Comparison of Different TEE-Guided Thrombolytic Regimens for Prosthetic Valve Thrombosis: The TROIA Trial

Study Questions:

What is the safest and most effective regimen among different thrombolytic treatment strategies for the treatment of prosthetic valve thrombosis?


Transesophageal echocardiography (TEE)-guided thrombolytic treatment was administered at a single center to 182 consecutive patients (156 women; mean age, 43.2 ± 13.06 years) with prosthetic valve thrombosis in 220 different episodes between 1993 and 2009, in the TROIA (Comparison of Different TRansesophageal Echocardiography Guided thrOmbolytic Regimens for prosthetIc vAlve Thrombosis) trial. Prosthetic heart valve thrombosis was diagnosed by TEE after patient presentation with either a thromboembolic event or persistently sub-therapeutic international normalized ratio (INR) and transthoracic echocardiography (TTE) revealed either prosthetic valve dysfunction or thrombus. Treatment regimens chronologically included rapid (3-hour) streptokinase (1993-1997, n = 16, Group I), slow (24-hour) streptokinase (1997-2001, n = 41, Group II), high-dose (100 mg) tissue plasminogen activator (t-PA; 2001-2002, n = 12, Group III), half-dose (50 mg) and slow infusion (6 hours) of t-PA without bolus (2002-2005, n = 27, Group IV), and low-dose (25 mg) and slow infusion (6-hour) t-PA without bolus (2005-2009, n = 124, Group V). TTE and TEE were repeated after therapy. Measured endpoints were thrombolytic success, in-hospital mortality, and nonfatal complication rates. Successful thrombolysis was defined as one (partial success) or all (complete success) of: Doppler documentation of decreased gradients, symptomatic improvement, and ≥75% decrease in thrombus diameter or area.


The overall success rate in the whole series was 83.2%; it did not differ significantly among Groups I-V (68.8%, 85.4%, 75%, 81.5%, and 85.5%, respectively; p = 0.46). The overall complication rate in the whole series was 18.6%. Although the overall complication rate was similar among Groups I-IV (37.5%, 24.4 %, 33.3%, and 29.6%, respectively; p > 0.05 for each comparison), it was significantly lower in Group V (10.5%, p < 0.05 for each). The combined rates of mortality and nonfatal major complications also were lower in Group V than in the other groups, with all differences significant except for comparison of Groups IV and V. By multivariate analysis, the predictors of combined mortality plus nonfatal major complications were any thrombolytic therapy regimen other than Group V (odds ratios for Groups I-IV: 8.2, 3.8, 8.1, and 4.1, respectively; p < 0.05 for each) and a history of stroke/transient ischemic attack (odds ratio, 3.5; p = 0.01). No mortality was observed among patients in Group V.


Low-dose slow infusion of t-PA repeated as needed and without a bolus provided effective and safe thrombolysis in patients with prosthetic valve thrombosis.


Prosthetic heart valve thrombosis is a relatively rare, but potentially catastrophic event. Cardiac surgery can be performed as definitive therapy, albeit with historically high rates of mortality. A number of smaller studies and case reports describe the use of thrombolytic therapy as an alternative to cardiac surgery, but there is no current consensus about thrombolytic agent type, dose, and administration. This report is of interest for the number of patients treated, and for its findings of maintained therapeutic success with fewer associated complications with slow infusion of t-PA 25 mg with no bolus. Of note, this study did not compare thrombolytic therapy with surgical intervention, and the optimal treatment of patients with prosthetic valve thrombosis will remain open to debate.

Clinical Topics: Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Cardiac Surgery and VHD, Lipid Metabolism, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound

Keywords: Heart Valve Prosthesis, Thrombolytic Therapy, Ischemic Attack, Transient, Streptokinase, Fibrinolysis, Heart Valve Diseases, Cardiovascular Diseases, Risk Factors, Fibrinolytic Agents, Tissue Plasminogen Activator, Cardiac Surgical Procedures, Echocardiography, Transesophageal

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