Can you describe the evolution of your pulmonary embolism program?
The Heart Hospital at the Detroit Medical Center has a program called Cardio Team One. Cardiologists and staff are in-house 24 hours a day in order to rapidly treat ST-elevation myocardial infarction (STEMI) patients. We have found that submassive and massive pulmonary embolism (PE) often mimics myocardial infarction (MI). There are some critical patients that present as a medical code, and have elevated troponin and electrocardiogram changes. These patients are directed to the cath lab, with the assumption of acute coronary syndrome (ACS), and yet the coronaries are normal. These patients start to decompensate. They didn’t actually have an MI, but instead had a submassive or massive pulmonary embolism causing severe right ventricular (RV) failure. The majority of patients with non-massive pulmonary embolism can be treated conservatively with anticoagulation. However, 45% of pulmonary embolism patients fall into the massive and submassive category. These patients are hemodynamically unstable, with very low blood pressure, and they are one step away from crashing. Previously, there was no effective treatment for these critically unstable patients. One frequently asked medical board question is, “If a patient comes in with a massive PE, what do you do?” The answer is surgical thrombectomy. However, a literature review revealed that that only one percent of massive and submassive PE patients actually went to surgery, because these patients are so unstable. There had to be an alternative, because massive and submassive PE are so undertreated and have a high mortality rate. If these patients make it to the hospital (the majority die before they make it to the hospital), their mortality rate is 58%. Pulmonary embolism is the third most common cause of death in the country. It is higher than MRSA, AIDS, breast cancer, and pneumonia, all combined. We researched medical literature, made calls throughout the country, and tried to sort out mechanical treatment options. We developed a “clot busters” program to help these patients. Ultimately, we instituted a collaborative effort, with our colleagues in the emergency room, intensive care unit, and interventional radiology. We formatted a program specifically to counteract submassive and massive pulmonary embolisms. We have a universal paging system accessible to everyone in the hospital system. They type in the pager number “PE-DVT” and there is 24-hour coverage by the “Clot Buster” team. If the patient qualifies with hemodynamic instability, the patient is directed to the cath lab. Soon enough, after instituting our program, a patient arrived with severe hypotension, blood pressure 70/40 requiring IV pressors. The angiogram revealed a massive clot. Manual extraction yielded minimal success. Subsequently administration of catheter-mediated tPA with the EKOS catheter (EKOS Corporation) yielded better results. The next day, the patient completely recovered: stable, walking around…it was a pleasant surprise.
The program has been very successful and we have saved hundreds of lives. In southeast Michigan, other competing hospitals have referred critical PE patients from their emergency rooms, because they have no such program. Hospitals from hundreds of miles away call us: “We have this patient post surgery, massive PE, and the patient is unstable.” They helicopter them in. I have been asked by some of these hospitals to develop the same program, and we are in the process of doing so. Our PE program is an important tool to treat unstable PE patients. We want to share our experience. I believe we will reach the phase where all hospitals institute a similar program for these critical patients. Acute PE is the next ST-elevation MI. Many years ago, before the urgency around STEMI existed, there were only a few centers treating STEMIs, and now all the centers do STEMIs. That is the importance of the cath lab; it permits us to do these procedures urgently. There is nowhere else better to treat this aggressive disease. Even our colleagues in interventional radiology don’t have the infrastructure that we have in the cath lab. The cath lab is very unique in that the staff is trained to deal with hemodynamically unstable patients. In the interventional radiology suite, this exists, but it is not as common. The vascular surgeons are also involved, but they are mainly in the operating room. As a result, we feel the ideal place for a PE treatment program to grow is the cath lab. At Detroit Medical Center, we have buy-in from all our departments, because they have seen the results. Our surgeons know that when faced with a post-operative massive PE, to send these patients to the cath lab. They get the lifesaving results instantly. A cancer center nearby has benefited from the success of our program. Cancer patients are at higher risk of having a DVT/PE — when this occurs, they too activate the “clot buster” pager. Wayne State University School of Medicine has given us an IRB approval to continue to research the massive and submassive PE patients. The preliminary data looks outstanding.
