By Apurva Badheka, MD
As part of my clinical training, I treated many patients with submassive pulmonary embolism (PE) using Acoustic Pulse Thrombolysis (EKOS® therapy). However, when I arrived to assume my current position at a hospital about 25 miles north of Seattle, this sort of approach was not yet available at the facility. In fact, I discovered that there was skepticism about the idea of ultrasound-assisted catheter-based treatment of submassive PE. Physicians in the intensive-care unit (ICU) were particularly resistant to introducing the therapy, since they saw no role for thrombolytics in the treatment of pulmonary embolism, favoring heparin, instead.
However, submassive PE is a major cause of mortality and my earlier experience had convinced me that Acoustic Pulse Thrombolysis is a safe and effective treatment that would benefit our patient population. When a submassive PE patient, whose right heart hemodynamics were consistent with acute cor pulmonale and obstructive shock, was successfully treated with Acoustic Pulse Thrombolysis in my hospital, we were able to eliminate internal resistance. The patient fared very well, and subsequently my colleagues recognized the utility of the approach.
Moreover, now that we are treating submassive PE with even lower doses of tPA and shorter duration of therapy in the wake of the OPTALYSE PE trial, my hospital colleagues have adopted an even more favorable view of Acoustic Pulse Thrombolysis, particularly in the ICU. In OPTALYSE PE, submassive pulmonary PE patients treated with this therapy experienced rapid and significant reduction in RV/LV ratio and reversal of RV dysfunction. Prior to OPTALYSE PE, we employed a protocol based on the earlier SEATTLE II trial, in which I would typically give a 5 milligram bolus of tPA bilaterally, followed by a drip of 1 milligram per hour for six hours, which worked out to roughly 22 milligrams of tPA. However, I now most often treat submassive PE with the regimen used in cohort 2 of OPTALYSE PE, which is 1 milligram bilaterally for four hours.
Lower dosing and shorter duration of therapy means patients spend significantly less time in the ICU, typically six to eight hours. Length of hospital stay for most patients is between 48 and 73 hours. That’s a significant improvement over our earlier days, when ICU stays for treatment of submassive PE typically involved anticoagulation alone, and patients would spend anywhere from three to five days in the hospital. And we can offer this faster treatment safely: We have had zero major bleeding complications with Acoustic Pulse Thrombolysis.
Before and After Adoption
Our program for treating submassive PE is now widely accepted in the hospital. Patients diagnosed with submassive PE who are positive for troponin or BNP elevation, or who have any right heart strain or a significant thrombus burden, are immediately seen in our interventional cardiology department for a pulmonary embolism response team (PERT) consultation. Since August 2016, we have treated roughly 50 patients in our hospital system with Acoustic Pulse Thrombolysis. One recent case offers a contrast in how the availability of this treatment has changed our approach to treating submassive PE.
The patient was a male, 41, who was very physically active: He organized and participated in Ironman competitions, which are among the most challenging individual sporting events, requiring athletes to run, swim and cycle long distances in a single day. The patient had Factor V Leiden thrombophilia, which increases the risk for blood clotting. Several years earlier, he had developed a submassive PE and been treated with heparin and Coumadin, requiring a hospitalization of five days.
Then, last summer, the patient injured his leg and developed pain and swelling that failed to improve. Medical evaluation at a walk-in clinic revealed that he had a deep vein thrombosis (DVT), and he was treated with warfarin and enoxaparin (Lovenox). Shortly thereafter, one morning the patient fainted in his bathroom and awoke on the floor, short of breath and perspiring profusely. He was evaluated at an emergency department and found to have submassive PE. Computed tomography angiography detected acute thrombus in the segmental artery supplying the right middle and right lower lobes and subsegmental artery supplying the posterior segment of the left lower lobe. We also detected evidence of right heart strain (the right ventricle was moderate-to-severely dilated).
I determined that this patient was a candidate for localized lytic therapy using the Acoustic Pulse Thrombolysis device and chose cohort 3 from OPTALYSE PE, which meant 1 milligram of tPA bilaterally for six hours, though I added a small bolus at the outset. Upon completion of the infusion, we removed the catheters and the patient was discharged after a stay of just 48 hours with a prescription for anticoagulation with rivaroxaban (Xarelto). At a follow-up visit several months later imaging found no evidence of pulmonary emboli and that his RV/LV ratio had improved from 1.2 to 0.9, a reduction of 25% reduction (which is similar to the typical RV:LV change measured in OPTALYSE PE). The patient’s symptoms were dramatically improved and he has resumed taking part in Ironman competitions.
Rapid Improvement of Symptoms
What’s particularly striking about Acoustic Pulse Thrombolysis is the rapid improvement we see in patients once we start the procedure. Within the first hour or so a patient’s shortness of breath begins to improve as the clot starts to dissolve. By the end of a typical four-hour procedure patients feel much better. Hemodynamically, we see dramatic improvements, too. At the outset, a patient’s pulmonary artery (PA) pressure may be in the 50 mm Hg range, but within four hours it usually closer to 30 mm Hg, or near normal. We have documented similarly rapid improvements in PA saturation. We continue to see these benefits even after moving to the lower doses used in the OPTALYSE PE trial.
Since we tend to treat patients from a hemodynamic perspective, observing these kinds of patient benefits were critical in helping to get the EKOS® program rolling at our hospital. I feel that there are minimal downsides to adopting this technology, while the upsides are massive. STEMI (ST-Elevation Myocardial Infarction) sites should absolutely offer Acoustic Pulse Thrombolysis, but the simplicity of the procedure and its track record of safety and efficacy should make it a priority for non-STEMI sites, too. As long as your facility has a catheter lab and fluoroscopy, then you are already performing many procedures that are significantly more complicated than administering Acoustic Pulse Thrombolysis therapy that may offer patients far less benefit. Patients with submassive PE deserve to receive advanced therapy in this day and age.
Apurva Badheka, MD
The Everett Clinic