Response to—Current evidence and future perspective for the management of left sided prosthetic valve thrombosis

We appreciated Guner et al.’s valuable comments regarding our study. We too believe that the ultraslow thrombolytic regimen in the treatment of obstructive mechanical prosthetic valve thrombosis (PVT), which was first introduced by the valuable work of Ozcan et al.1,2 and used in our study, is still underappreciated by many international guidelines and should probably become a first-choice strategy as an alternative to surgery. Notably, the latest American College of Cardiology (ACC)/American Heart Association (AHA) guidelines have endorsed the ultraslow thrombolytic regimen as the main thrombolytic strategy in non-critically-ill patients with right-sided PVT and also left-sided PVT without large clot burden.3 At variance, the latest European Society of Cardiology (ESC) guidelines still recommend urgent surgery as the preferred treatment strategy in all patients with PVT without much consideration of patients’ characteristics, such as the right- vs. left-sided location of thrombosis or the thrombotic burden.4 The latter guidelines do not consider newer thrombolytic infusion regimens, such as the ultraslow strategy tested by us. The ESC guideline recommendations were mainly based on the meta-analysis by Karthikeyan et al., comparing urgent surgery and fibrinolytic therapy in patients with PVT, and reporting that the rates of complete success (defined as the complete restoration of valvular function) and mortality were not different between the two treatment strategies, whereas thromboembolism, major bleeding, and recurrent PVT were higher with fibrinolysis.5 Notably, however, the majority of studies in their meta-analysis used full-dose systemic thrombolytic therapy, half of them used streptokinase as their main thrombolytic agent, and more than one-third of the patients were treated with a combination of two or more fibrinolytic agents. The lowest dose of fibrinolytic agents in studies included in that meta-analysis was 50 mg of recombinant tissue plasminogen activator (tPA) given in 3 h.5 Consequently, the ultraslow regimen applied by Ozcan et al.1,2 and used in our study6 was neither tested nor compared in that analysis. The pooled rates of different outcomes in the meta-analysis of Karthikeyan et al. and in two studies using the ultraslow thrombolytic regimens2,6 are summarized in Table 1.