Author + information
- Received April 17, 2015
- Accepted April 23, 2015
- Published online August 24, 2015.
- Gregory Piazza, MD, MS1,∗ (, )
- Benjamin Hohlfelder, PharmD1,
- Michael R. Jaff, DO2,
- Kenneth Ouriel, MD3,
- Tod C. Engelhardt, MD4,
- Keith M. Sterling, MD5,
- Noah J. Jones, MD6,
- John C. Gurley, MD7,
- Rohit Bhatheja, MD8,
- Robert J. Kennedy, MD9,
- Nilesh Goswami, MD10,
- Kannan Natarajan, MD11,
- John Rundback, MD12,
- Immad R. Sadiq, MD13,
- Stephen K. Liu, MD14,
- Narinder Bhalla, MD15,
- M. Laiq Raja, MD16,
- Barry S. Weinstock, MD17,
- Jacob Cynamon, MD18,
- Fakhir F. Elmasri, MD19,
- Mark J. Garcia, MD20,
- Mark Kumar, MD21,
- Juan Ayerdi, MD22,
- Peter Soukas, MD23,
- William Kuo, MD24,
- Ping-Yu Liu, PhD25,
- Samuel Z. Goldhaber, MD2,
- SEATTLE II Investigators
- 1Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- 2Cardiovascular Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- 3Syntactx, New York, New York
- 4East Jefferson General Hospital, Metairie, Louisiana
- 5Cardiovascular and Interventional Associates, INOVA Alexandria Hospital, Alexandra, Virginia
- 6Mt. Carmel East Hospital, Columbus, Ohio
- 7Gill Heart Institute, University of Kentucky, Lexington, Kentucky
- 8Florida Heart Group, Florida Hospital, Orlando, Florida
- 9Holmes Regional Medical Center, Melbourne, Florida
- 10Prairie Heart Institute, St. John’s Hospital, Springfield, Illinois
- 11St. Vincent Medical Group, Indianapolis, Indiana
- 12Holy Name Medical Center, Teaneck, New Jersey
- 13Vascular Medicine Division, Hartford Hospital, Hartford, Connecticut
- 14Lifelink Interventional Center, Memorial Medical Center, Modesto, California
- 15River Region Cardiology Associates, Baptist Medical Center, Montgomery, Alabama
- 16El Paso Cardiology Associates, PA, Providence Memorial Hospital and Sierra Medical Hospital, El Paso, Texas
- 17Leesburg Regional Medical Center, Leesburg, Florida
- 18Division of Vascular Intervention Radiology, Department of Radiology, Montefiore Medical Center, Bronx, New York
- 19Radiology and Imaging Specialists of Lakeland, Lakeland Regional Medical Center, Lakeland, Florida
- 20Christiana Care Center for Heart and Vascular Health, Newark, Delaware
- 21The Cardiovascular Care Group, Overlook Medical Center, Summit, New Jersey
- 22Macon Cardiovascular Institute, Medical Center of Georgia, Macon, Georgia
- 23Miriam Cardiology Inc., The Miriam Hospital, Providence, Rhode Island
- 24Stanford University, Stanford, California
- 25Fred Hutchinson Cancer Center, Seattle, Washington
- ↵∗Reprint requests and correspondence:
Dr. Gregory Piazza, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
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)
- catheter embolectomy
- catheter thrombolysis
- pulmonary embolism
- right ventricular failure
This study was funded by a research grant from EKOS, a BTG International group company. Dr. Piazza receives research support from EKOS, Bristol-Myers Squibb, Daiichi-Sankyo, and Janssen. Dr. Jaff is a noncompensated member of the Data Safety and Monitoring Board of EKOS and a Board member of VIVA Physicians, a 501(c)(3) not-for-profit education and research organization. Dr. Ouriel holds equity in and is an employee of Syntactx, which receives fees for core laboratory activities from EKOS. Dr. Jones receives honoraria for serving on the Speaker Bureau of Medtronic and EKOS; and receives consulting fees from Cordis. Drs. Engelhardt, Sterling, Gurley, Bhatheja, Kennedy, Goswami, Natarajan, Rundback, Sadiq, S.K. Liu, Bhalla, Raja, Weinstock, Cynamon, Elmasri, Garcia, Kumar, Ayerdi, Soukas, Kuo, and Goldhaber has received research support from EKOS, a BTG International Group company. Dr. P.-Y. Liu receives consulting fees from EKOS. Dr. Bhatheja is a speaker for St. Jude Medical and Cardiovascular Systems Inc. Dr. Goswami is a consultant for Boston Scientific. Dr. Gurley is a speaker for EKOS. Dr. Weinstock is a consultant for W.L. Gore. Dr. Hohfelder has reported that he has no relationships relevant to the contents of this paper to disclose.
The results of this prospective, single-arm, multicenter trial were presented in abstract form on March 30, 2014 at the American College of Cardiology Annual Scientific Sessions in Washington, DC.
- Received April 17, 2015.
- Accepted April 23, 2015.
- 2015 American College of Cardiology Foundation