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 Gender Frequency Percent Female 21 77.8 Male 6 22.2 Total 27 100.0 Table 2: Distribution of Causes in relation to the study cohort Cause Frequency Percent Irregular Dosage 6 22.2 Non-Compliant to Meds 12 44.4 Poor Diet 9 33.3 Total 27 100.0 Table 3 Distribution of Clinical Presentation among the study cohort Presentation Frequency Percent Breathlessness 11 40.7 Breathlessness, Palpitations 5 18.5 Chest Pain 2 7.4 Chest Pain, Dizziness 5 18.5 Chest Pain, Palpitations 4 14.8 Total 27 100.0 Figure 1: Outcome occurred among the study cohort Table 4: Distribution of clinical presentation of study cohort and their outcome Presentation Outcome Alive Death Total P value Breathlessness Count 9 2 11 0.534 % 81.8% 18.2% 100.0 Breathlessness, Palpitations Count 5 0 5 % 100.0 0.0 100.0 Chest Pain Count 2 0 2 % 100.0 0.0 100.0 Chest Pain, Dizziness Count 5 0 5 % 100.0 0.0 100.0 Chest Pain, Palpitations Count 4 0 4 % 100.0 0.0 100.0 Total Count 25 2 27 Table 5: Distribution of causes influencing patient outcome. Cause Outcome Alive Death Total P value Irregular Dosage Count 5 1 6 0.476 % 83.3 16.7 100.0 Non-Compliant to Meds Count 11 1 12 % 91.7 8.3 100.0 Poor Diet Count 9 0 9 % 100.0 0.0 100.0 Total Count 25 2 27 Table 6: Distribution age groups according to their outcome Age group (in years) Outcome Alive Death Total P value 11-20 Count 0 1 1 0.018 % 0.0 100.0 100.0 21-30 Count 2 0 2 % 100.0 0.0 100.0 31-40 Count 4 1 5 % 80.0% 20.0% 100.0 41-50 Count 8 0 8 % 100.0 0.0 100.0 51-60 Count 6 0 6 % 100.0 0.0 100.0 61-70 Count 4 0 4 % 100.0 0.0 100.0 71-80 Count 1 0 1 % 100.0 0.0 100.0 Total Count 25 2 27 Figure 2: Mean outcome of the study cohort in relation to duration (in hours) and replacement (in years)

The adaptation process for new complete denture wearers is normally challenging, involving both functional and psychological adaptation. Our study measured adaptation and levels of comfort among 50 Bangladeshi patients for six months, reflecting considerable trends in discomfort, time to adaptation, and general satisfaction.

Age and sex are confirmed factors in denture adaptation. Our study's most frequent age category (66%) was 50-69 years, as might be expected on the global scale for edentulism among older individuals [14]. Males were slightly more than females (54%), as expected of general health-seeking behavior, rather than by a gender disparity in denture adaptation [15].

Wearers commonly report a number of discomforts during the initial adaptation process, as evident from our findings. Discomfort and pain (44%) were the most commonly reported, followed by masticatory (36%) and speech (20%) difficulties. The findings are consistent with Trulsson et al., who indicated that first-time denture wearers experience significant functional and psychological discomfort from the altered oral environment [16]. Excessive salivation (16%) and gag reflex (10%) were also prominent complaints. Oral stereognostic ability has been reported by Eitner et al., to play a part in what patients think about their prostheses and are therefore responsible for their comfort levels [17]. Our results support the argument that discomfort at the beginning is a natural response to foreign objects within the oral cavity, which slowly decreases with time.

Adaptation to dentures varies in individuals. In the current study, most participants (70%) adapted within a month, 36% adapting between 1-2 weeks and 34% adapting between 3-4 weeks. Nonetheless, 20% of the participants adapted after over a month. The results were consistent with those of Müller et al., who opined that the adaptation period relies on patient motivation, experience, and psychological acceptance of dentures [18]. Patients who adjusted more quickly had fewer initial grievances, underlining the significance of patient education prior to denture placement. Carr & Brown emphasized that pre-treatment counseling greatly enhances acceptance and diminishes perceived distress [15].

Comfort levels showed remarkable improvement over six months. In week one, only 10% of participants felt comfortable, 56% experienced some discomfort, and 34% felt totally uncomfortable. These figures improved in step with time, with 84% feeling comfortable at six months. This gradual improvement is consistent with evidence by Kawai et al., who found that adaptation was an ongoing process of increasing tolerance over time [19]. Levin & Richardson also noted the importance of frequent follow-ups and minor adjustments to maximize comfort levels [20]. The decrease in discomfort supports the concept that neuroplasticity in oral sensory perception enables patients to functionally adapt to new prostheses [21].

Satisfaction is the best predictor of denture adaptation success. 74% were very satisfied or satisfied, and 14% were neutral at six months. Only 12% reported dissatisfaction, consistent with findings of Petričević & Rener-Sitar, who argued that denture fit, esthetics, and speech function are factors in overall satisfaction [14]. Psychosocial issues are also highly significant in denture satisfaction. Greenland & Margrain found a link between anxiety and patient satisfaction, with strong stress on reassurance and ongoing support during the adaptation period [22]. In our study, those who were not satisfied in the early stages were more likely to have more than one complaint to start with, highlighting the merits of early education and intervention.

Education of patients on the adaptation process can lower expectation levels and maximize long-term satisfaction [15]. Intermittent follow-ups facilitate required adjustments, lowering pain levels and increasing comfort levels as time passes [20]. Treatment of psychological issues discussed can increase adaptation, as it is evident from the reports by patients having decreased anxiety who noted increased comfort and satisfaction [20].

Limitations of the study

Despite its valuable insights, our study has some limitations. The small sample size (n=50) may not fully represent the broader population, and the study focused solely on conventional dentures without considering implant-supported prostheses. Future research should explore long-term adaptation beyond six months and assess the impact of different prosthetic techniques on patient comfort and satisfaction.

Our study confirms that first-time complete denture wearers experience significant adaptation challenges, particularly in the initial weeks. However, comfort levels improve over time, and most patients achieve satisfactory adaptation within six months. Pain, chewing difficulties, and speech issues are common early complaints, but regular follow-ups and patient education can enhance the adaptation process. These findings emphasize the need for comprehensive patient support to improve the overall experience of denture wearers.

Financial support and sponsorship

No funding sources.

Conflicts of interest

There are no conflicts of interest

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