Predictive value of ultrasound classification for autologous arteriovenous fistula stenosis in short-term efficacy of ultrasound- guided percutaneous transluminal angioplasty

doi:10.21203/rs.3.rs-3600663/v1

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Predictive value of ultrasound classification for autologous arteriovenous fistula stenosis in short-term efficacy of ultrasound- guided percutaneous transluminal angioplasty

https://doi.org/10.21203/rs.3.rs-3600663/v1

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To analyze the efficacy of percutaneous transluminal angioplasty (PTA) with ultrasound for different types of arteriovenous fistula (AVF) stenosis. Methods: Clinical data of 51 ESRD patients admitted to the Hemodialysis Center of Huashan Hospital for PTA due to AVF stenosis from January 2018 to May 2020 were analyzed retrospectively. According to the location and etiology of stenosis, AVF stenosis were divided into type I to III and type A to C. The postoperative stenosis recovery, flow improvement, technical success rate and short-term restenosis rate of different types after treatment were observed. Results: The success rate of PTA was 96.2%, and the 9 cases relapsed within 6 months. After operation, the flow volume was significantly increased(P<0.005), in which the type A and C were more markedly than type B (P<0. 05). Two cases without technical success were type AII, and the main short-term relapse stenosis were related to intimal hyperplasia. Conclusion: PTA is an effective treatment for AVF stenosis. The drainage vein was the predilection site of stenosis. The postoperative flow volume of type A and C were not as high as that of type B, while the type with intimal hyperplasia was easy to relapse, and open surgery might be considered if necessary.

Health sciences/Diseases

Health sciences/Medical research

ultrasound

arteriovenous fistula

stenosis

percutaneous transluminal angioplasty

intimal hyperplasia

Kidney transplantation is the only cure for patients with ESRD (end-stage renal disease) at present. However, many patients with ESRD had to rely on hemodialysis as an alternative treatment due to lacking suitable donors. During the treatment, artificial AVF (Arteriovenous Fistula) could connect the arteries and veins to supply sufficient blood flow for hemodialysis. At the same time, the AVF has the clinical advantages like longer lifespan and lower infection rate. It is the currently main vascular access for hemodialysis patients at present^[1].

In 1966, Brescia et al. firstly recorded the establishment of AVF vascular access for hemodialysis patients by surgical methods^[2]. In recent years, guidelines had emphasized the positive meaning of AVF as access for hemodialysis patients^{[3, 4]}. However, the stenosis always happened in AVF due to various reasons such as thrombosis and intimal thickening and they would result in reduced blood flow^[5]. Studies showed that AVF patency rates in the first year and the second year after surgery are 60% and 51% respectively^{[3, 6]}. PTA (Percutaneous transluminal angioplasty) had been proven to be the efficient way to open AVF stenosis and prolong its patency time^[7]. PTA has the advantages like small trauma, high safety, and quick recovery^{[8, 9]}. DSA-guided PTA surgery has become the gold standard treatment for AVF stenosis. Compared with radiography, ultrasonography has some clinical advantages such as safety, non-radiation, and real-time imaging^[10].

Due to ultrasound’s advantages, we could easily observe the location and the etiology of AVF stenosis. In this study, we collected the patients who accepted the PTA surge with AVF stenosis. We classified AVF stenosis into 4 classes based on the location and etiology. We analyzed the short-term efficiency of ultrasound guided PTA surgery for different types of AVF stenosis and discussed its clinical mean.

2.1 Patients

Patients with ESRD who were collected from the Hemodialysis Center of Huashan Hospital, Fudan University from January 1, 2018, to May 30, 2020. 51 patients who were unable to complete hemodialysis because of the AVF stenosis were included.

Inclusion criteria: 1. Meet the diagnostic criteria for ESRD in the "Clinical Practice Guidelines for Chronic Kidney and Dialysis" (K/DOQI Guidelines); 2. All cases’ AVF locations were settled on forearm or upper arm and the fistulation time was more than 1 month; 3. The flow of fistula was less than 200mL/min and the hemodialysis could not be completed. The AVF stenosis was clearly diagnosed by ultrasonography; 4. The patients had clear consciousness and their conditions were relatively stable without serious heart, lung, and brain complications.

Exclusion criteria: 1. The case with non-upper arm AVF or arteriovenous graft; 2. The fistulation time is less than 1 month; 3. Patients with AVF infection, coagulation dysfunction, severe cardiopulmonary insufficiency, stroke, and central venous return disorder; 4. Individuals who were unable to cooperate due to other reasons.

