Comparative study of modified HeRO grafts using bovine carotid artery as conduits versus polytetrafluoreythylene

Introduction

The number of patients with end-stage renal disease (ESRD) continues to grow nearly every year in the United States, with hemodialysis being the most common dialysis modality. ¹ Establishing and maintaining a reliable, long-term hemodialysis access site can be challenging. Hemodialysis reliable outflow (HeRO) device (Merit Medical Systems, Inc.; South Jordan, UT) provides an option for catheter-dependent dialysis patients with central venous stenosis who have exhausted all other upper extremity options. ² The HeRO graft is traditionally comprised of a proprietary polytetrafluoroethylene (ePTFE) graft component and venous outflow component. Although HeRO grafts have been shown to improve infection rates compared to tunneled catheters, infections remains an issue due to the synthetic arterial graft component where dialysis cannulation occurs.^2–4 The use of bovine carotid artery grafts (BCAG) for arteriovenous graft (AVG) conduits was described in previous studies which showed benefit in reducing infection when compared to PTFE, however, data on patency benefit have reported conflicting results.^5–9 There is no published data comparing PTFE versus BCAG in the use of HeRO grafts and our study is the first to study the use of BCAG for the arterial graft component of the HeRO graft. The main objective of this study is to compare infection rates, primary, primary-assisted, and secondary between PTFE and BCAG for HeRO grafts.

Methods

This study was approved through the MedStar Research Institute Institutional Review Board. This is a retrospective review of 107 HeRO grafts were placed at Washington Hospital Center between January 2015 to December 2022. All patients were older than 18 years-old. All patients had multiple fistulas that have failed and conventional upper extremity fistula or graft options were exhausted. Patients were eligible for the study for first time HeRO graft placement. Patients were typically assessed 2 weeks after implantation and were cleared for dialysis at that time. Documentation of a clinic follow-up appointment or documented dialysis session of at least 6 months was required if no intervention was performed. Follow-up time was concluded after graft abandonment, death, or if patient was lost to follow-up on the electronic medical record (EMR). Patients were included in the analysis if they required excision prior to the minimum 6-month follow-up requirement. The follow-up time ranged from 17 days to 6.4 years. Electronic medical records at the time of surgery were used to obtain demographic and baseline characteristics (Table 1). The BCAG used was the Artegraft (LeMaitre, Burlington, MA) and PTFE grafts used were the GORE-TEXStretch Vascular Graft (W. L. Gore and Associates, Flagstaff, AZ) and Venaflo (Bard, Temple, AZ). Of the 107 HeRO grafts placed, 15 patients (9 patients with PTFE and 6 patients with BCAG) were lost to follow-up. Nine patients with early cannulation grafts were not included in the analysis. Forty patients had HeRO graft placed using PTFE and 43 patients using BCAG were included in the analysis. Patient baseline characteristics were compared between cohorts using Fisher’s exact test and Mann-Whitney U test for categorical and continuous variables, respectively. Measured values were reported as percentages or mean ± standard deviation. Covariables included age, race, obesity, diabetes, gender, hypertension, smoking, laterality, graft size, total procedural time, and active smoking. Obesity was defined as body mass index (BMI) greater than 30. Primary outcomes were infection, primary, primary-assisted, and secondary patency rates. Infection was defined as clinical suspicion of graft infection requiring surgical excision with evidence of infection during graft explant. Both partial and complete excision of the graft with evidence of perigraft fluid, lack of incorporation, and mention of infected graft in the operative report was categorized as an infected graft. Additionally, positive cultures were sufficient but not necessary to be categorized as an infected graft. Definitions of arteriovenous access patency was based on the recommended standards per the Society of Vascular Surgery guidelines. ¹⁰ Primary patency was defined as the interval from HeRO graft placement until any type of intervention or graft failure. Primary-assisted patency was defined as the interval from graft placement until first episode of graft occlusion. Secondary patency was defined as the interval from graft placement to graft abandonment. Patency data was calculated using Cox regression analysis and Kaplan-Meier method in time-to-event analysis which was reported as hazard ratio with confidence intervals. Graft infection was calculated using multivariable logistic analysis. Statistical significance was considered at a two-sided p-value of ⩽0.05 for all analyses. Statistical analysis was performed using STATA 18 (STATAcorp, College Station, TX) and GraphPad Prism (GraphPad Software, Boston, MA).

