Abstract
Purpose
To evaluate the efficacy and safety of ultrasound-guided percutaneous transluminal angioplasty for hemodialysis-associated venous hypertension syndrome caused by central venous stenosis or occlusion.
Patients and methods
The clinical data of 24 treatment instances with color duplex ultrasound-guided percutaneous transluminal angioplasty from January 2021 to January 2023 were retrospectively analyzed. The primary endpoint of the study was clinical success rate, while the secondary endpoints were 6- or 12-month vascular patency rates.
Results
Of the 24 treatment instances enrolled, 20 were primary onset and treated initially with percutaneous transluminal angioplasty under color duplex ultrasound guidance. Of these 20 patients, 17 were treated successfully (85%), while 3 procedures failed, requiring reoperation. Six patients showed recurrence within 1 year, of which four received repeated ultrasound-guided percutaneous transluminal angioplasty. Three of these procedures were successful (75.0%). Therefore, the total success rate was 83.3%. The patency rates were 76.5% at the 6-month follow-up and 64.7% at the 12-month follow-up. No patient developed complications such as dissection or perforation of the target vessel wall.
Conclusion
Color duplex ultrasound-guided percutaneous transluminal angioplasty is a feasible technique for hemodialysis-associated venous hypertension syndrome.
Keywords
Introduction
Venous hypertension syndrome, commonly known as “puffy hand syndrome,” refers to a group of clinical conditions characterized predominantly by swelling of the limbs, neck and face, and chest wall. It is frequently caused by repeated peripheral venous injections and ensuing central vein stenosis or occlusion (central venous stenosis (CVS)). Venous hypertension syndrome is a common complication, leading to the failure of arteriovenous fistula (AVF) in patients receiving hemodialysis for chronic renal failure, with incidence ranging from 3% to 50%. 1 Common sites of occlusion include the subclavian vein, brachiocephalic vein (also known as innominate vein), and superior vena cava. These lesions may arise following central venous catheterization (CVC) or placement of cardiac implantable electronic devices via peripheral venous access. 2 At present, CVS is most commonly treated via percutaneous transluminal angioplasty (PTA) or percutaneous transluminal stenting (PTS) under computed tomography angiography (CTA) or digital subtraction angiography (DSA) guidance. 3 Although CTA and DSA can precisely localize surgical sites, these imaging modalities are expensive and necessitate radiation exposure.
Color duplex ultrasound is widely applied as an economical, effective, and noninvasive imaging modality for preoperative screening, monitoring of postoperative complications, maturity detection, and real-time guidance for PTA of AVF stenosis or occlusion in maintenance hemodialysis patients. 4 Brown also reported acceptable sensitivity and specificity of this technique for the diagnosis of upper limb CVS and occlusion under certain circumstances as an alternative to venography. 5 Therefore, we believe that color duplex ultrasound can be employed at least in some cases for interventional therapy of CVS and occlusion. In the current study, we evaluated the clinical efficacy and safety of PTA under color duplex ultrasound guidance for venous hypertension syndrome in hemodialysis patients.
Materials and methods
Study participants
Twenty-four treatment instances with venous hypertension syndrome receiving hemodialysis at the Department of Nephrology, Affiliated Banan Hospital of Chongqing Medical University, China, from January 2021 to December 2023 were retrospectively enrolled. All patients exhibited typical CVS symptoms such as swelling of the upper limbs, increased venous pressure, poor flow during hemodialysis, varicose veins in the chest wall, and swelling of the neck and face. Intravenous ultrasound was used to identify and characterize vascular stenosis, thrombus, or occlusion, and the location, length, and severity of the lesions were further validated by computed tomography venography (CTV) (Figure 1(a)). All patients demonstrated significant regional thickening and lumen narrowing on vascular ultrasound (Figure 1(b)). Longitudinal ultrasound images revealed a diameter reduction of >50%, increased regional blood flow, and >2-fold higher peak venous velocity ratio than baseline values across the stenotic segment at the beginning of the right innominate vein. In addition, color Doppler flow imaging (CDFI) yielded a mosaic pattern of multicolored blood flow signals beginning at the right innominate vein (right panel, Figure 1(b)), and continuous-wave duplex ultrasound showed maximum blood flow velocity at the lumen stenosis. Furthermore, CTA of the right upper limb and chest blood vessels revealed narrowing of the right brachiocephalic vein (Figure 1(c)). The standard treatment approach to CVS or occlusion is endovascular therapy guided by DSA. However, in cases where these lesions could be detected by color duplex ultrasound, endovascular therapy was first attempted with PTA under color duplex ultrasound guidance before PTA or PTS under DSA guidance. Patients were converted to DSA-guided PTS when stent implantation was considered mandatory to keep the venous route open; these cases were excluded from subsequent analysis.
