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Abstract

  1. Top of page
  2. Abstract
  3. Subjects and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Conflict of Interest
  8. Disclosures
  9. References

To examine the relationship between intra-access pressures and vascular stenosis, we measured the total (pT) and static (pS) pressures and the severity of stenosis before and after percutaneous transluminal angioplasty (PTA). The dynamic pressure (△p) and static intra-access pressure ratios (SIAPR) were calculated. We analyzed the clinical correlation of △p and SIAPR with the severity and location of stenosis, and searched potential predictive factors for the severity of stenosis using multivariate regression. While SIAPR was significantly decreased only in outflow stenosis after PTA (< 0.0001), △p was significantly increased in both inflow and in outflow stenosis (< 0.05). SIAPR was negatively correlated with the severity of stenosis only in outflow stenosis (< 0.0001), and △p was significantly correlated with both inflow and outflow stenosis (p < 0.05). △p was an independent predictor for the severity of stenosis in both inflow and outflow stenosis (< 0.05). Thus, our study suggests that △p may be more clinically useful than SIAPR not only in detecting access stenosis regardless of its location, but also providing information about the severity of stenosis.

Complications of vascular access for hemodialysis are major causes of morbidity and mortality in end-stage renal disease patients [1]. The most common complication of hemodialysis access is thrombosis due to flow-limiting stenosis, which eventually leads to access failure [2-4]. Therefore, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) recommended that accesses should be monitored regularly for the detection of the development of stenosis, and if detected, it should be treated with angioplasty or surgery prior to thrombosis [1]. Despite several proposed surveillance methods such as measurement of access flow, venous pressure, recirculation, or other physiologic parameters [5-9], their clinical use has not been fully established. Although one of those methods could allow salvage of vascular access by early detection of the stenotic lesion, planning an appropriate treatment strategy, and preparing an elective intervention rather than urgent procedures or replacement [10], several researchers emphasized the importance of physical examination by an experienced physician rather than using such surveillance techniques, especially in autogenous arteriovenous fistula (AVF) [11-13].

Among the surveillance parameters, the static intra-access pressure ratio (SIAPR), a surrogate of access flow rate (Qa), reflects vessel resistance and can be measured at the site of the arterial and venous needle during hemodialysis [14]. The significance of SIAPR is mainly based on a theoretical premise and is defined as static intra-access pressure normalized to the mean arterial pressure (MAP). A high SIAPR usually suggests a low Qa, which also suggests a hemodynamically significant outflow stenosis. Although SIAPR has been thought to be a valuable tool to determine outflow stenosis, its value has been unknown when a hemodialysis access has an inflow stenosis, for example, juxta-anastomosis stenosis, especially in autogenous AVFs. Moreover, the clinical criteria for the intervention to treat inflow stenosis have not yet been established [1]. Thus, in the present study, we examined the clinical significance of intra-access total pressure (pT) and static pressure (ps), and calculated dynamic pressure (Δp) on the basis of Bernoulli's theory. The values were measured and calculated before and after percutaneous transluminal angioplasty (PTA). Simultaneously, the severity of vascular stenosis was measured using radiologic imaging during the procedure. The purpose of this prospective study was to investigate the relationship between the total (pT), static (pS), and dynamic (△p) pressures in the access and the severity of stenosis on radiologic imaging, and to look for potential predictive factors for the severity of stenosis.

Subjects and Methods

  1. Top of page
  2. Abstract
  3. Subjects and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Conflict of Interest
  8. Disclosures
  9. References

Study Design

Patients with end-stage renal disease (ESRD) on hemodialysis requiring a PTA for the treatment of access dysfunction were enrolled in this study. The indications of PTA in this study population were inadequate blood flow, increasing access pressure, delayed hemostasis, and arm edema. We excluded cases of PTA procedures performed with arterial puncture, with the presence of intraluminal thrombus or complete occlusion of fistula vein, maturation failure of AVF, subcutaneous hematoma during the procedure, and severe tortuosity with aneurysmal change of AVF.

