Thrombus stiffness as an independent predictor of endovascular treatment success in hemodialysis fistulas: a study using ultrasound elastography
Article information
Abstract
Purpose
This study aimed to evaluate the prognostic value of thrombus stiffness, measured by strain elastography, in independently predicting the success of endovascular treatment for thrombosed hemodialysis fistulas.
Methods
The study employed a retrospective observational design. Forty-nine patients with chronic kidney disease undergoing hemodialysis and experiencing fistula dysfunction were included. Various factors were evaluated, including patient age, sex, comorbidities, arteriovenous fistula (AVF) type, use of antiplatelet agents, duration of thrombosed AVF dysfunction, thrombus length, thrombus stiffness, and thrombus strain ratio (SR). Thrombus stiffness was measured using strain ultrasound elastography.
Results
The presence of comorbidities (P=0.018), duration of AVF dysfunction due to thrombosis (P=0.005), thrombus stiffness (P<0.001), and thrombus SR (P<0.001) were statistically significant predictors of treatment success, while other factors were not. Thrombus stiffness and SR, assessed by two independent radiologists with excellent inter-reader agreement, demonstrated high reliability. The optimal SR cut-off for treatment success was 1.4 (sensitivity, 0.947; specificity, 0.901; area under the curve, 0.935). Multivariable logistic regression analysis revealed that both thrombus SR and thrombus stiffness significantly influenced treatment outcomes (P=0.003 and P=0.007, respectively). A 0.1-unit increase in thrombus SR was associated with 9.37% reduction in the likelihood of treatment success, while a smilar increase in thrombus stiffness exhibited an 8.06% reduction, underscoring their importance as prognostic factors in clinical setting.
Conclusion
This study demonstrates the utility of strain ultrasound elastography in assessing thrombus stiffness in thrombosed hemodialysis AVFs and its correlation with treatment success.
Introduction
Arteriovenous fistulas (AVFs) are the preferred vascular access for hemodialysis in patients with end-stage renal disease, valued for their durability and lower infection risk compared to alternatives such as arteriovenous grafts or venous catheters [1]. AVFs are typically created surgically by anastomosing an artery and a vein, most commonly in the non-dominant upper extremity [2]. This connection results in venous dilation and thickening under arterial pressure, providing the necessary blood flow for efficient dialysis. However, despite their advantages, AVFs are prone to complications that can compromise their functionality [3].
Complications such as stenosis, neointimal hyperplasia, thrombus formation, or infection can occur at any stage in the lifespan of an AVF, either early or late [4]. These issues can lead to inadequate blood flow, necessitating intervention [4]. Endovascular treatments, including percutaneous transluminal angioplasty, stenting, and thrombolysis, are minimally invasive procedures used to restore adequate blood flow in cases of significant luminal narrowing or thrombosis [5]. The success of these interventions, however, depends on several factors, including the location, size, and consistency of the thrombus. For instance, thrombi with a harder structure may resist dilation and dissolution, complicating treatment outcomes [6].
Thrombus stiffness, measurable through strain ultrasound elastography, offers a non-invasive method to assess thrombus characteristics that may influence the success of endovascular treatments [7]. This study focuses on evaluating thrombus stiffness as a prognostic indicator for treatment success in thrombosed AVFs. The research aims to establish specific stiffness thresholds that correlate with positive treatment outcomes, potentially refining patient selection and treatment approaches in clinical practice.
Materials and Methods
Compliance with Ethical Standards
This study was approved by the Mersin University Ethics Committee with the decision dated 20/03/2024 and numbered 2024/287, and conducted in accordance with the Declaration of Helsinki. Due to its retrospective nature, informed consent was waived.
Study Population
In this retrospective study, 49 patients who met the inclusion and exclusion criteria were evaluated from a total of 112 patients who underwent endovascular treatment at the authors’ interventional radiology clinic between August 2021 and August 2024. Inclusion criteria included patients aged 18 years and older who were unable to undergo dialysis due to thrombus formation in their AVF, exhibited no detectable thrill, and presented signs of stenosis due to thrombus on ultrasound. Patients with fistula dysfunction due to causes other than thrombus, pregnant women, and those with incomplete data were excluded. Among the participants, 29 were male and 20 were female, with an age range of 24-81 years (mean age, 61.7). All participants had chronic kidney disease and were receiving regular dialysis. The duration of dialysis ranged from 2 to 170 months, with a mean of 51 months.