(a) Clinical manifestations of patients include upper limb swelling and varicose veins in the chest wall. (b) Vascular ultrasound showing regional thickening, lumen narrowing, and increased regional blood flow at the beginning of the innominate vein; CDFI revealing multicolor blood flow signals in a mosaic pattern at the beginning of the right innominate vein (right panel) and (c) CTA of the right upper limb and chest (the image has been rotated to better demonstrate the right brachiocephalic lesion). CDFI: color Doppler flow imaging; CTA: computed tomography angiography.
Patient characteristics are summarized in Table 1. Twenty treatment instances (83.3%) had a history of CVC, twenty (83.3%) were currently receiving long-term hemodialysis via AVF access, and four (16.7%) had received arteriovenous grafting. The sites of central vein stenosis/occlusion were as follows: right brachiocephalic vein (11 patients, 45.8%), right subclavian vein (3 patients, 12.5%), left subclavian vein (2 patients, 8.3%), and right brachiocephalic vein plus right subclavian vein (8 patients, 33.3%). Of the 24 treatment instances enrolled, 14 (58.4%) developed thrombosis, 5 (20.8%) occlusions, and 5 (20.8%) stenosis. All cases were screened by vascular duplex ultrasound, which revealed that in the early stages of thrombus formation, blood flow is extremely slow. Additionally, the echo intensity of the thrombus can be used to estimate the time of thrombus formation, providing assistance in determining the appropriate clinical intervention. 6 Vascular stenosis, thrombus, or occlusion was detected by color Doppler ultrasound and was further confirmed by CTV. Vascular lesion severity was classified as follows: (a) mild if the stenosis accounted for <50% of the inner vessel diameter; (b) moderate if the stenosis accounted for 50%–75% of the inner vessel diameter; (c) severe if the stenosis accounted for >75% of the inner vessel diameter; and (d) occluded if there was detectable perfusion. 7
Baseline patient characteristics.
CVC: central venous catheterization; AVF: arteriovenous fistula; AVG: arteriovenous grafting; eGFR: estimated glomerular filtration rate; CVS: central venous stenosis; EVT: endovascular therapy; HD: hemodialysis.
The primary endpoint of this study was elastic retraction of residual stenosis by <50%, and the secondary endpoints were 6- and 12-month vascular patency rates. The PTA dilatation catheters were purchased from Bard Healthcare Science (Shanghai). Color Doppler ultrasound was performed using the Toshiba Apollo 500 ultrasonic system and a 10-MHz linear probe. We conducted our study in accordance with the Helsinki Declaration of 1975, as revised in 2013. This retrospective study was reviewed and exempted from approval by the institutional review board. We obtained informed consent prior to the procedure from all patients to review their documents for research purposes in the future. We have de-identified all patient details. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. 8
Interventional procedure
With the patient in the supine position, a single puncture point was selected in the fistula vein approximately 5 cm below the elbow joint. After routine disinfection, toweling, and 2% lidocaine infiltration anesthesia, a needle was inserted from the puncture point along the blood flow direction under color duplex ultrasound guidance, and a guide wire was inserted, followed by withdrawal of the puncture needle. A 7–8-Fr sheath catheter was inserted along the guide wire, the guide wire was withdrawn, and a super-smooth guide wire (hydrophilic guidewire) was advanced smoothly through the vascular stenosis under ultrasound guidance. Then, the ultrasound probe was positioned in the supraclavicular region and the angle was adjusted to achieve clear visualization of the central veins. Following systemic heparinization (heparin, 40–50 U/kg or 3000 U), a balloon was placed into the stenotic lesion along the super-smooth guide wire. For safety, a 8-cm diameter balloon was initially chosen, and the diameter was increased (to a maximum of 12 cm) until the point of maximum narrowing was dilated to the non-lesion diameter for approximately 1 min. The pressure was then released to observe the effect, and dilation was repeated 3 or 4 times to achieve maintained vein dilation. Elimination of the stenotic lesion and return of normal blood flow were then confirmed by ultrasound. In cases with residual stenosis (elastic retraction), a balloon 2 cm larger in diameter than that used previously was chosen, and the procedure was repeated. Alternatively, a stent was implanted under DSA guidance with repeated ultrasound to confirm elimination of the stenotic lesion. The puncture site was sutured subcutaneously and covered with a sterile dressing. To ensure procedural safety, detailed imaging to map the anatomy of the central venous system was performed prior to the procedure; the location, length, and degree of the lesions were validated by CTV after color duplex ultrasound detected vascular stenosis or occlusion. This helps identify any anatomical variations, stenoses, or potential challenges in accessing the outflow veins; moreover, color duplex ultrasound was used to obtain detailed cross-sectional images of the vessel walls and lumen during the procedure. This helps in assessing the integrity of the outflow veins and identifying any subtle injuries or malpositions. In cases where color duplex ultrasound alone is insufficient, we use real-time fluoroscopy combined with contrast injections to visualize the outflow veins and confirm the patency of the SVC and brachiocephalic veins. This allows us to monitor the passage of wires and devices and detect any abnormalities, such as vessel perforation or malposition.