Definition and Measurement of the Parameters

Intra-access static pressure (ps) is defined as the pressure inside the vascular access regardless of the motion of blood. It is measured while blood flow is maintained in the access. Intra-access total pressure (pT, stagnation pressure) is defined as the static pressure at a stagnation point at which the flow velocity is zero and all kinetic energy has been converted into potential energy. It is measured at the arterial side in the access when the blood flow is blocked with a balloon. Intra-access dynamic pressure (△p) is defined as the pressure difference between pT and pS, and is calculated by pT − pS. Mean arterial pressure (MAP) is measured using a noninvasive blood pressure measurement (NIBP) on the contra-lateral arm. We measured intra-access total pressure (pT) and static pressure (pS) before and after PTA. Dynamic pressure (△p), pT/MAP ratio, and SIAPR (pS/MAP) were also calculated. The severity of stenosis was measured before and after PTA on fistulography, and displayed as a percent of the adjacent normal diameter. In the initial fistulogram, accessory or collateral veins were also estimated.

Demographic variables such as age, gender, diabetes status, and the use of antiplatelet agents were recorded. Stenotic lesions were classified into inflow stenosis, outflow stenosis, and the combined stenosis on the initial fistulography as the center of the cannulation site during the PTA procedure. Combined stenosis was defined as lesions located at both the proximal and distal sides to the cannulation site.

All subjects who were enrolled in this study gave their written informed consent of the study protocol. This study was conducted according to the principles of the Declaration of Helsinki, following the approval from the Institutional Review Board of the Center (AJIRB-MED-OBS-11-226).

Percutaneous Transluminal Angioplasty

Vascular access was first examined to determine the most probable cause of the problem and its location. Based on this examination, a cannulation site was selected. The access was then cannulated using a Micropuncture needle (Cook, Bloomington, IN) under duplex ultrasound guidance. Fistulography was performed following the previously reported methods. After the initial fistulogram was performed, a guidewire was introduced and then a 6 or 7-F introducer (Terumo Co., Tokyo, Japan) was introduced via the previous puncture site. For lesions downstream (antegrade) from the cannulation site, the guidewire was passed through the draining veins up to the level of the central veins. If the lesion was upstream (retrograde) from the cannulation site, the guide wire was generally passed across the arterial-venous anastomosis. In this study, angioplasty was performed for significant lesions, defined as stenosis greater than 50% diameter reduction on the initial fistulography.

Pressure Measurements and Percent Stenosis Estimation

Pressures were obtained as described by Sullivan et al. [15]. Prior to and following the endovascular procedures, pressures were measured via an introducer with the use of a disposable pressure transducer (AutoTransducer®; ACE Medical, Inc., Goyang, Korea). At the same time, MAP was measured in the opposite arm using a digital sphygmomanometer (Intellivue MP30; Philips Medizin Systeme, Boeblingen, Germany). For pressure measurements, the pressure transducer was filled with saline and connected between the sidearm of the vascular sheath and the pressure monitor system (Intellivue MP30; Philips Medizin Systeme). pS was measured while fistula flow was maintained either in inflow and outflow stenosis (Figs. 1A and 1B). pT was measured during transient occlusion of the fistula flow with balloon inflation. For inflow stenosis, a balloon was inflated proximal to the stenotic lesion, and the pressure transducer was connected to the lumen for the guide wire of the balloon catheter after removal of the guidewire (Fig. 2A). For outflow stenosis, a balloon was inflated just distal to the stenotic lesion, and the pressure transducer was connected to the sidearm of the vascular sheath, in the same manner as the measurement of static pressure (Fig. 2B). For combined lesions, the pressures were measured using an introducer which was inserted antegrade to the blood flow, in the same manner as the outflow stenosis. However, another introducer was inserted in a retrograde fashion with respect to the flow for correction of inflow stenosis.

image

Figure 1. Diagram of intra-access static pressure measurement. Static pressure was measured when fistula flow was maintained either in inflow (A) and outflow stenosis (B).

