Cephalic arch stenosis in dialysis patients: review of clinical relevance, anatomy, current theories on etiology and management

INTRODUCTION

Arteriovenous hemodialysis fistulas (AVFs) serve as a lifeline for many individuals with end-stage renal disease and their failure results in significant morbidity and mortality. Failure of a functioning access in dialysis is clinically defined as absolute blood flow less than 500 mL/min, reduction of flow rate by greater than 20% from baseline, greater than 5% recirculation, dynamic venous pressures exceeding threshold levels three times in succession or clinical signs and symptoms such as pulsatile fistula, prolonged bleeding from puncture site, arm pain, arm swelling, thrombosis or stenosis anywhere along the fistula. Outflow obstruction is a common cause of AVF failure and several segments of the outflow tract are prone to stenosis. One such area is the cephalic arch. The prevalence of cephalic arch stenosis (CAS), compounded with its resistance to treatment, makes CAS a common cause of AVF failure.

ANATOMY

The cephalic vein originates in the radial part of the dorsal venous network of the hand, ascends along the radial border of the forearm, passes ventral to the elbow in the groove between the brachioradialis and the biceps brachii, then travels between the pectoralis major and deltoid before piercing the coracoclavicular fascia to enter the axillary vein just below the clavicle (1, 2).

The cephalic arch has been defined in radiological literature as the central perpendicular portion of the cephalic vein as it traverses the deltopectoral groove and joins the axillary vein (3). Kian and Asif described it as the final arch of the cephalic vein before it joins the axillary vein (4).

Yeri et al further described the anatomy of the cephalic vein in the deltopectoral triangle based on 50 shoulder dissections in corpses. They noted that all 50 cephalic veins were located in an aponeurotical conduit between the pectoralis major and deltoid muscles called the deltopectoral fascia. The deltopectoral fascia was noted to have a variable appearance, sometimes appearing thin or interrupted by segments of fat resembling subcutaneous tissue. From the deltopectoral fascia, the cephalic vein travels along the claviculopectoral fascia with the most proximal portion deep to the pectoralis major before draining into the axillary or subclavian veins. The degree of curvature of the proximal cephalic vein was variable (5).

Loukas et al reported that 80% of cephalic veins were easily identified in the superficial deltopectoral triangle; 20% were located deep to or in the deltopectoral fascia. This discrepancy with the study by Yeri et al may be due to variable interpretation of the deltopectoral fascia, especially in cases where it may have been thin and interrupted. Figures 1, 2 and 3 demonstrate the cephalic arch anatomy (6).

Fig. 1 - Fig. 2 -Fig. 3 -

DEFINING THE SCOPE OF CAS IN DIALYSIS PATIENTS

In the year 2000, based on a cohort of 364 patients from 1987 to 1999 with 439 hemodialysis accesses, Luc Turmel-Rodrigues et al demonstrated that the clinical presentation and location of stenosis in a failing access in large part depends on the type of access. For forearm AVFs, poor inflow was the dominant cause of failure with 49% of stenosis at the anastomosis (n=209). For upper arm fistulas and AV grafts, the most common indication for fistulogram was increased venous pressures, with 55% of upper arm fistula stenosis at the central cephalic vein (n=74) and 85% of the AF graft stenosis at the venous anastomosis. In this paper, the upper arm fistulas did not respond as well to interventional techniques compared to forearm fistulas with respect to rupture rate (14.9% versus 8.3%), resistance to dilatation (4.8% versus 1.3%) and mean interval between maintenance interventions (10.6 versus 18.3 months). The results suggest that most upper arm fistula failures are due to outflow disease. Although the authors note that most of the disease in upper arm fistulas involved the central cephalic vein, mainly the final arch of the cephalic vein, they did not provide specific numbers (7).

The earliest cohort of patients with specifically defined CAS was described by Rajan et al (3). Of 177 patients with dysfunctional autogenous fistulas, 26 (15%) were due to CAS. In this cohort, CAS was clearly more prevalent in brachiocephalic fistulas (BCFs, 24/61; 39%) versus radiocephalic fistulas (RCF, 2/116; 2%). These patients demonstrated 76% anatomic success postangioplasty, with a majority requiring high pressures defined as greater than 15 atm. They also required 1.6 interventions per year and had a rupture rate of 6%.

A smaller cohort of patients in a study by Hammes et al demonstrated an even higher prevalence of CAS in patients referred for angioplasty. In a cohort of 127 patients, 97 with BCFs and 30 with RCFs, there was 77% incidence of CAS in BCF and 20% incidence in RCF (8). Hammes also showed that thrombosis was more frequent in CAS versus non-CAS patients. In this cohort there was a 0.82% rupture rate with 2.1% requiring stents due to resistance to angioplasty.

The cohort of patients in Rajan et al is clearly different from the cohort of patients in Hammes et al based on prevalence of CAS as well as differences in response to angioplasty and complication rates. While this discrepancy is likely due to inherent biases in retrospective analysis with patient selection, both studies demonstrate a relatively increased prevalence of BCF failure due to CAS in patients referred for fistulograms.

