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Review

Angiology
2016, Vol. 67(2) 121-132
Endoscopic Versus No-Touch Saphenous The Author(s) 2015
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Vein Harvesting for Coronary Artery DOI: 10.1177/0003319715584126
ang.sagepub.com
Bypass Grafting: A Trade-Off Between
Wound Healing and Graft Patency

Tomislav Kopjar, MD, PhD1 and Michael R. Dashwood, PhD2

Abstract
The advantage in terms of wound infection, wound healing, and scarring has resulted in the recent adoption of endoscopic vein
harvesting (EVH) as a standard of care for coronary artery bypass grafting in some centers. However, concerns regarding the
quality of these grafts have been raised after recent evidence of decreased graft patency, increased reoperation rate, and
myocardial infarct, problems that are associated with vascular trauma caused when using this technique. Simultaneously, an
atraumatic, no-touch technique for harvesting the saphenous vein was developed producing grafts with improved patency
comparable to the internal thoracic artery. However, wound complications remain a problem using this technique. This review
outlines the need to consider the poor graft quality that may result from EVH and raises the question what is likely to be the best
practice principle in saphenous vein harvesting?

Keywords
coronary artery bypass grafting, no-touch vein harvesting, endoscopic vein harvesting, saphenous vein patency, vascular damage

Introduction An atraumatic, no-touch technique of harvesting the


saphenous vein (NTVH) provides a superior graft with a
The great saphenous vein is the most commonly used conduit
patency comparable to the ITA.10 Although no-touch saphe-
for coronary artery bypass surgery (CABG) since its introduc-
nous vein grafts (NTSVGs) are prepared by OVH via a long
tion by Favaloro in 1969.1 However, the patency of the saphe-
superficial incision, they are removed complete with cushion
nous vein is inferior to the internal thoracic artery (ITA),2 with
of surrounding tissue intact, minimizing surgical trauma, pre-
the radial artery recently being the second conduit of choice for
venting spasm, and obviating the need for intraluminal saline
many cardiac surgeons.3 Minimally invasive endoscopic vein distension, thus preserving the veins normal architecture.11
harvesting (EVH) introduced in 19964 reduces leg wound com-
So far, there have been no sufficiently powered multicenter
plications, infection rate, and pain and improves cosmetic
randomized trials comparing hard clinical outcome to favor
results. It is used in many centers worldwide and in the majority
NTVH over EVH. A number of studies into the improved per-
of CABG in the United States.5 Extensive skin incisions in
formance of NTSVGs have identified various features underly-
open vein harvesting (OVH) allow a harvest with minimal sur-
ing its success, from the advantages of reducing vascular
gical trauma to the conduit but at the risk of higher local wound
damage to preservation of tissue factors beneficial to the main-
complications and postoperative pain. In either technique, the
tenance of a healthy graft.12,13
vein should not be grasped with forceps, stretched, or overdis-
tended, since patency may be related to endothelial damage
during harvest and graft preparation. Although the benefits of
EVH and improved wound healing are well accepted, there are 1
University of Zagreb School of Medicine, Department of Cardiac Surgery,
conflicting reports regarding the patency of saphenous vein University Hospital Centre Zagreb, Zagreb, Croatia
grafts prepared by this method. At best, it appears that the 2
Surgical and Interventional Sciences, Royal Free Hospital Campus, University
patency of EVH grafts is comparable to those prepared by College Medical School, London, United Kingdom
OVH.6,7 Although EVH is minimally invasive in terms of
vessel exposure, wound healing, and scarring, manipulation Corresponding Author:
Michael R. Dashwood, Surgical and Interventional Sciences, Royal Free Hospital
by instruments and insufflation causes considerable vascular Campus, University College Medical School, Surgical and Interventional
trauma and damages the vein, impacting on its function as a Sciences, Pond Street, London NW3 2QG, United Kingdom.
bypass graft.8,9 Emails: m.dashwood@ucl.ac.uk; mickeydash@hotmail.com
122 Angiology 67(2)

Figure 1. Examples of EVH and OVH saphenous vein harvesting. Top, Diagrams showing superficial skin incisions for EVH (left) and OVH
(right). Lower panels show wound healing/scarring in patients after receiving EVH (left) and OVH (right) grafts. (Top Maquet Cardiovascular LLC
2014. All rights reserved. Leftrepublished with permission from Allen KB et al., 1998.70 Copyright Elsevier, 1998. Rightfrom Kopjar) EVH
indicates endoscopic vein harvesting; OVH, open vein harvesting.

