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Saphenous vein: advances

  • Ki-Bong Kim
  • Ho Young Hwang
  • Domingos Savio Ramos de Souza
  • David Paul Taggart
Review Article
  • 19 Downloads

Abstract

Although the saphenous vein (SV) is a widely used conduit for coronary artery bypass graft surgery (CABG), lower long-term graft patency rates and worse clinical outcomes have been reported after CABG performed with SV grafts compared with CABG performed with internal thoracic artery (ITA) grafts. Of various efforts to overcome the limitations of SV that are resulting from structural and functional differences from arterial conduit, recent improvement in harvesting techniques including no-touch technique, surgical strategy of using the SV as part of a composite graft over an aortocoronary bypass graft, and external stenting of the SV will be discussed in this topic.

Keywords

Coronary artery bypass graft surgery Saphenous vein Composite graft 

Introduction

Since the introduction of the saphenous vein of the SV as an aortocoronary bypass graft in early 1960s [1], the SV has been widely used for CABG. However, atherosclerotic failure, lower long-term patency rates and worse clinical outcomes have been reported after CABG performed with SV aortocoronary grafts compared with CABG performed with ITA grafts [2, 3, 4, 5].

Of various strategies, pharmacologic relaxation of the SV after harvest and strict medical therapy, including administration of antiplatelet and lipid-lowering agents after surgery, were suggested to improve SV graft patency [6, 7]. Further efforts to improve patency of the SV included external support using stents, intraoperative gene transfer, and improvement in harvesting technique [8, 9, 10, 11]. Improvement in harvesting techniques including no-touch technique, alternative surgical strategy of using the SV as a composite graft, and external stenting of the SV will be discussed in this topic.

Improvement in harvesting techniques and alternative grafting strategies

No-touch technique for SV harvesting

When the SV is harvested as originally described by Favaloro [1], using what has become the conventional technique, its surrounding tissue, including the perivascular fat, is removed and the vein is distended with saline at high pressure to alleviate spasm and check for leakage. This procedure is the main cause of injury to the vessel wall and endothelium [12]. The no-touch (NT) technique was introduced in 1996 [8], whereby the vein is harvested with its surrounding pedicle of fat, a procedure that protects the vein from direct handling by instruments that causes spasm (Fig. 1). Consequently, the need for high-pressure distention is obviated, providing a better preserved luminal endothelium/endothelial nitric oxide (NO) synthase and maintaining NO levels [12, 13]. Preservation of the surrounding cushion of fat plays an important role in reducing medial ischemia by maintaining the vasa vasorum, a microvascular network that supplies the vein wall with oxygen and nutrients [12, 14]. The surrounding tissue is also an important source of various vasodilators and adipokines, including NO, leptin, and adiponectin [15]. In addition, the surrounding tissue acts as an “external biological stent,” protecting the SV wall against the deleterious effects of manual distension and aortic hemodynamics [16]. A study using intravascular ultrasound assessment showed slower progression of atherosclerosis in SVs harvested by the NT technique compared with those prepared by the conventional technique [17]. Postmortem biopsies have revealed that an adequate arterialization is preserved in NT SV grafts when compared with conventional SV grafts (Fig. 2). The fat pedicle also possesses mechanical properties that protect the SV from kinking, a function that facilitates the application of sequential grafts (Fig. 3).
Fig. 1

A “no-touch” saphenous vein in situ after harvesting and without spasm

Fig. 2

10-year old postmortem specimens of conventional vein graft (CVG) and “no-touch” vein graft (NTVG)

