Marc H. Glickman

Distal revascularization–interval ligation for limb salvage and maintenance of dialysis access in ischemic steal syndrome☆☆☆★

PURPOSE Traditional options for treating ischemic steal syndrome related to a functioning dialysis access graft or fistula include banding or ligation. Unfortunately, these techniques usually result in inconsistent limb salvage, loss of a functional access, or both. We report our experience with an alternative method of limb revascularization that eliminates steal while maintaining continuous dialysis access. METHODS Patients who had critical limb ischemia and functioning arteriovenous fistulae (AVF) underwent color-flow duplex scanning, digital photoplethysmography, and arteriography. Arterial ligation distal to the AVF origin eliminated the steal physiologic mechanism while arterial bypass grafting from above to below the AVF revascularized the extremity (distal revascularization-interval ligation [DRIL] procedure). RESULTS From March 1994 through December 1996, 21 patients with functioning extremity AVFs presented with critical ischemia and steal syndrome. Eleven patients had chronic ischemia with rest pain, paresthesias, or ulcerations related to nine native fistulae (six brachiocephalic, two basilic vein transpositions, one radiocephalic) and two prosthetic bridge grafts (one upper arm, one lower extremity). Acute ischemia developed in 10 patients related to three native fistulae (two brachiocephalic, one radiocephalic) and seven prosthetic bridge grafts (three forearm, three lower extremity, one upper arm). All 21 patients were treated with the DRIL technique. Three of these patients required treatment for ischemia at the time of AVF construction. Nineteen of 21 bypass procedures were performed with autogenous vein, including nine brachial-brachial, three brachial-radial, two radial-radial, two brachial-ulnar, one popliteal-popliteal, one femoral-popliteal, and one femoral-peroneal. Polytetrafluoroethylene grafts were used for one external iliac-popliteal bypass graft and one axillary-brachial bypass graft. Limb salvage and maintenance of a functional fistula were achieved in 100% and 94%, respectively, at 18 months by life-table analysis. CONCLUSION The DRIL technique reliably restores antegrade flow to the ischemic limb, eliminates the potential pathway for the steal physiologic mechanism, and maintains continuous dialysis access in these difficult patients.

Failure of foot salvage in patients with end-stage renal disease after surgical revascularization ☆ ☆☆

PURPOSE This report ascertained factors responsible for for failure of foot salvage in patients with end-stage renal disease (ESRD) after undergoing infrainguinal bypass for critical ischemia. METHODS A retrospective review of 69 distal arterial reconstructions performed in 53 patients with ESRD (hemodialysis [n = 37], kidney transplantation [n = 10], peritoneal dialysis [n = 6]) for foot gangrene (n = 28), nonhealing ulcer (n = 25), or ischemic rest pain (n = 16) was conducted. Endpoints of surgical morbidity, limb loss, and graft patency were correlated with extent of preoperative tissue loss and presence of diabetes mellitus. RESULTS The 30-day operative mortality rate was 10%, and the patient survival rate at 2 years was 38%. The primary graft patency rate was 96% at 30 days, 72% at 1 year, and 68% at 2 years. Eleven of 22 foot amputations performed during the mean follow-up period of 14 months (range 3 to 96 months) occurred within 2 months of revascularization. Mechanisms responsible for limb loss included graft failure (n = 9), foot ischemia despite a patent bypass (n = 8), and uncontrolled infection (n = 5). Overall, 59% of amputations were performed in limbs with a patent bypass to popliteal or tibial arteries. Healing of forefoot amputations was prolonged, but all limb loss beyond 9 months of revascularization was due to graft failure. The limb salvage rate at 1 year decreased (p = 0.13) from 74% to 51% in patients admitted with gangrene. Only two of seven patients admitted with forefoot gangrene experienced foot salvage. CONCLUSION Failure of foot salvage in patients with ESRD and critical ischemia was due to wound healing problems rather than graft thrombosis. Earlier referral for revascularization, before development of extensive tissue ischemia and infection, is recommended. Primary amputation should be considered in patients admitted with forefoot gangrene, particularly if it is complicated by infection.