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image

Figure 2. Diagram of intra-access total pressure measurement. For inflow stenosis, a balloon was inflated at proximal to the stenotic lesion, and a pressure transducer was connected to the lumen for the guide wire of the balloon catheter after removal of the guide wire (A). For outflow stenosis, a balloon was inflated just distal to the stenotic lesion, and a pressure transducer was connected to the sidearm of the vascular sheath (B).

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A radiologist estimated percent stenosis visually by comparing the area of the greatest narrowing to the adjacent normal graft or blood vessel. The radiologist documented the location and visual percentage of stenosis before and after angioplasty. The severity of stenosis was measured by the automatic measuring system (CAAS; Cardiovascular angiographic analysis system) of the angiographic machine (Alluraxper FD 20; Philips, DA Best, The Netherlands). If there were two or more coexisting stenotic lesions, the highest grade of stenosis was recorded.

Statistical Analysis

We examined the correlations between intra-access pressures (pT, pS) and their indices pre- and postangioplasty using the paired t-test. We also examined the correlations between pressure indices, such as SIAPR and △p, and the severity of stenosis using Pearson's test, matrix scatter plot, and linear regression. We merged the data on pressure indices and the severity of stenosis obtained from preangioplasty data as well as from postangioplasty data into this analysis. We used SPSS 20.0 software for Windows (SPSS, Inc., Chicago, IL). We expressed all continuous variables as means ± standard deviation, and rejected null hypotheses of no difference if p-values were less than 0.05.

Results

  1. Top of page
  2. Abstract
  3. Subjects and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Conflict of Interest
  8. Disclosures
  9. References

Characteristics of Patients and Vascular Accesses

During the study period, 114 patients gave informed consent for pressure measurement before PTA. Among them, 28 patients were excluded based on the fistulographic criteria of this study: 19 cases of complete occlusion of fistula or graft, six cases of intraluminal thrombus, two cases of tortuous vein with aneurysmal change, and one case of subcutaneous hematoma during the procedure. In 86 patients who met the inclusion criteria of this study, 90 PTA sessions were performed, and their intra-access pressures and the severity of stenosis were assessed. The clinical characteristics of the patients and vascular access are described in Table 1. Inflow stenosis was detected in 22 (24.4%) patients on the initial fistulography, and outflow stenosis was detected in 62 (68.9%). Six (6.7%) of them had combined lesions at both inflow and outflow sites. All 17 patients with arteriovenous grafts had only outflow stenosis.

Table 1. Characteristics of the patients and vascular access
 Inflow stenosis (n = 22)Outflow stenosis (n = 62)Combined lesiona (n = 6)
  1. a

    Vascular access had both inflow and outflow stenosis.

Patients' characteristics
Age (years)57.7 ± 16.160.4 ± 12.558.7 ± 14.5
Gender, n (%)
Male13 (59.1)35 (56.5)4 (66.7)
Female9 (40.9)27 (43.5)2 (33.3)
Accesses characteristics
Right/left side, n13/947/152/4
Access age (months)34.0 ± 52.649.5 ± 52.235.5 ± 35.9
Graft, n (%)0 (0)17 (27.4)0 (0)
Autogenous, n (%)22 (100)45 (72.6)6 (100)
Radial-cephalic21 (95.5)18 (29.0)2 (33.3)
Brachial-cephalic1 (4.5)27 (43.6)4 (66.7)
Accessory or collateral veins (+), n (%)11 (50.0)26 (41.9)1 (16.7)

Difference of the Intra-access Pressures and Their Indices Prior to Following PTA

The mean percent stenosis of inflow stenosis decreased from 73.3 ± 13.6% before PTA to 17.3 ± 10.7% after PTA. For outflow stenosis, the mean percent stenosis also decreased from 72.2 ± 13.4% pre-PTA to 15.8 ± 11.2% post-PTA. In combined lesions, the mean percent stenosis of inflow lesions decreased from 65.3 ± 8.9% to 19.0 ± 12.8%, and that of outflow lesions also decreased from 69.2 ± 16.6% to 9.2 ± 11.6%. As a result of the treatment efficacy of PTA, intra-access pressures such as pT, pS, △p, and SIAPR also changed after the procedure. The differences in pressures and their indices before and after PTA are shown in Table 2. The pressure differences were distinct according to the location of stenosis. Although pT, pS, pT/MAP ratio, and △p significantly decreased after PTA for inflow stenosis (paired sample t-test, < 0.05), SIAPR was not significantly changed after PTA (= 0.291). Although △p, pS and SIAPR significantly decreased after PTA for outflow stenosis (< 0.0001), pT and pT/MAP ratio did not significantly change (= 0.205 and 0.218, respectively). Only △p increased significantly after PTA for combined lesions (= 0.029).