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Table 1.

Demographic characteristics and risk factors.

Variables	Artegraft	PTFE	p Value
Age	58.7 (1.89)	60 (1.95)	0.62
Gender			0.51
Male	19 (44.2%)	21 (52.5%)
Female	24 (55.8%)	19 (47.5%)
Race			0.8
White	9 (20.9%)	8 (20%)
Black	33 (76.7%)	29 (72.5%)
Hispanic	1 (2.3%)	2 (5.0%)
Other	0 (0%)	1 (2.5%)
Obesity	23 (53.5%)	21 (52.5%)	>0.999
Hypertension	38 (88.4%)	37 (92.5%)	0.71
Diabetes mellitus	30 (69.8%)	27 (67.5%)	>0.999
Active smoking	19 (44.2%)	16 (40.0%)	0.82
Coronary artery disease	18 (41.9%)	14 (35.0%)	0.65
COPD	10 (23.3%)	12 (30.0%)	0.62
Follow-up, years	1.6 (1.4)	1.7 (1.6)	0.82
Operative time, min	90.9 (25.9)	96.8 (31.8)	0.36
Graft size, mm	5.86 (0.63)	6 (0)	0.036

BMI: body mass index; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease.

Categorical variables are presented as number (percent). Continuous variables are presented as mean (standard deviation).

Results

Eighty-three patients were included in the analysis. Forty patients had HeRO graft placed using PTFE as the conduit, whereas 43 patients had used BCA.

Outcome

PTFE was associated with significantly increased rates of infection compared to BCAG (16.3% vs 40%, p = 0.026). The number of patients who required intervention was significantly lower for BCAG compared to the PTFE group (79.1% vs 95%, p = 0.03; Figure 1). However, there was no significant difference in the average number of interventions (2.88 ± 2.9 vs 2.73 ± 1.9, p = 0.65). After adjusting for baseline characteristics using the Cox multiple regression analysis, there were no differences in patients requiring intervention (HR = 1.16; 95% CI, 0.72–1.86, p = 0.76). no significant differences pseudoaneurysm formation or aneurysmal degeneration (2.3% vs 2.5%, p = 0.735; Figure 1).

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Figure 1.

Outcomes comparing BCAG versus PTFE. Difference in intervention, infection and pseudoaneurysm between bovine carotid artery graft (BCAG) and polytetrafluoroethylene (PTFE).

Comparing BCAG versus PTFE, the unadjusted Kaplan-Meier estimates of primary patency was 58.4% versus 59% at 6 months (p = 0.82) and 34.9% versus 34.1% at 1 year (p = 0.88; Figure 2). Primary-assisted patency was 88.6% versus 80.6% at 6 months (p = 0.35) and 69.7% versus 54.6% at 1 year (p = 0.21; Figure 2). Secondary patency was 94.3% versus 85.7% (p = 0.23) at 6 months and 82.4% versus 59.1% at 1 year (p = 0.12; Figure 2). The multivariable Cox regression analysis Reing for the covariables listed above revealed that there was no difference in primary patency when comparing BCAG versus PTFE (HR = 1.02; 95% CI, 0.58–1.79; p = 0.84; Figure 3). Additionally, there were no differences between primary-assisted patency (HR = 1.44; 95% CI, 0.74–2.81, p = 0.61; Figure 3) and secondary patency (HR = 1.95; 95% CI, 0.87–4.4, p = 0.22; Figure 3).

