Definitions
AVF with abrupt thrombosis (abtAVF): A thrombotic AVF with at least a >50% stenosis identified during ultrasound or angiography. The thrombosis occurred unexpectedly and without a preceding dysfunction, such as inadequate inflow or high dynamic venous pressure during hemodialysis. AVF without a history of abrupt thrombosis (n-abtAVF): These AVFs could have been dysfunctional or thrombotic. The thrombosis usually occurred by deferred correction of the culprit stenosis for AVF dysfunction. Positive quantitative physical examination indicators (qPE indicators) can detect severe stenosis-related hemodynamic derangement in stenoses with minimal luminal stenosis area of <2 mm (1). To save time, we did not perform a systemic physical examination (PE). Rather, we focused on the detection of qPE indicators, which included: 1) No pulse on palpation over the arterial cannulation site; 2) No detection of a pulse downstream of the stenosis in the inflow segment of an AVF (sPPL=0); and 3) An outflow score of 1- or PE significant outflow stenosis (PESOS) for detecting outflow stenosis. Thrombosis-high-risk-stenosis (THRS): In the literature, THRS is a stenosis that is both anatomically (>50% or minimal luminal diameter <2 mm) and hemodynamically (Qa<350, PSVR>2, dQa>25%) significant (2). THRS was considered hemodynamically significant in the present study when a positive qPE indicator was detected. Index of patency function (IPF): IPF was the time interval between the index procedure at enrollment and the end of the study or AVF abandonment divided by the number of interventions to maintain the access circuit for hemodialysis. IPF can be considered the mean time between reinterventions (3). Restenosis interval and restenosis rate: Restenosis interval is the time from when a stenosis is fully dilated to when it is narrowed again to meet the action criteria for angioplasty. For a given period, the shorter the stenosis interval, the higher the restenosis rate. The protocol rate refers to the restenosis rate for AVFs under a given follow-up protocol. These are the on-demand, outpatient, and angiographic sub-protocols in the present study; the target rate refers to the restenosis rate for a given follow-up group of AVFs, such as the abtAVF and n-abtAVF(periodic) groups. The protocol rate should be greater than or equal to the target rate to allow time for the THRS to be dilated before AVF thrombosis occurs.
Patient population
This study was based on data collected prospectively from November 2021 to February 2022. During the study period, all AVFs and arteriovenous grafts (AVGs) were treated and followed according to our routine protocols. Informed consent for treatment was obtained from each participant included in the study. Patients referred to our institution for treatment of vascular access (VA) sites were enrolled in this study. The patients' electronic imaging and medical records were reviewed after approval was obtained from our hospital's institutional review board committee. Inclusion criteria were as follows: 1) Mature AVF and AVG (>6 months old) that was superficial and visible at least around the arterial and venous cannulation segments; 2) Dysfunctional AVFs that had been referred to us because of inadequate inflow (Qb <250 ml/min), elevated dynamic intra-access pressure (>180–200 mmHg) during dialysis or prolonged needle-site bleeding following dialysis, difficult needling, or inadequate clearance; 3) AVFs without dysfunction during dialysis that had been referred to us for treatment because abnormal PE results suggested the presence of VA site stenosis, including abnormal thrill and pulse on palpation, or decreased/abnormal bruit on auscultation. The following VA sites were excluded: AVGs, hemodialysis catheters, immature fistulas, poor candidates for performing a PE to detect stenosis (calcification, deeply located), and AVFs that were treated only once in our angiographic suite. Additionally, thrombotic AVFs without a detectable >50% stenosis on angiography or sonography were excluded.
Clinical indicators for detection of stenoses and the action criteria for angioplasty
In the present study, the clinical indicators described below were used for clinical monitoring (Table 1). The accuracy of qPE indicators for detecting <2-mm stenoses was recently verified (1).
Table 1. Diagnostic elements of the clinical indicators
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Inflow stenosis
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Outflow stenosis
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Needling site stenosis
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Thrombosis and others
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qPE indicators
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1) No pulse on compression over the arterial needling area; 2) No pulse detected downstream of the detected inflow stenosis (sPPL=0).
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1) Bounding pulse with no thrill on finger compression, and upon arm elevation, there was a systolic-only thrill (1-) or no thrill (PESOS).
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A localized jet thrill at or around the needling site.
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Hard on palpation without thrill/pulse or bruit.
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Hemodialysis indicators (4)
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1) Inability to achieve the target dialysis blood flow, tube shaking; 2) >20%–25% decrease of Qb.