A successful case (Case #1) is illustrated in Figure 2. Both preoperative intravascular ultrasound and CTV revealed a thrombus in the right brachiocephalic vein (Figure 2(a)). Intraoperatively, the guide wire and balloon were gradually expanded through the stenosis (Figure 2(b)). Vascular stenosis was absent and blood flow significantly increased immediately after the procedure (Figure 2(c)). By 3 days post-surgery, no swelling of the affected upper limb was observed (Figure 2(d)).
An example of a successful case (Case #1). (a) Both preoperative intravascular ultrasound and CTV showing thrombus in the right brachiocephalic vein stenosis. (b) Intraoperatively, the guide wire and balloon were gradually expanded through the stenosis. (c) Compared with preoperative blood flow spectrum, postoperative vascular stenosis was absent, and blood flow was increased significantly and (d) at 3 days postoperatively, the swelling of the affected upper limb was absent and healed. CTV: computed tomography venography.
Data collection and definitions
Estimated glomerular filtration rate and hemoglobin levels were measured at admission. In addition, a history of CVC and types of hemodialysis access were confirmed. The etiology of CVS was evaluated by color duplex ultrasound and CTV or by transesophageal echocardiogram if needed. Vessel characteristics were classified based on consensus definitions of the Peripheral Academic Research Consortium. Postoperative vascular patency was confirmed in all cases by color duplex ultrasound and CTV. In most cases, patency was reconfirmed at both 6- and 12-month follow-ups using the same imaging examinations. The overall vascular patency rate was calculated at the end of postoperative follow-up to evaluate the overall efficacy. Acceptable vascular patency was defined as the absence of clinical CVS symptoms and successful hemodialysis.
Evaluation of the efficacy of color duplex ultrasound-guided PTA
To provide an objective evaluation, successful PTA was defined as <50% elastic retraction of residual stenosis as measured by color duplex ultrasound vascular ultrasound, absence of CVS symptoms and signs, and successful hemodialysis. Vascular lesion severity was graded before and after PTA as 0 for complete vessel occlusion and nonperfusion, 1 for >75% stenosis of the inner vessel diameter, 2 for 50%–75% stenosis of the inner vessel diameter, and 3 for <50% stenosis of the inner vessel diameter.
To assess interobserver variability, vascular stenosis and PTA efficacy were rated by two independent ultrasound physicians who were blinded to the clinical and procedural data. Furthermore, one of the two observers evaluated all angiograms again after the initial evaluation to assess intraobserver variability. In the case of disagreement, the evaluation was conducted by a third observer, and the final decision on the efficacy of PTA guided by color duplex ultrasound was made by consensus.