Each patient signed a written informed consent in advance and the study was approved by the Ethics Committee of Huashan Hospital, Fudan University.

2.2 Ultrasound-guided PTA

The ultrasound instruments which were used to evaluate AVF were the HIVSION Priers color Doppler ultrasound diagnostic instrument produced by HTACHI ALOKA, Japan, with a linear array probe (Frequency 5–13 MHz). Before surgery, gray-scale ultrasound was used to observe the thrombus, plaque, and the intima of the inflow arteries, the arteriovenous fistulas, and the draining veins. At the same time, the relative data was reordered. After the location of the AVF stenosis was identified, its pattern and shape were observed from multiple views. The ultrasound typing was performed according to its etiology. The Color Doppler ultrasonography was used to observe and record the blood flow direction, waveform, velocity and flow volume of the brachial artery, inflow arteries, and draining veins. The Ultrasound machine during the operation was the LOGIQ E portable color doppler ultrasound diagnostic instrument from GE Company in the United States and the linear array probe (Frequency 5–10 MHz) was applied in operation. Routine disinfection and draping were performed before the operation. The puncture was performed under the guidance of ultrasound for the placement of guide sheath, guide wire and balloon after the local anesthesia. Stenosis involving the inflow artery was dilated by the normal balloon and the remaining stenosis was dilated by the high-pressure balloon. For mature patients, the balloon with diameter from 4 to 6 mm was used according to the inner diameter of the blood vessel and the balloon with 6 mm diameter was used for non-matured patient. The balloon inflation pressure was 8 to 18 atmospheres (1 standard atmosphere = 101.325 kPa). The balloon inflation duration was 1 to 3 mins. For avoiding the blood coagulation and thrombus re-formation, the heparinization was maintained during surgery and the anticoagulant drugs were generally not used after surgery. After the balloon dilation, the improvement of the original stenosis, hemodynamic changes, flow recovery and the presence of thrombus were observed. After the operation, the original stenosis was re-evaluated by ultrasonography. The scope and shape of the stenosis were observed. The blood flow direction, waveform, flow velocity and flow volume of the brachial artery, the inflow artery and the draining vein were also observed and recorded. When measuring the flow, the patients should stay in a resting state, the cross-section of the selected point should be as circular as possible, the frequency spectrum should be regular, and the sampling gate could basically cover the entire blood vessel.

2.3 The classification of AVF stenosis

According to the location, the AVF stenosis were classified into 3 types before surgery. Arterial anastomosis type (type I) included the stenosis in the input artery and/or anastomosis. Venous anastomosis type (type II) included the stenosis in drainage vein segment. Compound type (type III) included the stenosis involving both the anastomotic site and/or the input artery on the base of drainage vein stenosis.

According to the etiology of stenosis. The cases of AVF stenosis were also classified into 3 types such as endometrial hyperplasia type (type A), mechanical constriction or simple thrombotic type (type B) and complex type (type C). The stenosis of type A was caused by vascular intimal hyperplasia. The stenosis of type B was caused by local simple mechanical constriction or thrombosis. The stenosis of type C was caused by two or more etiologies. (Fig. 1).

The ultrasound evaluation was performed after the PTA operation. Non-mature patients were considered technically successful with conditions like the satisfied palpation tremors or successfully undergo at least once hemodialysis with a blood flow volume above 200mL/min. The mature patients were considered technically successful with the condition of the brachial artery flow volume is more than 300mL/min in a short-term (1-month). If the PTA surgery was successful but the hemodialysis time was less than 3 months, it was considered short-term restenosis and the classification method for restenosis was the same as the pre-operation.

2.4 Statistical analysis

The data was analyzed using SPSS 23 statistical analysis software. Measurement data was represented by x ± s, comparisons between measurement data were conducted by ANOVA test and t test based on the homogeneity of variance test. P < 0.05 indicated a statistically significant difference.

