**Saphenous Vein Conduit in Coronary Artery Bypass Surgery — Patency Rates and Proposed Mechanisms for Failure**

Maseeha S. Khaleel, Tracy A. Dorheim, Michael J. Duryee, Geoffrey M. Thiele and Daniel R. Anderson

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/55098

**1. Introduction**

Coronary artery disease is the single leading cause of death in the United States. Every year more than 1 million open coronary revascularization procedures are performed in the United States. Most commonly the greater saphenous veins and internal mammary and/or radial arteries are used as bypass conduits. Long term patency and avoiding repeat revascularization is every surgeon's goal following coronary artery bypass grafting. Unfortunately it is estimated that during the first year after surgery; between 10 - 15% of venous grafts occlude. The graft attrition rate is estimated to be 1 - 2 % per year during the first five years following surgery. By 10 years only 50 % of vein grafts remain free from significant stenosis [1].

The reasons for premature graft closure include; biologic, conduit quality, unsatisfactory harvest/preparation, and inappropriate operative strategy or poor surgical technique [2]. Many of these factors can be avoided with proper technique and experience of the surgical team. Currently much of the research being performed on graft failure is leading to the hypothesis of early thrombosis and neointimal hyperplasia as the physiologic basis for graft failure, although the exact mechanism is not well established.

This chapter will discuss current knowledge and ongoing research regarding the thrombosis, intimal hyperplasia and atherosclerosis of vein grafts. It will highlight harvesting techniques and preservation methods, as well as discuss proposed mechanisms that lead to intimal

hyperplasia, graft atherosclerosis, and the evolving strategies and current research for longterm prevention of graft failure.

bypass grafting; depending upon what vein harvest method was used in surgery. It was felt veins harvested using an EVH technique failed more often and earlier than veins harvested in the traditional open technique. Studies performed by Desai et al in 2011, confirmed the relationship between the learning curve of EVH and the patency rates based on beginner and expert level of experience in harvesting vein tissue [11]. It has since been shown that when a novice is performing the procedure the vein is subjected to much more stress from trying to better visualize the vein, and 50% of the veins had discrete areas of injury [11]. It was noted that if a section of vein had more than 4 areas of injury, it had a greater than 50% risk of failure of patency [11]. Early studies, which compared the traditional open harvest method to EVH, were published in the infancy stages of EVH when all harvesters were novices to this new technique. Thus, it is now recognized that this confounding issue may have contributed to the decreased long-term patency that was noted. However, this has changed in the past years with "novice" level practitioners becoming experts. It has recently been found that when procured by expert level harvesters the physical damage to the vein is similar to that of open harvest [12], [13]. Thus, it is hypothesized that EVH and open harvest when performed by an expert will

Saphenous Vein Conduit in Coronary Artery Bypass Surgery — Patency Rates and Proposed Mechanisms for Failure

http://dx.doi.org/10.5772/55098

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have similar patency rates if all other factors are equal.

of these 2 mitogens together initiates intimal hyperplasia [17].

**4. The graft "environment" at a cellular level**

**3. The role of pressure distention and wall stress during harvest**

Standard procedure in the United States is to distend the saphenous vein graft after procure‐ ment prior to myocardial implantation to ensure that all branches are ligated. The majority of the time during harvest, the vein is distended to supra-physiologic pressures [14]. While saphenous veins *in vivo* are rarely subjected to pressures greater than 60 mmHg, recorded pressure measurements during harvest easily reach 300-400 mmHg [15]. This supra-physio‐ logic pressure severely damages the endothelium and ultimately leads to premature graft closure. This high pressure is inadvertently used to overcome vasospasm as well as to ensure ligation of all side branches [16]. The pressure causes shear wall stress that denudes the protective endothelial layer (Figure 1). As a mechanism to protect itself, the endothelium releases basic fibroblast growth factors and platelet-derived growth factors [17]. Basic fibro‐ blast growth factor, a heparin-binding polypeptide that is present in the nucleus and cytoplasm of smooth muscle and endothelial cells and in the intracellular matrix, is normally a nonsecreted cell product [18]. Platelet derived growth factor is also widely acknowledged in the process of angiogenesis and most specifically in cell migration and proliferation. The release

The vascular endothelium has many protective functions, and it releases factors that maintain vein graft patency. The endothelium serves as the physical barrier between the blood compo‐ nents and the sub-endothelium, damage to this endothelium by either direct or indirect stress can disrupt this protective environment causing the formation of atheromas and subsequently