The patients’ age, sex, duration of dialysis, use of antiplatelet agents, duration of AVF dysfunction due to thrombosis, thrombus length, thrombus stiffness, strain ratio (SR), and history of diabetes and hypertension were evaluated.
Acquisition and Interpretation of Strain Elastography
All strain elastography data were obtained using a LOGIQ E9 ultrasound machine (GE Healthcare, Little Chalfont, UK). Measurements were taken twice by two independent radiologists to assess repeatability and reproducibility. The thrombus SR was calculated using the values of E1 and E2 obtained from strain elastography. E1 represents the elastic modulus of the surrounding adipose tissue, while E2 represents the elastic modulus of the tissue within the region of interest (ROI) where the thrombus was located. The thrombus SR was calculated using the formula: SR=E2/E1. E2 was measured within the thrombotic segment of the AVF, and E1 was measured in the perivascular adipose tissue. This approach compares the stiffness of the thrombus against the surrounding softer tissue, providing a ratio that reflects the relative stiffness of the thrombus. The ROIs were carefully placed to encompass the entire thrombus for E2 and the perivascular adipose tissue for E1, ensuring accurate assessments of elastic moduli (Fig. 1). E2 represents thrombus stiffness, while the E2/E1 ratio is defined as the thrombus SR.
Strain elastography (A) and elastography map (B) images of a patient with hemodialysis arteriovenous fistula dysfunction due to thrombosis.
The surrounding soft tissue is identified as the reference point and marked with the E1 region of interest (ROI) circle. The thrombus within the vascular lumen was identified with the E2 ROI circle, and the ratio to the reference tissue (E1) was calculated by the device using the formula strain ratio=E2/E1. In this shared case, the strain ratio was calculated as 1.7, and the endovascular treatment performed was unsuccessful.
Thrombus length was measured using grayscale ultrasonography. The ultrasound transducer was placed longitudinally along the thrombus, and the maximum length from its proximal to distal ends was recorded.
Scanner settings were standardized to optimize acquisitions based on initial clinical experience: frequency range of 4-9 MHz, maximum acoustic power, medium smoothing (setting 6), persistence (off), and gain (65%-70%).
Endovascular Treatment
The endovascular treatment protocol included fistulography, angioplasty, thromboaspiration, and stenting. Fistulography, angioplasty, and thromboaspiration were routinely performed on all patients. After antiseptic measures and local anesthesia were administered, transradial or transvenous access was established, and a radial sheath was placed to image the fistula region. A hydrophilic guidewire and balloon catheters were used to access the stenotic area, and the narrowing was dilated using high-pressure balloon inflation. Thromboaspiration was then performed in the thrombosed segment to mechanically remove the thrombus. Post-procedural angiography was conducted to confirm procedural success, and bleeding was controlled through manual compression. Stenting was performed in three patients with central venous stenosis, where selfexpanding, uncovered stents approximately 10% larger than the stenotic segment were deployed following angioplasty. Appropriate anticoagulation and thrombotic therapy protocols were administered during and after the procedure at optimal doses and durations.
Evaluation of Treatment Success
Treatment outcomes were classified as successful or unsuccessful based on Doppler ultrasound measurements performed 24 hours post-treatment. Success was defined as a flow volume exceeding 300 mL/min in the Doppler ultrasound results and the completion of at least one routine hemodialysis session. Conversely, treatment failure was defined as a flow volume less than 300 mL/min or the inability to complete a hemodialysis session. Based on these criteria, treatment was successful in 30 patients and unsuccessful in 19 patients.
Statistical Analysis
All statistical analyses were performed using IBM SPSS Statistics version 21.0 (IBM Corp., Armonk, NY, USA).
The reliability of thrombus SR measurements obtained by two independent radiologists on two separate occasions was evaluated using the two-way mixed intraclass correlation coefficient (ICC), which assesses the degree of agreement between observers and the consistency of measurements across evaluations.
The Shapiro-Wilk test was used to assess whether the data followed a normal distribution. Continuous variables were analyzed using either the independent samples t-test (for normally distributed data) or the Mann-Whitney U test (for non-normally distributed data). Categorical variables, such as patient sex, comorbidities, antiplatelet use, and type of dialysis fistula, were analyzed using the chi-square test. Since thrombus stiffness and thrombus SR data did not follow a normal distribution, the Mann-Whitney U test was used to evaluate differences between the two groups. Variables such as thrombus length, duration of AVF dysfunction due to thrombosis, and patient age were analyzed using the independent samples t-test to assess their relationship with treatment success.