3.1 Clinical data of patients and the classification

Total 51 patients in this group and there were 30 males and 22 females with an average age of 62.4 ± 11.0 years. The time of AVF establishment was 1 to 156 months with an average of 28.0 ± 36.1 months. The cases of anastomosis between the radial artery and cephalic vein in the forearm were 42. The cases of anastomosis between brachial artery and basilic vein were 3. The cases of anastomosis between brachial artery and cephalic vein, brachial artery and cubital median vein were separately 2. The cases of anastomosis between ulnar artery and basilic vein were 1. According to the location of stenosis, 51 cases were classified into 3 types. Type I in 3 cases (5.9%), type II in 35 cases (68.6%), and type III in 13 cases (25.5%). According to the etiology of stenosis, they were also divided into 3 types. Type A in 12 cases (23.5.0%), type B in 14 cases (27.4%), and type C in 25 cases (49.0%). The result of statistics showed that the number of types A and C with endometrial hyperplasia was separately more than types B respectively (P < 0.05). And the number of types II and III with involvement of drainage vein was separately more than types I respectively (P < 0.05).

3.2 Treatment effect

The success rate of PTA surgery in 51 patients was 96.1% (49/51) and 9 patients experienced short-term re-stenosis within 6 months (6/49,12.2%). After PTA surgery, the flow volume of the AVF was significantly higher than the state of pre-operative (P < 0.005), the diameter of AVF also had statistically significant difference after the surgery(P < 0.001) (Table 1). Among them, the blood flow increment of type A and type C was not as good as that of type B after PTA (P < 0.05, P < 0.005). The vessel diameter had the similar result (P < 0.005, P < 0.005) (Fig. 2,3).2 cases that did not achieve technical success were all the type AII. Among the 9 cases of stenosis recurrence within 6 months after PTA surgery, 1 case were type AII,1 case were type BIII,1 case were type CI,3 case were type CII and 3 case were type CIII. Among these, there were 8 cases accompany with endometrial hyperplasia and 8 cases’ drainage veins were involved. The intimal hyperplasia and drainage vein stenosis were essential factors in AVF stenosis short-term re-stenosis.

Table 1

PTA efficacy
Time	Flow volume /mL	AVF vascular diameter/mm
Before PTA	251.7 ± 142.1	1.11 ± 0.47
After PTA	573.1 ± 229.7	2.60 ± 0.93
p	< 0.0001	< 0.0001

Table 1 The increment of flow volume and vascular diameter before and after PTA.

3.3 Histopathological staining

One 63-year-old male patient, who underwent radial artery and cephalic vein anastomosis in the forearm, developed type AII stenosis after 57 months. After PTA surgery, the same type of stenosis appeared again in a short period. Fistulectomy and high reconstruction surgery were performed. The samples of the proximal, middle, and distal segments of the excised drainage vein near the anastomosis were stained with HE, Masson, and alizarin red. The result showed the significant hyperplasia of the entire intima of the stenosis. A large amount of collagen fibers was deposited in the intima and media of the drainage vein located near the anastomotic site (Fig. 2).

Currently, hemodialysis is the main treatment for ESRD patients at present^[11]. As the most commonly vascular access in hemodialysis, AVF has a tight relation with patient’ survival period. In this study, the AVF stenosis was classified by locations and reasons. The number of type II and type III stenosis which was involved in drainage vein was more than type I. The 2 cases of technical failure were all type AII and 8 cases among 9 cases which reappeared within 6 months were induced by intimal hyperplasia. The histopathological staining showed that intimal hyperplasia and collagen fibers was deposited in the intima and media of the drainage vein near the anastomotic site. Since the establishment of autologous arteriovenous fistula, the original blood flow pressure gradient had changed. The most influential change is the WSS (wall shear stress). Unstable shear stress is the main etiology of intimal hyperplasia and endothelial cell damage^[13]. The location of low and unstable vessel wall shear stress is the predilection site of AVF stenosis and it could be seem in the inner wall of the anastomotic origin vein and the posterior segment of the curvature draining vein^[14].The hemodynamics in blood vessels changes with the body's metabolism and needs. Compared with this change, the structure of the blood vessel wall is relatively stable. In some situation, the vessel would change its structure chronically under the acute vascular tone altering. Due to the factors such as WSS, the hemodynamic in AVF has formed a high compliance and low resistance environment. This co-adaptation of vascular structure and function is called vascular remodeling^[15–18]. Vascular remodeling determines whether AVF will develop into the valuable vascular access. Benign vascular remodeling could contribute to AVF maturation while malignant vascular remodeling can directly lead to AVF failure. Abnormal hemodynamics stimulates vascular remodeling and promotes vascular cells to release various growth factors^[19]. The cytokines, proteolytic enzymes, and matrix components respond to AVF’s expansion. At the same time, the migration of myofibroblasts increased and the intimal hyperplasia. Endothelial progenitor cells are activated to repair damaged endothelium and inhibit intimal hyperplasia^[20]. Vasodilation and intimal hyperplasia occur at the same time. It is benign vascular remodeling When the vasodilation is well, the intimal hyperplasia is inhibited, and the endothelium is repaired in time. However, it is malignant vascular remodeling with the poor vasodilation, severe intimal hyperplasia, and poor endothelial repair. The predominant type of vascular remodeling determines whether the AVF is mature or stenotic and the degree of stenosis. Kokubo et al. found that the degree of intimal hyperplasia in mice with chronic kidney disease after AVF anastomosis was twice of the mice with normal renal function because of the vascular smooth muscle’s proliferation and migration^[21]. Ultrasound-guided PTA could restore blood flow volume in AVF under a short period, but it cannot eliminate the root etiology of intimal hyperplastic AVF stenosis. It also cannot inhibit and reverse malignant vascular remodeling. Therefore, after PTA surgery, the AVF stenosis caused by intimal hyperplasia has a higher recurrence rate than other types. In addition, PTA has a certain degree of damage to the vessel wall, it may aggravate intimal hyperplasia and cause the stenosis. PTA also has the possibility of complications such as thrombosis, hematoma, and wall dissection^[22]. The complications are essential factors of PTA’s technical success. Furthermore, the anticoagulant drugs, postoperative fistula care and reasonable functional exercise are all influencing factors of postoperative recurrence.

