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The Challenge of Submassive Pulmonary Embolism
Catheter-based thrombolysis best implemented on a case-by-case basis.
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With a lack of a large body of randomized clinical trial evidence on the use of catheter-based treatments in patients with pulmonary embolism, physicians face challenges in making the best decisions for each patient.
It is in the patients with submassive pulmonary embolism that the field is finding controversy, experts told Cardiology Today’s Intervention. Catheter-based technologies are at the forefront of the discussion for this group of patients.
“Submassive pulmonary embolism is a very complicated and challenging area” Sahil A. Parikh, MD, FACC, FSCAI, director of the Center for Research and Innovation and director of the interventional cardiology fellowship program at the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, said in an interview.
The debate surrounds the best strategy to manage patients with submassive pulmonary embolism, Parikh said. A significant percent of patients with submassive thrombus will survive, but these patients may have long-term consequences such as pulmonary hypertension that may result in chronic disabilities and higher mortality rates even if patients survive the original embolism.
Use of catheter-directed therapy — for example, inserting a catheter directly in the pulmonary artery and infusing tissue plasminogen activator (tPA) — is attractive because one can use a dose that is about one-quarter of the dose used systematically.
John P. Reilly
“Catheter-directed therapy allows us to treat patients at possibly lower risk than when treated with systemic thrombolysis,” said John P. Reilly, MD, FACC, FSCAI, vice chairman of the department of cardiology; section head of the interventional cardiology program; and director of fellowship in interventional cardiology at Ochsner Health System, Jefferson Parish, La.
Some data suggest that there is less risk for bleeding overall with this approach because there is less use of tPA. The risk is not zero, but it is certainly less than with systemic tPA, Parikh said.
“Patients with massive pulmonary embolism and submassive pulmonary embolism stand to benefit from catheter-based treatment,” Gregory Piazza, MD, MS, assistant professor of medicine at Harvard Medical School and staff physician in the cardiovascular division of Brigham and Women’s Hospital, told Cardiology Today’s Intervention.
Treatment Challenges
Philosophies differ from center to center mainly due to the lack of large randomized clinical trial evidence to support the use of catheter-based treatments for pulmonary embolism.
“One of the first challenges is access to the therapy. Not all medical centers offer catheter-based approaches for the treatment of pulmonary embolism,” Piazza said. “For hospitals that do have this technology, selecting patients for this therapy is often a challenge because the risk of bleeding has to be considered.”
Although catheter-directed therapy is associated with a reduction in the risk for major bleeds such as intracranial hemorrhage, patients still need to be screened for contraindications related to bleeding,” he said.
“It is difficult to know in which cases you should choose this therapy compared with a more conservative therapy such as anticoagulation alone or intravenous tPA or a more aggressive therapy such as surgery,” Parikh said.
The greatest risk associated with thrombolytic therapy is bleeding, and patients treated with thrombolysis have more bleeding than patients treated with anticoagulants. It seems that the oldest patients — those older than 75 years — are at increased risk for intracranial hemorrhage, Reilly said.
Patient Selection
Patients with low-risk pulmonary embolism do not benefit from thrombolytic therapy, either catheter-directed or systemic, Reilly said. He noted that most of those will manage fine with standard therapy with anticoagulation.
“However, patients with massive or submassive pulmonary embolism are at high risk for recurring pulmonary embolism, and they are the patients who are going to benefit from treatment thrombolysis,” he said.
Nils Kucher, MD, from the division of vascular medicine, Swiss Cardiovascular Center, University Hospital Bern, Switzerland, and colleagues conducted the randomized controlled ULTIMA trial of ultrasound-assisted catheter-directed thrombolysis (EkoSonic endovascular system, EKOS Corp.) in patients with pulmonary embolism and acute and intermediate risks. The researchers found that in intermediate-risk patients with pulmonary embolism, ultrasound-assisted catheter-directed thrombolysis was superior to anticoagulation with heparin alone for improving right ventricular dilatation at 24 hours. The intermediate-risk patients with pulmonary embolism treated with ultrasound-assisted catheter-directed thrombolysis also did not have increased in bleeding complications at 24 hours.
Parikh said at his institution, “in general, it is in patients who have life-threatening clots where there is shock or significant dysfunction of the heart that we will often select more aggressive therapies such as catheter-based therapies or surgery.
“Treatment selection is individualized patient by patient in our practice. Some patients are better candidates for surgery than others, and some are worse candidates for surgery. In those cases, we might choose a less-invasive catheter-based therapy or an intravenous tPA approach,” he said.
Patient selection also is typically done by a team of experts.
Sahil A.
Parikh
“There is an evolving therapy diagnostic evaluation called pulmonary embolism response teams, or PERT, which is being developed in centers such as Massachusetts General Hospital and others where there is a multidisciplinary conference contemplating the care for each individual patient and deciding on a case-by-case basis what might be the best therapy,” Parikh said.
Reilly discussed the protocol at Ochsner Health System. “We have a protocol for using catheter-based treatments for pulmonary embolism for those patients with submassive pulmonary embolism who are showing evidence of hemodynamic instability, borderline hemodynamic instability and patients who have evidence of right ventricular strain or right ventricular failure either by echo imaging or patients who have abnormal biomarkers such as CNT or troponin,” he said.
Success Rates
A meta-analysis published in JAMA in July 2014 examined 16 studies that compared thrombolytic vs. anticoagulant therapy in 2,115 patients with pulmonary embolism. Saurav Chatterjee, MD, from St Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System in New York, and colleagues reported lower all-cause mortality rates in patients treated with thrombolytic therapy. This finding included patients who were hemodynamically stable with right ventricular dysfunction; however, the researchers noted that the results may not apply to patients who are hemodynamically stable without right ventricular dysfunction. Thrombolytic therapy was associated with a greater risk for bleeding and intracranial hemorrhage in elderly patients. The increased bleeding events were not significantly increased in patients aged 65 years and younger. The researchers also found that, compared with anticoagulant therapy, thrombolysis was associated with a lower risk for recurrent pulmonary embolism.
“This treatment appears to be very successful at resolving right ventricular dysfunction related to pulmonary embolism, reducing pulmonary artery pressure and then clearing the obstruction of the thromboembolic material,” Piazza said.
Results from the SEATTLE II trial presented by Piazza at the 2014 American College of Cardiology Scientific Sessions demonstrated that ultrasound-delivered catheter-directed low-dose thrombolysis using the EkoSonic endovascular system (EKOS Corp.) was associated with improved right ventricle function and reduced risk for pulmonary hypertension and intracranial hemorrhage among patients with acute pulmonary embolism.
“One of the special features of catheter-based techniques for pulmonary embolism is that this type of technology appears to minimize risk for intracranial hemorrhage compared with systemic fibrinolytic therapy because it uses a much lower dose of the fibrinolytic drug. Even though it uses a lower dose, it is still effective at restoring right ventricular function,” Piazza said.
However, Parikh noted that the currently available clinical trial data do not show that this technique is associated with a mortality benefit. “It doesn’t necessarily save lives, but it increases the rapidity in which the right ventricle and the heart recover, and there is a suggestion that it may potentially have a long-term benefit by reducing the incidence of pulmonary hypertension,” he said.
“We have found that many physicians are hesitant or reluctant to call for thrombolysis because there is an increased risk for major bleeding. And that is true. But, we should balance that with the benefits of catheter-directed thrombolysis and the opportunity to reduce the mid- and long-term effects of pulmonary hypertension,” Reilly said. “I think we can make a positive impact on these patients.” – Suzanne Bryla