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Atherosclerosis: Practical Implications for Pathologists
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Section 4 -
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Prior Coronary Arterial Bypass Grafting - CABG

Jagdish Butany John Veinot
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Case 3 - Prior Coronary Arterial Bypass Grafting - CABG
This 60-year-old female presented to emergency with jaw pain, and complaints of nausea, vomiting,
diaphoresis and recent syncope. She was in cardiogenic shock with a BP of 70/40 mm Hg. She was known to
have coronary artery disease with prior aorto-coronary artery bypass grafting (CABG) done a year ago with
the following grafts placed:
- saphenous vein (SVG) to right coronary artery (RCA),

- radial
artery to first marginal artery (M1), and

- left
internal thoracic artery (LITA) to left anterior descending (LAD) artery.
She had type 2 diabetes mellitus and had peripheral vascular disease. She had not smoked since her
CABG. Emergent cardiac catheterization was done via her remaining radial artery (no access to leg
vessels due to peripheral vascular disease). This demonstrated a significantly stenotic left main
lesion, diffuse narrowing of the vein graft to the RCA, a narrowed radial artery graft, and a patent LITA
with severe distal LAD disease.

Percutaneous coronary intervention (PCI) of her left main was successful with a stent positioned.
Despite a patent stent, her hypotension did not improve. She was noted to be neurologically unresponsive
with probable severe anoxic brain injury. Despite maximum doses of norepinephrine, and dopamine she died
shortly after the procedure.

Findings at complete autopsy:
- Old subendocardial inferolateral left ventricular myocardial infarct,

- Recent transmural anterolateral left ventricular myocardial infarct

- SVG (saphenous vein graft) to RCA - graft ostium patent; diffuse graft fibrointimal thickening; moderate
to severe stenosis at anastomosis; moderate distal RCA disease

- Radial artery graft to M1 - graft ostium severely stenotic; diffuse graft fibrointimal thickening; severe
stenosis at anastomosis; moderate distal M1 disease

- LITA graft to LAD - LITA graft patent with small fibrointimal plaque; mild stenosis at anastomosis; mild
distal LAD disease

- Left main stent open

- Diffuse anoxic ischemic cerebral injury
Bypass Graft Surgery - Coronary Artery Bypass Grafting - CABG
CABG is one of the most commonly performed surgical procedures in the world. It is done for stable
angina, unstable angina and myocardial infarct, as well as heart failure. The benefit of the surgery is
greatest in the most high-risk patients - those with advanced disease, multivessel disease and left
ventricular failure. Many procedures are now re-operations, as the grafts do not stay patent
indefinitely.

In selected patients balloon angioplasty and stenting (percutaneous coronary intervention - PCI) is as
effective as bypass surgery. The chest need not be entered, which is an advantage to the patient.
However, the benefit of PCI may diminish over time, especially in patients with multi-coronary disease,
as re-vascularization is required. There is also a concern of late thrombosis with the utilization of
drug eluting stents. It should be remembered that the CABG procedure is one of the most studied surgical
procedures and has evidence based medicine supporting many of its indications. [1]

The extent of re-vascularization achieved by bypass surgery has usually been higher than that achieved
with PCI. Recent developments have included hybrid intervention/surgery procedures with balloon
angioplasty/ PCI and bypass grafting performed within a short period of time in the same patient. Drug
eluting stents are also changing the playing field.

Bypasses are done using grafts of autologous reversed saphenous vein, internal thoracic (mammary)
artery or other arterial conduits including the radial artery or gastroepiploic artery.

Saphenous Vein Grafts
Saphenous veins from the leg are the usual vessels used for bypass grafting. The five-year patency
rate is about 85 %. This decreases to about 50 % at 10 years due to early thrombosis, fibrointimal
thickening and graft atherosclerosis. [2] Acutely the grafts may thrombose, which may cause death or
myocardial infarct. Usually this is caused by a defective anastomosis between the artery and the vein,
or due to poor distal vessel run off. The intima of the blood vessel is exposed to arterial pressures
and this causes neointimal proliferation. Chronically these graft vessels get soft atherosclerotic
plaque, which may be complicated by plaque rupture, thrombosis and aneurysms. Most vein graft
atheromatous plaques could be considered vulnerable plaques in morphology and risk. Patients usually do
well for extended periods, but may develop late recurrence of symptoms due to graft disease or
progression of atherosclerosis in their native coronary arteries distal to the grafting.

