Clinical Assessment of Sequential Slow and Ultra-Slow Thrombolysis Approaches for Stuck Prosthetic Valve Thrombosis as a Novel Dose-Adjusted Regimen Analysis (The Multicenter CASSANDRA Study)

Thrombolytic therapy (TT) using low-dose, slow, and ultra-slow infusions of tissue-type plasminogen activator (tPA) has become an established first-line treatment for prosthetic valve thrombosis (PVT). However, PVT with stuck valves represents a distinct clinical entity requiring tailored management. This study aimed to evaluate the effectiveness and safety of sequentially combining different TT regimens in patients with PVT and stuck valves. We enrolled 52 patients with PVT and stuck valves female: 34 (65.4%), mean age: 47.5 ± 12.4 years who underwent TT with sequential administration of slow (25 mg/6 h) and ultra-slow (25 mg/25 h) low-dose tPA regimens, based primarily on New York Heart Association (NYHA) functional class. All patients were assessed with cinefluoroscopy, transthoracic echocardiography, and transesophageal echocardiography. TT was successful in 46 patients (88.4%), with a median cumulative tPA dose of 120 mg (96-175). Major complications occurred in 3 patients (5.7%), including one cerebrovascular accident, one intracranial hemorrhage, and one gastrointestinal bleed requiring transfusion, while 6 patients (11.5%) experienced minor complications. One in-hospital death occurred (1.9%). Increased thrombus area was the only independent predictor of both failed TT and adverse events. A moderate positive correlation was observed between thrombus area and total tPA dose (r = 0.479; p < 0.001). In conclusion sequential use of slow and ultra-slow low-dose tPA infusion appears to be a safe and effective strategy for managing PVT with stuck valves. Nevertheless, patients with larger thrombus burden remain at increased risk for treatment failure and complications.