Coronary artery bypass surgery saphenous vein graft disease


 * Associate Editors-in-Chief:, Mohammed A. Sbeih, M.D. [mailto:msbeih@perfuse.org]

Pathophysiology of saphenous vein graft disease
The pathophysiology of aortocoronary saphenous vein graft disease has classically been divided into three components:
 * Early degeneration in the first month due to thrombosis.
 * Mid course degeneration from month one to one year due to intimal hyperplasia.
 * Late degeneration due to atherosclerosis.

Early failure of saphenous vein grafts
While thrombosis predominates during this period, early failure of saphenous vein grafts can be precipitated by a variety of factors.

Technical failures
This is due to a technical failure at the site where the conduit is sutured to the aorta proximally or to the native target vessel distally. This technical failure then leads to thrombosis of the conduit. This failure can in some cases be treated by emergency re-operation or percutaneously by angioplasty and stenting. Care must be taken during the percutaneous approach to assure that the sutures are not disrupted and that there is not a rupture at the site of the anastomosis.

No reflow Downstream in the myocardium
Despite restoration of into or improved flow down the epicardial artery, myocardial edema, embolization, and capillary blistering may result in impaired perfusion into the myocardium. This in turn may lead to poor flow through the graft, and subsequent thrombosis.

Midcourse failures of saphenous vein grafts
Midcourse degeneration from one month to one year is classically described as being due to intimal hyperplasia. The process is complex and the response of the SVG wall is likely biphasic. Days to weeks after CABG, there is an increase in the area of both the intima (due to smooth muscle cell proliferation) and the adventitia (due to fibroblast proliferation). After the first 4 to 6 weeks, the SVGs then undergo "negative remodeling", that is to say there is a loss in the total vessel diamter. In one study using CT angiography, there was a mean loss of SVG lumen diameter of 9% (a decrease from 3.69 mm to 3.36 mm) but a decrease in the thickness of 0.13 mm in the SVG wall thickness over this time. The mechanism underlying this negative remodeling thought to be the reaction of the venous conduit to the greater than normal flow, wall stretch, shear stress as well as humoral factors such as cytokines and vasoactive substances.

Late failure of saphenous vein grafts
Multiple pathophysiologic processes contribute to late graft degeneration or late graft failure. These processes including intimal hyperplasia, atherosclerotic plaque formation, and graft remodeling. Additionally, arterialization of the graft accelerates atherosclerosis. In addition to mechanically obstructing flow, these blockages are more "friable" (i.e. they easily break into small pieces and embolize downstream into the myocardium impairing perfusion) and more prone to thrombus than plaques found in native vessels. Another pathophysiologic mechanism whereby SVGs are more susceptible to thrombotic occlusion is the fact that they lack side branches.

Goals of treatment of saphenous vein graft disease
Primarily, the goal should be to detect and treat a SVG stenosis early in the development of ischemia while the SVG is still patent. Although intervention on a chronic total occlusion of a SVG may seem like an effective treatment strategy, it is best avoided. As long as the SVG is not completely occluded, intervention can be performed.

Two additional overall goals of treating SVG stenosis include the resolution of symptomatic ischemia and the prevention/treatment of distal embolization.

Definitions
The rate of saphenous vein graft failure varies depending upon the defnition used and the nature of the study design. Rates estimated based upon retrospective studies of patients who are symptomatic underestimate the true rate of SVG failure because only those patients who survive who are symptomatic undergo catheterization. The most accurate assessment is based upon prospective studies in which all patients undergo mandatory cardiac catheterization at a uniform timepoint. The rates will also vary depending upon the complexity of disease, the diffuse nature of the disease, the extent of revascularization, and whether a per-lesion or a per-patient analysis is undertaken.

Saphenous vein graft occlusion is defined as a complete, 100% occlusion of a saphenous vein graft.

Saphenous vein failure is defined as an occlusion of the vein graft or a 75% or greater stenosis.

The rate of occlusion or failure of saphenous vein grafts is calculated on a per graft basis and a per patient basis. The per patient basis is higher, because only one vein graft out of several must fail for the patient to be characterized as a failure.

Current rates of graft occlusion and failure are as follows:


 * The rate of per patient vein graft occlusion at 12-18 months is about 42%


 * The rate of per patient vein graft failure at 12-18 months is about 46%


 * The rate of per graft vein graft occlusion at 12-18 months is about 26%


 * The rate of per graft vein graft failure at 12-18 months is about 29%

As a comparison, the rate of internal mammary artery failure at 12-18 months was only 8%.

Time course of SVG failure

 * Early failure: Withing the first month, 8% to 18% of SVGs fail again largely due to the factors cited above that precipitate thrombosis.
 * Mid course failure: From one month through a year an additional 10—15% of SVGs occlude. Again, during this period the pathophysiology is predominantly due to smooth muscle cell hyperplasia emanating from the intima of the vein.
 * Late Failure:After year 1, the annual rate of occlusion is about 1—4% per per year. Again, this process of late failure is predominantly due to atherosclerosis and some intimal hyperplasia.
 * Very Late Failure: SVG occlusion after 5 years is predominantly mediated by atherosclerosis. A convenient and often quoted statistic is that at 10 years, approximately 50% of SVGs remain patent

Determinants of sapheous vein graft patency
Graft patency is dependent on a number of factors, including the type of graft used (internal thoracic artery, radial artery, or great saphenous vein), the size or the coronary artery that the graft is anastomosed with, and, of course, the skill of the surgeon(s) performing the procedure. Arterial grafts (e.g. left internal mammary (LIMA), radial) are far more sensitive to rough handling than the saphenous veins and may go into spasm if handled improperly.