For AVF stenosis in ESRD patients, the current treatments are PTA and open surgery. The success rate of PTA in the treatment of AVF stenosis is greater than 90%^[23]. Open surgery is to re-anastomose on the excised stricture and its long-term patency is high and costs are like PTA. However, the trauma of open surgery is relatively large, and the limited autologous vascular resources cannot be reserved for patients. Therefore, the timing of the choice of the two methods is very important. AVF stenosis caused by intimal hyperplasia was prone to recurrence after PTA and the increased flow volume of type A was less than type B. The open surgery could be considered in this situation. In addition, DSA is still the gold standard for diagnosing vascular lesions. Except the advantages of economy and simplicity that other inspections do not have, ultrasound can more clearly display the structure of the vessel wall and blood flow before surgery. It also more accurately determines the exact location, extent, and true cause of AVF stenosis. Determining the type of AVF stenosis is more conducive to select the effective intervention methods, so that patients with AVF can restore fistula function and undergo hemodialysis in a short time^{[24, 25]}. In addition, intraoperative ultrasound can guide puncture and catheterization to evaluate blood flow and PTA effect in real time, reduce the risk and time of surgery and reduce the possibility of intraoperative complications.

Ultrasound-guided PTA is an effective method for the treatment of AVF stenosis in ESRD patients. The draining vein is a frequent site in stenosis, and it should be observed during follow-up. Stenosis which was induced by intimal thickening is prone to recurrence after PTA. If necessary, Open surgery or reconstructive fistula after reassessment can be considered.

Statement of Ethics

This study was conducted with approval from the Ethic committee of Ethics Committee of Fudan University. Written informed consent to participate the clinical details and images of the patient was obtained. All methods were carried out in accordance with relevant guidelines and regulations. And we confirmed that informed consent was obtained from all subjects and/or their legal guardian(s).

Conflict of Interest Statement

All authors declare they have no conflict of interests to disclose.

Funding Sources

This study was supported by Fudan University Original Research Personalized Support Project under award number IDF151039/010.

Author contribution

Jie Lin wrote the main manuscript. Renhua lv analyzed the data in article by SPSS software. Hong Ding and Yong Wang supplied relative guidance. Li Chen，Zhifang Huang，Jinyun Tan and Qing He separately provided the clinical cases and ultrasound relative data. All authors read and approved the final manuscript.

Data Availability Statement

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

All data generated or analyzed during this study are included in this published article.

Corresponding author

Correspondence to Renhua Lv.

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No competing interests reported.

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Predictive value of ultrasound classification for autologous arteriovenous fistula stenosis in short-term efficacy of ultrasound- guided percutaneous transluminal angioplasty

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Abstract

Figures

1. INTRODUCTION

2. MATERIALS AND METHODS

2.1 Patients

2.2 Ultrasound-guided PTA

2.3 The classification of AVF stenosis

2.4 Statistical analysis

3. RESULTS

3.1 Clinical data of patients and the classification

3.2 Treatment effect

3.3 Histopathological staining

4. DISCUSSION

5. CONCLUSION

Declarations

References

Additional Declarations

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