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1) Prolonged bleeding; 2) Dynamic venous pressure >180–200 mmHg.
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1) Aspiration of clots; 2) New difficulty with cannulation when previously not a problem.
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Kt/V <1.2 or URR <65.
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The action criteria for angioplasty were as follows: 1) A >50% stenosis with at least one positive hemodialysis indicator; 2) A >50% or <2mm stenosis with at least one positive qPE indicator but no positive hemodialysis indicator (4).
Follow-up protocol and sub-protocols for follow-up of AVFs after angioplasty
Our follow-up protocol includes three sub-protocols for different situations that may be encountered during AVF follow-up.
1. The on-demand (od) sub-protocol (Figure 1a): This sub-protocol was for detecting stenoses by clinical monitoring. Patients followed up under this protocol returned for an outpatient AVF check only when positive clinical indicators such as AVF dysfunction were observed during dialysis, or there were abnormal findings on PE. If a culprit stenosis was detected on sonography, the stenosis was slated for angioplasty.
2. The outpatient (opd) sub-protocol (Figure 1b): This sub-protocol was for detecting stenoses for preemptive intervention by periodic outpatient ultrasound and PE check of AVFs. Patients under this protocol generally returned at an interval of 2–3 months. At the outpatient visit, if point-of-care ultrasound detected a THRS, angioplasty was slated whether AVF dysfunction occurred or not.
3. The angiographic (ang) sub-protocol (Figure 1c): This sub-protocol was for performing preemptive intervention by detecting and treating any >50% stenoses during the same session as the angiographic study. Patients under this protocol returned periodically for angiographic checks of AVF stenosis, generally at an interval of 2–4 months. If a >50% stenosis was detected on angiography, subsequent angioplasty was performed.
Selection of follow-up sub-protocols (Figure 2):
abtAVFs were eligible for periodic follow-up under either the opd or ang sub-protocols. For n-abtAVFs and IPF ≥ 4 months, patients could choose to be followed up under the od or bi-monthly opd sub-protocol. For n-abtAVFs with IPF< 4 months, we adopted the ang or monthly opd sub-protocol.
Outcome measures for the protocol and sub-protocol follow-ups
The following parameters were used to assess the follow-up outcomes of the protocol and sub-protocols: 1) Thrombosis rate and thrombosis-free primary patency, 2) AVF loss rate and secondary patency, and 3) The restenosis rate for AVFs under the protocol and each sub-protocol (the protocol rates).
We did not report restenosis rates as did Razdan et al. (5) by calculating the % luminal reduction per day or month. However, it was possible to determine the relative restenosis rate, either faster or slower, between two given groups, according to the following rules:
- For two groups with insignificantly different thrombosis rates and procedure rates, they had a similar restenosis rate.
- For two groups with insignificantly different thrombosis rates, the group requiring a higher procedure rate had a faster restenosis rate.
- For two groups with insignificantly different procedure rates, the group that yielded a higher thrombosis rate had a faster restenosis rate.
- For two groups with similar restenosis rates, the group with a higher procedure rate yielded a lower thrombosis rate.
Characterization of AVFs with a history of abrupt thrombosis
Identification of abtAVFs: We reviewed the electronic medical records and referral sheets of patients enrolled during the study period. For thrombotic AVFs followed up under the od sub-protocol, we routinely questioned the patients or their dialysis staff, and reviewed their referral sheets to determine if there were any dysfunctions during dialysis, episodes of low systemic blood pressure (<90 mmHg), or overzealous compression of the access site before the AVF thrombosis occurred. If none of these conditions were present, the AVF was considered an abtAVF. We routinely noted this in patients' electronic procedure reports, and following treatment, these abtAVFs were followed up periodically, according to either the opd or ang sub-protocol.
Characterization of abtAVFs: The target follow-up groups in this study were the abtAVF, n-abtAVF, n-abtAVF(od), and n-abtAVF(periodic) groups. We compared the outcome measures in the abtAVF group with those in the other target groups.
Statistical analysis
Thrombosis rate, AVF loss rate, and procedure rate were calculated and are presented as the number of events/patient-year (/pt-yr). Poisson's analysis was used to estimate differences in rates. The thrombosis-free primary patency and secondary patency were calculated using survival analysis with the Kaplan–Meier method. Between-group comparisons of IPF were performed using the unpaired t-test. The receiver operating characteristic (ROC) analysis and the aforementioned analyses were performed using Prism Version 9.0 for Mac software (GraphPad Software, La Jolla, CA, USA).