Table 2. Differences in intra-access pressures and their indices before and after angioplasty (paired t-test)
 Mean ± SD (pre-/post-PTA)Paired difference
Inflow stenosis (= 22)
Mean ± SDLower/upper (95% CI)p-value
  1. PTA, percutaneous transluminal angioplasty; pS, static pressure; pT, total pressure; MAP, mean arterial pressure; Δp, dynamic pressure (pT − pS); SIAPR, static intra-access pressure ratio; CI, confidence interval. Bold values are statistically significant.

pS (mmHg)25.3 ± 10.3/33.8 ± 8.7−8.6 ± 7.2−11.8/−5.6 <0.0001
pT (mmHg)79.4 ± 31.7/105.5 ± 23.0−26.1 ± 23.2−36.4/−15.8 <0.0001
pT/MAP0.81 ± 0.34/1.08 ± 0.23−0.27 ± 0.24−0.4/−0.2 <0.0001
Δp (mmHg)53.5 ± 29.0/71.5 ± 19.9−17.9 ± 23.3−28.3/−7.7 0.002
SIAPR0.30 ± 0.21/0.35 ± 0.09−0.05 ± 0.20−0.1/0.10.291
  Outflow stenosis (n = 62)
pS (mmHg)84.2 ± 23.9/38.6 ± 16.245.5 ± 21.440.1/50.9 <0.0001
pT (mmHg)117.8 ± 17.9/116.6 ± 18.41.1 ± 6.9−0.6/2.90.205
pT/MAP1.21 ± 0.16/1.20 ± 0.170.01 ± 0.06−0. 1/0.10.218
Δp (mmHg)33.5 ± 21.6/78.0 ± 20.3−44.4 ± 21.4−49.9/−38.9 <0.0001
SIAPR0.86 ± 0.22/0.40 ± 0.160.47 ± 0.210.4/0.5 <0.0001
  Combined lesion (n = 6)
pS (mmHg)62.0 ± 28.2/46.2 ± 18.015.8 ± 36.3−22.2/53.80.334
pT (mmHg)88.7 ± 35.6/111.7 ± 10.7−23.0 ± 30.8−55.3/9.30.127
pT/MAP1.07 ± 0.43/1.38 ± 0.19−0.31 ± 0.46−0.8/0.20.156
Δp (mmHg)26.7 ± 22.0/65.5 ± 16.6−38.8 ± 31.4−71.7/-5.9 0.029
SIAPR0.77 ± 0.39/0.57 ± 0.230.19 ± 0.47−0.3/0.70.352

Correlation Between Pressures and their Indices, and Percent Stenosis

When inflow stenosis was greater than 50%, the mean △p was 53.8 ± 30.4 mmHg and SIAPR was 0.31 ± 0.22. When stenosis was less than 50%, the mean △p was 69.7 ± 19.9 mmHg and SIAPR was 0.33 ± 0.09. When outflow stenosis was greater than 50%, △p was 33.5 ± 21.8 mmHg and SIAPR was 0.86 ± 0.22, whereas in less than 50% stenosis, △p was 77.3 ± 22.0 mmHg and SIAPR was 0.40 ± 0.16. We could not find any significant association between the differences in pre-/post-PTA percent stenosis and △p or SIAPR (Linear regression, > 0.05). As displayed in Fig. 3, although percent stenosis was not statistically correlated with SIAPR (r = −0.203, = 0.186), pT/MAP ratio and △p were negatively correlated with inflow stenosis (r = −0.435, = 0.003 and r = −0.351, = 0.019, respectively). In outflow stenosis, although pT/MAP ratio was not correlated with percent stenosis (r = −0.017, = 0.853), the other indices showed a strong correlation with it (r = −0.728, < 0.0001 in △p, and r = 0.761, < 0.0001 in SIAPR, respectively). SIAPR had a positive correlation, whereas △p had a negative correlation with the severity of outflow stenosis. Only △p had a correlation with percent stenosis in both inflow and outflow stenosis.

