Ultrasound Thrombolysis a Quick Clot Buster



NEW YORK – Ultrasound-accelerated thrombolysis treatment of submassive pulmonary embolism reduced right ventricular dilatation and the risk of heart failure, according to the results of a retrospective study of 29 patients at one facility.

"My end point is not so much seeing 100% clot clearance. My main goal of therapy is to see that regression of the right ventricle. We want to see that [right ventricle/left ventricle] ratio go back to normal to prevent long-term sequelae," said Dr. Tod C. Engelhardt, who presented the study results at the Veith Symposium on Vascular Medicine sponsored by the Cleveland Clinic.

Dr. Engelhardt and his colleagues found that ultrasound-accelerated thrombolysis (USAT) significantly reduced the right ventricle/left ventricle (RV/LV) ratio from 1.37 to 1.02 following treatment. All patients survived to hospital discharge, with a median time to follow-up CT of less than 48 hours. Symptoms such as dyspnea and difficulty speaking resolved 2-3 hours after the initiation of treatment.

"This is an interesting group because when they present, they don’t look too bad on paper or clinically," he said. These patients usually have normal blood pressure with minimal oxygen supplementation, but more than 90% have some dyspnea with exertion. About 40% of patients with PE have the submassive type, which has a 90-day mortality of 22%, compared with 58% for massive PE.

"The thing that separates them is right ventricular enlargement. They have impending right heart failure because of the right ventricular dilatation." An RV/LV ratio greater than 0.9 is considered significant, noted Dr. Engelhardt, chair of cardiovascular and thoracic surgery at East Jefferson General Hospital in Metairie, La.

Patients with persistent RV dysfunction at discharge are approximately eight times more likely to have recurrent PE and four times more likely to die, compared with patients in whom RV dysfunction had regressed at discharge.

"There has to be a high index of suspicion of PE," he said in an interview. Usually the emergency physician will have chest computed tomographic angiography (CTA) done. "Once you get the scan, you can see the PE and the right heart size. Then I get an echocardiogram and a duplex scan of the lower extremities" to look for deep vein thrombosis.

However, "I have found that the CTA gives me everything that I need in order to make a decision and to proceed with therapy. The CTA does two things for me. I can see the extent of the involvement of the pulmonary embolism, and I can measure the relative sizes of the right and left ventricles to generate that ratio. This allows me to categorize the patient as a submassive PE patient and to move forward with therapy," he said.

"Patients with massive and submassive emboli can be treated with USAT."

Once the diagnosis of PE is made, the patient is started on anticoagulant therapy. "I don’t think that hinders what I do; in fact, it complements it."

With a submassive PE patient, "once I make the diagnosis and the patient is already anticoagulated, my next step is to move to the cath lab to place catheters and start [USAT] treatment."

With USAT, ultrasound energy causes fibrin strands to thin and loosen, exposing plasminogen receptor sites. Thrombus permeability and thrombolytic penetration are dramatically increased. Ultrasonic pressure waves force the thrombolytic deep into the clot, allowing the drug to work faster and clear the clot sooner with a lower drug dose and without hemolysis.

The goal of USAT is to accelerate thrombolysis and rapidly reverse right ventricular dilatation and reduce pulmonary clot burden. This improves pulmonary perfusion and reduces right heart load. Because a lower drug dose (no more than 20 mg of recombinant tissue plasminogen activator [TPA]) is used than with conventional treatment, the risk of bleeding is significantly lowered. Aggressive management of submassive PE can prevent more harmful consequences later, according to Dr. Engelhardt.

Dr. Engelhardt reported on the experience at his center, where surgeons treated 32 PE patients with ultrasound-accelerated thrombolysis between February 2009 and June 2011.

They performed retrospective data analysis on 29 consecutive patients with pre- and posttreatment contrast-enhanced CT imaging, clinical history, RV/LV ratio reduction, and clot burden reduction. They used this information to identify the optimum drug dose as a maximum of 20 mg recombinant TPA over 12 hours. This dose resulted in good clinical outcomes with no bleeding complications.

Adverse effects were limited. There were no intracranial hemorrhages or systemic bleeding complications. Four patients had puncture site bleeding that required transfusion. One patient had suspected recurrent PE.

Although there has been "trepidation in changing the status quo of anticoagulation alone," he said, "patients with massive and submassive emboli can be treated with USAT. Certainly patients who are in cardiogenic shock may have time for a catheter placement and can be treated with systemic TPA. Many massive PE patients can be resuscitated so that they do have time for catheter placement."


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