—  SHORT COURSE #57  —

Atherosclerosis: Practical Implications for Pathologists

Section 9 - Large Vessel Disease, Aortic Aneurysms and Stent Therapy

Jagdish Butany
John Veinot


Case #8:
This 19-year-old woman was a passenger in an automobile involved in a head on collision. She suffered extensive trauma including "laceration" of the thoracic aorta resulting in a leaking aortic aneurysm (TAA). The latter was noted after attempts at stabilizing her other injuries. After special permission was obtained from the hospital authorities and ethics board, permission was obtained from the FDA for use of an endovascular aortic stent to treat the leaking TAA. The endovascular stent was deployed and the aortic injury stabilized. However, she remained in a coma and ultimately died, nearly 12 months after the injury. The aorta was made available for analysis.

Most aortic disease results in aneurysm formation. Aneurysms are commonest in the abdominal aorta, followed by the ascending arch and thoracic aortas in that sequence.

The aortic aneurysms are honest comment than many of the cut or ask the conditions. However they can be life-threatening and it is an unfortunate fact that even a large aneurysms may be totally asymptomatic little

Abdominal aortic aneurysms (AAA) are amongst the commonest of vascular conditions with life-threatening complications. When diagnosed early (diameter up to 5.0 cm and without evidence of leakage) they are easily treated surgically with the use of interposition grafts. However, aneurysms frequently occur in elderly individuals and individuals with many other co-morbid conditions, making surgical management difficult. These patients were often refused surgery, in the past and today.

At the same time, thoracic aortic aneurysms (TAA) are an uncommon but equally life-threatening condition. Three percent of all aortic aneurysms are believed to be TAA and are commonly due to atherosclerosis and chronic aortic dissection. (I personally believe that aortopathies also play a role in the incidence of TAA. However these aneurysms are more likely to be large, fusiform or spindle shaped rather than the localized saccular type that are seen with atherosclerosis.)The actual prevalence and mortality rate of TAA (and of AAA) in any particular population is not well established. [29, 30]

The purpose of treating aortic aneurysms is two-fold:
  1. To prevent rupture

  2. To eliminate compression symptoms related to the mass effect of the aneurysm, damage to the spinal cord and dysphagia.
Open surgical repair with prosthetic vascular graft interposition is the traditional and accepted method of treating TAA as well as AAA [31].

Perioperative morbidity and mortality rates however remain high and these are due to many reasons, the chief of which is the patient population and their age, and high incidence of co-morbidities. Other factors include the morbidity associated with a major thoracotomy, the use of cardiopulmonary bypass, post operative complications including bleeding, paraplegia, stroke, renal insufficiency and a necessity for ventilatory support (often prolonged). In thoracoabdominal aortic aneurysms, the mortality rate was reported at 4.8% and the incidence of paraplegia at 4.6% by Cosellie JS et al. [32] In view of the persistent morbidity and mortality associated with open surgical repair of descending TAA, thoracoabdominal aortic aneurysms (TAAA) and leaking abdominal aortic aneurysms, a less invasive and potentially safer technique for aneurysm repair was clearly necessary.

Parodi et al were the first to describe the treatment of AAA with an endovascular stent graft in 1991. [33, 34] These grafts were initially devised for the purpose of treating aortic aneurysms in individuals with likely high morbidity and mortality. Progress has been made and several reports substantiate the safety and effectiveness of stent grafts in the repair of AAA and TAAA [35].

With increasing experience in the use of stent grafts for TAA and AAA, many other aortic diseases, such as traumatic aortic injury, aortic dissection, penetrating atherosclerotic ulcers, aortopulmonary fistulae and acute aortic rupture related to blunt chest trauma or mycotic aneurysms have been treated as indications for endovascular treatment.

The endovascular treatment of aortic aneurysms entails the use of a fairly large balloon catheter, with a collapsed stent graft mounted on it. The grafts may be open, covered or a combination. The length of most of these stent grafts can be increased by attaching additional segments to their end. The device is inserted following a femoral artery cutdown. No thoracotomy or clamping of the aorta is necessary. The length of the aorta that is likely to be "covered" by the graft is generally short and limited to the diseased segment so that the risk of spinal cord ischemia is reduced. There is no need for full heparinisation and major bleeding complications or bleeding from cerebral vascular lesions, is excluded.

Stent graft systems:
The initial endovascular devices used were homemade devices. Technological innovations, continued at a brisk pace, and an increasing number of commercially available aortic stents have been developed and refined endovascular prosthetic devices. Today, custom designed, homemade and commercially available stent grafts are used in the treatment of thoracic aortic disease as well as abdominal aortic disease. The homemade stent grafts used at Stanford University are comprised of a series of self-expanding Z-shaped stainless steel stents, boxcar together and interconnected by two zero polypropylene sutures. This skeleton is covered with a woven-Dacron polyester tube graft attached to the stent with five zero polypropylene sutures. These are loaded onto a delivery capsule, advanced through a delivery sheath on a 28 French catheter.