What specifically is the research grant looking at?
Patients that have a submassive or massive pulmonary embolism are being compared with similar patients who are treated conservatively. Right now, the standard is that submassive and massive PE patients are treated conservatively, because few take the risk of treating these very unstable, critical patients in either the cath lab or the OR. Previously, systemic tPA was used, but suboptimal results were noted. In the majority of our submassive and massive patients, catheter-directed therapy (CDT), an EKOS procedure (EKOS Corporation) is frequently used successfully. The tPA used in the “clot buster” program is only a fraction of the dose used in the standard systemic tPA. We utilize all the cutting-edge technology for thrombectomy in the cath lab, such as the Indigo (Penumbra). The Indigo is also one of the tools used for extraction of the pulmonary embolism. Our newest armament in our toolbox is the Impella RP (Abiomed) for patients that have right ventricular (RV) failure. This RV assist device allows hemodynamic support in severe failure. These tools can be accessible to all cath labs throughout the country when starting a PE program. We want to share our knowledge and tricks of the trade with other cath labs that are thinking of doing a similar program.
How did you create algorithms (Figure 1) for submassive and massive PE patients?
We researched all the data. We first reviewed the American Heart Association (AHA) guidelines for defining massive, submassive, and minor pulmonary embolism.1 All minor pulmonary embolism patients were excluded. These patients don’t need a CDT intervention. They are stable and can be treated the traditional way, by giving systemic anticoagulation. By definition of the AHA, submassive and massive PE involve either RV infarct or hemodynamic instability. If the patient falls under this definition, then the algorithm kicks in and continues on as these patients make their way to the cath lab. While they are in the cath lab, the decision is made to institute the interventional procedure or attempt thrombectomy with RV support if indicated.
How is a hemodynamically unstable patient with PE differentiated from a STEMI?
There are many similarities. Both have elevated troponins and elevated BNPs (B-type natriuretic peptide), and they may or may not have EKG changes. The ED will either have a computed tomography (CT) scan or an echo to assess the right ventricle. If the right ventricle is blown out and dilated, then it is less likely that it is acute MI, and more likely that it is some type of strain on the RV. If it is not an RV infarct, there are only a very few causes. If a rapid heart rate and respiratory distress are also present, then it tends to signify PE, not acute MI.
Can that determination be made before the cath lab or is that something done in the cath lab?
There are two approaches. Our algorithm allows our emergency department physicians to use their clinical judgment, and either obtain a CT scan or an echocardiogram. If CT scan is done and shows a massive PE, the patient is rushed to the cath lab. If an echocardiogram shows an RV infarct, patients will bypass CT and go straight to the cath lab. Based on the symptoms, and if the patient is hemodynamically unstable — defined as having a blood pressure less than 90 for over 15 minutes or requiring IV pressors — the patient is now defined as having a submassive or massive PE, and sent directly to the cath lab.
Once they get to the cath lab, what happens?
We have a dedicated team for PE. In our “clot buster” program, each person plays an intricate role with individual responsibilities and duties. For example, it is the cardiovascular technologist’s (CVT’s) main responsibility to monitor the rhythm, because these patients often go into heart block. It is not so much the blood pressure as it is the rhythm, because these patients can spiral down quickly. Our CVTs are continuously monitoring the hemodynamics. The radiologic technologist (RT) is involved in two aspects. First is helping to get the angiographic pictures, which is unique to the coronary angiogram. We are dependent on the RT, because we are assuming entire lung fields are exposed, and the timing of the injection is very important. Second, the RT helps with the devices. They prepare and prep some of the devices, and having them on board saves a lot of time. For example, the EKOS catheter requires three lines that need to be aired out. After the images are obtained, the RT will air out these lines. It is a very specific duty to save time, because the patient can become unstable at any time. The nurse in the cath lab also has specific duties, and like the CVTs, they keep their eyes on the hemodynamics. Our nurses are also administering medications to make sure the patient doesn’t go into respiratory distress. They check the respiratory status and airway, because these patients sometimes will need to be intubated due to respiratory distress. They have a checklist that they follow during our procedures. The RT, CVT, and RN all play an intricate role in placing the RV assist device. All staff is extensively trained with the Impella RP. At the start of our program, we took a very specific group of RTs, CVTs, and nurses, and trained them in order to get everyone comfortable with unstable PEs. Once they knew the program, then we swapped each individual until there was no one left, and now every single one of the cath lab staff is trained to handle PE procedures. It took us about a year to cycle through everybody, but all cath lab staff members now know their duties and responsibilities when it comes to critical PE. They have all rotated and they now have the experience.