Fig. 3

Excessive long no-touch saphenous vein graft (arrow) without kinking

Clearly, tissue or cellular damage to each separate layer of the SV may affect its performance as a graft in patients undergoing CABG. However, preservation of the surrounding tissue that remains intact in NT SV grafts influences the effect of harvesting, having both direct and indirect actions on each of the vein’s layers, thus contributing to the various mechanisms underlying the improved performance of NT SV grafts. Therefore, the presence of the surrounding tissue may contribute to the significantly higher long-term patency rate of NT SV grafts compared with conventionally harvested SV grafts; CABG performed with NT SV aortocoronary grafts showed a high patency rate (83%) that was comparable to left ITA graft patency at a mean time of 16 years postoperatively [18, 19]. Concerns have been raised regarding the issue of increased leg-wound complications in NT technique. Preoperative mapping of the SV course using an ultrasonographic Doppler assessment is essential in NT technique because this procedure allows for a rapid and accurate location of the SV without causing excessive soft tissue injury and the creation of tissue flap. Future aim will be developing an endoscopic or minimally invasive NT technique.

Minimally manipulated SV as a composite graft based on ITA

Although the NT technique demonstrated an improved patency, it may have a high risk of SV wound complications [20]. The minimal manipulation technique of SV harvesting, in which the manipulation and tension of the SV were minimized and manual intraluminal dilatation was avoided during harvest, has also been suggested to overcome the limitations of SV grafts when used as a composite graft based on the in situ left ITA [21, 22, 23, 24, 25]. The SV was gently separated from the bed using scissors, leaving perivascular scanty adipose tissue in place. The minimal manipulation technique, which is a NT technique without surrounding pedicle tissue, may have a lower risk of SV wound complication than the NT technique with surrounding pedicle tissue [26]. Immediately after the harvest, the reversed SV was anastomosed to the side of the left ITA without any pharmacologic treatment to construct a Y-composite graft. The minimally manipulated SV composite graft showed immunohistochemically to be beneficial in preserving endothelial structure and function [21]. Endothelial cells were well preserved in histologic and immunohistochemistry studies, and endothelial function was preserved in endothelial NO synthase staining (Fig. 4). The use of SV as a composite graft demonstrated conflicting clinical results. One study recommended against the use of a SV composite graft because it could steal flow from the left ITA graft and lead to suboptimal short-term ITA patency results (perfect patency of ITA grafts, 76% at a mean 2.5 years) [27]. Other studies demonstrated comparable hemodynamic and early patency results between the SV versus right ITA composite grafts [24, 28]. In a hemodynamic study, no differences between the SV versus right ITA composite grafts were observed for pressure gradients or fractional flow reserve measured in the proximal left ITA or in the distal branches grafted by the SV or right ITA [28]. In another randomized trial, the SV composite grafts were non-inferior to the right ITA composite grafts in terms of 1-year angiographic patency rates (SV versus right ITA, 97.1% [238/245] vs. 97.1% [198/204], p = 0.958) and overall survival and major adverse cardiac and cerebrovascular event-free survival rates up to 4 years after surgery [24]. In addition, a 1-year intravascular ultrasound study performed with serial quantitative coronary angiograms at early and 1 year after CABG revealed that the SV lumen diameter decreased significantly without accompanying abnormal intima-media thickening during the first year after CABG (Figs. 5 and 6) [29]. Another study evaluating the endothelial shear stress (ESS) of the SV composite grafts demonstrated that the ESS of the SV composite graft increased and became similar to that of the ITA at 1 year postoperatively, which was significantly lower than that of the ITA intraoperatively [30]. These findings suggested that the SV composite grafts went through a process of advantageous negative remodeling during the first postoperative year. One recent study demonstrated that minimally manipulated SV composite grafts were equivalent to arterial composite grafts in 5-year graft patency rates and midterm clinical outcomes; the SV composite grafts had a 5-year patency rate of 93.9% (77 of 82), which was not significantly different from that of arterial composite grafts (89.1% [98 of 110]) in the propensity-score matched study [25]. Theoretical advantages of SV composite graft based on the in situ left ITA over an aortocoronary bypass graft include: (1) the SV composite graft is continuously exposed to endothelium-protective substances, such as NO released from the left ITA; (2) the length of the SV needed to reach the target vessel is shorter than that of an aortocoronary SV graft when using a sequential anastomosis technique; (3) the SV conduit anastomosed to the left ITA is exposed to less circulatory stress than a conduit anastomosed to the ascending aorta; and (4) complications such as embolic stroke and aortic dissection could be reduced by avoiding aortic clamping for proximal anastomosis. Additional benefits of SV composite grafts compared with bilateral ITA composite grafts are (1) the right ITA, the second conduit of choice after the left ITA, is reserved for later redo CABG, and (2) the risk of perioperative morbidity, such as sternal infection, which can occur after bilateral ITA use, is decreased [24].
Fig. 4