Commercially available stent grafts: Several different manufacturers have introduced grafts. Some of these unfortunately have suffered significant problems at intermediate term and are now no longer available. The Talent endoluminal stent graft device, the AneurX stent graft and the Excluder endoprosthesis are some of the devices that have been available for current use and are available in the market.(See Butany et al, J Clin Pathol in press)

These devices are still in the early stages of clinical use and long term results are not available, especially results based on pathologically examined explants (whether at autopsy or at surgical re-exploration. While they have been studied to a good extent in experimental animals, human experience is still relatively small, and reports are awaited. It is therefore critical for pathologists who get these cases at autopsy to examine them in detail or to send them to someone who will examine them in detail. The detailed examination is a fairly intense and expensive, time consuming process but the results should be very relevant. Additionally, since many of these devices are still in the clinical trial stages, the results often need to be conveyed to the Food and Drug Administration or the Device Control Agencies in the country in which they are being use for explanting.

Major considerations to keep in mind when examining these devices include getting ALL the relevant clinical and imaging information, and at the time of examination :
  1. Radiologic examination to see if the metal components are intact -rule out poor strut expansion and strut fractures.

  2. Detailed examination of the covering fabric to see if there is fraying or damage due to fractured device components, tearing / ripping the fabric

  3. Excessive movement of the device, beyond the point of implantation—migration of the device

  4. Rupture of the aorta - Leakage of blood

  5. Damage to the aorta (generally away from the diseased or torn segment)

  6. Endoluminal leak(hemorrhage of any kind)

  7. Dissection

  8. Thrombosis

  9. Intimal hyperplasia at the ends of the device
We will present some examples of cases of use of this device and associated changes.

Abdominal aortic aneurysms (AAA) repaired by endovascular grafting offer a tremendous promise of effective and durable repair by improving morbidity and mortality as compared to the open or surgical correction. This, in time, will also likely lead to significantly reduced hospital costs [37].

To summarize, endovascular stent grafts are comprised of a metal stent (stainless steel or nitinol - an alloy of nickel and titanium) covered with a fabric graft, which resembles a usual vascular graft except that it has a metal stent or frame inside it. The device is therefore known commonly as a stent-graft. These grafts may be straight or tubular grafts, in which case the two ends are meant to be anchored to the infrarenal aorta (they have little hooklets which help them to get so attached) or, the grafts may be bifurcated with the proximal end attached to the infrarenal aorta or another part of the aorta if necessary, while the distal end is bifurcation (like a pair of pantaloons) and the two limbs are fastened to the iliac arteries. The stents used are self expanding stents and some of the devices have little hooks on their outer aspect which allow them to get embedded in the surrounding wall. For obvious reasons, it is imperative for the operator to be able to anchor the device against the vessel wall.

Complications associated with the device include: thrombosis, dislodgement of the device (inadequate attachment to the walls) with movement (migration) of the device, often away from the site at which it should be attached, infection and twisting or kinks in the device leading to vascular obstruction. Structural failure, related to the metal component and / or the fabric covering it with the associated possibility of hemorrhage (generally slow and ongoing). A complication not associated with other devices, is the occurrence of an "ENDOLEAK".

An endoleak means that either because of inappropriate placement', damage to the fabric, or retrograde blood flow , blood leaks into the perigraft space, that is into the aneurysm or into the lumen of the endoluminal graft and into the native vessel This blood is contained by the aneurysm wall. However, it can lead to ongoing aneurysm expansion and potentially likely to rupture [38].

Examination of these specimens when obtained at autopsy or even at surgical "redo" procedures is often difficult. The specimen is large as the device used is implanted inside the aneurysmal segment and anchored above it with the two limbs extending into the iliac vessels beyond it. The device should be examined radiologically to look for evidence of changes in the metal components.

Perhaps the single most significant problem associated with these devices, certainly unusual and associated largely with this type of device alone, is the endoleak. An endoleak is due to the incomplete "plastering" or sealing of the device to the wall of the vessel. It may happen at the time of implantation when the proximal end does not attach fully or leaves a small space between the graft and the wall of the native vessel.or when the fabric tears for some reason. It is entirely possible that the fabric was defective or that retrograde blood flow has occurred through small aortic branches. In some instances reoperation has been necessary and the incidence of this complication is reportedly approximately 6% [39] In a small number of cases, AAA have been reported to continue to increase in size. The explanation for this is not known and has been reported to occur even without an endoleak. A few possible explanations have been offered for this. These can be suspected at CT scan,

With improved devices, better delivery systems and the good results that are being reported, the device is now being used more extensively and in some instances as a first line procedure, in essence the device has gone "mainstream"-and has made it to "prime time"! That is, though it was meant initially for use in individuals who were "inoperable" for many reasons they are now being used in individuals who do not wish to have the usual surgery.