PROPOSED ETIOLOGIES OF CAS

Despite the clinical significance of CAS and its resistance to treatment, the pathophysiology of CAS is poorly understood. Among many possible etiologies are altered flow in the vein (pulsatile nature and increased pressure) causing intimal hyperplasia as a compensatory mechanism; extrinsic compression by fascia and the pectoralis major muscle preventing the fistulized cephalic vein from dilating in response to increased shear stress; turbulence from increased flow rate, venous valves and cephalic arch morphology causing endothelial damage and intimal hyperplasia and renal failure causing intimal hyperplasia (9-10-11-12-13-14-15-16-17-18-19).

Altered flow in a fistulized cephalic vein

The effect of altered flow in a cephalic vein serving as an outflow conduit for an AV fistula is poorly understood. Arterial diameter increases or decreases in response to changes in blood flow to maintain a constant shear force. Increased flow rates inhibit neointimal hyperplasia and causes arteries to dilate (9).

The effect of flow rate in veins is less well understood. Vein grafts used as arterial bypass grafts in which veins remodel to handle both pulsatile flow and increased pressure are analogous to hemodialysis fistulae and have been studied. Vein graft disease, characterized by excessive vascular smooth muscle cell hyperplasia that causes intimal thickening, provides insight into the fistula outflow tract. Gusic et al showed that increasing shear stress decreased intimal hyperplasia, similar to what has been seen in arteries. However, increasing pressure associated with arterial pressures induced intimal hyperplasia and medial hypertrophy in an ex vivo porcine saphenous vein model (10). Thus, shear stress and pressure serve as opposing forces in mediating vein size. Intimal hyperplasia and medial hypertrophy occur when the balance is shifted to increase in pressure out of proportion to increase in shear stress.

A third component of fistula flow, pulsatile stretch, was found to induce vascular smooth muscle cell hyperplasia in saphenous veins but not internal mammary arteries cultured in identical conditions (11, 12). Increased pulsatile flow leading to intimal hyperplasia has been supported by several animal and human studies. Fillinger et al conducted a study using a canine AV loop graft model where banded and unbanded grafts were implanted in a paired fashion. The flow-limiting band placed on the polytetrafluoroethylene grafts reduced volumetric flow rate by 50%, with resultant decrease in turbulence, flow velocity, flow pulsatility and pressure and the venous anastomosis site. Eight weeks after implantation, the unbanded grafts were associated with increased intimal hyperplasia compared with banded grafts (13). Jaberi et al demonstrated statistically significant correlation between CAS and flow rate measured using the HD01 hemodialysis monitor from Transonic Systems. Miller et al supported this hypothesis by showing that reducing flow rates in patients with CAS resulted in reduced cephalic arch intervention rate per access year from 3.34 prebanding to 0.9 postbanding (14). While these studies successfully demonstrate that hyperplasia and CAS are more common in patients with higher pulsatile flows, they do not explain why stenosis specifically occurs in the cephalic arch and not along the rest of the outflow tract.

External compression by fascia (deltopectoral and claviculopectoral) and pectoralis major

The terminal portion of the cephalic vein, including most of the cephalic arch, is within or deep to the deltopectoral and then claviculopectoral fascia. It is possible that in some patients, the fascia prevents appropriate dilatation of the cephalic arch at a focal location of fascial penetration. What happens when the vessel is not allowed to normalize the shear stress by expanding is less well understood. If the vein cannot dilate to meet physiologic demand, there is potential for increased pressure resulting in intimal hyperplasia and medial hypertrophy (10). Secondly, if the cephalic vein is unable to dilate to handle the flow rate, the flow is more likely to become turbulent, especially in cases where the baseline flow is already high causing endothelial damage and hyperplasia (15).

Morphology of the cephalic arch and angle of cephalic vein entry into the axillary vein

The geometry of the cephalic arch has been proposed as a potential cause of stenosis. One theory is that turbulence due to the angle of the arch in combination with increased flow injures the endothelial cells causing hyperplasia. Hammes et al demonstrated that diabetic patients with BCFs are less likely to get CAS than their nondiabetic counterparts (16). In a follow-up paper, the same group showed a statistically significant difference in cephalic arch geometry in diabetic and nondiabetic patients (17). The diabetic patients tended to have larger alpha angles (defined as the angle between lines tangent to the straight portions of the cephalic vein before and after the cephalic arch) and larger radius of curvature. While the data suggest that diabetics are less prone to CAS and tend to have different arch morphology, causation is uncertain because a confounding factor, flow rate, was not evaluated in these studies. It is possible that increased flow in nondiabetics causes both difference in cephalic arch geometry and stenosis.

Likewise, there are no data to support that the angle of cephalic vein entry into the axillary vein causes CAS. Jaberi et al demonstrated no statistical difference in the angle of cephalic vein entry into the axillary vein between CAS and nonstenosis cases (15).

