5 years or so, this model of care will become a standard protocol in healthcare delivery. Hospitals that invest in PE teams today are reaffirming their commitment to improving patient care and reducing in-hospital mortality rates, key performance areas that are essential for healthcare to accomplish its mission. 

References

1. Prabhu W, Soukas P. Pulmonary embolism in 2017: increasing options for increasing incidence.  R I Med J. 2017; 100(5): 27-32.
2. Dentali F, Riva N, Turato S. Pulmonary embolism severity index accurately predicts long-term mortality rate in patients hospitalized for acute pulmonary embolism. J Thromb Haemost. 2013; (12): 2103-2110.
3. Carroll B, Pemberton H, Bauer KA, et al. Initiation of a multidisciplinary, rapid response team to massive and submassive pulmonary embolism. Am J Cardiol. 2017; 120(8): 1393-1398.
4. Kabrhel C,  Rosovsky R, Channick R, et al. A multidisciplinary pulmonary embolism response team: initial 30-month experience With a novel approach to delivery of care to patients with submassive and massive pulmonary embolism. Chest. 2016; 150 (2):384-393.
5. Mahar JH, Haddadin I, Sadana D, et al. A pulmonary embolism response team (PERT) approach: initial experience from the Cleveland Clinic. J Thromb Thrombolysis. 2018; 46(2): 186-192.

Simon Hogan is Senior Director of Medical Strategy at BTG International Group, a company that develops life-enhancing and lifesaving treatments for vascular thrombosis, including the EkoSonic Endovascular System.