Case B:
29 year old male, History of Dilated cardiomyopathy .New onset Severe Congestive Heart Failure.Ventricular Assist Device (Heartmate) inserted: Bridge to transplant

Readmitted 17 months later---"device malfunction"

Device adjusted and placed again on urgent transplant waiting list:

Heart transplant : end Feb '05.Device removed and examined.

Case C
A 62 year old patient with long standing ischemic heart disease (refused heart transplant) underwent VAD placement as Destination Therapy. On day 9 he started developing refractory ventricular arrhythmias, and died on day 11, despite all efforts. (the pathology will be discussed).

At this time, the best form of treatment for intractable congestive heart failure or end stage heart disease is heart transplantation. However, the number of hearts available for transplantation is limited and this precludes the use of this approach for all patients. In addition, hearts are not available exactly when needed. Hence, the availability of a device, which takes the place of a graft heart, even if temporarily, provides a valuable adjunct to treatment. Ventricular assist devices are one such group of mechanical devices, which serve this purpose - that is they are a bridge to transplantation. Some of these devices are meant only for short-term use (that is a week to two weeks), white others can be used for several months and even long to. These devices are expensive and do have complications. There are peri and postoperative considerations when managing a critically ill patients whose life depends on the mechanical circulatory support or ventricular assist device. Careful patient selection and care of a patient with such a device is obviously essential.

Mechanical circulatory support is today "a standard of care" for some patients having acute or even chronic heart failure. One of the major criteria for the use off a VAD is, inadequate cardiac output, for preservation of end organ perfusion.

Table : Currently available Ventricular Assist Devices
Device Name Type-Chamber to which attached Mechanism of Blood propulsion Duration of Implantation Position/Location of Device
Abiomed BVS5000 BiVAD Pneumatic Days-Weeks Paracorporeal
Thoratec BiVAD Pneumatic Months Paracorporeal
HeartMate LVAD Electrical Months Implantable
Novacor LVAD Electrical Months Implantable
Cardiowest TAH BiVAD Pneumatic Months Paracorporeal
Debakey LVAD Axial Flow Months Implantable
Jarvik 2000 LVAD Axial Flow Months Implantable
HeartMate II LVAD Axial Flow Months Implantable
Abiomed BiVAD BiVAD Pneumatic Months Paracorporeal

LVAD--Left ventricular assist device. BiVAD-Biventricular assist device.

(Modified from Ventricular Assist Devices, in 'A practical approach to perioperative care in cardiac anesthesia and surgery".

Complications associated with VAD:
  1. The mortality associated with VAD insertion is about 25%. Most patients today are stabilized on the VAD are sent home while awaiting heart . transplantation.

  2. General complications include :
    1. coagulopathy

    2. Drive line infections

    3. other infections

    4. prostheses thrombosis and thromboembolic events

    5. HLA sensitization
Late complications associated with VAD usage, are likely to be device specific. However there are few morphological reports documenting these in devices that have been explanted and analyzed and hence no reference is available for. Complications that have been seen and recorded by us include:
  1. the development of thrombus around the device cannulae

  2. the development of host tissue reaction or pannus around the cannulae at each site

  3. infection around the cannulae

  4. fibrous adhesions around the device cannulae

  5. changes in the prosthetic valves in the device, including:
    1. bio prostheses tissue degeneration

    2. cusp tear

    3. thrombosis
Ventricular assist devices are now accepted as standard of care devices. The new generation of devices is smaller and has a lower morbidity, mortality and likely lower complication rate. However, in the absence of detailed pathological analyses of the devices, and reporting of these, further progress would appear to be hindered. I would therefore urge you to to examine these devices or send them to a colleague interested in these devices and help accumulate a body of knowledge about their complications and changes post implantation.

Table.1 Endothelial Cell Functions

Function Size of Molecules Mechanisms
Permeability Large Molecules Vesicular transport through intercellular junctions
"Filter" Small Molecules Vesicles, Junctions, through cytoplasm
Vascular Tone S.M.C. Relaxation Nitric Oxide, etc.
  S.M.C. Contraction Endothelin-1, Angiotensin 2
Hemostasis / Inflammation Activate - Platelet Adhesion Von Willebrand Factor
P-Selectin, E-Selectin
Thrombomodulin, t=PA
U-PA, PAI -1
[S.M.C Stimulation] Growth Factors
[PDGF, B-FGF]

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Stents (coronary):
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Aortic stent Grafts:
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Ventricular Assist Devices:
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