To differentiate between successful and unsuccessful treatment groups, statistical models were developed using univariable and multivariable logistic regression analyses with the enter method. Independent variables, including thrombus stiffness, thrombus SR, patient age, sex, presence of comorbidities, type of AVF, and duration of dysfunction, were assessed using univariable regression analysis. Variables with P<0.05 were included in the multivariable regression analysis. Due to the high multicollinearity between thrombus stiffness and thrombus SR, these variables were evaluated in separate models. The model including thrombus SR is designated as model 1, while the model including thrombus stiffness is designated as model 2.
A receiver operating characteristic analysis was performed to evaluate the model's ability to discriminate between treatment success and failure. The cut-off values for thrombus SR, thrombus stiffness, and duration of AVF dysfunction due to thrombosis, as well as the area under the curve (AUC), were calculated to optimize the balance between sensitivity and specificity for the patient population. All analyses were conducted with a 95% confidence interval (CI) and a significance level of P<0.05.
Results
The study demonstrated exceptionally high reliability for both intraobserver and interobserver measurements. The ICCs for intraobserver single measures and average measures were 0.999 (95% CI, 0.998 to 0.999) and 0.999 (95% CI, 0.999 to 1.000), respectively. Similarly, interobserver measurements yielded ICC values of 0.999 (95% CI, 0.998 to 0.999) for single measures and 0.999 (95% CI, 0.999 to 1.000) for average measures. These results indicate a high level of consistency across different observers, reinforcing the reliability of the measurement methods.
While patient age, thrombus length, use of antiplatelet medications, and type of AVF were not statistically significant (P>0.050), the presence of comorbidities, duration of AVF dysfunction due to thrombosis, thrombus stiffness, and thrombus SR were found to be statistically significant (P=0.019, P<0.001, P<0.001, and P<0.001) (Table 1).
Comparison of clinical and demographic characteristics between successful and failed endovascular treatments
Univariable and multivariable logistic regression analyses revealed that thrombus length, use of antiplatelets, patient age, type of AVF, sex, and duration of AVF dysfunction due to thrombosis were not statistically significant independent predictors of treatment success (P>0.050) (Table 2).
Univariable and multivariable logistic regression analyses for predictors of treatment success
Thrombus SR and thrombus stiffness were significant predictors of treatment outcomes. Each 0.1-unit increase in thrombus SR reduced the likelihood of treatment success by 9.37% (P=0.003), while each 0.1-unit increase in thrombus stiffness reduced the likelihood by 8.06% (P=0.007). The odds ratios for both variables (odds ratio, 0.063 and 0.194) and their 95% CIs support their strong and consistent effects on treatment outcomes, highlighting their importance as prognostic factors in clinical practice.
In the receiver operating characteristic (ROC) analysis, the AUC for thrombus SR was 0.935 (95% CI, 0.858 to 1.000), for thrombus stiffness was 0.928 (95% CI, 0.854 to 1.000), and for the duration of AVF dysfunction due to thrombosis was 0.884 (95% CI, 0.786 to 0.982) (Table 3). The ROC curve analysis is illustrated in Fig. 2.
Diagnostic performance metrics for thrombus strain ratio, thrombus stiffness, and duration of AVF dysfunction due to thrombosis: receiver operating characteristic analysis results
A receiver operating characteristic (ROC) curve comparing the performance of thrombus stiffness, thrombus strain ratio (SR), and the duration of arteriovenous fistula (AVF) dysfunction caused by thrombosis in predicting treatment success.
The green line represents thrombus SR, the blue line represents thrombus stiffness, and the red line represents the duration of AVF dysfunction due to thrombosis. Thrombus stiffness and thrombus SR are shown to be effective prognostic indicators based on their classification power.
Discussion
In this study, thrombus stiffness in thrombosed AVFs was evaluated using strain elastography, and its impact on treatment success was investigated. The findings indicate that thrombus stiffness may serve as an important prognostic marker for treatment success. The statistically significant relationship between thrombus stiffness and treatment outcomes underscores the potential clinical relevance of incorporating strain elastography into routine practice.
