Abstract
We read with great interest the article by Sadiq et al reporting a 10-year single-center experience with thrombolysis for left-sided mechanical valve thrombosis, including a comparative analysis between streptokinase and tenecteplase and the identification of independent predictors of treatment failure. 1 The authors should be commended for providing one of the largest contemporary real-world cohorts in this challenging clinical scenario and for addressing a clinically relevant question that remains incompletely resolved in routine clinical practice. Their findings further highlight an increasingly important contemporary issue in prosthetic valve thrombosis management: although fibrin-specific agents and protocolized imaging-guided strategies may offer superior outcomes, streptokinase continues to represent a clinically relevant therapeutic option in carefully selected patients, particularly in resource-limited settings.
Several findings merit further discussion. First, the overall success rate of 76.3%, with an in-hospital mortality of 6.8% and a low incidence of major hemorrhage, is consistent with international registries and reinforces the continued relevance of fibrinolytic therapy in appropriately selected patients. Importantly, tenecteplase was associated with higher success (82.4% vs 70.9%) and lower mortality than streptokinase, despite a higher frequency of dosing deviations. These observations further support the growing preference for fibrin-specific agents when thrombolysis is chosen and suggest more predictable pharmacodynamics with the potential for faster clot resolution.
However, despite the growing preference for fibrin-specific agents in contemporary practice, streptokinase remains a useful therapeutic alternative in many low- and middle-income regions because of availability and cost considerations. Earlier prospective and observational experiences demonstrated that streptokinase can achieve acceptable efficacy and safety when applied in carefully selected patients. In our cohort of 68 patients with prosthetic valve thrombosis, thrombolysis—predominantly with streptokinase—was used as first-line therapy and achieved satisfactory hemodynamic and clinical outcomes, supporting its role as a viable strategy in resource-constrained settings. 2 Although observational, our earlier cohort predates contemporary low-dose slow-infusion protocols and modern multimodality imaging strategies, limiting direct comparability with current practice. The higher failure rate observed with streptokinase in the present study may therefore reflect not only intrinsic pharmacologic differences but also heterogeneity in patient risk profile, thrombus burden, dosing strategies, and diagnostic confirmation prior to treatment—factors that are difficult to fully control in retrospective analyses.
The emergence of newer randomized data further contextualizes these findings. The TENET randomized clinical trial demonstrated the efficacy and safety of tenecteplase compared with alteplase in mechanical prosthetic valve thrombosis, further supporting the evolving role of fibrin-specific agents in contemporary thrombolytic strategies. 3 However, the trial did not directly evaluate comparisons with streptokinase. Together with the results of Sadiq et al, these findings suggest that agent selection may increasingly influence outcomes as treatment strategies evolve toward greater precision and protocolization.
Another clinically important observation is the strong association between failure of thrombolysis and the absence of fluoroscopic assessment before therapy (adjusted OR 3.77). 1 Misclassification of pannus, structural degeneration, or mechanical dysfunction as thrombotic obstruction may expose patients to ineffective fibrinolysis and unnecessary risk. This finding underscores the need for a multimodality imaging approach before initiating thrombolytic therapy, integrating transthoracic and transesophageal echocardiography with cine-fluoroscopy to improve diagnostic accuracy and differentiate thrombus from pannus or structural dysfunction. Current guideline frameworks also support the selective use of cardiac computed tomography when diagnostic uncertainty persists or pannus formation is suspected. 4 Moreover, the lack of standardized imaging protocols and centralized adjudication may introduce diagnostic variability, potentially influencing treatment allocation and observed outcomes, an issue that warrants further prospective evaluation.
The identification of female sex, anemia, and double valve replacement as independent predictors of failure is also noteworthy. Recognition of these variables may help refine clinical risk stratification and support individualized decision-making when considering thrombolysis versus surgical intervention.
An additional aspect deserving attention is the thrombolytic regimen itself. Contemporary protocols increasingly favor low-dose, slow, or ultra-slow infusion strategies guided by serial imaging, as exemplified by the PROMETEE study 5 and the CASSANDRA multicenter experience. 6 These approaches aim to minimize embolic and bleeding complications while preserving efficacy. In contrast, the current study reflects heterogeneous real-world dosing practices and did not systematically evaluate standardized low-dose protocols, thrombus burden, or dynamic response to therapy. The absence of quantitative thrombus assessment and protocol-driven escalation strategies may partially explain outcome variability and limits direct comparability with modern trials. Residual confounding by indication also cannot be excluded.
From a clinical perspective, the study reinforces several practical messages. Thrombolysis remains an effective option in carefully selected patients with mechanical valve thrombosis, while tenecteplase appears to offer superior efficacy and safety compared with streptokinase. Confirmatory multimodality imaging, particularly fluoroscopy, should be encouraged before fibrinolysis to improve diagnostic accuracy and treatment selection. In addition, patient-specific factors such as sex, anemia, and the presence of double prostheses should inform individualized risk assessment and clinical decision-making.
Future research should prioritize prospective multicenter studies comparing protocolized low-dose or ultra-slow infusion strategies using fibrin-specific agents versus streptokinase, particularly in resource-limited settings where therapeutic availability remains heterogeneous. Incorporating standardized multimodality imaging protocols, thrombus quantification, and centralized adjudication may help clarify optimal agent selection, improve risk stratification, and better define long-term clinical outcomes.
We congratulate the authors for their valuable contribution and believe their findings provide important insights into agent selection, diagnostic rigor, and patient stratification in the management of mechanical valve thrombosis.