Luminal endothelium of the saphenous vein in the a normal control, b conventional harvest, and c minimally manipulated composite grafting groups. CD34 was stained as a brown color (a: × 200; b, c: × 100). Note the defects in staining (black arrows), particularly in the conventional harvest group. Endothelial nitric oxide synthase staining also showed defects in staining (black arrows), particularly in the e conventional harvest group compared to the d normal control and f minimally manipulated composite groups (× 100) (reprinted from [21] with permission from Elsevier)

Fig. 5

Angiographic findings of the saphenous vein (SV) composite grafts based on the left internal thoracic artery (LITA) at a, b 1 day and c, d 1 year after coronary artery bypass graft surgery. The graft diameter of the SV became smaller and flow rate increased. p-LITA, Proximal LITA; d-LITA, distal LITA; OM, obtuse marginal coronary artery; LAD, left anterior descending coronary artery; PDA, posterior descending coronary artery (reprinted from [29] with permission from Elsevier)

Fig. 6

Images of intravascular ultrasound of the proximal left internal thoracic artery (LITA) and saphenous vein (SV). The lumen of the proximal LITA (p-LITA) and SV showed a thin intima-media without any abnormal plaque (reprinted from [29] with permission from Elsevier)

NT SV with surrounding pedicle tissue as a composite graft based on ITA

Although no differences in the 1-year patency rates between the SV and right ITA composite grafts were demonstrated in a previous study, the SV composite grafts showed a trend toward a lower patency rate in the right coronary artery territory than in the other coronary artery territories (early vs. 1-year patency rates: right coronary artery territory, 97.4% vs. 93.4%; left coronary artery territory, 99.4% vs 98.8%, respectively) [24]. One recent observational study demonstrated that the NT SV conduits with surrounding pedicle tissue further improved the early and 1-year patency of SV composite grafts compared with those of NT SV composite grafts without surrounding pedicle tissue, which might result from improving patency of the competitive SV conduits by maintaining pulsatility of the cushioned graft [26]. Insertion of a Jackson-Pratt drain in the SV harvest site and careful closure of the leg wounds could decrease the possibility of wound complications [26].

External stenting of the SV

The concept for external stenting of saphenous veins was first proposed more than 50 years ago [31]; the rationale was that external supports would reduce diameter mismatch between the vein and target vessels and reduce the tendency of vein to dilate when exposed to arterial pressures. It was also postulated that they might reduce intimal hyperplasia and the risk of thrombosis.

The initial studies to examine the potential benefits of external stents were all conducted in animal models using femoral or carotid arteries but did not involve coronary implantation. The first study of using external stents in the coronary circulation was a proof of principle study in 2013 in a sheep model [32]. This demonstrated a reduction in risk of graft thrombosis, degree of intimal hyperplasia, and improved lumen regulatory at 12 weeks. Despite the encouraging results in animal models, the initial results of external stents for vein grafts in coronary artery bypass grafting produced uniformly poor results with patency rates of 0 to 30% up to 1 year after implantation [33, 34]. Potential explanations for the poor results were due to excessive stent rigidity, oversizing of the stents, and the potential of kinking of the grafts at the proximal or distal anastomosis.