Strain elastography is an ultrasound imaging technique that measures the mechanical properties of tissues, particularly stiffness and elasticity. This method evaluates tissue stiffness by assessing deformation caused by applied mechanical stress. Due to its noninvasive nature, rapid results, and ability to directly measure tissue stiffness, it has been widely used in conditions such as breast, liver, and prostate diseases [8]. Recent studies suggest that strain elastography can provide insights into the internal structure of thrombi and the changes occurring during the subacute and chronic phases [9]. Research has shown that as thrombi age, increased collagen and fibrin production leads to a stiffer thrombus structure [10]. For instance, a study on patients with acute ischemic stroke found a strong positive correlation between fibrin and platelet concentration and thrombus stiffness, indicating that stiffer thrombi are more resistant to treatment and may require modifications to treatment protocols [9]. Emelianov et al. [11] identified changes in the elastic properties of clots over time, with chronic clots exhibiting a higher Young’s modulus as measured by ultrasound elastography. In this study, parameters such as thrombus stiffness, thrombus SR, and the duration of dysfunction due to thrombosis were found to differ significantly between successful and failed treatment groups (P<0.001). The mean thrombus SR was 0.82 for patients with successful treatment, compared to 2.33 for those with failed treatment. This difference was also statistically significant (P<0.001). A cut-off value of 1.4 for thrombus SR was established to predict treatment success, with a sensitivity of 0.95, specificity of 0.90, and an AUC of 0.935. These findings align with existing literature and highlight the clinical utility of thrombus stiffness and SR as prognostic indicators.
This study also reported higher reproducibility and reliability values for strain elastography compared to previous studies [12]. Several factors may have contributed to these results. Standardization of measurement settings for each patient enhanced consistency, while the accessible anatomical structure of the upper extremity allowed for repeated measurements, improving accuracy. Additionally, the superficial location of AVFs and the ability to apply sufficient compression further supported the reliability of the measurements.
However, this study has certain limitations. Firstly, the patient population was relatively small, and larger studies are needed to enhance the generalizability of the findings. Secondly, the singlecenter design may limit the reproducibility of the results; multicenter studies could address this limitation. Lastly, the operator-dependent nature of strain elastography introduces potential variability, which should be considered in future research.
Future studies should focus on prospective designs to explore the impact of changes in thrombus histological composition on long-term treatment outcomes. Additionally, further research could investigate not only the effect of thrombus stiffness on treatment success but also its influence on treatment protocols and material selection, such as the use of longer, stronger, and higher-pressure balloons for stiffer thrombi.
In conclusion, this study highlights the effectiveness of strain elastography in evaluating thrombus stiffness in thrombosed AVFs and emphasizes the predictive value of these measurements in determining treatment success. The findings suggest that thrombus stiffness and SR play a crucial role in treatment outcomes, offering valuable insights for refining clinical decision-making and treatment strategies.
Notes
Author Contributions
Conceptualization: Zirek S, Özyurt GM, Özen A, Olmaz R, Esen K. Data acquisition: Zirek S, Özyurt GM, Özen A. Data analysis or interpretation: Zirek S, Özyurt GM, Özen A. Drafting of the manuscript: Zirek S, Özyurt GM, Özen A, Olmaz R, Esen K. Critical revision of the manuscript: Zirek S, Özyurt GM, Özen A, Esen K. Approval of the final version of the manuscript: all authors.
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Acknowledgments
We would like to express our sincere gratitude to all those who contributed to this research. Firstly, we extend our heartfelt appreciation to Dr. Altan Yıldız whose guidance and expertise were invaluable throughout the course of this study. We are also grateful to Mersin City and Research Hospital for providing the necessary resources and facilities to conduct this research.
Special thanks are due to the participants who generously volunteered their time and insights, without whom this study would not have been possible. Their contributions have enriched our understanding and shaped the outcomes of this research significantly.
We would also like to acknowledge the reviewers and editors for their constructive feedback and suggestions, which have enhanced the quality and clarity of this manuscript. Their expertise and diligence are sincerely appreciated.
Lastly, we express our gratitude to our families and friends for their unwavering support and encouragement throughout this endeavor.
References
Article information Continued
Notes
Key point
Strain ultrasound elastography is a valuable prognostic tool for independently predicting treatment success in thrombosed hemodialysis arteriovenous fistulas (AVFs). The duration of thrombosed AVF dysfunction and thrombus stiffness are significant factors determining treatment outcomes, as supported by findings in the literature.