Comparison between the 0- and 30-s balloon dilation time in percutaneous transluminal angioplasty for restenosed arteriovenous fistula among hemodialysis patients: a multicenter, prospective, randomized trial (CARP study)

This study was conducted from 20 September 2016 to 31 March 2021 at 14 facilities in Japan. All patients who met the indication criteria for PTA were considered for entry, as described in the 2011 update Japanese Society for Dialysis Therapy Guidelines of Vascular Access Construction and Repair for Chronic Hemodialysis [9]: 50% stenosis and clinical abnormalities, such as decreased blood flow, aneurysm formation, elevated venous pressure, abnormal high blood urea nitrogen, unexpected reduction of dialysis efficiency, and an abnormal physical condition. Inclusion criteria for this study consisted of patients who underwent a single-lesion PTA procedure on the forearm for a failed AVF within a 6-month period. Exclusion criteria encompassed patients who were younger than 20 years old, those with thrombosed access, those with suspicion of acute infection of access, those who underwent an initial PTA, those with multiple lesions, those with lesions located above the elbow, those who underwent duplicate PTA procedures during the observation period, and those who were unable to provide written informed consent. Patients with allergies to contrast agents, severe heart failure, and pregnancy were also excluded. Indications for PTA were determined based on the assessment of the attending nephrologists. Across the 14 facilities, a total of 8013 PTA procedures (2029 cases) were performed during the observational period. Among those, 66 cases met the indication criteria, and finally, 51 cases were included in this study. Almost all individuals excluded were those who underwent duplicate PTA procedures or those with multiple lesions. This study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Hiroshima University (approval number: C-113-1). This study was registered in the University Hospital Medical Information Network (UMIN; 000024331) and written informed consent was obtained from all individual participants included in the study.

We designed a multicenter, prospective, randomized study comparing two groups. The study aimed to evaluate the patency rates between 0- and 30-s dilation as there is no previous report on this comparison. The target sample size was set at 40 patients for the first evaluation. The study was originally planned to run for 24 months, but due to the low enrollment rate, we extended the registration period by 19 months and increased the number of institutions from 5 to 12. Patients were randomly assigned to either the 0- or 30-s dilation group, using an allocation table that considered sex and the presence of diabetes mellitus (DM).

The patency period was defined as the duration of time from the present PTA to the next PTA or surgical revision. Baseline characteristics collected including age, gender, DM, access creation date, date of the previous PTA, location of the stenosis, diameter of the stenosis site, its proximal and distal veins, and the length of the stenosis. The diameter and the length of stenosis were measured using angiography. Data on dilation pressure, device used, and degree of residual stenosis after treatment were also collected. The observation period was 6-month, during which the rate of complete dilation, initial success rate, incident of complication, and degree of pain using VAS during the PTA procedure were also examined. Considering that previous prospective studies reported an increasing incidence of access failure occurring after 3 months [12, 13], we set a 6-month observation period to prevent an excessively prolonged duration beyond the critical 3-month mark.

A 4- or 5-F vascular sheath was inserted toward the stenosis, and heparin was intravenously injected from the sheath at a dose of 2000U. The following sheaths were used: Vaivt A Sheath (Medikit, Tokyo, Japan), Ultrahigh-flow Sheath (Medikit), Mosquito Sincere Catheter Introducer (Boston Scientific Japan, Tokyo, Japan), Goodtec Sheath Introducer (Goodman, Nagoya, Japan). Next, a guidewire was traversed through the stenotic lesion. The following guidewires were used; Radifocus guidewire GT (Terumo, Tokyo, Japan), Kyousha NT (Boston Scientific Japan), Radifocus Guidewire (Terumo), and Buddy Wire (Piolax, Kanagawa, Japan). PTA was performed using a SHIRANUI EX balloon (Kaneka Medical Products, Osaka, Japan) or OHICHOIII balloon (Kaneka) with a diameter of 4–6 mm, which was the same as the previous PTA. The balloon was pressurized by 1 atm every 2 s and expanded to a maximum of 22 atm. Before concluding the procedure, angiography was performed to confirm whether the stenosis was successfully dilated.