You mentioned the EKOS procedure. Can you describe some of the other therapies you use to treat submassive and massive PEs in the cath lab?
Catheter-directed therapies have evolved for treatment of massive PE, which is widely under-treated. Many modalities are now available for treatment for mechanical treatment of massive PE. Thrombectomy devices such as AngioJet (Boston Scientific) and Penumbra Indigo evolved from peripheral use to pulmonary applications. Thrombolysis via ultrasound-guided technology such as EKOS remains a viable treatment option. The ultrasound permits more lysis and breakdown of fibrin with minimal doses of tPA. The selective placement of tPA directly into the clot elicits a better outcome than systemic use. Sufficient data suggests lower complications and less bleeding. The right ventricular cardiac assist device Impella RP is a welcome addition to our armament for treating massive PE. The Impella RP is used for RV failure and hemodynamic compromise as a bridge to recovery.
What is your volume?
Massive PE are like massive STEMIs. You are only going to get 100-200/year. The first year of our program, we were probably around 60-70/year. In 2015, we treated over 100 patients. I think this is because success breeds more success. When other physicians see that these patients are discharged a few days later and the program is working, it encourages them to refer additional unstable patients that would normally not be treated.
Do patients typically go to the ICU post procedure?
It depends on which therapy they receive. Assuming they get the EKOS catheter and a thrombolytic drug in the cath lab, everything is sutured in place. We have a technique to stabilize the catheters, because these patients move from gurney to stretcher to bed. We take the equipment, loop it, and maintain it, knowing that it is going to come out roughly the next day. The patient is then transported to the ICU, where a pharmacist maintains the tPA at the dose required. The patient’s hemodynamics are monitored overnight. Then the patient is brought down to the cath lab 12 to 18 hours later. If the patient requires RV support, the Impella RP is placed, and the patient is transferred to the ICU/CCU. We image the lungs, and if the clot burden is dissolved or the majority of it has resolved, everything is removed. The patient is placed on direct thrombin inhibitors such as apixaban (Eliquis) or rivaroxaban (Xarelto). Part of our algorithm involves a venous Doppler. There still may be some residual acute venous thrombosis that can embolize and cause a recurrent PE. The patient may or may not get a temporary inferior vena cava (IVC) filter, depending on whether there is any clot burden in the leg that may be doomed to dislodge. If there is resolution of acute deep vein thrombosis (DVT), then the filter is not placed. If there is, a filter is placed and scheduled to be removed within 2 weeks. Every one of our patients that gets an IVC filter has it removed within 2 weeks.
How common is it to address residual thrombus in the legs for PE patients?
Every hospital has core measures for venous thromboembolism prevention and prophylaxis. The concern is that despite these core measures, patients are still getting venous thromboembolism (VTE). Post PE treatment, if there is still an acute DVT in the leg, it can embolize to the lungs again. We have experienced recurrent PE in the same setting, believed to be from a large mobile acute DVT. The care team had a false sense of security that the patient would not have another acute PE because of therapeutic anticoagulation. During hospitalization, the patient experienced new onset of respiratory distress. In the cath lab, a pumonary angiogram revealed a new, progressive clot. A venous ultrasound later revealed an acute clot that was seen earlier and subsequently dislodged. A new clot was diagnosed in the cath lab. There needs to be some kind of protection for large acute DVT that are at risk for embolization. There is some risk involved with long-term IVC filters, but in our experience in over 150 patients where we have placed filters and removed them within 2 weeks, there have been no incidents. Short-term data for IVC filters demonstrate no complications with this approach. It is the long-term, permanent placement that causes problems. Once the risk is gone and there is no clot, then there is no reason for a long-term IVC filter. We use retrievable IVC filters at a rate of 95%.
