Earlier in the day, a 55-year-old senior executive of our hospital system was demonstrating a feature on our new electronic medical record system to a physician in our emergency department (ED). The executive, who had traveled to Kentucky from Georgia, grew increasingly short of breath as he spoke, until the physician insisted he have a computed tomography (CT) scan on the spot, which showed a huge bilateral pulmonary embolism (PE).
The ED called me to evaluate the visiting executive. His right ventricular/left ventricular (RV/LV) diameter ratio was 1.2, RV dysfunction was severe, and he was hypoxic. This patient had a submassive PE and was an ideal candidate for ultrasound-assisted, catheter-directed thrombolysis (USAT).
I had performed a few USAT procedures using the EkoSonic Endovascular System (EKOS), and had been impressed with how quickly RV dysfunction improved, typically within 48 hours after initiating the procedure. The trial data were also compelling. The 2014 ULTIMA trial randomized 59 patients with intermediate-risk PE to unfractionated heparin and low-dose (10 mg to 20 mg tPA) USAT or to unfractionated heparin alone. The mean decrease in RV/LV ratio from baseline to 24 hours was a statistically significant 0.30 ± 0.20 in the USAT group (P < 0.001) versus a non-significant reduction of 0.03 ± 0.16 (P = 0.31) in the heparin-only group.1 The larger, single-arm SEATTLE II trial evaluated USAT in 150 patients with acute high-risk and intermediate-risk PEs and found no intracranial hemorrhages. The mean RV/LV ratio in the study decreased from 1.55 pre procedure to 1.13 at 48 hours post procedure, a statistically significant difference of 0.42 (P < 0.0001).2
With nine cath labs at our institution, one was available for me to do the USAT procedure on this patient. Within 45 minutes of starting the procedure, the patient looked and felt significantly better, which was much remarked upon by his executive traveling companions. Having several hospital administrators be firsthand witnesses to the dramatic effectiveness of EKOS treatment was a definite advantage when we submitted a purchase request for this technology. Another major selling point was that the typical length of stay for patients treated with USAT at our hospital is two to three days compared to five or six days for patients who receive standard systemic thrombolytics.
It was equally important for the cath lab nurses and technologists to see the rapid results on this patient, which contributed to gaining their trust with the technology. Getting staff buy-in is critical for the institution to smoothly adopt innovation.
Similar technique, different protocol
As an interventional cardiologist accustomed to using right-heart catheters, learning the EKOS technology was easy. The USAT technique is similar to performing a right heart catheterization, except it employs different catheters, which are advanced into the lower lobes of the lung. For PE, the infusion rate is set to deliver 24 mg of tissue plasminogen activator (tPA) over 12 hours — less than 1/4 the dose of systemic lytics — thereby reducing the risk of hemorrhagic complications. The ultrasound energy causes fibrin strands to thin and loosen, and forces the drug deep into the clot, so less tPA is needed to clear the thrombus.
To treat submassive and massive PE with USAT, we had to change our existing protocol, which gave responsibility for PE therapy to ED physicians and pulmonologists. They used clinical criteria such as PESI score (Pulmonary Embolism Severity Index), troponin, D-dimer and BNP levels, extent and location of the thrombus burden on CT scan, the patient’s age, and duration and severity of symptoms, to determine whether to treat with systemic thrombolytic therapy or anticoagulants. Ultimately, however, it was a judgment call, and the aggressiveness of the pulmonologist or the ED physician typically steered therapy toward thrombolytics or anticoagulants.
Today, our ED physicians and our pulmonologists call our STEMI (ST-segment elevation myocardial infarction) hotline when a patient’s CT scan indicates a massive or submassive PE. The on-call interventionalist will quickly evaluate the patient for evidence of right-heart strain based on the RV/LV ratio on CT scan or from an echocardiogram. Our protocol is to treat with USAT if the patient has a RV/LV ratio ≥ 0.9, consistent with the inclusion criteria for participants in the SEATTLE II trial.
Placing one call to the STEMI hotline made it easy for ED physicians and pulmonologists to consider USAT as a treatment option. My partners and I also gave presentations to the pulmonologists and ED physicians on the EKOS technology. We discussed the limitations of standard treatment for submassive PE with anticoagulation alone, which prevents new clots from forming and relies on the body’s endogenous hemolytic capabilities to resolve the existing clot. With USAT, the ultrasound energy in combination with the tPA dissolves the clot, which may prevent patients from developing chronic pulmonary hypertension. Treatment with anticoagulants alone may not resolve RV dysfunction, making patients eight times more susceptible to recurrent PE and to long-term complications, such as heart failure.
Currently, our interventional pulmonologist and three interventional cardiologists perform the EKOS procedure. Our goal is to train all our interventional cardiologists taking STEMI calls to do USATs for PE. After the USAT procedure, we admit the patient to the pulmonologist and the ICU.
Majority of massive and submassive PEs treated with USAT
Simplifying and clarifying the post-procedure anticoagulation protocol is also important. The protocol had varied depending on which physician was performing USAT. We met with the pharmacist and the interventional pulmonologist to develop the protocol and order set. It is now clear to the ICU nurses when to remove the catheters and whether to administer rivaroxaban (Xarelto) or heparin and/or enoxaparin (Lovenox).
About 75% to 80% of our patients with massive and submassive PEs are now being treated with USAT. As more of our ED physicians get comfortable with the technology, we hope that they will call the STEMI hotline for all patients with massive or submassive PEs. We will also be sharing the results of the registry we are creating to study our patients’ outcomes with the technology, which we anticipate will echo our early, strong patient results. None of our patients treated with USAT thus far has had an intracranial hemorrhage or a fatal bleed.
And we may be able to further reduce the risk of bleeding. The newly announced OPTALYSE PE trial, for which I am a principal investigator, is designed to determine the optimum dose of thrombolytic and duration of USAT to treat acute submassive PE. If we can reduce the 12-hour regimen of USAT and the dose of tPA without sacrificing effectiveness, we may be able to lower the thrombolytic-associated risk of bleeding.
For now, it’s gratifying to offer USAT to patients with massive and submassive PE who are in their 40s and 50s, knowing that the technology will more likely restore their right ventricular function more completely than standard therapy. Fifteen hours after I performed USAT on a 47-year-old patient with submassive PE, I found him sitting in his chair eating lunch in the ICU as he waited for a bed elsewhere in the hospital. If I ever experience a PE, that is exactly the way I would like to look the next day.
- 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.
- Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, et al; SEATTLE II Investigators. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv. 2015 Aug 24; 8(10): 1382-1392. doi: 10.1016/j.jcin.2015.04.020.
Disclosure: Dr. Piracha reports no conflicts of interest regarding the content herein.
Dr. Amir Piracha can be contacted at email@example.com.