The natural history of autologous fistulas as first-time dialysis access in the KDOQI era

BACKGROUND Patients on hemodialysis depend on durable, easily maintained vascular access. The autologous arteriovenous fistula (AVF) has been the gold standard since the introduction of the Brecia-Cimino fistula in 1966 and is echoed in the current Kidney Disease Outcomes and Quality Initiative (KDOQI) guidelines. The purpose of this study is to determine the natural history of AVF in patients requiring first-time permanent access in a large academic vascular surgery practice. METHODS We performed a retrospective review of patients undergoing new access creation from January 1, 2005 to June 30, 2005. The study group consisted of patients with no prior permanent access that underwent AVF creation. Categorical data was compared using chi2 analysis, nominal data was compared using Student t-test, and patency was determined by Kaplan-Meier curves. RESULTS During the 6-month period, there were 80 first time AVF creations. The majority of patients were male (69%), African American (55%), and a history of diabetes (55%) and hypertension (96%). Seventy-five percent of patients were already undergoing hemodialysis via catheter access. Seventy-six percent of patients underwent preoperative vein mapping with a mean vein diameter of 3.1 mm. Twenty-six radiocephalic AVF (RCAVF) and 54 brachiocephalic AVF (BCAVF) were created with a mean follow-up of 278 days. At the end of follow-up, 38 (48%) AVF were being used for hemodialysis and only nine (11%) matured without the need for additional intervention. Mean time for AVF maturation was 146 days. Thirty AVF (37%) were abandoned, 16 (20%) of which were primary failures. Mean time to abandonment was 162 days. Twelve (15%) AVF remained patent but were never cannulated. The intervention rate was 1.33 interventions/patient/year and 75% of interventions were percutaneous. Kaplan-Meier analysis determined primary, primary-assisted, and secondary patency was 36% +/- 8.3, 55% +/- 6.5, and 55% +/- 6.5 at 1 year, respectively. Cumulative functional patency was 63% at 1 year. CONCLUSIONS In patients receiving a first time permanent access, we found that the majority were AVF and they resulted in low primary patency rates at 1 year and long maturation times. KDOQI encourages AVF creation in order to increase AVF use for dialysis, but the strategy of simply increasing the number being created may not lead to the desired result and potentially lead to an increase in catheter dependence.

Initial experience and outcome of a new hemodialysis access device for catheter-dependent patients

OBJECTIVE The effects of a new long-term subcutaneous vascular access device were studied in access-challenged patients who were poor candidates for fistulas or grafts due to venous obstruction. Bacteremia rates, patency, and function of the Hemodialysis Reliable Outflow (HeRO) Vascular Access Device (Hemosphere Inc, Minneapolis, Minn) were evaluated. METHODS The HeRO device consists of a 6-mm expanded polytetrafluoroethylene graft attached to a 5-mm nitinol-reinforced silicone outflow component designed to bypass venous stenoses and enter the internal jugular vein directly, providing continuous arterial blood flow into the right atrium. The HeRO device was studied in a multicenter clinical trial to test the hypothesis that access-challenged patients would experience a statistically significant reduction in bacteremia rates compared with a tunneled dialysis catheter (TDC) literature control of 2.3/1000 days. HeRO-related bacteremia rates, adequacy of dialysis, patency, and adverse events were analyzed. RESULTS The HeRO device was implanted in 36 access-challenged patients who were followed for a mean 8.6 months (9931 HeRO days). The HeRO-related bacteremia rate was 0.70/1000 days. All HeRO-related bacteremias occurred during the bridging period when a TDC was still implanted before HeRO graft incorporation. HeRO adequacy of dialysis (mean Kt/V) was 1.7. HeRO primary patency was 38.9%, and secondary patency was 72.2%. CONCLUSIONS In access-challenged patients, a statistically significant reduction in HeRO-related bacteremia was noted compared with TDC literature. The device had similar function and patency compared with conventional arteriovenous graft literature.

Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials

BACKGROUND For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. METHODS We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. FINDINGS Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47-72) of patients had primary patency, 73% (57-81) had primary assisted patency, and 97% (85-98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17-40) had primary patency, 38% (26-51) had primary assisted patency, and 89% (74-93) had secondary patency. INTERPRETATION Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. FUNDING Humacyte and US National Institutes of Health.

