ULTIMA: Ultrasound Accelerated Thrombolysis Shows Promise for Pulmonary Embolism
SAN FRANCISCO, CA—A novel method of delivering drug therapy via ultrasound assistance appears effective in reversing right ventricular enlargement and dysfunction in patients with submassive pulmonary embolism, according to results from a small study presented March 9, 2013, at the American College of Cardiology/i2 Scientific Session.
In the international, multicenter ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism (ULTIMA) trial, investigators led by Nils Kucher, MD, of University Hospital Bern (Bern, Switzerland), randomized 59 patients with submassive pulmonary embolism to IV heparin plus accelerated ultrasound with an endovascular device (EkoSonic Endovascular System, EKOS, Bothell, WA; n = 30) or heparin alone (n = 29). Patients in the device arm received a low dose (10 mg over 15 hours) of recombinant t-PA.
The endovascular device incorporates small ultrasound transmitters that cause fibrin strands to thin and loosen and expose plasminogen receptor sites. This results in increased thrombus permeability and thrombolytic penetration. Simultaneously, the ultrasonic pressure waves force the thrombolytic agent (recombinant t-PA) deep into the pulmonary thrombus.
Reduction Seen in Ventricular Ratio
The device was placed successfully in all patients randomized to receive it. Mean placement time was 42 minutes (range, 15 to 102 min). Patients in both groups were similarly matched with no differences in troponin status or pulmonary occlusion score.
The majority of patients (83%) in the device arm received 2 device implantations. Total recombinant t-PA dose per device was 12.2 ± 3.8 mg.
Overall, the ultrasound-accelerated strategy was superior to anticoagulation with heparin alone in reversing right ventricular dilatation and dysfunction at 24 hours. Furthermore, despite a late catch-up with heparin alone, there was greater improvement in right ventricular dilatation and dysfunction after low-dose, catheter-directed ultrasound-accelerated thrombolysis at 90 days. Bleeding outcomes, meanwhile, were equivalent (table 1).
Table 1. Reduction in Right Ventricular/Left Ventricular Ratio
|
|
Device + Heparin |
Heparin Alone |
P Value |
|
24 Hours |
0.30 |
0.03 |
< 0.0001 |
|
90 Days |
0.38 |
0.22 |
0.03 |
|
Major Bleeding at 90 days |
0 |
0 |
1.00 |
|
Minor Bleeding at 90 Days |
10% |
3% |
0.61 |
There was 1 death in the heparin-alone group unrelated to pulmonary embolism and no deaths in the accelerated ultrasound group. No cases of recurrent venous thromboembolism were reported in either group.
At a mean of 18 ± 3 hours after intervention, accelerated ultrasound resulted in a reduction from baseline in mean invasive pulmonary artery pressure (30.2 mm Hg vs. 24.6 mm Hg; P = 0.002) and an increase in cardiac index (2.5 l/min/m2 vs. 3.9 l/min/m2; P = 0.01).
Enhanced Thrombolysis
According to Dr. Kucher, the study demonstrates that the catheter-based strategy is “probably as effective as full-dose systemic thrombolysis” since reduction in ventricular ratio has been demonstrated to be similar.
He added that further studies are warranted to investigate whether the observed hemodynamic benefit from ultrasound-accelerated thrombolysis translates in improved clinical outcomes.
Session co-moderator Gary S. Mintz, MD, of the Cardiovascular Research Foundation, (New York, NY), asked if the ultrasound alone might be effective without the addition of a thrombolytic agent. But Dr. Kucher said there would likely be “no effect whatsoever,” adding that the mechanistic advantage appears to be enhancement of drug therapy through application of the ultrasound.
Study Details
The device used in the study was approved by the US Food and Drug Administration in 2005 for the treatment of blood clots and was further cleared for use in the pulmonary artery in 2008. It received CE mark approval in 2011 for massive and submassive pulmonary embolism.
Note: Dr. Mintz serves as Medical Director and Editor-in-Chief of TCTMD.
Source:Kucher N. The ULTIMA Trial: A prospective, randomized, controlled study of ultrasound accelerated thrombolysis for the treatment of acute pulmonary embolism. Presented at: American College of Cardiology Annual Scientific Session; March 9, 2013; San Francisco, CA.
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Read Full BioDisclosures
- Dr. Kucher reports receiving consulting fees and honoraria from Bayer, EKOS Corporation, and Sanofi Aventis.
- Dr. Mintz reports receiving consulting fees/honoraria from Boston Scientific, Volcano, and Lightlab, and serving on the speaker’s bureau for Pfizer.
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