—  SHORT COURSE #57  —

Atherosclerosis: Practical Implications for Pathologists

Section 4 - Prior Coronary Arterial Bypass Grafting - CABG

Jagdish Butany
John Veinot


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:
  1. saphenous vein (SVG) to right coronary artery (RCA),

  2. radial artery to first marginal artery (M1), and

  3. 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:
  1. Old subendocardial inferolateral left ventricular myocardial infarct,

  2. Recent transmural anterolateral left ventricular myocardial infarct

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

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

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

  6. Left main stent open

  7. 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
  1. Graft ostium/ proximal anastomosis

  2. Graft body

  3. Distal anastomosis

  4. 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


Coronary Artery and Graft Diagram


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

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

  3. 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.

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

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

  6. 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.

  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.

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

  9. 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.

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