Outcome-based anatomic criteria for defining the hostile aortic neck

OBJECTIVE There is abundant evidence linking hostile proximal aortic neck anatomy to poor outcome after endovascular aortic aneurysm repair (EVAR), yet the definition of hostile anatomy varies from study to study. This current analysis was undertaken to identify anatomic criteria that are most predictive of success or failure at the aortic neck after EVAR. METHODS The study group comprised 221 patients in the Aneurysm Treatment using the Heli-FX Aortic Securement System Global Registry (ANCHOR) clinical trial, a population enriched with patients with challenging aortic neck anatomy and failure of sealing. Imaging protocols were not protocol specified but were performed according to the institutions standard of care. Core laboratory analysis assessed the three-dimensional centerline-reformatted computed tomography scans. Failure at the aortic neck was defined by type Ia endoleak occurring at the time of the initial endograft implantation or during follow-up. Receiver operating characteristic curve analysis was used to assess the value of each anatomic measure in the classification of aortic neck success and failure and to identify optimal thresholds of discrimination. Binary logistic regression was performed after excluding highly intercorrelated variables, creating a final model with significant predictors of outcome after EVAR. RESULTS Among the 221 patients, 121 (54.8%) remained free of type Ia endoleak and 100 (45.2%) did not. Type Ia endoleaks presented immediately after endograft deployment in 58 (58.0%) or during follow-up in 42 (42.0%). Receiver operating characteristic curve analysis identified 12 variables where the classification of patients with type Ia endoleak was significantly more accurate than chance alone. Increased aortic neck diameter at the lowest renal artery (P = .013) and at 5 mm (P = .008), 10 mm (P = .008), and 15 mm (P = .010) distally; aneurysm sac diameter (P = .001), common iliac artery diameters (right, P = .012; left, P = .032), and a conical (P = .049) neck configuration were predictive of endoleak. By contrast, increased aortic neck length (P = .050), a funnel-shaped aortic neck (P = .036), and neck mural thrombus content, as measured by average thickness (P = .044) or degrees of circumferential coverage (P = .029), were protective against endoleak. Binary logistic regression identified three variables independently predictive of type Ia endoleak. Neck diameter at the lowest renal artery (P = .002, cutpoint 26 mm) and neck length (P = .017, cutpoint 17 mm) were associated with endoleak, whereas some mural neck thrombus content was protective (P = .001, cutpoint 11° of circumferential coverage). CONCLUSIONS A limited number of independent anatomic variables are predictive of type Ia endoleak after EVAR, including aortic neck diameter and aortic neck length, whereas mural thrombus in the neck is protective. This study suggests that anatomic measures with identifiable threshold cutpoints should be considered when defining the hostile aortic neck and assessing the risk of complications after EVAR.

Outcomes comparison of HeRO and lower extremity arteriovenous grafts in patients with long-standing renal failure

OBJECTIVE The Hemodialysis Reliable Outflow (HeRO) graft is becoming a recognized alternative to lower extremity arteriovenous grafts (LEAVGs) as an option for patients who have exhausted traditional upper extremity access; however, which should be applied preferentially is unclear. METHODS A retrospective review of LEAVG and HeRO implants from January 2004 to August 2010 was performed. Patient demographics, medical history, procedural data, and outcomes were evaluated. RESULTS Within the time periods, 60 HeROs were placed in 59 patients and 22 LEAVGs were placed in 21 patients. Demographics were similar between the two groups for many factors; however, the patients who underwent HeRO placement had significantly higher body mass index compared with the LEAVG group. Mean follow-up was 13.9 months for the HeRO group and 11.9 months for the LEAVG group. The HeRO patients underwent a mean of 6.3 previous tunneled dialysis catheter insertions and 3.1 previous AVG/arteriovenous fistula placements. The LEAVG patients underwent placement of a mean of 4.1 previous tunneled dialysis catheters and 2.6 previous AVG/arteriovenous fistulas. The principal difference was the number of interventions to maintain patency, which was 2.21 per year in the HeRO group and 1.17 per year in the AVG group (P = .003) Secondary patency at 6 months was 77% for the HeRO patients and 83% for the LEAVG patients (P = .14). The HeRO and LEAVG groups had no difference in infection rate per 1000 days (0.61 vs 0.71; P = .77) or mortality rate (22% vs 19% respectively; P = .22) at 6 months. CONCLUSIONS In access challenged patients, LEAVG and HeRO offer similar rates of secondary patency, infection, and all-cause mortality. The LEAVG required fewer interventions to maintain patency, and the HeRO maintains the benefit of utilizing the upper extremity site of venous drainage. In our practice, we prefer the HeRO to LEAVG, especially in patients with peripheral arterial disease and in the obese population, because it preserves lower extremity access options.