image

Figure 3. Correlation between percent stenosis and intra-access pressures and their indices. (A, inflow stenosis [n = 44]; B, outflow stenosis [n = 124]; the pre- and postangioplasty data were merged in this analysis). In inflow stenosis (A), the percent stenosis was not correlated with static intra-access pressure ratio (r = −0.203, p = 0.186), but correlated with △p (r = −0.531, p = 0.019). In outflow stenosis (B), percent stenosis was correlated with both SIAPR and △p (r = 0.761, p < 0.0001 and r = −0.728, p < 0.0001, respectively).

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Multivariate Analyses to Detect a Predictive Factor for Stenosis

By multivariate linear regression analyses, △p was an independent predictor for the severity of both inflow stenosis and outflow stenosis (beta −0.43, 95% confidence interval [CI] −0.8/−0.1, p = 0.028 for inflow stenosis and beta −0.29, CI −0.5/−0.1, = 0.021 for outflow stenosis, respectively), as displayed in Table 3. SIAPR was an independent predictor for the severity of only outflow stenosis (beta −15.54, CI −74.3/43.3, p = 0.596 for inflow stenosis and Beta 52.45, CI 28.1/176.7, p < 0.0001 for outflow stenosis, respectively). SIAPR was significantly affected by the type of vascular access (fistula or graft) according to the results of linear regression, but the value of △p was not (R2 = 0.154, CI = 0.1/0.2, = 0.047 in SIAPR, vs. R2 = 0.043, CI = −14.5/8.2, = 0.582 in △p).

Table 3. Multivariate linear regression analysis showing independent variables associated with percent stenosis (The pre- and postangioplasty data was merged in this analysis)
VariablesInflow stenosis (n = 44)Outflow stenosis (n = 124)
Beta95% CIp-valueBeta95% CIp-value
  1. SIAPR, static intra-access pressure ratio; Δp, dynamic pressure (pT − pS); CI, confidence interval.

SIAPR−15.54−74.3/43.30.59652.4528.1/176.7<0.0001
Δp (mmHg)−0.43−0.8/−0.10.028−0.29−0.5/−0.10.021
Collaterals−8.12−27.3/11.30.398−0.88−8.6/6.80.821
Graft−3.28−11.3/4.70.419

Discussion

  1. Top of page
  2. Abstract
  3. Subjects and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Conflict of Interest
  8. Disclosures
  9. References

This study provides valuable insights into the effect of intra-access pressures and their indices such as pT, pS, △p, and SIAPR on clinically significant stenosis which causes vascular access dysfunction. To the best of our knowledge, the present report is the first study in the literature examining the association of pT, pS and calculated △p with vascular access function based on Bernoulli's theory.