The saphenous vein is dissected from the leg soft tissues, the branches ligated and flushed to
identify leaks and overcome spasm. The vein thus may be stretched and traumatized leading to endothelial
and medial damage. Attempts to minimize this trauma from the dissection include the practice of
harvesting the grafts with an endoscope. Various graft preservation solutions and temperatures have also
been investigated. Hypothermia has been found to extensively damage the endothelium.

When assessing bypass grafts, all the anastomoses and components must be accounted for, including:

a) The proximal aortic anastomosis for vein grafts and free arterial
grafts, (or the proximal anastomosis of a sequential graft - vein to vein or artery to artery)

b) The body of the bypass graft itself which may become diseased with
fibrointimal hyperplasia, thromboses or atherosclerosis,

c) The distal anastomosis which may undergo fibrointimal hyperplasia,

d) The distal native vessel disease, which may cause poor distal flow
even with a technically good graft.

Areas to assess with bypass grafts
- Graft ostium/ proximal anastomosis

- Graft body

- Distal anastomosis

- Distal coronary artery

Sites of Possible Bypass Graft Compromise

(modified from original by W.D. Edwards)

Grafts may fail from obstructions at any of these sites. Sequential grafts may be done with another
anastomosis, vein to vein or artery to artery.

Often the vein grafts are not normal to begin with. Surgeons will not use obviously
varicose veins, but the veins that are used often have phlebosclerosis with intimal thickening, medial
hypertrophy, and medial fibrosis. [3]

There are considerable physiological and anatomical differences between arterial and venous grafts.
The venous wall is supplied by vasa vasora (the small vessels of the adventitia that locally nourish the
vessel), whereas the arterial wall may be supplied through the lumen in addition to the vasa vasora. The
endothelium of arteries is different and may secrete more nitric oxide. The structure of the vein is
accustomed to low pressure, whereas the artery is designed for high pressure. [4] Veins may be more
susceptible to thrombosis than arteries as they may produce less prostacyclin (a vasodilator and
inhibitor of platelet aggregation) than arteries do.
[3]

Often the choice of the conduit depends on the age of the patient, the surgeon's experience and
preference and surgical factors including the length of the graft required.

With multiple re-do bypass grafting, the previously placed grafts are often excised. The
anastomoses, both proximal and distal may be reused. The new graft is most often placed distal to the
old one. When one assesses these hearts after explantation at transplant or at autopsy, one may not find
all the grafts but one may be surprised how many old anastomoses can be found. The use of an elastic
stain is invaluable to detect these.

Internal Thoracic (mammary) Artery Grafts
The internal thoracic artery (ITA) graft was demonstrated to have superior patency compared with
saphenous vein grafts in the early 1980's. [5]
The internal thoracic (mammary) artery has a longer
patency rate with 90 % patency at about 10 years. These arteries are small elastic arteries and
therefore behave entirely different than vein grafts. They are adapted to arterial pressure and do not
undergo the same neointimal proliferation and atherosclerosis as grafted veins. The thoracic artery also
maintains its nutrient blood supply and there is no need for a proximal anastomosis, as there is with
aorto-coronary artery bypass grafts. The artery originates from the subclavian artery. It is dissected
from the chest wall and its distal end anastomosed to the coronary artery for grafting.

Vineburg used the internal thoracic artery to achieve indirect myocardial revascularization in the
1950's. [5] Direct implantation of the bleeding artery in the myocardium was done. Despite no distal
vascular anastomoses, many of these arteries are patent when examined pathologically many years after the
surgery.

Internal thoracic arteries may have some age related intimal disease, but atherosclerosis is very
rare. There has been a trend towards utilization of bilateral right and left internal thoracic arteries
and free grafting using the internal thoracic artery. This free arterial graft may be anastomosed to the
aorta, similar to a vein graft or anastomosed to a vein, pericardial patch, or sequentially grafted to
the in situ contralateral internal thoracic artery.

The problems related to the use of internal thoracic artery grafts in contrast to vein grafts are
that arterial conduits may be more difficult to harvest, more easily damaged, more demanding to
anastomose owing to fragility and small size and more complicated by spasm and technical error which may
result in graft closure or inadequate flow. [5] Each arterial conduit has a learning curve and graft
patency is related to technical considerations associated with harvesting, handling, routing, and
anastomoses.

