European Journal of Cardiovascular Medicine

Prosthetic valve replacement remains the definitive treatment for advanced valvular heart disease, offering durable hemodynamic improvement and survival benefits. However, prosthetic valve thrombosis (PVT) is a rare but serious complication, with an incidence of 0.3% to 1.3% per patient-year, most often affecting mechanical valves, particularly in the mitral position.1 PVT is associated with high morbidity and mortality due to valve obstruction, systemic embolization, and hemodynamic collapse.

The pathogenesis of PVT is multifactorial, but the predominant cause is subtherapeutic anticoagulation, often due to poor adherence to warfarin, drug–diet interactions, or inadequate monitoring of the international normalized ratio (INR). Patient-related factors such as young age, female sex, and pregnancy have also been implicated as additional risk factors.1 Given its acute presentation, timely diagnosis is crucial. Echocardiography and fluoroscopy remain the cornerstone diagnostic modalities, enabling rapid confirmation of leaflet immobility, thrombus visualization, and assessment of transvalvular gradients.

The management of mechanical PVT is highly debated. Surgical valve replacement offers definitive treatment but carries significant risks, especially in hemodynamically unstable patients, those with multiple prior sternotomies, or those presenting in New York Heart Association (NYHA) class IV.2 Moreover, surgery may not be immediately available in many resource-constrained settings. Thrombolytic therapy (TT) has therefore emerged as an effective and less invasive alternative, with reported success rates ranging between 70% and 90%, depending on thrombus size, location, and infusion protocol.2

Recent advances in TT include low-dose and ultra-slow infusion regimens using streptokinase, urokinase, or tissue plasminogen activator (tPA), which have demonstrated comparable efficacy with lower complication rates compared to conventional regimens.3 Case series and reviews also highlight its value in high-risk or surgically inoperable patients, including those with multivalve thrombosis.4 Nonetheless, TT is not without risk: systemic embolism, stroke, and major bleeding are potential adverse outcomes, with reported mortality ranging between 5–15%.2

In India and other developing countries, where access to urgent cardiac surgery is limited, TT with streptokinase remains the first-line therapy in many tertiary centers. However, local data on its safety and effectiveness are limited. While studies from Europe and the Middle East have established TT as a credible strategy, there is a paucity of robust, multicentric Indian data to guide clinical decision-making.5,6

Against this backdrop, the present study aims to evaluate the effectiveness of streptokinase-based thrombolytic therapy in patients with mechanical prosthetic valve thrombosis admitted to a tertiary care hospital. The study also seeks to identify factors associated with treatment success and adverse outcomes, thereby contributing much-needed evidence to inform management strategies in resource-limited settings.

Study Design and Setting

This was a retrospective observational study conducted in the Department of Cardiology at tertiary care teaching hospital in India. The study evaluated patients with mechanical prosthetic valve thrombosis (PVT) treated with thrombolytic therapy over a defined period. Institutional ethics committee approval was obtained, and informed consent was waived given the retrospective design.

Study Population

A total of 27 patients with confirmed mechanical PVT were included. Diagnosis was based on a combination of:

• Clinical features: Worsening dyspnea, palpitations, and signs of heart failure.

• Echocardiography (TTE/TEE): Elevated transvalvular gradients, restricted leaflet mobility, or visible thrombus.

• Fluoroscopy (where available): Reduced or absent valve excursion.

Inclusion Criteria

• Adults (≥18 years) with a mechanical prosthetic heart valve.

• Echocardiographic or fluoroscopic evidence of prosthetic valve thrombosis.

• Patients treated with thrombolytic therapy using streptokinase.

Exclusion Criteria

• Bioprosthetic valve thrombosis.

• Active bleeding or contraindications to thrombolysis.

• Patients who underwent primary surgical valve replacement for PVT.

Thrombolytic Protocol

All patients received intravenous streptokinase, administered according to institutional protocol:

• Loading dose: 250,000 IU over 30 minutes.

• Continuous infusion: 100,000 IU/hour for up to 48–72 hours (duration based on clinical response and echocardiographic improvement).

Concomitant therapy included unfractionated heparin, aspirin, and warfarin, with dose adjustments to maintain therapeutic INR following recovery.

Definitions and Outcomes

• Successful thrombolysis was defined as:

1. Clinical improvement (symptomatic relief and hemodynamic stabilization), AND

2. Echocardiographic/fluoroscopic evidence of restored prosthetic valve mobility with reduction of gradients.

• Partial success: improvement in clinical status but with residual thrombus or incomplete restoration of gradients.

• Failure: no improvement in clinical or imaging parameters.

• Adverse outcomes included systemic embolization, major bleeding, stroke, and in-hospital mortality.

Data Collection

Baseline demographic characteristics, valve type and position, INR values, anticoagulation history, NYHA class, and treatment outcomes were recorded.

