Prostheses (endovascular)

Background on Aortic Aneurysms
An aneurysm forms when the walls of the artery become thin and balloon outwards from the pressure of the circulating blood, forming a sac. An aortic aneurysm occurs in the main vessel from the heart supplying blood to the body. As the size of an aortic aneurysm and the pressure inside increase, it is at risk of rupturing (or busting), which is life-threatening.

Disease or injury can be responsible for the weakening of a blood vessel or the thinning of the walls leading to aneurysm formation. Aneurysms may also form due to arteriosclerosis (thickening of arterial walls), embolism (blood clot or foreign matter that passes through the bloodstream and becomes lodged in an artery), physical injury, syphilis or congenital defects.

Methods of treatment
The treatment of an aneurysm depends on the size and location of the defect. The standard therapy for large AAA is surgical repair in which the abdomen is opened and the affected section of the aorta is bypassed with a prosthetic graft, usually made from polyester. However some patients are not well enough to undergo open surgery. Until about 10 years ago, the only option for these patients was conservative treatment with drugs alone.

However, another alternative has emerged, involving a minimally invasive endovascular (through blood vessels) procedure avoiding the need for open surgery. This requires instead only small incisions in the groin through which a prosthesis or stent-graft is passed, within a delivery catheter (tube). It is guided through the femoral and iliac arteries until it completely covers the aortic aneurysm form the inside.

In most patients, the abdominal aneurysm is close enough to the iliac bifurcation (where the aorta divides into the two iliac arteries for the legs) that bifurcated stent graft is required. This comprises a larger diameter section to reside within the abdominal aorta and two 'trouser' legs which are placed within the left and right iliac arteries. Aneurysms located higher in the aorta, or which do not cover the aortic bifurcation can be treated with a single straight tube endovascular prosthesis, but this is less common.

Endovascular Prostheses
Endovascular prostheses, stent-grafts or endografts as they are often called, were first introduced at the start of the 1990s. Pioneering clinicians initially attempted to treat patients unfit for surgery with 'home-made' prostheses using commercially available stents (supporting frame structures) and vascular grafts. However, increasingly, cardiovascular implant manufacturers have been developing and introducing commercial endovascular prostheses. The prostheses comprise a tube of material, usually polyester or PTFE, which is sometimes supported along its length by a metal frame. It serves as an 'inner tube' within the aorta through which the blood flows, excluding further flow into the aneurysm sac.

Statistics on numbers of stent-grafts implanted in the UK were collected by RETA, the Registry of Endovascular Treatment of Aneurysms, based at the Northern General Hospital in Sheffield until the start of the UK EVAR trials referenced below.

EVAR Trials
In addition to the RETA Registry, the Department of Health has also funded through its Health Technology Assessment Programme, a large prospective randomised clinical study aimed at establishing whether endovascular repair has a place in the management of patients fit or unfit for open surgery.

These trials, known as EVAR I where endovascular treatment is compared with conventional surgery, and EVAR II where it is compared with best medical treatment alone for those unfit for surgery, began in September 1999. All patients need to have an aneurysm of at least 5.5 cms and be aged over 60 years, results of the analysis of the 30-day mortality and medium-term success of endovascular vs surgical or best medical treatment were announced in July 2005. The Department of Health has agreed continued funding of these trials to gain further insight into the long-term success of this treatment option.

EVAR trialists are encouraged to report any device-related adverse events to MHRA in addition to the Trial Data Centre. MHRA liaises with the Trial Data Monitoring and Ethical Committee to ensure any serious safety issues are investigated and necessary action taken.

Endovascular Prostheses Experience to Date
Some of the first commercially available models of endovascular prostheses demonstrated significant limitations as they reached and exceeded a two to three year implant duration. A number of these problems have led to graft migration (slippage down within the aorta), various types of endoleak (persistence of blood flow into the aneurysm) or even aneurysm rupture. As a result, there had been numerous device recalls, 'cease sale actions', market withdrawals, and subsequent release of second and third generation designs aimed at addressing these limitations. The success of all current endovascular prostheses appears highly dependent upon factors such as the patients' vascular anatomy and the effects of aneurismal remodeling after device implantation.

In May 2002 the MHRA publsihed a Device Update providing a summary of all endovascular prostheses known to have been CE-marked for sale within Europe at that time, including their current availability in the UK, together with details of general performance trends identified and consequent patient management advice. (This Notice is currently under review to determine whether it should be updated and republished.)

The 2002 Device Update included the following table (Table 1 below) giving information on any relevant published advisory notices for those prostheses with significant clinical experience. It also included Table 2 (below) which listed endovascular prostheses that first received CE-marking during the year 2000/2001 and hence were unlikely to have had sufficient clinical exposure for performance limitations or complications to become apparent by that time.

The 2002 Update cited the following:

A. Emerging Trends Associated with Current Endovascular Prostheses
1. Deployment complications

• Deployment-related complications, leading to emergency conversion and/or patient death, have occurred during the implantation of some single piece abdominal endovascular prostheses designs that have more complex delivery systems.

2. Inadequate proximal fixation/seal

• The risk of Type I endoleak and/or graft migration, especially in the event of neck dilation, depends upon the effectiveness of the proximal fixation and sealing mechanisms used by the endovascular prostheses.