Results
Patient characteristics and results of color duplex ultrasound-guided PTA
The etiologies of all CVS cases, surgical characteristics, surgical outcomes, postoperative complications, and causes of failure are summarized in Table 2. Stenosis (n = 5, 20.8%), thrombosis (n = 14, 58.3%), and occlusion (n = 5, 20.8%) were the main etiologies of CVS. A total of 24 patients were treated using color duplex ultrasound-guided PTA, of which 20 received PTA guided by color duplex ultrasound as the initial treatment. Of these 20 cases, 17 (85%) were treated successfully according to predefined criteria (elastic retraction of residual stenosis <50%, sufficient blood flow for normal hemodialysis, and significant alleviation of clinical symptoms and physical signs), and 3 did not achieve the threshold patency (>50%). Six patients experienced recurrence within 1 year, four of whom required secondary PTA. Three of these four secondary surgeries were successful, and one was unsuccessful (for a patency rate of 75%). Thus, the overall success rate was 83.3% (20/24). Postoperative recurrence of thrombosis was the main cause of treatment failure. Vascular lesion severity was graded as measured by vascular ultrasound: score 0 for complete vessel occlusion, nonperfusion; 1 for stenosis accounting for >75% of the inner vessel diameter; 2 for stenosis accounting for 50%–75% of the inner vessel diameter, and 3 for stenosis accounting for <50% of the inner vessel diameter. The preoperative score was 0 in 10 cases and 1 in 14 cases, whereas after successful treatment, the score was 3 in 18 cases and 2 in 2 cases. No patient experienced severe surgical complications. Figure 3 summarizes the data related to the primary endpoint.
Operative characteristics and early complications.
CVS: central venous stenosis; US: ultrasound.
Clinical success of PTA guided by color Doppler ultrasound. (a) Entire postprocedural angiographic results and (b) success rate after PTA guided by color Doppler ultrasound. PTA: percutaneous transluminal angioplasty.
As shown in Figure 4, 17 patients successfully treated with ultrasound-guided interventional therapy received a 12-month follow-up examination. Of the six patients experiencing recurrence within 12 months after PTA, four experienced recurrence within 6 months. The 6-month patency rate was 76.5% (13/17), and the 12-month patency rate reached 64.7% (11/17).
The 6- and 12-month vascular patency rates.
Discussion
The survival time of patients with end-stage kidney disease is gradually increasing due to improvements in hemodialysis treatment. However, vascular access complications are a leading cause of hospitalization among hemodialysis patients (second only to cardiovascular diseases), as the quality of vascular access directly affects dialysis efficacy and patient’s quality of life.8,9 Vascular stenosis due to vascular remodeling and intimal hyperplasia is the most common complication of vascular access,10,11 and CVS (including narrowing of bilateral brachiocephalic veins, internal jugular veins, and subclavian veins) is a more frequent complication than fistula stenosis among patients receiving maintenance hemodialysis. CVC is the most common risk factor for CVS and associated venous hypertension syndrome among patients receiving AVF treatment for chronic renal failure. 12 In the current study, among 20 cases of CVS receiving PTA under color duplex ultrasound guidance as the first-line treatment, 17 (85%) had a history of CVC, consistent with the previously reported range of 80%–95%. 13
DSA is the gold standard for the diagnosis of central venous diseases. However, two-dimensional DSA may miss certain stenotic lesions, whereas ultrasound can display the details of blood flow and both internal and external vessel structures by flexibly scanning in multiple orientations. Color duplex ultrasonography is widely applied for the evaluation of vascular access, but diagnostic accuracy for CVS largely depends on operator skill, as the most common lesion sites in central veins can be difficult to view. Thus, color duplex ultrasonography is still used primarily for preliminary screening of CVS and follow-up after interventional therapy 14 but not for surgical guidance.