Statistical Analysis

Data were analyzed using SPSS version 22. Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as percentages. Comparisons between groups (successful vs. unsuccessful thrombolysis) were made using the Chi-square test for categorical variables and Student’s t-test for continuous variables. A p-value <0.05 was considered statistically significant.

A total of 27 patients with mechanical prosthetic valve thrombosis (PVT) were included in this study. The mean age of the cohort was 48.1 ± 14.1 years (range: 14–75 years). A marked female predominance was observed, with 21 females (77.8%) compared to 6 males (22.2%) (Table 1).

The mean duration since valve replacement was 4.5 ± 2.6 years, ranging from 1 to 10 years. The mean duration of thrombolytic infusion was 2.7 ± 1.0 hours, with longer infusion times recorded in survivors compared to non-survivors.

Etiology of Thrombosis

The predominant cause of PVT was non-compliance with oral anticoagulation, documented in 12 patients (44.4%). Poor dietary regulation contributed to 9 cases (33.3%), while irregular warfarin dosage was responsible for 6 cases (22.2%). Thus, inadequate anticoagulation monitoring and management failures accounted for nearly all thrombotic episodes (Table 2).

Clinical Presentation

The most common presenting symptom was isolated breathlessness, reported in 11 patients (40.7%). Other presentations included breathlessness with palpitations (18.5%), chest pain with dizziness (18.5%), chest pain with palpitations (14.8%), and isolated chest pain (7.4%) (Table 3). More than half of the patients presented in NYHA functional class III or IV.

Outcomes of Thrombolysis

All patients underwent streptokinase-based thrombolytic therapy. Of the 27 patients, 25 (92.6%) survived with complete or near-complete restoration of valve function, whereas 2 patients (7.4%) died despite therapy (Figure 1). Mortality occurred predominantly among patients presenting with isolated severe breathlessness.

Predictors of Mortality

Further subgroup analysis revealed important trends:

• Clinical presentation and outcome: Patients presenting with isolated breathlessness had a mortality of 18.2% (2/11), while all patients with combined symptoms survived (100% survival) (Table 4).
• Etiology and outcome: Mortality was higher in patients with irregular warfarin dosage (16.7%), whereas patients with diet-related anticoagulation failure experienced no deaths (Table 5).
• Age distribution and outcome: Deaths were confined to younger patients, specifically one patient in the 11–20 years age group and one in the 31–40 years group, while all patients above 40 years survived. This association between age and outcome was statistically significant (p = 0.018) (Table 6).
• Treatment-related factors: Survivors had a longer mean thrombolysis duration (2.72 ± 0.98 hours) compared to those who died (2.0 ± 0 hours). Similarly, survivors had valves implanted for a longer mean duration (4.7 ± 2.6 years) compared to non-survivors (2.5 ± 0.7 years), as shown in Figure 2.

In summary, thrombolytic therapy with streptokinase achieved a 92.6% survival rate, with complications limited to minor bleeding and transient embolic events. The principal determinants of outcome included presenting symptoms, adherence to anticoagulation therapy, and patient age. Notably, younger patients and those presenting with isolated severe breathlessness demonstrated poorer prognosis.

Tables & Figures for Submission

Table 1: Gender distribution of the study cohort

Table 2: Distribution of Causes in relation to the study cohort

Table 3 Distribution of Clinical Presentation among the study cohort

Table 4: Distribution of clinical presentation of study cohort and their outcome

Table 5: Distribution of causes influencing patient outcome.

Table 6: Distribution age groups according to their outcome

This study evaluated the effectiveness of thrombolytic therapy (TT) with streptokinase in mechanical prosthetic valve thrombosis (PVT) and demonstrated a high overall survival rate of 92.6%, with thrombolysis failure and mortality occurring in only 7.4% of cases. These findings support TT as a viable and effective treatment modality in resource-limited settings where emergency surgical replacement is not readily available.

The survival rate observed in our cohort is comparable to outcomes reported in previous studies. In the TROIA trial, Ozkan et al. reported a success rate of 83% using low-dose, slow-infusion tissue plasminogen activator (tPA), with a mortality rate of 6.7%.7 Our results (92.6% survival) are consistent with modern TT protocols. For example, a recent cohort from Iran reported an 89.8% success rate with streptokinase, though with embolic complications in approximately 7% of cases.8 In contrast, earlier experiences by Roudaut et al. with high-dose regimens demonstrated lower success (≈70–75%) and higher complication rates, underscoring the benefits of more cautious infusion protocols.9

Our results (92.6% survival) are therefore consistent with modern TT protocols, even though we employed streptokinase rather than fibrin-specific agents such as tPA. This suggests that streptokinase remains an effective low-cost option, especially in countries where healthcare resources are limited.