A multi-center, dose-escalation study of human type I pancreatic elastase (PRT-201) administered after arteriovenous fistula creation

Purpose To explore the safety and efficacy of PRT-201. Methods Randomized, double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.0033 to 9 mg) applied after arteriovenous fistula (AVF) creation. Participants were followed for one year. The primary outcome measure was safety. Efficacy measures were the proportion with intra-operative increases in AVF outflow vein diameter or blood flow ≥25% (primary), changes in outflow vein diameter and blood flow, AVF maturation and lumen stenosis by ultrasound criteria and AVF patency. Results The adverse events in the PRT-201 group (n=45) were similar to those in the placebo group (n=21). There were no differences in the proportion with ≥25% increase in vein diameter or blood flow, successful maturation or lumen stenosis. There was no statistically significant difference in primary patency between the dose groups (placebo n=21, Low Dose n=16, Medium Dose n=17 and High Dose n=12). In a subgroup analysis that excluded three participants with early surgical failures, the hazard ratio (HR) for primary patency loss of Low Dose compared with placebo was 0.38 (95% CI 0.10-1.41, P=0.15). In a Cox model, Low Dose (HR 0.27, 95% CI 0.04-0.79, P=0.09), white race (HR 0.17, 95% CI 0.03-0.79, P=0.02), and age <65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P<0.10) with a decreased risk of primary patency loss. Conclusions PRT-201 was not different from placebo for safety or efficacy measures. There was a suggestion for improved AVF primary patency with Low Dose PRT-201 that is now being studied in a larger clinical trial.

The phase I multicenter trial (STAPLE-1) of the Aptus Endovascular Repair System: Results at 6 months and 1 year

OBJECTIVE This phase I IDE study (STAPLE-1) evaluated the primary endpoints of safety (major device-related adverse events at 30 days) and feasibility (successful deployment of all endograft components) of the Aptus Endovascular abdominal aortic aneurysm (AAA) Repair System (Aptus Endosystems, Inc, Sunnyvale, Calif) to treat AAAs. METHODS A prospective, single arm Federal Drug Administration (FDA) Phase I IDE study was performed. The Aptus endograft is a three-piece modular device with a flexible unsupported main body and two fully supported limbs in a 5.3 mm outer diameter (OD) (16F) delivery system for all iliac limbs and two of three main body sizes. The largest main body (29 mm diameter) is in a 6 mm (18 F OD) delivery system. EndoStaples measuring 4 mm (length) by 3 mm (diameter) designed to provide transmural graft fixation to the adventitia are applied independent of the endograft delivery system. Inclusion criteria included a proximal aortic neck length of 12 mm and iliac landing zone of 10 mm. Secondary endpoints included freedom from endoleaks, rupture, migration, and device integrity. RESULTS Twenty-one (21) patients were enrolled at five centers. All patients received the Aptus Endograft and EndoStaples. Ninety-six EndoStaples (range, 2-10; median, 4) were implanted. All patients (n = 21) completed 1-month and 6-month follow-up evaluation and 14 completed 1-year follow-up. Two proximal cuffs and one limb extension were used as adjunctive endograft components at implantation. Three secondary interventions were performed in 2 patients for limb thrombosis. There were no EndoStaple-related adverse events, device integrity failures, migrations, or conversions. CONCLUSION These results of the STAPLE-1 trial document the acute safety and feasibility of the Aptus Endograft and EndoStaples. Early follow-up demonstrates excellent 6-month and 1-year results. A pivotal phase II trial is underway at 25 US centers.

Elderly patients with CKD—dilemmas in dialysis therapy and vascular access

The population of elderly patients with end-stage renal disease (ESRD) is growing rapidly worldwide. The high prevalence of comorbidities, limited life expectancy and complex quality of life issues associated with this population pose substantial challenges for clinicians in terms of clinical decision-making and providing optimal care. The first dilemma encountered in the management of an elderly patient with ESRD is deciding whether to initiate renal replacement therapy and, if so, selecting the most-suitable dialysis modality. Planning vascular access for haemodialysis is associated with additional challenges. Several clinical practice guidelines recommend an arteriovenous fistula, rather than a central venous catheter or arteriovenous graft, as the preferred access for maintenance haemodialysis therapy. However, whether this recommendation is applicable to elderly patients with ESRD and a limited life expectancy is unclear. Selection and planning of the most appropriate vascular access for an elderly patient with ESRD requires careful consideration of several factors and ultimately should lead to an improvement in the patients quality of life.