Can you tell us about pulmonary embolism and the evolution of treatment?
Normally, the body makes and breaks down clots at the same rate. Something changes that equilibrium, whether it is medications that make people prone to clotting, cancer, which also makes people prone to clotting, immobility, or injury to the vessel. On the dissolution side, the body makes tPA endogenously in the cells of the inner lining of the blood vessel. Essentially, something throws that equilibrium off and now the patient makes clots, which can migrate to the lungs and become a pulmonary embolus. Categories of PE include minor, submassive, and massive. A majority of pulmonary emboli, around 55%, are minor, meaning that it could be anything from subclinical, a tiny clot no one notices but is caught on a CT scan, to somebody that comes in with a little chest pain that resolves by the time anybody looks at it. Submassive is the intermediate category. Patients are very symptomatic, short of breath, and they have a large clot burden. They may show signs of right heart strain. Their labs are abnormal, but they are hemodynamically stable. Massive PE patients, the smallest category, present in cardiogenic shock and have high mortality.
Unless you are in a major medical institution, the standard treatment all over the world is to give heparin, a blood thinner that does nothing to dissolve blood clots, but prevents clot progression. Before heparin is administered, clots are being made faster than the body can dissolve them. If you decrease that level of production by giving heparin, then the body can now dissolve the clots. The trouble is that over time, clots, even while they are dissolving, will age. They turn from acute to subacute to chronic, and during that process, the body reabsorbs the water out of the clot, and it becomes more cellular and solid. It is harder to dissolve or even break up mechanically, and by the time a clot is chronic, there is no effective treatment.
The EKOS procedure (EkoSonic Endovascular System, EKOS Corporation) is one of the latest advances in treatment and it involves the use of tPA through a multi side-hole infusion catheter with an ultrasound wire through the center. The ultrasound works to push tPA out further into the surface of the clot. Since tPA works on the surface area of the clot, the more clot that is bathed in it, the better it works. The EKOS ultrasound also vibrates at the resonant frequency of fibrin. You know how a singer hits a certain note and then a glass will vibrate until it breaks? The note being sung is the resonant frequency of that glass. Everything has its own resonant frequency, and the EKOS ultrasound vibrates at the resonant frequency of fibrin, which in addition to pushing the tPA out into the clot, causes the fibrin strands to vibrate apart. This allows for the use of significantly less tPA. In the old days, when they gave tPA through an IV (and they still do it in some places), they would give 50 mg bolus of tPA and then a second 50mg aliquot either over 1 or 2 hours with a side effect of a high chance of bleeding. Yes, it would help dissolve clot, but it would also dissolve clot if someone had bleeding from the colon (diverticulitis). If somebody had a kidney stone, recent trauma, recent surgery, a tumor in the brain that nobody knew was there — all those things could start to bleed as well. The incidence of complications with peripheral tPA was high because the dose was high. Also, because the tPA only treats the small surface of the clot in contact with the open vessel, this method also didn’t dissolve clot as well as it could. The next development was the use of a multi side-hole infusion catheter, offering a lower dose of tPA and better result than tPA administered peripherally, because it treated more surface area of the clot. The EKOS procedure is the next advancement. It allows us to obtain much more effective lysis of the clot much faster, with lower doses of tPA. It is also safer, with less bleeding. We started doing the EKOS procedure in bypass grafts, thrombosed arteries and veins, and then began using it for other clots, becoming involved in some of the PE trials. Overall, our cases number more than 600 and we have treated well over 200 PE cases with the EKOS procedure. We treat over 24 hours, using 24 to 36mg of tPA, depending on time and clot burden. We try to do it overnight. If we are starting at 8pm or if the patient is really sick, we may give a bolus through each side first. If we are starting at 8am, we may not give a bolus. Once the treatment is done, patients are usually discharged within a few days. After we completed our first 75 PE cases, we reviewed our results, which were very good, with zero complications. We were able to significantly decrease thrombus load and decrease pulmonary artery pressures almost uniformly across the board.
Do you have an organized clot program at Tampa General Hospital?