Recurrent ischemia can occur in the territory of an internal thoracic artery graft. This may be due
to significant atheroma in the distal native vessel. Less commonly, there is stenosis within the
internal thoracic artery graft itself or intimal hyperplasia at the anastomosis. Technical errors at the
anastomosis or graft arterial dissection may account for early graft failure. Atherosclerosis of the
graft itself is rare. Subclavian artery stenosis proximal to the origin of the pedicled thoracic artery
graft may occur.

It is important for the pathologist to realize that the distal end of the internal
thoracic artery resembles a muscular artery in structure, rather than a small elastic artery as it is
along most of its course. Without this knowledge this may be very confusing when one looks at the distal
anastomosis and observes two muscular arteries anastomosed, having expected an elastic artery.

Other Arterial Grafts
Surgeons have also used the gastroepiploic and radial arteries as bypass grafts. These are muscular
arteries and may contain vascular pathology including atherosclerosis and medial calcification, which can
compromise them as grafts. They also may be prone to spasm. The long-term patency is still under study
but radial artery studies seem favorable.
[6,
7]

The radial artery is an alternative arterial conduit. The radial artery is a small muscular artery.
It may have age related changes including calcification of the internal elastic lamina and Monckeberg's
medial calcinosis. The artery is prone to spasm during harvesting as the media layer of the radial
artery is thick and the spasm may be intense and difficult to reverse. Surgeons have dealt with this
problem using solutions and anti-spasm agents such as papaverine and calcium channel blockers. Care is
also taken not to mechanically or hydrostatically damage the vessel during harvest and preparation. [5]

The radial artery is usually harvested from the non-dominant arm after assessment of collateral
circulation to the hand (Allen test). The radial artery is anastomosed proximally to the aorta with a
punch biopsy taken out of the aorta to make the proximal anastomosis. Alternatively, the artery can be
anastomosed to a vein graft or a pericardial patch. [8] The radial artery may be longer than the
internal thoracic artery and can provide good flow. Radial artery grafts are all free grafts and thus
both the distal and proximal anastomoses must be carefully examined if these grafts fail.

The right gastroepiploic artery may be brought through the diaphragm for anastomosis with the
coronary arteries, especially the right coronary. This artery may also be used as a free graft. The
inferior epigastric artery has also been utilized but its patency rate is not as good as the other
conduits. [8]

Free grafts are different than pedicle grafts. Pedicle grafts have an intact vasa vasora supplying
the wall of the graft, whereas free grafts are only nourished from the intra-luminal blood supply.
Internal thoracic arteries may be both free or pedicled types, as are most arterial grafts. All radial
artery grafts and vein grafts are by definition always free grafts.

Types of grafts - internal thoracic (ITAs) and gastroepiploic arteries (GEA) - independent and sequential grafts are possible

(modified from reference [9]
)

| Artery Type | Structure | Pedicle or free | Spasm |
| SVG | vein | free | yes |
| ITA | elastic artery | both | low |
| Radial | muscular artery | free | yes |
| Gastroepiploic | muscular artery | both | yes |

The major changes or evolution in coronary artery bypass
grafting surgery include off-pump grafting (OPCAB), minimally invasive surgery (MICAB) and the increased
use of arterial conduits including multiple arterial conduits. Sequential vein grafts have been used for
some time, but sequential arterial "T" or "Y" grafts are now being used for attempted complete arterial
revascularization. These grafts are technically challenging and may have more risk of hypo-perfusion as
both grafts get blood from the same source. [8]

New innovations in CABG include novel methods of anastomosis without sutures, using magnets and
special devices. Some of these innovations have developed due to increased "off pump" surgery on the
beating heart and coronary arterial bypass surgery through a thoracotomy - minimally invasive surgery.
Hybrid procedures are also being done with combinations of angioplasty, stenting and bypass grafting done
at the same treatment.
Minimally Invasive Coronary Artery Bypass Grafting - MICAB
The increasing selection of the internal thoracic artery, the conduit of choice for LAD
revascularization, has lead to the development of minimally invasive coronary artery bypass grafting.
This does not involve the usual cardiopulmonary bypass or median sternotomy. Via a small incision in the
left chest, the internal thoracic artery is harvested, the pericardium is opened and the left internal
thoracic artery is grafted to the LAD. This only treats one vessel, an important consideration. Wider
application of this minimally invasive procedure may include grafting of the right internal thoracic
artery or gastroepiploic artery grafting of the right coronary artery.