Technical factors during surgery
A large VA cooperative study evaluated the technical factors associated with 3 year patency among those SVGs that were patent at 7 to 10 days following CABG. SVG occlusion was associated with the following:
 * Cross-clamp time > 80 min (p < 0.001)
 * Vein preservation solution temperature > 5 degrees C (p = 0.009)
 * Bypass time > 2 hours (p = 0.042)
 * Number of proximal anastomoses > 2 (p = 0.018)
 * Operation time > 5 hours (p = 0.044)
 * Intermittent instead of continuous cross-clamp technique (p = 0.024).
 * Sequential vs single Y vein graft (p = 0.060).

In-situ vs free grafts
Generally the best patency rates are achieved with the in-situ (the proximal end is left connected to the subclavian artery) left internal thoracic artery (a LIMA) with the distal end being anastomosed with the coronary artery (typically the left anterior descending artery or a diagonal branch artery). Lesser patency rates can be expected with radial artery grafts and "free" internal thoracic artery grafts (where the proximal end of the thoracic artery is excised from its origin from the subclavian artery and re-anastomosed with the ascending aorta).

Venous vs Arterial conduits
Saphenous vein grafts have poorer patency rates than arterial grafts, but are more available, as the patients can have multiple segments of the saphenous vein used to bypass different arteries.

LITA grafts are longer-lasting than vein grafts, both because the artery is more robust than a vein and because, being already connected to the arterial tree, the LITA need only be grafted at one end. The LITA is usually grafted to the left anterior descending coronary artery (LAD) because of its superior long-term patency when compared to saphenous vein grafts.

Impact of harvesting method on saphenous vein graft patency
The method of harvesting vein grafts may be associated with late vein graft patency. In one small study of 40 patients randomized to endoscopic vs traditional techniques, no difference was seen in angiographic patency at 3 months. Another small randomized study of 144 patients who returned for angiography  at 6 months and demonstrated an occlusion rate of 21.7% for the endoscopic approach vs  17.6% for the open approach. In a non-randomized subgroup analysis from the PREVENT IV study, harvesting of vein-grafts with the use of endoscopy (endoscopic harvesting) was associated with a higher rate of saphenous vein graft failure at 12-18 months compared with open harvesting of the veins under direct visualization (46.7% vs. 38.0%, P<0.001 at 12-18 months). Likewise, clinical outcomes were worse at 3 years: use of endoscopy was associated with higher rates of death, myocardial infarction, or repeat revascularization (20.2% vs. 17.4%; p=0.04), death or myocardial infarction (9.3% vs. 7.6%; p=0.01), and death (7.4% vs. 5.8%; adjusted hazard ratio, 1.52; 95% CI, 1.13 to 2.04; p=0.005). Although these observational data are provocative, further randomized clinical trials involving large numbers of patients from multiple centers with long term follow-up would be needed to compare the safety and effectiveness of the two harvesting techniques.

Perioperative MI is associated with a higher rate of SVG failure
The rate of one-year saphenous vein graft failure has been documented to be 62.4% of patients with and 43.8% of patients without perioperative MI (p <0.001).

Smaller target vessels are associated with a higher rate of SVG failure
The rate of SVG occlusion at one year is about twice as high in those SVGs that are anastomosed to a target vessel with a diameter < 2.0 mm. The rate of SVG occlusion at one year in target vessels less than or equal to 2.0 mm in diameter was 20.1% on aspirin and 32.3% off aspirin (p = 0.008), while in those SVGs anastomosed to target vessels > 2.0 mm in diameter the rates were lower: 8.7% and 9.0% respectively. The converse of this, is that larger conduits have been associated with higher rates of SVG occlusion.

Target artery location
In a multivariate model in a small study, SVG grafting to the diagonal branch has been associated with 1.76 times higher rates of SVG occlusion.

Graft flow
Poorer graft flow has been associated with higher rates of SVG occlusion.

Serum cholesterol
A serum cholesterol > 225 mg/dl has been associated with higher rates of SVG failure at 3 years in a multivariate model from a large VA cooperative study.

Pharmacotherapy
Early post-operative aspirin has been associated with a lower rate of SVG failure for the first 3 years after CABG in a large number of randomized trials.

Factors not associated with saphenous vein graft patency
Although a creatinine clearance < 60 ml / sec has been associated with higher rates of death / MI/ and revascularization, it was not associated with a higher rate of SVG or internal thoracic artery failure rates. In one large VA cooperative study, age, race, smoking history, high density lipoprotein cholesterol, vein source (thigh vs. calf) were not associated with 3 year SVG patency.

Association of saphenous vein graft failure with clinical events
In the PREVENT IV study, SVG failure was associated with a 13.9% rate of death and MI (122/878) vs 0.9% (9/1,042) for those patients without SVG failure (these numbers exclude peri-operative MI). Likewise, the rate of death / MI / and revascularization was higher among patients with SVG failure (26.0% vs 1.8%). Despite these elevated rates of adverse events, it shoud be noted that about half of the patients with SVG failure did not have clinical events. This may be because the native artery remained open or because there was extensive collaterals. It should slo be noted that the development of heart failure or angina following SVG failure may not be captured in the endpoint of death / MI / and revascularization.

In a large cohort of 1,388 patients who underwent a first coronary artery bypass graft procedure, vein  graft patency was temporally related both to reoperation as well as survival.