ABSTRACT
OBJECTIVES: This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND: Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS: Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS: Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS: Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).
Subject(s)
Catheterization, Peripheral , Fibrinolytic Agents/administration & dosage , Pulmonary Embolism/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Ultrasonic Therapy , Acute Disease , Adult , Aged , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/instrumentation , Catheterization, Peripheral/mortality , Equipment Design , Female , Fibrinolytic Agents/adverse effects , Hemorrhage/chemically induced , Humans , Hypertension, Pulmonary/etiology , Hypertrophy, Right Ventricular/etiology , Male , Middle Aged , Prospective Studies , Pulmonary Embolism/complications , Pulmonary Embolism/diagnosis , Pulmonary Embolism/mortality , Risk Factors , Severity of Illness Index , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/instrumentation , Thrombolytic Therapy/mortality , Time Factors , Tissue Plasminogen Activator/adverse effects , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonic Therapy/adverse effects , Ultrasonic Therapy/instrumentation , Ultrasonic Therapy/mortality , United States , Vascular Access DevicesABSTRACT
OPINION STATEMENT: Submassive pulmonary embolism (PE) represents a patient population that is under-recognized and under-treated. Recent clinical trials demonstrated the hemodynamic benefit of IV thrombolytic therapy among these patients; however, it came at the cost of a significantly increased risk of major, particularly intracranial, hemorrhage. Catheter-based treatment modalities have garnered considerable clinical interest in recent years. In particular, ultrasound accelerated thrombolysis, a catheter-based technology that enhances the process of thrombolytic delivery into the thrombus, has emerged as a treatment modality with an increasing number of single-center studies, as well as randomized, controlled clinical trials. Results from these experiences are consistent in achieving outcomes of thrombus resolution and hemodynamic recovery with a low dose thrombolytic infusion protocol, but without the high risk of bleeding complications associated with IV thrombolysis. The clinical data will hopefully be impactful to the development of the next edition of the treatment guidelines, in support of overall recommendations for catheter-based interventions. When available and with appropriate expertise, this modality should be considered as the preferred treatment of both massive and submassive PE.
ABSTRACT
BACKGROUND: Systemic thrombolysis rapidly improves right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) but is associated with major bleeding complications in up to 20%. The efficacy of low-dose, catheter-directed ultrasound-accelerated thrombolysis (USAT) on the reversal of RV dysfunction is unknown. MATERIALS AND METHODS: We performed a retrospective analysis of 24 PE patients (60 ± 16 years) at intermediate (n = 19) or high risk (n = 5) from the East Jefferson General Hospital who were treated with USAT (mean rt-PA dose 33.5 ± 15.5mg over 19.7 hours) and received multiplanar contrast-enhanced chest computed tomography (CT) scans at baseline and after USAT at 38 ± 14 hours. All CT measurements were performed by an independent core laboratory. RESULTS: The right-to-left ventricular dimension ratio (RV/LV ratio) from reconstructed CT four-chamber views at baseline of 1.33 ± 0.24 was significantly reduced to 1.00 ± 0.13 at follow-up by repeated-measures analysis of variance (p < 0.001). The CT-angiographic pulmonary clot burden as assessed by the modified Miller score was significantly reduced from 17.8 ± 5.3 to 8.7 ± 5.1 (p < 0.001). All patients were discharged alive, and there were no systemic bleeding complications but four major access site bleeding complications requiring transfusion and one suspected recurrent massive PE event. CONCLUSIONS: In patients with intermediate and high risk PE, low-dose USAT rapidly reverses right ventricular dilatation and pulmonary clot burden.