The presence of a normal distribution was evaluated by the Shapiro–Wilk test. Data are presented as mean values ± standard deviation (SD) or median and interquartile range (25th–75th percentiles. Continuous variables between the 0- and 30-s dilation groups were compared using the t test or the Mann–Whitney U test, while categorical variable were compared using the chi-square test. The patency rates were compared using the Kaplan–Meier methods with the log-rank test. Multivariate Cox proportional hazard model was carried out to identify clinical factors that are independently associated with the patency rate. Dilation pressure and VAS was compared using Wilcoxon signed-rank test and Mann–Whitney U test, respectively. All analyses were performed using Statistical Package for the Social Sciences software (ver. 21.0; IBM, Armonk, NY, USA). P values < 0.05 was considered statistically significant.

In this study, a total of 51 patients were included, with 19 patients in the 0-s dilation group and 32 patients in the 30-s dilation group, as shown in Fig. 1. One patient in the 30-s dilation group was excluded due to not undergoing prior PTA within 6 months, resulting in a total of 50 patients who underwent successful PTA. No adverse events, such as vascular rupture, were observed during the procedure. However, 2 patients in the 0-s dilation group died during the observation period due to pneumonia and myocardial infarction. The clinical characteristics of all patients are presented in Table 1, which shows that there were no significant differences in age (P = 0.54), sex (P = 0.13), or the presence of DM (P = 0.94). Furthermore, there were no significant differences in diameter of the site of stenosis (P = 0.69), stenosis length (P = 0.11), and diameter of the proximal (P = 0.94) and distal (P = 0.88) sides of the stenosis.

To clarify the effect of dilation time on the patency rates at 3- and 6-month, Kaplan–Meier methods and log-rank tests were used to conduct a comparative analysis. The 3-month patency rate showed a significant difference between the 0- and 30-s dilation groups (72% and 94%, respectively; P = 0.0050), whereas, at 6 months, there was no significant difference between the two groups (24% and 42% in the 0- and 30-s groups, respectively; P = 0.28) (Fig. 2).

Given that the 3-month patency rate is higher in the 30-s dilation group compared to the 0-s dilation group, we next investigated whether this beneficial effect was independent of other clinical factors. Multivariate Cox proportional hazard model revealed that 30-s dilation (hazard ratio (HR) 0.027; P = 0.0072), diameter of proximal site of stenosis (HR 0.32; P = 0.031), and dilation pressure (HR 0.63; P = 0.014) were independently associated with the 3-month patency rate; however, age (P = 0.15), presence of DM (P = 0.97), diameter (P = 0.081) and length (P = 0.77) of stenosis, and diameter of the distal site of stenosis (P = 0.35) showed no significant association (Table 2).

To determine the difference in dilation pressure between the previous and present PTA procedures, we next compared the balloon pressures used in both 0- and 30-s dilation groups. The Wilcoxon signed-rank test revealed that there was no significant difference between the two groups (P = 0.15, P = 0.16, respectively) (Fig. 3A, B).

In comparison of the patency rates between previous and present PTA at 3- and 6-months in both 0- and 30-s dilation groups, 0-s dilation appeared to exhibit a slightly lower 3-month patency rate without significant differences (P = 0.18), while 6-month patency rate did not show significant differences between the two groups (P = 0.63; Fig. 4A). On the other hand, 30-s dilation did not significantly improve 3-month patency rate within previous and present PTA. However, 6-month patency rate in present PTA (42%) was found to be significantly better than that in previous PTA (10%) in 30-s dilation groups (P = 0.015; Fig. 4B).

To evaluate the level of pain during PTA procedure, we compared the VAS scores between 0- and 30-s dilation groups. The Mann–Whitney U test revealed no significant difference in VAS scores between the two groups (P = 0.51) (Fig. 5).