Submassive Pulmonary Embolism: The Impact of Early Clot Reduction with Ultrasound-Accelerated Thrombolysis on Pulmonary Hypertension
Rationale: Submassive pulmonary embolism (PE) is an established risk factor for the development of chronic thromboembolic pulmonary hypertension (CTEPH), particularly when the initial pulmonary artery systolic pressure (PASP) is >50 mmHg. Ultrasound-accelerated thrombolysis (USAT) rapidly reduces clot burden in submassive PE. We investigated the impact of early clot reduction by USAT on pulmonary hypertension following submassive PE.
Methods: Patients with acute submassive PE treated with concurrent intravenous unfractionated herapin and USAT with the EkoSonic MACH4e Endovascular System (EKOS Corporation, Bothwell, WA) were retrospectively studied. PE was diagnosed by CT angiography (CTA). Submassive was defined as right ventricular dysfunction (RVD) with hemodynamic stability. RVD criteria included a combination of: Right Ventricular/Left Ventricular (RV/LV) diameter ratio on CTA >1.0, RV systolic dysfunction or estimated PASP>50 mmHg by transthoracic echocardiogram, and elevated troponin I or brain-type natriuretic peptide. TPA dose was 0.5 mg/hr/catheter for bilateral USAT (unilateral: 1.0 mg/hr). Pulmonary artery pressure (PAP) was obtained during catheterization immediately pre/post-USAT. Targeted activated partial thromboplastin time during USAT was 40-60 seconds. Clot burden was assessed by the Miller index, calculated by two independent observers. utilizing arteriography. Safety outcomes were assessed.
Results: Nineteen patients (9 men, 10 female; age 36±18) were identified. Eighteen patients underwent bilateral USAT. Mean tPA infusion time was 22 hours. Mean RV/LV ratio was 1.37. Clot burden was reduced by 72% (Miller index 18±3 to 5±2; p<0.0001). Mean PAP decreased by 6 mmHg (40 mmHg±9 to 34 mmHg±9; p<0.0029). A subgroup (n=5) was identified who despite a 76% reduction in clot burden, mean PAP did not change at 23 hours. Furthermore, 3/12 patients with initial PASP>50 mmHg showed no change in PAP after USAT and on follow-up. No bleeding complications occurred.
Conclusions: USAT with continuous herapin proved safe and effective in reducing clot burden at 22 hours. Pulmonary hypertension was reduced in a majority of cohort; however, one fourth of the patients had no improvement in mean PAP despite over 70% clot burden reduction. this finding suggests factors other than thrombotic obstruction, such as pre-existing CTEPH, other causes of PH, or vasoconstriction may be driving PH association with submassive PE. Lack of hemodynamic improvement despite clot reduction immediately following USAT may identify patients at risk for or pre-existing CTEPH. Long-term follow-up is essential to evaluate the impact of USAT on the development of CTEPH.
American Thoracic Society International Conference (ATS)
Reber, Ryan D., Ravi Desai, Matthew Hegewald, Daniel Sheibley, Joseph Bonn, Peter A. Villas, Haresh Rochani, Lee W. Greenspon.
"Submassive Pulmonary Embolism: The Impact of Early Clot Reduction with Ultrasound-Accelerated Thrombolysis on Pulmonary Hypertension."
Biostatics Faculty Presentations.