Acute pulmonary embolism (PE) is a potentially life-threatening condition, reporting an overall mortality rate of 15% in the first three months after diagnosis. The literature describes a three-tier risk stratification scale (massive, submassive and minor) based on the hemodynamic status and presence of signs/symptoms. Tod C. Engelhardt, MD, Louisiana Heart, Lung and Vascular Institute, East Jefferson General Hospital (Metairie, LA) reported at the 40th Annual VEITHsymposium in New York stating, "Massive PE patients present with critical conditions, such as severe right ventricular (RV) dysfunction, systemic arterial hypotension or cardiogenic shock, and require immediate intervention. Submassive PE patients, while systemically normotensive, exhibit RV dysfunction and are typically managed conservatively. These patients represent a serious unmet need for advanced therapy to restore the hemodynamic impairment, given that RV dysfunction if unresolved promptly predicts poor outcome, including death."
Engelhardt reports that intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA) allows reversal of hemodynamic compromise and gas exchange derangement, and is considered a life-saving therapy for massive PE patients. For submassive PE patients, the recently completed PEITHO trial demonstrated a reduction of a combined endpoint of 7-day cardiopulmonary collapse and mortality with treatment by IV Tenecteplase compared to placebo. However, widespread adoption of IV thrombolysis is hampered by increased risk of major bleeding, including intracranial hemorrhage reported at 3% historically and at 2% specifically in PEITHO. Engelhardt said, "Ultrasound-accelerated thrombolysis (USAT), enabled by the EkoSonic® Endovascular System is an advanced catheter-directed modality that facilitates localized delivery of rtPA into the pulmonary thrombus. The ultrasonic energy increases thrombus permeability and facilitates deep penetration of the drug into the thrombus, which accelerates clot dissolution using only a fraction the standard IV rtPA dose."
In his presentation Engelhardt cited his institutional approach for acute PE, employs USAT as the primary therapy for both massive and submassive patients. Upon identification of signs/symptoms consistent with PE and confirmation of PE by computer tomographic angiography (CTA) of the chest, the patient is referred to Cardiovascular and Thoracic Surgery. Based on presence of RV strain defined as the right-ventricle-to-left-ventricle diameter (RV/LV) ratio at end-diastole exceeding 0.9, the patient undergoes USAT using a low-dose rtPA infusion protocol. The early experience with USAT examined varied doses and infusion durations. He went on to report that the current protocol has been standardized to a total dose of 24 mg rtPA infused at 1.0 mg/hour/catheter (12 hours in bilateral; 24 hours in unilateral PE) with no bolus.
Engelhardt emphasized, "We retrospectively evaluated PE patients treated with USAT with follow-up chest CTA at 48±6 hours post infusion. 57 patients (age 58±15 yrs) have been included during the study period from 2009-2013, with 15 new patients enrolled since last reported in 2012. There were 7 massive and 50 submassive PE cases. 52 patients (91%) presented with bilateral PE. Overall, a rtPA dose of 29.5±14.8 mg was infused over 17.2±6.6 hours. Following USAT, the RV/LV ratio was reduced from 1.5±0.4 at baseline to 1.0±0.2 at follow-up CTA (p<0.001). 30-day follow-up CTA available in 6 patients demonstrated further decrease of the RV/LV ratio (to a range of 0.6-0.9). Overall, median length of stay was 1 day in the ICU and 7 days in the hospital. All patients were discharged alive. There were no systemic bleeding complications, but 4 access site bleeding complications requiring transfusion and 1 suspected recurrent massive PE event; all reported in our early experience involving higher rtPA doses at the range of 45 mg, but no bleeds reported in the current protocol with 24 mg. In summary, our analysis demonstrated rapid resolution of RV dysfunction among both massive and submassive PE patients from USAT, with evidence of continued improvement with time." "These results support that the catheter-based modality allows hemodynamic recovery consistent with that observed in IV thrombolysis, while minimizing the serious bleeding risks associated with IV therapy," concluded Engelhardt.