Larger number of valves in the cephalic outflow

There are at least twice as many valves in the central cephalic vein compared to other areas. A venous valve is present at the central portion of the cephalic vein at its insertion into the axillary vein in 8% of patients (18). This likely causes turbulent flow and alters shear stress mechanics leading to intimal injury and subsequent stenosis.

Renal failure

The cephalic vein in patients with renal failure is pathologically different than it is in patients without renal failure. Wali et al demonstrated that cephalic vein specimens in 20 renal failure patients had thickening of the wall and intimal hyperplasia prior to AV fistula creation compared with specimens from 3 normal patients without renal failure or an existing AV fistula. While the study shows intimal hyperplasia in cephalic veins of dialysis patients it does not address the cephalic arch specifically (19).

MANAGEMENT OF CAS

The effectiveness of angioplasty, cutting balloon angioplasty, bare metal stents, stent grafts and flow reduction techniques has been studied in the setting of CAS. However, the most effective treatment for cephalic vein stenosis is yet to be clearly defined. Furthermore, the definition of initial treatment failure is not well understood. Clark et al showed no relationship between anatomical procedural success and clinical success and further demonstrated that a greater than 30% stenosis immediately postangioplasty was not correlated with clinical failure (20). Most current treatment is limited to repeat angioplasty and stenting with a stent graft until fistula failure.

Angioplasty has limited efficacy in the cephalic arch with 6- and 12-month primary patency of 42% and 23%, respectively; 6- and 12-month primary assisted patency of 83% and 75%, respectively and 1.6 interventions per patient-year (3). Bare metal stents have not been directly compared to balloon angioplasty in the cephalic arch but demonstrate no improvement in 6-month primary patency compared with balloon angioplasty in cases of peripheral venous stenosis (21).

Stent grafts have outperformed bare metal stents in the cephalic arch and offer a potential alternative to balloon angioplasty. Shemesh et al in a prospective randomized trial compared angioplasty with stent graft vs. bare metal stents in 25 consecutive patients with recurrent CAS, defined as greater than 50% stenosis within 3 months of successful balloon angioplasty. The bare metal stent group had 6- and 12-month primary patencies of 39% and 0%, respectively. The stent graft group had 6- and 12-month primary patencies of 82% and 32%, respectively (22). The primary patency in the stent graft group is favorable when compared to angioplasty results from other studies (3).

An alternative endovascular technique for CAS involves usage of a cutting balloon. Heerwagen et al showed that in 17 consecutive fistulas treated with cutting balloon angioplasty (Boston Scientific, Natick, MA), 6- and 12-month primary patency was 81% and 38%, respectively; 6- and 12-month primary assisted patency was 94% and 77%, respectively, with 0.9 interventions per year (23). These results are better than expected with balloon angioplasty alone and similar to stent grafts (3, 22).

Surgical options for CAS include venovenostomy with transposition of the cephalic arch and anastomosis to the basilic or brachial venous system (24, 25). Based on 13 patients, Kian et al demonstrated primary 6- and 12-month patency of 69% and 39% postsurgery versus 8% and 0% presurgery, respectively, with angioplasty in the same patients. The presurgery primary patency rates for balloon angioplasty are low and likely reflect selection bias.

A less invasive surgical option is banding of the juxta-anastomotic segment. The effect of fistula flow reduction after banding of the juxta-anastomotic segment on the recurrence of CAS was studied by Miller et al. A retrospective analysis of 33 patients who underwent this procedure demonstrated 6- and 12-month primary patency of 76% and 57%, respectively, with reduction in interventions per access year from 3.34 preintervention to 0.9 postintervention (14). These results are also comparable to cutting balloon angioplasty and stent graft placement.

While the available data suggest that primary patency rates for venovenostomy, banding, cutting balloon angioplasty and stent graft placement are better than balloon angioplasty, primary assisted patencies do not appear to be significantly different. Furthermore, the published data on CAS consist of retrospective studies and a few small prospective studies. Further study with larger prospective trial is needed to determine optimum management.

Drawing of the cephalic vein as it travels in the deltopectoral groove and pierces the claviculopectoral fascia.

A) Cephalic vein in the deltopectoral groove. White star: deltoid muscle. Black star: pectoralis major muscle. Arrowheads: cephalic vein. Arrows: clavicle. B) Cephalic vein diving under the claviculopectoral fascial layers. White star: deltoid. Black star: reflected pectoralis major. Arrowheads: cephalic vein. Arrow: cephalic vein penetrating the claviculopectoral fascia. C) Cephalic vein confluence with the axillary vein after coursing through the claviculopectoral fascia. Star: axillary vein. Arrowheads: cephalic vein. Arrow: fascial rings.

Angiogram of the cephalic arch. White arrow: cephalic arch. Black arrow: axillary vein. Star: coracoid process.

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