Among the useful parameters used to detect access dysfunction, SIAPR surveillance is an attractive methodology because it can be performed during dialysis sessions and does not require additional equipment other than a dialysis machine with a digital pressure display. However, the degree of elevated venous pressure, demonstration of actual stenosis, or prediction of underlying thrombosis cannot be demonstrated by SIAPR. Thus, utilization of static intra-access pressure (SIAP) measurement to screen has been reported by Dember et al. [16] to be a problematic solution for detecting vascular stenosis. Spergel et al. [17] demonstrated that SIAPR does not correlate with access flow in a prospective multicenter study. They also reported that SIAPR measurement cannot discriminate between two different causes of high-pressure ratio such as low inflow resistance with excellent access function or high outflow resistance with access dysfunction. Thus, we tried to find a new pressure parameter that could be correlated with both inflow and outflow stenosis. On the basis of the physics law of energy conservation, the sum of potential energy represented as pT and kinetic energy represented as pS is always constant. According to the Bernoulli's theory, fluid velocity is determined by the difference of the two pressures (dynamic pressure, △p). Therefore, pressure difference (△p) was chosen as the focus of this study. To estimate the relationship between the severity of vascular stenosis and intra-access pressures and their indices, pre- and post-PTA pressure values were compared. The alterations of intra-access pressures and their indices before and after PTA were presented differently according to the location of stenosis. Although SIAPR significantly decreased in outflow stenosis (< 0.0001) after PTA, it did not in inflow stenosis (= 0.291). After PTA, △p significantly increased regardless of stenosis location (i.e., inflow, outflow, or even combined lesions). In this study, angioplasty was performed for significant lesions, which were lesions having stenosis of greater than 50% diameter reduction on the initial fistulography. Unfortunately, this study could not provide any useful data about the alteration of pressures and indices in mild stenosis.

The intra-graft pressure ratio significantly decreased after the procedures in a previous study with 179 cases of graft angioplasty, which rarely included inflow stenosis [18]. Although static venous pressure measurements derived from computerized algorithms have been validated in arteriovenous grafts (not in autogenous AVFs), Tessitore et al. [19] recently reported that static venous pressure measurement and arterial pressure ratio were poor diagnostic tests for the determination of inflow stenosis.

Some evidence has demonstrated that a certain pressure increased gradually with increasing stenosis severity [20, 21]. In dialysis grafts, Sullivan et al. [20] determined the relationship between static intra-graft pressures and anatomic stenosis for 34 grafts, and found a positive correlation between graft pressure and the severity of stenosis. This remarkable correlation was present only in arteriovenous grafts and not in autogenous AVFs. Our data demonstrated that SIAPR was not significantly correlated with percent stenosis in inflow stenosis (r = −0.203, p = 0.186), but was significantly correlated with outflow stenosis (r = −0.761, p < 0.0001), compared with a previous report [21]. In particular, △p was significantly correlated in both inflow- and outflow stenosis (r = −0.351, p = 0.019 in inflow, and r = −0.728, p < 0.0001 in outflow) regardless of access type.

Despite the changes in SIAP in vascular access depending on the location of stenosis, the type of vascular access (fistula or graft), and the presence or absence of collateral veins [15], our study demonstrated that the value of △p was not affected by the type of vascular access. Furthermore, in multivariate analysis including the variables presence of collaterals or grafts, the △p was determined as an independent predictor for the severity of both inflow and outflow stenosis, but SIAPR had statistical significance only in outflow stenosis (Table 3). Therefore, further study should be required to determine the cut off value of access dysfunction.

To calculate △p in the present study, it was required to measure pT by interrupting the blood flow using a catheter balloon. In clinical practice, the method to interrupt blood flow in the access could be applied without a catheter balloon by compressing the superficial fistulated veins or grafts with a tourniquet or the fingers of the examiner.

Our study had two primary limitations. (i) Our study did not contain data about measurement differences by the varied diameters or directions of blood flow in the catheters. (ii) Even though △p is one of the most important determinants of flow rate, it was impossible to build up clinical criteria for access dysfunction because of individual variation in vessel diameter, especially in autogenous AVFs.

Conclusion

  1. Top of page
  2. Abstract
  3. Subjects and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Conflict of Interest
  8. Disclosures
  9. References

The results of our study demonstrated the relationship between access stenosis and intra-access pressures and their indices. In conclusion, △p may be useful for not only detecting stenotic lesions of hemodialysis access regardless of the location of stenosis, but also providing information about the severity of the stenosis. Therefore, △p could be a new surrogate marker for access flow in clinical practice.

Conflict of Interest

  1. Top of page
  2. Abstract
  3. Subjects and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Conflict of Interest
  8. Disclosures
  9. References

The authors have no potential conflict of interests to disclose.

References

  1. Top of page
  2. Abstract
  3. Subjects and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. Conflict of Interest
  8. Disclosures
  9. References