Efficacy and safety of the ultraslow low-dose thrombolytic regimen for mechanical prosthetic valve thrombosis: a prospective cohort study

Abstract Background Mechanical prosthetic valve thrombosis (MPVT) remains a significant and life-threatening complication. While surgery is here considered the gold standard therapy, it has a high perioperative risk in the acute setting. Preliminary evidence suggests that an ultraslow low-dose thrombolytic regimen may offer a safer and equally effective alternative compared to both conventional fast-infusion thrombolytic approaches or surgical options. Purpose We aimed at evaluating efficacy and safety of a previously described ultraslow low-dose thrombolytic regimen for treating acute MPVT in hospitalized adult patients. Methods This prospective single-center cohort study included all consecutive adult patients with acute MPVT treated with our ultraslow low-dose thrombolytic regimen. Patients with contraindication to thrombolytic therapy or left-sided MPVT with a minimum thrombus size of 0.8 cm2 or severe dyspnea with NYHA FC IV were excluded, and considered candidate to surgery. The regimen here used consisted of 25 mg rtPA infused over 25 hours. If initially failed, a repeat 6-hour infusion of 25 mg rtPA was administered up to a maximum total cumulative dose of 150 mg or until an adverse event occurred. The primary objective was the rate of complete MPVT resolution, defined as >75% reduction in the obstructive gradient by transthoracic echocardiography, less than 10 degrees residual constraint in opening and closing valve motion angles as quantified by fluoroscopy, and alleviation of patients’ thrombosis-associated symptoms or signs. Results From April 2018 to November 2023, 135 infusions of thrombolytic therapy were administered in 118 patients (median age: 35 years (IQR, 25-49); 59 [50%] women) (Table 1). 12 patients had more than one episode of MPVT during the study period. Obstructive prosthetic valve thrombosis occurred in 89.6% (121/135) of cases. Pulmonary valves were most frequently affected (n = 84, 62.2%), followed by tricuspid (n = 34, 25.2%), mitral (n = 10, 7.4%), and aortic (n = 7, 5.2%) valves. A complete thrombolysis success was achieved in 119/135 episodes of thrombolytic therapy (88.1%); of these, 47/119 patients (39.5%) responded after the first thrombolytic dose. The median total dose administered was 50 mg (IQR, 25-75) over a median infusion duration of 30 hours (IQR, 25-36). Four patients responded partially to the regimen, six patients were candidates for bailout surgery, and only one fatal intracranial bleeding occurred. No other thromboembolic or bleeding adverse events were observed. Conclusion This is the largest prospective evaluation on the safety and efficacy of the ultraslow low-dose thrombolytic regimen, which proved highly effective - in this prospective cohort - in achieving prosthetic valve thrombosis resolution with minimal complications. Further larger clinical trials are warranted.Table 1- baseline CharacteristicsStudy Outcomes