What follow-up do patients experience?
All patients will follow up with their primary care physician or cardiologist within 30 days. They get an echocardiogram to assess for any chronic pulmonary hypertension, which is the most common sequela of PE. These patients, if they survive, are prone to have chronic pulmonary hypertension and respiratory distress. However, similar to the data from the ULTIMA trial2, we have found that after use of catheter-directed thrombolysis, many of these massive and submassive patients recover. Our echo data has shown that very few actually end up with chronic pulmonary hypertension. When treated with CDT within 3-6 months, if there is a reversible cause for venous thrombosis, patients are removed from their anticoagulation. We go one step further and make sure that these patients are very well hydrated at all times. We express to them the importance of being well hydrated, and encourage them to stay active and ambulatory. This has been pretty effective for the prevention of recurrent PE.
What do you see as the future of your program?
We are going to continue to modify as we go along. The results we have seen with the current program have been exceptional. I have presented our experience at different cardiology conferences across the country, and there is a tremendous amount of interest. Cardiologists, interventional radiologists, and vascular surgeons are all eager to know more about the program and how to set one up. Last year, I presented some cases at the LINC meeting in Germany and European physicians also wanted to know how to start such a program. I have been invited to go to China, Egypt, and Turkey to set up a program. For any clinician who has faced a massive pulmonary embolism and felt defenseless, now there is a mechanical answer. We hope other centers piggyback on our program and modify it to their needs. Once physicians are comfortable, they can train junior and interventional fellows. I will be delighted when every hospital in the country has a PE program.
Massive and submassive PE patients tend to have certain co-morbidities. Can you describe your patient demographics?
Generally, massive and submassive PE patients are within five general categories: 1) Patients who are post surgery, either orthopedic surgery or surgery where they were not ambulatory. 2) Patients with some type of hypercoagulable state or some type of cancer resolving or residual cancer. 3) Any patient that has had some type of trauma — they fractured or hurt their leg, for example, and developed a clot that caused a PE. 4) Other patients with a sedentary lifestyle. These patients tend to be older, overweight, or inactive. 5) Finally, a smaller category includes patients that are born with a hypercoagulable disorder, a genetic blood disorder that causes them to clot. We have seen PE patients as young as a pregnant woman in her early twenties, all the way up to very elderly patients.
Any final thoughts?
It is an honor to witness the evolving technology and be able to use it to help treat critically unstable patients with massive and submassive PE. We are proud to be the first and only PE program in Michigan. We take pride in utilizing emerging technology to better serve our patients. We are the first in the state of Michigan to use catheter-directed thrombolysis with EKOS and the Impella RP to treat hemodynamically compromised patients with PE. We are the second in the country to combine these two technologies for these otherwise critical untreated patients. Each patient that survives is celebrated and a testimony to our commitment to better serve the community.
All of our achievements were made possible because of the collaborative effort and support of Dr. Theodore Schreiber, DMC Heart Hospital President, Dr. Brian O’Neil, Specialist-in-Chief of Emergency Medicine, and Dr. Ayman Soubani, Director of the ICU. These three departmental heads helped foster the program and were a vital part of our success.
Our team is passionate about this program and we are excited about its success. My wish is for more cath labs across the country to get involved and share this interest. Collaboration must be multidisciplinary, involving the ED, ICU, vascular surgery, interventional radiology, and other health care providers. Success can only be achieved when the program is truly a TEAM approach. I would like to ask that anyone reading this article reach out to our team. We will share our experience and help develop your program. Visitors are welcome to observe our systematic approach. You can come visit and see our system. Knowledge is only good if you share it.
Dr. Mahir Elder can be contacted via Rana Srour at firstname.lastname@example.org.
- Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26; 123(16): 1788-1830. doi: 10.1161/CIR.0b013e318214914f.
- Kucher N, Boekstegers P, Müller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28; 129(4): 479-486. doi: 10.1161/CIRCULATIONAHA.113.005544.