Dr. Tod C. Engelhardt, Discusses Catheter-Directed, Ultrasound-Accelerated Thrombolysis to Treat Pulmonary Embolism
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This is a really exciting new thing for me, and actually a new thing for the world for that matter, in the treatment of pulmonary embolism. Pulmonary embolism can be and frequently is a life-threatening condition and we’re taking patients now with a significant clot burden, a significant degree of debility from pulmonary embolism, and treating them with ultrasound-assisted thrombolysis, which means that we are using a drug to dissolve blood clots in combination with ultrasound technology. The 2 combined have resulted in rapid dissolution of the clot from the pulmonary circulation, which immediately lessens the risk of death in these patients.
I treated 24 patients who had massive or submassive pulmonary emboli. This is really the main cause of death in pulmonary embolism patients: right heart failure. If you can reverse that debilitation of the right heart using this new technology, within 12 to 24 hours, the right heart goes back to normal dimensions, immediately lessening the risk of death from heart failure. We’re also showing that the patients symptomatically get better and it involves placement of catheters, very small catheters with tiny ultrasound transducers spaced 1 cm apart placed directly into the pulmonary artery through a transvenous approach. In other words, we go through the groin, the femoral veins, bilaterally or unilaterally. We don’t have to stick both sides even to place catheters in both pulmonary arteries. We run a drip of TPA, tissue plasminogen activator, a clot-dissolving drug. That is a continuous slow drip through the catheter that’s placed in the pulmonary artery within the clot in the artery and we activate the ultrasonic transducers simultaneously with drug administration. The whole reason why this works so well is the ultrasound technology. The ultrasound causes acoustic pressure waves, which break up the clot and expose fibrin receptor cites and the TPA can get into the inner surface of the clot where it can do its work in dissolving the blood clot.
We have great results. One of the best things is that we proved safety with this. The 2 things I like to do when we do a study like this is safety and efficacy. We need to know number 1 that the device we are going to use is safe. We also need to know that it’s effective. It does us no good if the safety profile is poor or if it’s just not effective to use. Delightfully, we were able to prove both in the first 24 patients that we treated and we were able to show with pretreatment compared to post-treatment CAT scans that the clot burden was relieved to a significant degree. With the enlarged right heart when compared to the left heart (we compared a right ventricular to left ventricular ratio), we proved that ratio can be brought down to normal or near-normal. So far, we have no deaths and we are showing safety and efficacy with this technology.
What was the success rate of the patients you treated in this study?
We’ll need to talk about 2 definitions of success rate. We were able to successfully place the catheter and do the treatment in 100% of patients without difficulty, which was truly a success. In the article, it lists exactly how many patients we treated and gives you a graph on how many patients had regression of right ventricular enlargement and I would say that all of our patients had improvement in their condition based upon symptoms and objective criteria, or the CAT scan measurements. Some had more dramatic positive results than others but 100% went the right way, experiencing symptomatic relief and we were able to objectively measure beneficial effects of the therapy.
What other devices have you used and what do you find helpful about those?
For my treatment with pulmonary emboli, I have only been using the EKOS ultrasonic catheter and the drug, TPA. The catheter itself is not used alone; it has to be used in conjunction with the TPA. I don’t use other devices. I know about other devices and I follow articles written about them, but I feel that the way I’m doing with it with this device is safer than other methods and it’s more effective than traditional therapy. Traditionally for pulmonary embolism, patients are treated with anticoagulation. They’re put on heparin and then transferred to coumadin, which is an oral form of anticoagulant. We find that this is not the optimal treatment for many of these patients. They go on to experience right heart failure despite anticoagulation. The other method is when patients come in and they’re so sick from the embolism, they receive systemic TPA, which is a much larger dose of the clot-dissolving drug. The problem that we see there is a 20% risk of a major bleeding episode. In other studies, they’ve shown a 0%-3% risk of intracranial bleed with systemic TPA. Really, what we’re trying to do is use TPA in such a low-dose that you eliminate the bleeding risk and in order to intensify the effect of the TPA, we use the ultrasound to help drive the drug deeply into the clot. That’s another thing we’re seeing in safety. We have not had any major bleeding episodes with such a low-dose of TPA. I’ve been using about 20 mg total dose over 12 hours, which is such a miniscule dose of TPA compared to 100 mg-200 mg as a given insibolus dose. We have virtually eliminated major bleeding problems but still get the desired effect. That was our goal to begin with.
