Ultrasound Catheter Speeds Clot Lysis, Recanalization

BY MITCHEL L. ZOLER

MIAMI BEACH -- A catheter that delivers ultrasound energy while infusing a lytic drug led to fast clot lysis and artery recanalization, and a low rate of major bleeds in a series of 66 patients with peripheral artery occlusions treated at 13 medical centers in the United States.

Faster clot lysis makes same-day treatment possible and lowers treatment cost, Dr. Thomas O. McNamara said at the 18th International Symposium on Endovascular Therapy.

For peripheral vessel occlusions, "the future of lysis is to shorten it. If we can reduce the duration of thrombolysis we can probably cause less bleeding," said Dr. McNamara, chief of the interventional radiology service at the University of California, Los Angeles.

The Lysus catheter is a 5-French diameter device that comes in 6-50 cm lengths. It contains channels for infusing a drug along the entire length, as well as spaced transducers that produce ultrasound pulses at 2.2 MHz for every 1 cm of catheter length. Ultrasound opens the fibrin matrix of a clot in a way that's similar to abciximab, the antiplatelet IIb/IIIa inhibitor, said Dr. McNamara. It also helps drive the lytic solution throughout the clot. In the patients treated so far, a variety of thrombolytic drugs have been used: tenecteplase (TNKase), reteplase (Retavase), alteplase (Activase), and urokinase. The lytic agent is selected at the discretion of each treating physician. The catheter received FDA approval in 2004, but widespread marketing did not start until this year. Dr. McNamara is a consultant to Ekos, which makes the Lysus catheter.

By December 2005, 145 patients had been treated with the catheter at 13 centers in the United States. The total included 77 patients with peripheral arterial occlusions, 40 patients with deep vein thrombosis, and the remaining 28 with other occlusions, including some patients with strokes. Dr. McNamara presented results for 66 patients who had complete follow-up information available. The 66 patients had occlusions that had been in place for 3-180 days.

For the entire series of 66 patients, follow-up angiographic assessments were done an average of 17.5 hours after the start of treatment. At follow-up, complete clot lysis had occurred in 58 patients (88%), with 1 patient (1.5%) having a major bleed (a bleeding event that required transfusion, surgery, or cessation of treatment) and 1 patient (1.5%) with distal embolization. In all 145 patients who had been treated with the ultrasound catheter through the end of last year, 3 (2.1%) had major bleeds.

As a comparison, Dr. McNamara, cited data collected for conventional thrombolysis with urokinase in the Thrombolysis or Peripheral Arterial Surgery (TOPAS) trial, published in 1998, which established catheter-based thrombolysis as an alternative to surgery for peripheral occlusions (N. Engl. J. Med. 1998;338:1105-11). In TOPAS, the average angiographic follow-up was after 24.4 hours of treatment, at which time 68% of the 243 treated patients had complete clot lysis. The rate of major bleeds was 12.5%, and the rate of distal embolization was 14.6%.

In the current Lysus study, a subgroup of 27 patients treated with the Lysus catheter system were assessed by angiography 2-8 hours after treatment, and 82% had complete clot lysis. This subgroup included 13 patients who were examined 4-6 hours after treatment; of them, 62% had complete lysis and 85% had some degree of restored blood flow. The 4-6-hour subgroup was noteworthy because it corresponded to a subgroup of 49 patients in the TOPAS study who also were examined by angiography 4-6 hours after the start of treatment. In the TOPAS early subgroup, complete lysis occurred in 22%, with 69% having some degree of restored flow, said Dr. McNamara. Among the arterial patients treated with the ultrasound catheter so far, 70% had their treatment finished on the same day it started, and in this subgroup 76% were discharged the same day.

The ultrasound catheter has a temperature sensor at its distal tip to monitor restoration of blood flow without angiography. The ultrasound produces local warming of the patient's blood, but as flow is restored and more blood flows past the tip, the warming effect diminishes and measured temperature falls.

When asked to comment upon this article, Dr. Brian G. Rubin, associate professor of surgery and radiology, section of vascular surgery at the Washington University School of Medicine, St. Louis, stated: "Several aspects of Lysus catheter-assisted thrombolysis make it appealing to interventional proceduralists. First, the clots treated with the Lysus catheter were older than those treated in the TOPAS trial, suggesting that ultrasound-assisted lysis will allow clinicians to tackle more chronic or mature occlusions.

"Second, while the numbers in the Lysus trial are small, the rate of procedure-related major bleeding appears to be substantially lower than rates reported in other trials of thrombolytic therapy alone. Finally, the measurement of tip temperature to detect restoration of flow can serve as a simple method of knowing when to return the patient to the fluoroscopy suite for re-imaging of the treated area. This combination of advances will allow for treatment of a broader range of thrombotic occlusions with increased safety, expedience, and efficiency," Dr. Rubin concluded.