These failures led to the development of second-generation external stents, including the venous external stent (VEST) (Vascular Graft Solutions, Tel Aviv, Israel). VEST is a cobalt-chromium braid with axial plasticity (which allows elongation) and radial elasticity (resulting in a kink and crush resistant stent). After the encouraging animal results with this stent [32], the first clinical trial (VEST I) was of 30 patients where each patient in addition to receiving an internal mammary artery to the left anterior descending coronary artery received two vein grafts that were randomized to act as a control vein graft or to receive a stent [11]. All vein grafts underwent transit-time flow measurement assessment before chest closure and all were widely patent with no technical failures. At 1 year angiographic follow-up, all ITA grafts were patent, but there was an overall failure rate of vein grafts, defined as occlusion or > 50% narrowing, of approximately 30% in both groups. It was noted that there was a higher failure rate of vein grafts, particularly to the right side, when metallic clips had been used to secure side branches within the stent and also if and there had been fixation of stent to the proximal or distal anastomosis. This raised the possibility of disturbance of the geometrical alignment of the anastomosis after chest closure. In the vein grafts that remained patent, the perfect patency was 80% with the stent versus 50% for the controls with significantly reduced intimal hyperplasia [11]. Simultaneous studies showed that in the patent stented vein graft there was considerably superior hemodynamic flow and less oscillatory shear index resulting in lower intimal hyperplasia [35]. Likewise, optical coherence tomography findings confirmed superior luminal regularity and less intimal hyperplasia in the stented vein grafts [36].

A second study examining the use of stents to the vein grafts to the right coronary artery but without fixation to proximal or distal anastomosis and securing side branches with sutures rather than metallic clips, resulted in an almost 90% patency at 6 months [37].

A number of randomized clinical trials are now under way including the VEST III study (180 patients randomized as in in VEST I), and the results of this will be available in 2019 with a primary endpoint of perfect vein graft patency at 2 years. Similarly, a study is underway sponsored by the Food and Drug Administration in the USA of 220 patients using the same methodology as VEST I.

In the VEST IV study (Professor Taggart personal communication), patients came back for 5 year follow-up. In this small cohort of patients (N = 20) of the stented vein grafts that had perfect patency at 1 year, this was maintained out to 5 years with no further deterioration in the vein graft (Fig. 7). In the control group, one further vein graft had occluded and despite progressive ectasia there was still 50% perfect patency. If the larger ongoing trials confirm the ability of the external stent to maintain perfect patency over the long term, this may have important implications for routine practice because of its ease of use.
Fig. 7

Angiographic findings of the saphenous veins (SVs) at 4.5 years after surgery. a Unsupported SV to the first obtuse marginal artery and b VEST supported SV to the second obtuse marginal artery in the same patient

Conclusions

Recent advances in SV harvesting techniques including no-touch technique, grafting strategy of SV as a composite graft based on the in situ ITA and external stenting of the SV may improve long-term patency of the SV conduits in CABG. Preserved SV endothelial wall structures and exposure to substances of the in situ ITA may lead to favorable negative remodeling of the SV. With pre-existing advantages of the SV conduit, such as ease of access, enough length, and short-operation time by simultaneous harvesting with the ITA, the improved SV patency will make this conduit more valuable for CABG.

Notes

Compliance with ethical standards

Conflict of interest

Prof. David Taggart states that he has received research funding, speaking, and traveling honoraria from Vascular Graft Solutions (VGS), and also has share options in VGS.

Ki-Bong Kim, Ho Young Hwang, and Domingos Souza state that they have no conflict of interest.

Human and animal rights and informed consent

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Indian Association of Cardiovascular-Thoracic Surgeons 2018

Authors and Affiliations

  • Ki-Bong Kim
    • 1
  • Ho Young Hwang
    • 1
  • Domingos Savio Ramos de Souza
    • 2
  • David Paul Taggart
    • 3
  1. 1.Department of Thoracic and Cardiovascular SurgerySeoul National University HospitalSeoulSouth Korea
  2. 2.Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine and HealthÖrebro UniversityÖrebroSweden
  3. 3.Department of Cardiovascular SurgeryUniversity of OxfordLondonUK

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