Overview

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of cardiovascular mortality. While systemic thrombolysis is the standard treatment for high-risk PE, its bleeding risk limits use in some patients, highlighting the need for alternative reperfusion strategies such as catheter-directed thrombolysis (CDT). This prospective study will evaluate the safety and efficacy of CDT using the EkoSonic Endovascular System (EKOS; Boston Scientific) in patients with intermediate-high and high-risk PE. The primary outcome is all-cause mortality through 360 days of follow-up, with secondary outcomes including changes in echocardiographic parameters such as the RV/LV diameter ratio.

Eligibility

Inclusion Criteria:

• Adults aged ≥ 18 years at time of enrollment;
• Ability to provide written informed consent (or legally authorized representative consent where applicable);
• Objectively confirmed acute pulmonary embolism (PE) by contrast-enhanced computed tomography pulmonary angiography (CTPA) demonstrating intraluminal filling defects in at least one segmental, lobar, or more proximal pulmonary artery;
• Hemodynamically stable at presentation (i.e., not meeting high-risk PE criteria of sustained hypotension, shock, or need for vasopressor support per ESC 2019 and AHA/ACC risk stratification);
• Evidence of right ventricular (RV) dysfunction on imaging (e.g., RV/LV ratio \> 1.0 on CTPA or echocardiography);
• Elevated cardiac biomarkers, including troponin I or T above the upper limit of normal;
• Intermediate-high risk features defined as the combination of imaging RV dysfunction and positive cardiac biomarkers, consistent with ESC stratification;
• At least one clinical indicator of elevated early risk such as:
  1. Tachycardia (e.g., HR ≥ 100 bpm),
  2. Mild systolic blood pressure reduction (e.g., SBP ≤ 110 mmHg but not meeting high-risk thresholds),
  3. Hypoxemia (SpO₂ \< 90% on room air).

Exclusion Criteria:

• Presence of hemodynamic instability, defined as at least one of the following:
  1. Systolic blood pressure (SBP) \< 90 mmHg or a drop ≥ 40 mmHg from baseline for \> 15 minutes not attributable to arrhythmia, hypovolemia, or sepsis,
  2. Requirement for vasopressors to maintain SBP ≥ 90 mmHg,
  3. Cardiogenic shock, defined by clinical signs of end-organ hypoperfusion (e.g., altered mental status, oliguria, lactate elevation),
  4. Need for ECMO or other mechanical circulatory support initiated prior to assessment,
  5. Cardiac arrest requiring resuscitation.
• Active major bleeding or conditions with high bleeding risk (e.g., known intracranial pathology predisposed to hemorrhage or associated with ongoing pharmacotherapy);
• Recent (\< 3 months) intracranial or intraspinal surgery, major trauma, or stroke;
• Known central nervous system neoplasm or metastatic cancer with high bleed risk.
• Administration of systemic thrombolytic agents or catheter-directed thrombolysis prior to registry assessment for the index PE episode;
• Known hypersensitivity to alteplase, unfractionated heparin (UFH), or any of their excipients.
• Requirement for intensive care admission for conditions unrelated to the index PE;
• Duration of symptoms attributable to the index PE \> 14 days at presentation, as defined in contemporary trial criteria;
• Known severe thrombocytopenia (e.g., platelet count \< 100 × 10⁹/L) or coagulopathy precluding safe catheter access;
• Life expectancy \< 6 months due to advanced comorbid disease unrelated to acute PE;
• Pregnancy.