VDM Speaks with Dr. Tod C. Engelhardt About Ultrasonic-Enhanced Thrombolysis for PE

Dr. Tod C. Engelhardt, Chairman of the Cardiovascular and Thoracic Surgery Division of East Jefferson General Hospital in Metairie, Louisiana, spoke with VDM following his presentation on ultrasonic-enhanced thrombolysis for pulmonary embolism at the 2011 ISET meeting in Miami Beach, Florida

Tell us about your experience with the EkoSonic®, an ultrasonic-enhanced thrombolytic system to treat pulmonary embolism.

My initial experience with the EkoSonic^® Endovascular System (EKOS Corporation, Bothell, Washington) involved the venous and arterial circulation. I used this ultrasonic-enhanced thrombolysis system to treat deep venous thrombosis (DVT) as well as thrombolysis of clotted bypass grafts in the arterial system, with excellent results. I was impressed with the efficacy and ease-of-use of this system. PE can be divided into three main categories: 1) Massive PE: This category accounts for approximately 5% of PE patients. These are patients who are in cardiogenic shock, are hemodynamically compromised and very symptomatic. The American College of Chest Physicians established recommendations 2 years ago calling for the definite use of systemic thrombolytics to treat massive PE. Despite the bleeding risk, it is worthwhile to give these patients thrombolytics. 2) Submassive PE: This category accounts for about 40% of PE patients. These patients are admitted to the hospital with symptoms — usually dyspnea and sometimes coughing up blood — but they are hemodynamically stable. They have right ventricular enlargement and are either on their way to sliding back into the normal range, or they will continue to develop increased pulmonary resistance, leading to a massive PE. It is important to note that the American College of Chest Physicians states that thrombolytics should be considered for these submassive PE patients, but the mandate is not very strong. Most of the patients (27/30) we treated had submassive PE. Per our protocol, they underwent ultrasonic-enhanced thrombolysis. Since we implemented a 20 mg dose of t-PA, no bleeding complications occurred, and all patients had rapid reversal of their PE, a return to normal right ventricular size within 48 hours, and were placed on warfarin for 6 months. We are convinced that this is the optimal treatment strategy for this category of patients. 3) Minor PE: The remaining 50–55% of PE patients are considered to have minor PE and are not treated. Symptoms are minimal and diagnosis is sometimes made by incidental finding on CAT scans. My experience in the pulmonary circulation came about in a case involving an 82-year-old patient who was dying of a pulmonary embolism (PE) 3 weeks after coronary bypass surgery. This patient presented to the emergency room in cardiogenic shock, and despite the medication used to raise his blood pressure, the administration of oxygen and the administration of enoxaparin, his condition continued to deteriorate. I was asked to do whatever I could. My options, therefore, were to take him up to the operating room, re-open his chest 3 weeks after major bypass surgery, place him on the bypass machine, then open his pulmonary artery and fish out the clot (Trendelenburg procedure). Every cardiothoracic surgeon has an anecdote about this procedure — even surgeons now in their 80s. The Trendelenburg procedure has occasionally produced a heroic result that has saved the patient; however, I did not think my patient would survive it. In this patient, the clot was not only in the pulmonary artery, but had extended into the right ventricle and the right atrium. Thus, this involved a huge clot that had obviously broken loose from a lower extremity vein, as well as a large clot from the pulmonary artery down into the right heart. I convinced the cardiologist to let me try a new procedure that I thought this patient would have a better chance of surviving. With a systolic pressure of about 60, the patient was transported to the cardiac catheterization laboratory where we quickly assembled the tools, acquired access and placed the catheters. This was the first time I had performed this procedure for PE, and I later learned that this was the first patient to be treated with the EkoSonic system for right ventricular and atrial clot as well. After 2 minutes of giving a bolus dose of t-PA and activation of the catheter’s ultrasonic core, the patient was hemodynamically stable. Within a few hours, he was off all inotropic support. Six hours after that, an echocardiogram was repeated, which showed a total absence of intracardiac thrombus. The next day, treatment was stopped and the patient underwent repeat CTA, which showed a significantly reduced thrombus burden in the pulmonary artery. The patient went home on post-procedure day 4 on warfarin, and has done well ever since. My first experience with the EkoSonic device in a PE patient was borne of necessity. Since that time, I have performed 30 procedures in a similar fashion and have refined the protocol. My protocol now involves the administration of no more than 20 mg of t-PA over a 12-hour period, which I think is a lot safer than the 100 mg bolus dose of systemic thrombolysis. This drug works so well at a low dose because it is administered directly into the clot. The catheter is thus embedded in the clot and its ultrasonic component allows the fibrin strands to loosen, allowing the drug to be driven deeply and immediately into the clot. An analogy I use with my patients to describe this technique is that of dissolving an ice cube versus a snow cone by dripping a drop of water on each of these every second. It will take much longer for the ice cube to melt in this way than a snow cone of similar size, as the latter has much greater surface area exposed to the water droplets. The same applies to the clot in the ultrasound technique, as so much more surface area of the clot is exposed to the drug being driven directly into it. This technique is safe and effective because we do not see the major bleeding complications that are observed in 20% of the patients with large-dose systemic thrombolysis (and a 1–3% incidence of intracranial hemorrhage). Furthermore, this technique, which uses only 20 mg of t-PA, is at least as effective as the 100 mg systemic dose because complete clot lysis is achieved with the EkoSonic system. Most importantly, what we are really after in the acute period is to ensure that these patients do not die from right-heart failure caused by pulmonary circulatory obstruction. If this can be reversed immediately, then we can keep the patient alive. In the 30 PE patients treated at our center to date, we were able to demonstrate a statistically significant decrease in the size of the right ventricle as measured by a pre-procedure CAT scan and a post-procedure CAT scan at 48 hours. Furthermore, there were no bleeding complications with these patients when we limited the total t-PA dose to 20 mg. The traditional treatment for PE has been administration of the anticoagulants heparin and warfarin, which do not dissolve clot, but just prevent its propagation. The body has its own intrinsic fibrinolytic system that will dissolve clot over a period of weeks and months. Everyone’s biochemistry is unique in terms of how long this process takes. Approximately 44% of patients, if they leave the hospital with an enlarged right ventricle, will have permanent pulmonary hypertension and potentially right-heart failure, which are the risks of allowing the body to do its own thrombolytic work. If the right-heart dilatation can be reversed immediately, not only will these patients have a brighter long-term outlook, their immediate hospital stay is much shorter. Traditionally at East Jefferson Hospital, if these patients were admitted to the ICU and could be converted to warfarin after being given heparin, they were in the hospital for 10 days, 3-to-4 of which were spent in the ICU. Today, our protocol calls for completion of treatment in 12 hours in the ICU, with a total hospital stay of only 5 days. Thus, the patient’s length of stay is literally cut in half, which is naturally of interest to our administrators.