#### **2. How vein harvesting methods can affect patency rates**

Dr. Rene Favaloro developed the first saphenous vein harvesting technique in 1967 [2]. This technique required a longitudinal incision along the length of the greater saphenous vein entering the fascial canal surrounding the vein and thus causing inadvertent damage to the adventitial layer. Following vein isolation from the surrounding tissues, ligation of side branches, as well as a transection of the vein for completion of the harvest is performed. Since that original description, many methods have evolved from Dr. Favaloro's original technique. As well, research has focused on the best method of harvesting grafts without damage. In addition to Favaloro's original technique, current and popular harvesting techniques included; "no touch", stab phlebectomy, and most recently endoscopic techniques. It is inherit that manipulation of the vein conduit causes damage to the vein itself, but the extent was unknown. Multiple studies have been done to compare; "open", "no touch", and "endoscopic vessel harvesting (EVH)" techniques [3]. The traditional open technique which is performed under direct visualization of the vein was found to preserve the endothelium of the vein quite well, but also came with the complications of leg pain i.e. wound healing, post operative cellulitis, and increased length of hospital stay [4], [5]. Initial studies performed on the long-term outcome of vein grafts harvested using the open technique did show that the vein was often stripped of the beneficial adventitial layer as well as distended to high pressures to overcome the associated vasospasm [6]. Unfortunately, the increased distention pressures caused shear stress damage to the vein intima and subsequent endothelial wall [7]. When viewed histolog‐ ically the endothelial cells appeared deformed, flattened, polymorphic, and contained an abundance of cytoplasmic vesicles [8]. As a method to avoid over-handling of the vein and increased distention pressures a pedicle technique was developed and named the "no touch" technique. It was thought that veins procured in this manner would eliminate the need for conduit distention and its associated morbidities since the perivascular adipose tissue surrounding the vein was left intact [9]. It had been shown that this surrounding tissue in internal thoracic mammary arteries provided a vasodilatory effect with less arterial conduit vasospasm. Increased patency rates were demonstrated with the "no touch" technique compared to the conventional open technique [9]. 1997 began a new era in coronary artery bypass grafting with the use of EVH to harvest the saphenous vein. Endoscopic harvesting techniques were found to eliminate the need for invasive incisions, and decrease the associated risks that accrued with an open technique. Furthermore veins harvested via an EVH method were hypothesized to be promising for graft patency, since endothelial integrity was main‐ tained following EVH harvest compared to other conventional harvesting techniques. This new technique soon became the standard of care with greater than 70% of saphenous vein conduits being retrieved in this manner [10]. Endoscopic harvesting had lower complication rates including less post-operative pain, and decreased patient length of stay. However, controversy arose about the long-term patency of the vein conduits after coronary artery bypass grafting; depending upon what vein harvest method was used in surgery. It was felt veins harvested using an EVH technique failed more often and earlier than veins harvested in the traditional open technique. Studies performed by Desai et al in 2011, confirmed the relationship between the learning curve of EVH and the patency rates based on beginner and expert level of experience in harvesting vein tissue [11]. It has since been shown that when a novice is performing the procedure the vein is subjected to much more stress from trying to better visualize the vein, and 50% of the veins had discrete areas of injury [11]. It was noted that if a section of vein had more than 4 areas of injury, it had a greater than 50% risk of failure of patency [11]. Early studies, which compared the traditional open harvest method to EVH, were published in the infancy stages of EVH when all harvesters were novices to this new technique. Thus, it is now recognized that this confounding issue may have contributed to the decreased long-term patency that was noted. However, this has changed in the past years with "novice" level practitioners becoming experts. It has recently been found that when procured by expert level harvesters the physical damage to the vein is similar to that of open harvest [12], [13]. Thus, it is hypothesized that EVH and open harvest when performed by an expert will have similar patency rates if all other factors are equal.

hyperplasia, graft atherosclerosis, and the evolving strategies and current research for long-

Dr. Rene Favaloro developed the first saphenous vein harvesting technique in 1967 [2]. This technique required a longitudinal incision along the length of the greater saphenous vein entering the fascial canal surrounding the vein and thus causing inadvertent damage to the adventitial layer. Following vein isolation from the surrounding tissues, ligation of side branches, as well as a transection of the vein for completion of the harvest is performed. Since that original description, many methods have evolved from Dr. Favaloro's original technique. As well, research has focused on the best method of harvesting grafts without damage. In addition to Favaloro's original technique, current and popular harvesting techniques included; "no touch", stab phlebectomy, and most recently endoscopic techniques. It is inherit that manipulation of the vein conduit causes damage to the vein itself, but the extent was unknown. Multiple studies have been done to compare; "open", "no touch", and "endoscopic vessel harvesting (EVH)" techniques [3]. The traditional open technique which is performed under direct visualization of the vein was found to preserve the endothelium of the vein quite well, but also came with the complications of leg pain i.e. wound healing, post operative cellulitis, and increased length of hospital stay [4], [5]. Initial studies performed on the long-term outcome of vein grafts harvested using the open technique did show that the vein was often stripped of the beneficial adventitial layer as well as distended to high pressures to overcome the associated vasospasm [6]. Unfortunately, the increased distention pressures caused shear stress damage to the vein intima and subsequent endothelial wall [7]. When viewed histolog‐ ically the endothelial cells appeared deformed, flattened, polymorphic, and contained an abundance of cytoplasmic vesicles [8]. As a method to avoid over-handling of the vein and increased distention pressures a pedicle technique was developed and named the "no touch" technique. It was thought that veins procured in this manner would eliminate the need for conduit distention and its associated morbidities since the perivascular adipose tissue surrounding the vein was left intact [9]. It had been shown that this surrounding tissue in internal thoracic mammary arteries provided a vasodilatory effect with less arterial conduit vasospasm. Increased patency rates were demonstrated with the "no touch" technique compared to the conventional open technique [9]. 1997 began a new era in coronary artery bypass grafting with the use of EVH to harvest the saphenous vein. Endoscopic harvesting techniques were found to eliminate the need for invasive incisions, and decrease the associated risks that accrued with an open technique. Furthermore veins harvested via an EVH method were hypothesized to be promising for graft patency, since endothelial integrity was main‐ tained following EVH harvest compared to other conventional harvesting techniques. This new technique soon became the standard of care with greater than 70% of saphenous vein conduits being retrieved in this manner [10]. Endoscopic harvesting had lower complication rates including less post-operative pain, and decreased patient length of stay. However, controversy arose about the long-term patency of the vein conduits after coronary artery

**2. How vein harvesting methods can affect patency rates**

term prevention of graft failure.

150 Artery Bypass