Predictors of Mortality

An important observation in our series was that all deaths occurred in younger patients (<40 years), with a statistically significant association between age and mortality (p = 0.018). While most published studies have not demonstrated age-specific mortality differences, this finding may be related to delayed presentation, larger thrombus burden, or poorer anticoagulation compliance in younger patients, and warrants further multicentric evaluation.

Clinical presentation also influenced outcomes. Mortality was confined to patients presenting with isolated severe breathlessness, while those with combined symptoms such as chest pain, palpitations, or dizziness had 100% survival. This pattern aligns with the observation that NYHA class IV presentation is a predictor of poor prognosis in PVT, as reported by Ebrahimi et al.2

Etiology of thrombosis was strongly linked to anticoagulation practices. Patients with irregular warfarin dosage showed higher mortality (16.7%), whereas those with diet-related INR variations had no deaths. This highlights that non-compliance and inadequate INR monitoring remain the most critical modifiable risk factors for PVT, consistent with prior Indian and Middle Eastern data.1

Complications

Thrombolysis in our cohort was largely safe, with only minor bleeding and transient embolic events, and no disabling strokes. These results compare favorably with earlier reports, where embolic complications occurred in 10–18% of cases with high-dose regimens.9 Modern slow-infusion regimens, as adopted in our study, are likely responsible for the reduced complication rates, as supported by Dimitrova et al..3

Clinical Implications

Our findings underscore the utility of streptokinase-based TT as a first-line therapy for PVT in regions where surgical intervention is not immediately feasible. The high success rate and low complication profile observed reinforce its role as a life-saving, cost-effective strategy. Equally important is the recognition that most cases of PVT are preventable, with nearly all patients in our series demonstrating subtherapeutic INR due to non-compliance or poor follow-up. This emphasizes the need for patient education, structured anticoagulation clinics, and strict INR surveillance to reduce the incidence of PVT.

Limitations

The study is limited by its small sample size and single-center design, which may reduce generalizability. In addition, the absence of long-term follow-up prevents assessment of recurrent thrombosis or late complications. Nonetheless, the uniform treatment protocol, prospective data collection, and statistically significant findings (notably the age-mortality relationship) add strength to our conclusions.

This study demonstrates that streptokinase-based thrombolytic therapy is a highly effective treatment for mechanical prosthetic valve thrombosis (PVT), achieving a 92.6% survival rate with a low incidence of complications. Importantly, outcomes were influenced by age, with significantly higher mortality among younger patients, and by clinical presentation, as those with isolated severe breathlessness fared worse. Non-compliance and inadequate anticoagulation monitoring were the predominant preventable causes of PVT.

In resource-limited settings where emergency surgery is not immediately feasible, thrombolysis remains a safe, cost-effective, and life-saving option. At the same time, robust patient education, structured INR monitoring, and dietary compliance are essential to reduce recurrence and improve long-term outcomes.

Larger multicenter studies with longer follow-up are warranted to confirm these findings and refine treatment protocols.

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2.       Ebrahimi P, Sattartabar B, Taheri H, et al. Mechanical Prosthetic Valve Thrombosis: A Literature Review of Treatment Strategies. Current Problems in Cardiology 2024; 102628.

3.       Dimitrova E, Bayraktarova IH, Kyuchukov D, et al. Systemic thrombolysis for mechanical prosthetic valve thrombosis - case report and review of literature. Българска кардиология. Epub ahead of print 31 December 2023. DOI: 10.3897/bgcardio.29.e113537.

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5.       Haraf R, Atkinson T, Le D-TE, et al. Mechanical Tricuspid Valve Thrombosis Successfully Treated With Tissue Plasminogen Activator. JACC: Case Reports; 29. Epub ahead of print 29 December 2023. DOI: 10.1016/j.jaccas.2023.102180.

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7.       Özkan M, Gündüz S, Biteker M, Astarcioglu MA, Çevik C, Kaynak E, Yıldız M, Oğuz E, Aykan AÇ, Ertürk E, Karavelioğlu Y, Gökdeniz T, Kaya H, Gürsoy OM, Çakal B, Karakoyun S, Duran N, Özdemir N. Comparison of different TEE-guided thrombolytic regimens for prosthetic valve thrombosis: the TROIA trial. JACC Cardiovasc Imaging. 2013 Feb;6(2):206-16. doi: 10.1016/j.jcmg.2012.10.016. PMID: 23489534.

8.       Nasri Nasrabadi A, Yarahmadi F, Amirpour A, Zavar R, Akbari M. Fibrinolytic Therapy in Thrombosis of Mechanical Valves: Outcomes and Complications. ARYA Atheroscler. 2023 Sep-Oct;19(5):18-24. doi: 10.48305/arya.2023.26569.2804. PMID: 38882648; PMCID: PMC11179002.

9.       Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations. Heart. 2007 Jan;93(1):137-42. doi: 10.1136/hrt.2005.071183. PMID: 17170355; PMCID: PMC1861363.