Is an embolic filter device used when performing this procedure?

I don’t find it necessary to use a filter to prevent more clot from embolizing when performing the procedure. However, after the procedure is performed, an inferior vena cava (IVC) filter is placed in selected patients. All of our patients undergo a hematology consultation before the procedure to rule out hypercoagulable inheritable disorders such as protein C and protein S deficiencies, factor V Leiden, and so forth. Four of the 30 patients we treated were found to have one of these disorders. If a patient tests positive for one of these clotting disorders, he will receive a filter and will remain on warfarin lifelong, because the risk of re-formation of DVT or PE is significant. Cancer patients with a massive or submassive PE are hypercoagulable, and will therefore also receive a filter. If, however, a patient with DVT is young, has just spent long hours in an airplane — a known risk for DVT — and proves not to be hypercoagulable, we will tend to treat this patient with warfarin for 6 months without the use of a filter. I have treated a series of patients with clotted filters and have used the EkoSonic device to de-clot the filter. Thus, filter placement is not without its complications. These are good devices, but we must individualize each case and use these filters to the best advantage of our patients.

What about the ULTIMA trial that was recently launched?

The ULTIMA trial (Ultrasound Accelerated Thrombolysis of Pulmonary Embolism) commenced a few weeks ago in Europe. Dr. Nils Kucher, in Bern, Switzerland, is the primary investigator. This is a randomized clinical trial comparing anticoagulation alone versus ultrasonic-enhanced thrombolysis using a catheter. ULTIMA will not include the United States. However, EKOS Corporation is planning a single-arm U.S. study which will start in 2011. The details of the study have not yet been determined.

Do you think ultrasonic-enhanced thrombolysis will be the new definitive treatment modality for massive and submassive PE?

Yes. I think that ultrasonic-enhanced thrombolysis will be the treatment of choice for massive and submassive PE. Its proven safety and efficacy, in my view, will be realized not just with the 30 patients I have treated, but with the other patients who have been treated throughout the country — as well as patients who will be treated in the single-arm U.S. study.

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Tod C. Engelhardt, MD, FACS, has served as Chairman of Cardiovascular & Thoracic Surgery at East Jefferson General Hospital as well as Hospital Chief of Staff. He has published numerous articles in a variety of peer-reviewed medical journals. Dr. Engelhardt earned his medical degree from the Tulane University School of Medicine and completed his Cardiovascular-Thoracic Fellowship at the Ochsner Foundation Hospital. Dr. Engelhardt has completed three medical missions to Nicaragua, performing cardiac surgery to indigent patients and was honored for his performance of the first coronary artery bypass in the history of Nicaragua.