title: A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study.
abstract: OBJECTIVE
  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).
authors: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: gpiazza@partners.org.
authors: Gregory
authors: G
authors: Piazza
authors: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Benjamin
authors: B
authors: Hohlfelder
authors: Cardiovascular Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Michael R
authors: MR
authors: Jaff
authors: Syntactx, New York, New York.
authors: Kenneth
authors: K
authors: Ouriel
authors: East Jefferson General Hospital, Metairie, Louisiana.
authors: Tod C
authors: TC
authors: Engelhardt
authors: Cardiovascular and Interventional Associates, INOVA Alexandria Hospital, Alexandra, Virginia.
authors: Keith M
authors: KM
authors: Sterling
authors: Mt. Carmel East Hospital, Columbus, Ohio.
authors: Noah J
authors: NJ
authors: Jones
authors: Gill Heart Institute, University of Kentucky, Lexington, Kentucky.
authors: John C
authors: JC
authors: Gurley
authors: Florida Heart Group, Florida Hospital, Orlando, Florida.
authors: Rohit
authors: R
authors: Bhatheja
authors: Holmes Regional Medical Center, Melbourne, Florida.
authors: Robert J
authors: RJ
authors: Kennedy
authors: Prairie Heart Institute, St. John's Hospital, Springfield, Illinois.
authors: Nilesh
authors: N
authors: Goswami
authors: St. Vincent Medical Group, Indianapolis, Indiana.
authors: Kannan
authors: K
authors: Natarajan
authors: Holy Name Medical Center, Teaneck, New Jersey.
authors: John
authors: J
authors: Rundback
authors: Vascular Medicine Division, Hartford Hospital, Hartford, Connecticut.
authors: Immad R
authors: IR
authors: Sadiq
authors: Lifelink Interventional Center, Memorial Medical Center, Modesto, California.
authors: Stephen K
authors: SK
authors: Liu
authors: River Region Cardiology Associates, Baptist Medical Center, Montgomery, Alabama.
authors: Narinder
authors: N
authors: Bhalla
authors: El Paso Cardiology Associates, PA, Providence Memorial Hospital and Sierra Medical Hospital, El Paso, Texas.
authors: M Laiq
authors: ML
authors: Raja
authors: Leesburg Regional Medical Center, Leesburg, Florida.
authors: Barry S
authors: BS
authors: Weinstock
authors: Division of Vascular Intervention Radiology, Department of Radiology, Montefiore Medical Center, Bronx, New York.
authors: Jacob
authors: J
authors: Cynamon
authors: Radiology and Imaging Specialists of Lakeland, Lakeland Regional Medical Center, Lakeland, Florida.
authors: Fakhir F
authors: FF
authors: Elmasri
authors: Christiana Care Center for Heart and Vascular Health, Newark, Delaware.
authors: Mark J
authors: MJ
authors: Garcia
authors: The Cardiovascular Care Group, Overlook Medical Center, Summit, New Jersey.
authors: Mark
authors: M
authors: Kumar
authors: Macon Cardiovascular Institute, Medical Center of Georgia, Macon, Georgia.
authors: Juan
authors: J
authors: Ayerdi
authors: Miriam Cardiology Inc., The Miriam Hospital, Providence, Rhode Island.
authors: Peter
authors: P
authors: Soukas
authors: Stanford University, Stanford, California.
authors: William
authors: W
authors: Kuo
authors: Fred Hutchinson Cancer Center, Seattle, Washington.
authors: Ping-Yu
authors: PY
authors: Liu
authors: Cardiovascular Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Samuel Z
authors: SZ
authors: Goldhaber
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D002406:Catheterization, Peripheral / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D004867:Equipment Design; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012307:Risk Factors; D012720:Severity of Illness Index; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D014481:United States; D062666:Vascular Access Devices
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: catheter embolectomy; catheter thrombolysis; fibrinolysis; pulmonary embolism; right ventricular failure; thrombolysis