In the present study, all 24 cases of suspected vascular stenosis, thrombosis, or occlusion based on color duplex ultrasound were subsequently confirmed by CTV, confirming high diagnostic sensitivity and specificity. Razek et al. acquired color duplex ultrasound images of the subclavian, internal jugular, and brachiocephalic veins in 35 patients with suspected CVS receiving maintenance hemodialysis and reported highly consistent vascular lumen diameters, peak venous flow velocity ratios, turbulence after stenosis, waveform changes, and thrombosis between two ultrasound experts. 14 A report by Rad et al. also supported color duplex ultrasound as an economical, effective, and noninvasive screening approach with acceptable sensitivity and specificity for the diagnosis of CVS in certain cases. 15
Vascular stenosis is characterized not only by wall thickening and lumen stenosis on two-dimensional ultrasound images but also by blood flow thinning and multicolor turbulence signals on color duplex ultrasound images. 14 Labropoulos et al. suggested that a downstream-to-upstream peak venous flow velocity ratio of 2.5 is highly predictive of CVS >50%. This finding, combined with downstream turbulence and in-plane measurement of vascular lumen diameter, can further increase the accuracy of diagnosis. Thus, color duplex ultrasonography is a sensitive method to identify clinically significant vein stenosis. We propose that a peak vein velocity ratio >2.5 across the lesion is the best indicator for a 3-mmHg pressure gradient. In such cases, color duplex ultrasonography can be used to select patients for intervention and also to monitor the success of the treatment during follow-up. 16 Currently, CT- and DSA-guided endovascular treatments are more frequently adopted in clinical practice, as these modalities provide comprehensive vessel imaging for clear localization of the surgical site and facilitation of surgical procedures. However, both are expensive and can expose patients and physicians to irradiation. Compared with DSA, intravascular ultrasound requires less equipment and can be conducted in general operating rooms or procedure rooms designated by the nephrology ward. Indeed, ultrasound-guided PTA has been recommended as the first-line treatment for AVF stenosis in international guidelines. 17
Nonetheless, there are few reports of ultrasound-guided endovascular treatment for CVS. In the current study, CVS was detected by preoperative ultrasound and confirmed by CTA in all patients. Initial PTA under color duplex ultrasound guidance not only clearly displayed the location and severity of CVS but also served as a feasible presurgical and postsurgical monitoring technique. To the best of our knowledge, this is the first report of the use of ultrasound-guided PTA to treat venous hypertension syndrome caused by CVS and occlusion, and the success rate of initial PTA reached 85% according to the preset criteria. Swelling of the right upper limbs, in particular, was significantly mitigated at postoperative day 2, and blood flow met the requirements for successful hemodialysis. This success rate is similar to that of DSA-guided PTA 18 but without the obvious limitations such as radiation exposure and high cost. In addition, the success rate of ultrasound-guided PTA was up to 75% even after recurrence. Moreover, no patient experienced severe complications, indicating that ultrasound-guided PTA is a feasible treatment for CVS. The 6-month vascular patency rate reached 76.5%, and the 12-month vascular patency rate was still 64.7%, consistent with the previous reports of treatment using DSA.3,18
Study limitations
This study had several limitations. First, we did not directly compare this technique with other interventional therapies at our center. Hence, it remains uncertain whether this technique is generally superior to conventional DSA-guided treatment or if it is advantageous for specific patients. Second, this was a retrospective single-center study with a relatively small number of patients and short follow-up durations. Based on these results, a large-scale multicenter randomized study comparing interventional techniques is warranted. Third, it is not possible to completely rule out selection bias. For instance, it was challenging to detect certain lesions by ultrasound, such as those in the superior vena cava and left brachiocephalic vein. Fourth, due to the small number of patients, we could not assess the efficacy and safety of the technique using a statistical procedure. Finally, conventional DSA-guided treatment was performed after unsuccessful interventional procedures. Central venous lesions that cannot be adequately assessed by ultrasonography should not be intervened using this technique; such cases require alternative imaging guidance (e.g. DSA) to ensure procedural safety. The role of ultrasound-guided PTA in the management of hemodialysis-associated venous hypertension syndrome requires further investigation.
Conclusion
These findings support color duplex ultrasound as a noninvasive, cost-effective, and reproducible approach for locating central venous stenoses and guiding surgical treatment. Unique advantages include multiple view orientations and analysis of both blood flow state and velocity upstream and downstream of the lesion. Therefore, color duplex ultrasound may serve as an alternative to DSA, at least in some cases. However, the long-term therapeutic efficacy of vascular interventions under color duplex ultrasound requires further validation.
Footnotes
Acknowledgements
We would like to acknowledge the Department of Medical Ultrasonography of the Affiliated BaNan Hospital of Chongqing Medical University for assistance in color duplex ultrasound technical support.
Author contributions
Jianbin Zhang: Writing—Original draft preparation; Yongjun Hu: Conceptualization; Runhong Tang: Methodology; Jie Liu: Writing—Reviewing and Editing; Yi Li: Writing—Reviewing and Editing; Hongmin Zhao: Visualization; Lili Hong: Manuscript Revision; Yan Chen: Investigation and Editing; Zhen Li: Supervision. All the authors read and approved the final version.
Availability of supporting data
The data supporting this study’s findings are not publicly available due to ethical restrictions but can be obtained from the corresponding author (email:
Declaration of conflicting interests
The authors declare that there is no conflict of interest.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