Yes. We saw how good the results were in treating pulmonary embolus with the EKOS procedure and decided to start a pulmonary embolus program with the emergency department (ED). We have given multiple lectures and grand rounds, and emphasized that we would take care of everything. If a patient came in with chest pain and shortness of breath, the ED would do the workup and that would include a computed tomography angiography (CTA) and labs: BNP, troponins, d-dimer, etc. We primarily use a CT scan of the chest. We can estimate the burden of clot and estimate the right heart strain. We also use the BNP; the others are only tiebreakers if we have questions. If anything is abnormal, then the ED calls us, and in the beginning of our program, whoever was there at the time would go down and evaluate the patient immediately. If the patient was a good candidate for the EKOS procedure, then we would have the patient sent up to the interventional radiology (IR) suite and we would do the procedure. At the same time, we wanted to include our pulmonary critical care colleagues, so we would call them and have them involved as well. Our challenges included encountering some people who weren’t really familiar with EKOS or who were afraid of complications associated with tPA. Now that our program is more established, the protocol is that the patient comes in, the ED clinically suspects PE, and they order a CTA and BNPs. We look at the CTA, look at the labs, and if warranted, then they send the patient to us and we do the EKOS procedure. We consult pulmonary and critical care, who come to see the patient. The patient is usually admitted to the ICU, we follow them to discharge, and see them for follow-up in clinic.
The EKOS procedure is performed in the IR lab?
IR has 6 rooms, and we are adding one more. During the day, 3 of our rooms have full-time anesthesiologists as well. We are well versed in handling these patients. Our cardiovascular center actually has 12 rooms. Six are IR and right across the hall, 6 rooms are cardiology. We are under the same umbrella, but we work separately. We do help each other when needed.
What do you see as the future of the PE program?
It is growing. For the last 5 or 6 years, the EKOS procedure has been the only advanced treatment for pulmonary embolus. Three months ago, we had a case that could have been tragic. It was a woman in her forties who was a single mom and a grandmother. She had fractured her ankle and ended up with a massive pulmonary embolus. She had a code blue, was dead, and was brought back. The ED brought her right to us per our protocol. In general, people put the EKOS system in and leave it overnight, because it is a small dose administered over 24 hours. The drawback is that someone who is critically ill with a massive pulmonary embolus may not survive that long. In this case, faced with a patient who coded already, we called cardiothoracic surgery for a surgical embolectomy. They declined, feeling that she might not survive it. Since we already had her on our table, we said, okay, this is our only choice, and put in the EKOS catheters. Three days later, she went home. We saw her in clinic and she was still in a wheelchair because her ankle was in a cast, but she said she felt back to baseline. We saw her at follow-up twice in clinic. She is doing great.
People are realizing now that pulmonary embolus may not be a death sentence; it can be treated and people are working on different ways to treat it. But EKOS was really the first modern treatment. There are other things coming on the market now that are also going to be useful. Two are mechanical suction embolectomies: AngioVac (AngioDynamics) and CAT 8 (Penumbra). As with EKOS, the AngioVac was first approved for IVC and lower extremity veins, and it is not approved for pulmonary embolus or intracardiac use. The first dozen cases that we did with the AngioVac were all IVC and iliac veins, and we recently did a case with an intracardiac thrombus, with excellent results. We have done three of those cases thus far, and may end up using it for pulmonary embolus at some point as well. I don’t think AngioVac is going to replace EKOS. It is a different tool. The EKOS system does not damage the red blood cells at all, it can clear clot completely or almost completely, and reduces the pressures down to normal or near normal — all of which is great, but it works overnight. In a patient with a major pulmonary embolus, their heart is straining because the pulmonary arteries are blocked with clot. Basically, the heart is pumping against a brick wall. In some massive PE patients, the heart may just get tired and give out before the brick wall dissolves, so time is an issue with these patients. EKOS has started a trial (OPTALYSE PE) where they are reevaluating patients after treatment at 8 hours, 6 hours, and 4 hours. Perhaps we will find out that the patients don’t need to have the system in place overnight.
Any final thoughts?
The EKOS procedure is the newest standard for thrombolysis. We have used it in not only arteries and veins, but in transplant livers where the portal vein thromboses and the transplant liver is going to die. We will place the catheter via transhepatic access through the liver into the portal vein and do thrombolysis overnight, dissolving the clot completely and saving the liver. The EKOS procedure is not approved by the FDA for liver transplants. But if the patient is going to die, you have to do something. And it works well.
Disclosure: Dr. Shube reports no conflicts of interest regarding the content herein.
Dr. Samuel Shube can be contacted at email@example.com.