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Figure 2.

Six month and 1-year adjusted primary, primary-assisted and secondary patency comparing bovine carotid artery graft (BCAG) to polytetrafluoroethylene (PTFE).

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Figure 3.

Kaplan Meier curve showing primary (a), primary-assisted (b), and secondary patency (c), number at risk shown below.

Discussion

Due to improved survival in patients with ESRD, there is an increasing number of patients who have limited access options (1). Since approval by FDA in 2008, the HeRO graft has shown great promise as a durable access device. Although, the graft has been shown to reduce infections compared to tunneled catheters, patients are still susceptible to infection due to the synthetic graft that is cannulated during dialysis. ³ Additionally, complex patients who require HeRO graft are even more susceptible to infection due to the tunneled dialysis catheter fibrin sheath as well as comorbidities. There have been previous studies comparing bovine carotid artery graft to PTFE for conventional arteriovenous grafts, however our study is the first to describe the use of BCAG in place of PTFE for the arterial graft conduit of the HeRO graft.

Previous studies comparing BCAG to PTFE for conventional arteriovenous grafts have reported conflicting results. Arhuidese et al. demonstrated improvement in secondary patency, but found no difference in primary patency and infection. ¹¹ Kennealey et al. demonstrated improved primary patency, primary-assisted patency, and decreased number of interventions. ⁸ Our results were in-line with the systematic review by Kostakis and Loukopoulos, showed lower graft infection, but no difference in patency. ⁷ We found a significant decrease in infection for BCAG, however there was no difference in patency between BCAG and PTFE. However, there were no statistically significant difference in time to infection for BCAG (633 days ± 624.7 days) compared to PTFE (418.7 days ± 330.7 days, p = 0.42).

Although there were concerns about degradation of above carotid artery grafts in the past (add citation), more recent studies including this study shows the viability of bovine carotid artery grafts. High rates of aneurysmal degeneration and pseudoaneurysm formation were seen with previous bovine carotid artery grafts.^12–14 However, technological advances in processing the grafts have led to a decline in the more recent generations.^15–17 In our study, there were no significant differences in aneurysmal degeneration or pseudoaneurysm formation for BCAG (2.3% vs 2.5%, p = 0.735) which is in line with the reported 0%–4% rate found in other studies with newer generation bovine carotid artery grafts. ⁷

We demonstrated bovine carotid artery grafts are comparable in primary patency, primary-assisted patency, and secondary patency versus PTFE grafts. Primary patency for 6 and 12 month was in-line with the largest HeRO graft study to date which shows a primary patency of 60% and secondary patency of 90.8% at 6 months. ² The primary and secondary at 6 month was 58.41% and 94.3%, respectively.

The study has several limitations that are worth mentioning. Our study was a retrospective, single-institutional study with limited sample size. It is likely that the small sample size limits the power of the study to detect differences in patency rates. Furthermore, many patients who qualified for the study after the index procedure did not have any follow-up and were subsequently excluded from the study. Most patients in the earlier years had PTFE graft placement whereas most patients within the past 2 years of data collection had bovine carotid artery graft placed due to surgeon preferences. Although there were no differences in follow-up time, it is not possible to eliminate confounding due to experience obtained by the surgeon. HeRO graft placement is a relatively novel procedure and patients who had bovine carotid graft placement had the benefit of improved surgeon experience. Additionally, the analysis did not take into consideration the type and number of prior vascular accesses and the effect this might have. Most patients in the study had multiple previous arteriovenous fistula or graft placed prior to HeRO graft placement which may confound results. Lastly, previous medical history of infection was not accounted for in the regression analysis.

Conclusion

Our study shows a benefit in reducing rates of graft infections with similar rates of patency when using BCAG compared to the traditional PTFE. These data demonstrate that bovine carotid artery grafts are a suitable conduit in the use of HeRO grafts especially in patients who are high-risk of graft infections.