Off Pump Surgery - OPCAB
Off-pump surgery is bypass surgery on the beating heart without the use of cardiopulmonary bypass or
cardiac arrest. This is independent of the method of surgical access to the heart. In conventional
bypass surgery, access to the heart is obtained from full sternotomy, the heart and ascending aorta are
cannulated for cardiopulmonary bypass, cardiac arrest is induced and the ascending aorta is manipulated
for construction of proximal anastomoses for vein grafts or free arterial grafts. These steps may
contribute to patient trauma, microemboli, and may provoke biological reactions. [10] Manipulating a
heavily calcified ascending aorta is best avoided.

Avoiding cardiopulmonary bypass and manipulation of the aorta and heart may decrease the incidence of
atherosclerotic and other microemboli. It is possible that this will decrease the risk of peri-operative
neurological complications, especially in elderly or high risk patients. The use of arterial grafting
and avoidance of aortic manipulation also may contribute to this reduction in complications.

In addition to microemboli, cardiopulmonary bypass induces an inflammatory response due to activation
of compliment due to contact of the blood with the bypass circuit. Organs may become dysfunctional,
often involving the brain, lungs, heart, bowel, kidneys and coagulation system. Avoiding cardiopulmonary
bypass reduces oxidative stress, inflammation and peri-operative morbidity.

Off pump surgery may offer a smaller incision, but it is important to remember that this should not be
done at the cost of incomplete re-vascularization. It also must never compromise the quality of the
coronary anastomoses. Training and patient selection are vital to the success of the procedure.

Advances in the field of off pump surgery have included regional mechanical stabilizers that reduce
the motion of the target area to allow workable conditions for the surgeons. Robotic assisted procedures
are also under investigation. Studies of modalities to image the ascending aorta and choose patients
that might benefit from off pump surgery are of much interest.

Muscular artery - coronary, GEA, radial arteries

Internal elastic lamina (IEL)
External elastic lamina (EEL)
Adventitial collagen

Vein

IEL only after arterialization (grafting)
EEL irregular
Adventitial longitudinal muscle bundles

Elastic artery - internal thoracic arteries

Multiple elastic lamellae
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Coronary Artery and Graft Diagram

References
- Munsch C. What cardiology trainees should know about coronary artery surgery--and coronary artery surgeons: ischaemic heart disease. Heart 2008; 94(2):230-6.

- Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998; 97(9):916-31.

- Cox JL, Chiasson DA, Gotlieb AI. Stranger in a strange land: the pathogenesis of saphenous vein graft stenosis with emphasis on structural and functional differences between veins and arteries. Prog Cardiovasc Dis 1991; 34:45-68.

- He GW. Arterial grafts for coronary artery bypass grafting: biological characteristics, functional classification, and clinical choice.Ann Thorac Surg 1999; 67(1):277-84.

- Barner HB. The continuing evolution of arterial conduits. Ann Thorac Surg 1999; 68(3:Suppl):Suppl-8.

- Al-Ruzzeh S, Modine T, Athanasiou T, Mazrani W, Azeem F, Nakamura K, et al. Can the Use of the Radial Artery Be Expanded to All Patients with Different Surgical Grafting Techniques? Early Clinical and Angiographic Results in 600 Patients. J Cardiac Surg 2005; 20(1):1-7.

- Cameron J, Trivedi S, Stafford G, Bett JHN. Five-Year Angiographic Patency of Radial Artery Bypass Grafts. Circulation 2004; 110(11 suppl 1): II-23.

- Barner HB. Arterial grafting: techniques and conduits. Ann Thorac Surg 1998; 66(5 Suppl):S2-5.

- Lev-Ran O, Paz Y, Pevni D, Kramer A, Shapira I, Locker C, et al. Bilateral internal thoracic artery grafting: midterm results of composite versus in situ crossover graft. The Annals of Thoracic Surgery 2002; 74(3):704-11.

- de Jaegere PPT, Suyker WJL. Off-pump coronary artery bypass surgery. Heart 2002; 88(3):313-8.
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