Are there any specific conclusions that you came to that you’re most excited about?
What we’re looking at now is what this means for the hospital and for the patients. Traditionally, patients who were admitted to the ICU with a massive or submassive pulmonary embolism would get anticoagulated with heparin converted over to coumadin. Some of them were on coumadin for the rest of their lives. What we’re looking at now is the length of stay for the patient and the economics for the patient and the hospital. We can treat these patients now and my patients are now discharged in 3-4 days from the hospital after suffering a massive or submassive pulmonary embolism whereas in the past, we were looking at 7-10 days or even longer. This has shaved days off of the ICU and off of the total hospital stay, which is nice for patients and hospitals combined. We’re comparing our pre-experience to our post-treatment of these patients, which is an ongoing study that hopefully will have enough data to publish a second article in the near future.
Is there another phase of the study that you plan to explore further?
Number one, we’re continuing the original study to get a larger patient base. That’s ongoing and we work through our investigational review board here at the hospital. It’s a sanctioned study and we apply to the IRB yearly to continue the study.
Secondly, we are looking at the additional study of length of stay. That’s a new arm of the study and thirdly, what I’ve done at my institution is set up a protocol, whether it’s the emergency room or primary care physicians, where patients immediately get channeled into the most efficacious therapy. When patients are admitted to the hospital emergently with this problem, instead of just anticoagulating, we know about them and if they’re candidates, I can intervene earlier on these patients, hopefully making a difference in survival and preventing long-term sequelae from the pulmonary embolism, which leads to pulmonary hypertension.
That’s the third thing we would like to look at: setting up protocols in hospitals, letting them be aware that there are other options besides systemic TPA and coagulation alone to help the patients.
Are there limitations that you ran into during the course of the study and would have changed given the opportunity?
The only limitation is the age of the clot, or thrombus. I’ve had great experience with patients who all want to be helped. These are patients who can barely speak because they’re so short of breath and whatever you can do to help them, they are all too happy to get help. The only limitation is that sometimes patients present a month or 2 after becoming symptomatic. They just didn’t go see about it; they didn’t go to the hospital; they didn’t go to their doctor; and the one thing that’s most important for a patient is that the sooner we get to this clot, the better the results. If the patient waits too long, the clot gets organized, and the therapy doesn’t work, or doesn’t work as well. Many patients come in right away because they are found unconscious. One of the presenting symptoms can be syncopy where they pass out and then they’re resuscitated. Those patients do the best that come in right away so the limitation would be if the patient waits too long, the therapy isn’t effective.
Is there anything that you would like to mention that wasn’t covered?
I would hope to see a larger study with more patients. We have, so far, identified an optimal dosing regimen for the drug and the therapy. This can be tweaked and it may need to be changed because there’s evidence in some patients that I had that possibly giving more of the drug over a prolonged period of time may help those chronic clot patients. I have not proven that yet but that is something we have to look at with more patients.
Dr. Tod C. Engelhardt, MD, FACS, specializes in thoracic surgery at the Louisiana Heart, Lung, and Vascular Institute at East Jefferson Hospital in Metairie, Louisiana. He has served as Chairman of Cardiovascular & Thoracic Surgery at East Jefferson General Hospital as well as Hospital Chief of Staff. He earned his medical degree from the Tulane University School of Medicine and completed his Cardiovascular-Thoracic Fellowship at the Ochsner Foundation Hospital in New Orleans, Louisiana.