3. In vivo stent frame fractures and row separation

• Stent-frame fractures have been identified among the implanted population of virtually all fully supported models of endovascular prostheses.
• Separation of the top rows of the stent frame, usually where there has been breakage of suture ties intended to attach the frame to the graft, has been found among some models of endovascular prostheses with the most clinical experience.
• Stent frame fractures or row separations have occurred irrespective of whether the stent frame is on the inside or outside of the graft material.

4. Limitations of the graft material

• Graft holes or seam separation has been found among some implanted polyester endovascular prostheses.
• The polyester used in some prostheses has demonstrated unusually high porosity and/or weave separation following implantation.

B. Patient Management Recommendations
1. Patient/device selection

• Special care should be taken in patient selection to ensure that the aneurysm's proximal neck length, neck diameter and angulation are fully compatible with the advice on prosthesis usage given in the manufacturer's instructions. Expect this advice to be regularly updated as a result of feedback from clinical experience.
• When selecting the most appropriate endovascular prosthesis, consideration should be given to the method by which the device achieves proximal seal and fixation (eg presence of hooks, anchors, radial force or columnar support etc).

2. Implantation procedure

• All clinicians involved with device placement should be fully familiar with the manufacturers' instructions and have detailed knowledge of the specific deployment technique associated with each iteration of each individual model, as this can vary considerably. Procedures should initially only be carried out under supervision from someone experienced in the use of the particular device. Facilities to deal with emergency surgical conversion should be available at all times.

3. Patient follow-up

Irrespective of whether patients have been enrolled with the UK EVAR Trials, they should undergo thorough and regular follow-up to monitor for progressive changes in the structure and effectiveness of the implanted endovascular prosthesis.

• Patients should undergo plain abdominal or thoracic X-ray screening (multiple projections) at least annually, to identify incidents of stent-frame fracture or separation of the rows of the stent-frame (Examples of films illustrating stent frame fractures/row separations can be found at the end of the document). Films should be reviewed by experienced radiologists and equivalent projections should be compared to those taken at implant. Endoleak may or may not be evident as a result of frame fracture/row separation.
• Where there is evidence of significant stent frame fracture/row separation patients should be re-screened at more frequent intervals to assess aneurysm status and the need for re-intervention.
• Patients should be regularly screened (at least annually) using contrast enhanced CT for signs of persistent endoleak, either at the proximal neck (Type I), sidebranch flow (Type II), between modular components of the prosthesis (Type III endoleak) or through the graft material (Type III/IV endoleak).
• The routine use of other imaging modalities such as ultrasound, angiography, and Magnetic Resonance Angiography (MRA) is currently being assessed, and these techniques may also be helpful in some cases.
• Incidents of suspected/confirmed stent frame fracture, row separation, or device-related endoleak (not Type II) should be reported to MHRA's Adverse Incident Centre and to the relevant device manufacturer. Any explanted endovascular prostheses should be retained for examination by the MHRA or the relevant device manufacturer.

In addition to the above, clinicians should also follow any detailed advice on specific device models given in MHRA/manufacturer advisories, where these have been published (see Table 1 and references).

References:

MHRA Notices
MDA Device Alert DA2002(05) May 2002. 'TALENT stent graft system: connector bar and stent spring fracture after implantation'.

Manufacturer customer letters

Boston Scientific Corporation, Tel: +33 1464 97561
Letters of October 1997 and November 1998.
Recall letter of 16th November 1999 due to risk of plastic particles on EAG.
Letters of 10th October 2000 and 10th November 2000 referencing wire-form separation and wire breakage.

Medtronic AVE, Tel: +353 91 708686
AneuRx Safety Notice May 2000.
Letter 24th January 2001 ' AneuRx Stent-Graft Performance Update'.
Talent Tips and Techniques: Issue 1 February 2001.
Talent Product Update April 2001.
Talent Product Update April 2002.

Guidant Corporation: +32 2 714 1526
Device Recall, March 27th 2001.

Edwards Lifescienes, Tel: +49 89 954 12582
Letter dated 20th April 2000 - cease sale action.

W.L. Gore & Associates Inc, Tel: 01506 460 123
Letter dated 5th November 2001 - voluntary suspension of thoracic device.

William Cook, Tel: +45 56 86 85 12
'Request for X-ray Follow-up' - implants prior to June 2000, 3rd April 2002.

Enquiries
Enquiries to the MHRA should quote reference number 20020124.005-8 and be addressed to:

Technical aspects:
Hazel Randall or Alex McLaren
MHRA
Market Towers
1 Nine Elms Lane
Vauxhall
London SW8 5NQ

Tel: 020 7084 3287/3292 
Fax: 020 7084 3106

Clinical aspects:
Dr Susanne Ludgate
MHRA
1 Nine Elms Lane
Vauxhall
London SW8 5NQ

Tel: 020 7084 3123
Fax: 020 7084 3111

Examples of X-rays illustrating stent frame fractures/row separations

	Implanted AneuRx prosthesis
	Implanted Excluder prosthesis
	Implanted LifePath prosthesis
	Implanted Talent prosthesis
	Implanted Vanguard prosthesis
	Implanted Zenith prosthesis