Here we have an interesting paradox whereby wound com- vasorum. Surrounding the adventitia is a cushion of perivascu-
plications are reduced when saphenous veins are prepared by lar fat. The inner border of the media and intima is divided by
EVH, but grafts have a similar patency to those prepared by the internal elastic lamina and thrown into folds, features only
conventional OVH; while wound complications persist where seen in normal, nondistended, sections and not truly repre-
saphenous veins are harvested by the no-touch technique, the sented in those published examples that have been perfusion
patency is superior to the other harvesting techniques. Unfortu- fixed. The media and adventitia are separated by the external
nately, the difficulty related to visualization and maneuvrabil- elastic lamina, which is less distinct in veins than arteries. Vas-
ity inherent to EVH has inhibited the development of a cular, autonomic nerves located in the adventitia penetrate the
technique that would produce a NTSVG through EVH. Efforts media as does the vasa vasorum, a microvascular network that
to obtain such a graft by EVH are ongoing. Although EVH is may also extend into the vessel lumen.
commonly used in the United States5 and other countries, it was
not recommended in the United Kingdom.14 The question
arises, is wound healing and cosmetic outcome more important Methods of Harvesting the Saphenous Vein
than graft performance and potentially the survival of patients
undergoing CABG?
Conventional OVH
In conventional CABG, the great saphenous vein is harvested
by open surgery. Exposure is made by a longitudinal incision,
Saphenous Vein Structure overlying the vein and extended directly over its trajectory
Like the majority of blood vessels, the saphenous vein is char- (Figure 1). Sharp dissection is then used to free the vein from
acterized by the following 3 layers: the intima, consisting of lit- the surrounding tissue and the saphenous nerve (Figure 2). Dur-
tle more than a thin basement membrane and its endothelial ing this process, perivascular fat and adventitia are stripped off,
lining; the media, containing vascular smooth muscle cells contributing to the traumatic stimulus. The side branches are
separated by collagen in which the vasa vasorum is located; and ligated and divided in situ. Once dissection is completed, the
the adventitia, which is the thickest layer composed of collagen vein is ligated and divided proximally and distally. A blunt-
fibers and fibroblasts merging with the surrounding connective tipped cannula is placed in the distal end. Generally, veins are
tissue. Within the adventitia, are the vascular nerves and vasa then flushed and manually distended with saline to check for
Kopjar and Dashwood 123

Figure 2. The NTSVG, OVH, and EVH conduits from patients undergoing coronary artery bypass surgery (CABG). Top left, A NTSVG that has
been removed complete with its cushion of surrounding perivascular fat (kindly provided by Dr. Domingos Savio Ramos de Souza). Middle,
Conventional, OVH, graft that has been stripped of its surrounding tissue, much of which is perivascular fat (kindly provided by Dr. Domingos
Savio Ramos de Souza). Right, EVH graft that has been stripped of its surrounding tissue. (Kindly provided by Drs Bhatnagar and Poston.) Scale
bar 3 mm. Bottom, Intraoperative photographs of saphenous vein harvesting matching the grafts from the upper panel. (Left and middle
republished with permission from Souza et al.15 Copyright Oxford University Press, 2009. RightKopjar) EVH indicates endoscopic vein
harvesting; NTSVG, no-touch saphenous vein graft; OVH, open vein harvesting.

leakage, often at high pressures reaching or exceeding 400 mm dioxide embolism and consequent hemodynamic instability
Hg to overcome the spasm that occurs due to surgical trauma.16 have been reported.17 Bipolar scissors or ligaclips are used for
The conduit is then stored in a heparinized saline solution at a side branches. Once the dissection is completed and after
variable time frame. removing the vein from the leg, side branches are ligated with
4-0 silk ties. The vein is flushed and distended, again at high
pressure, to visualize side branches and leakage. Avulsed
Endoscopic Vein Harvest branches are repaired with 6-0 polypropylene sutures. The
Techniques described for EVH are usually aided with insuffla- EVH requires forces to be applied to the vein that are usually
tion of carbon dioxide, while others require physical retraction. avoided in OVH or NTVH, including traction, adventitial strip-
A 2.5- to 3.0-cm skin incision is made (usually) above the knee ping, and venous compression. For an example of EVH saphe-
(Figure 1) and a small space created for introduction of the nous vein see Figure 2.
endoscope (Figure 2). Harvesting is directed toward the groin No-touch vein harvest has previously been described in
and the ankle if necessary. Carbon dioxide is insufflated into detail.15 Briefly, the preserved pedicle of tissue protects the
the subcutaneous tunnel to a maximum pressure of 15 mm vein from spasm obviating the need for distension (Figure 2).
Hg allowing for an easier separation from surrounding tissue, Side branches are ligated at the edge of the pedicle. The adven-
reducing bleeding, and facilitating visualization. Carbon titia and the structures contained within the pedicle possess
124 Angiology 67(2)

Figure 3. Scanning electron micrographs of NTSVG, OVH, and EVH saphenous veins. Appearance of luminal surface of veins showing regions of
endothelial denudation and endothelial cell shape change as well as platelet adhesion in EVH and OVH compared with undamaged NTSVG. The
arrow shows a termination of the vasa vasorum in the lumen of a NTSVG. The NTSVG and OVHrepublished with permission from Vasilakis
et al.19 Copyright Bentham Science Publishers Ltd (2004). The EVHrepublished with permission from Alrawi et al, 2001.71 Copyright The
Heart Surgery Forum (2001). EVH indicates endoscopic vein harvesting; NTSVG, no-touch saphenous vein graft; OVH, open vein harvesting.

properties that protect the vein. Timing of heparin administra- previously ignored. There are scant data regarding the func-
tion, a crucial step during a standard CABG, is dictated by var- tional consequences of the vascular damage described previ-
ious factors not directly related to saphenous vein harvesting. ously. However, an in vitro study comparing the effect of
An experienced surgeon can easily complete vein harvesting dilator and constrictor compounds on OVH versus NTSVG
prior to the moment of mandatory heparinization. The impor- showed that the vasodilator response of SVGs was signifi-
tance of leaving the vein in situ and covered with moistened cantly higher in NTSVG when compared with OVH. Conver-
swabs at least until a few minutes after heparinization, as advo- sely, the constrictor responses were significantly higher in
cated in NTVH, has been proven to be beneficial when using OVH versus NTSVG. On the basis of these results it was con-
other harvesting techniques.9 This eliminates the need for rin- cluded, no-touch harvesting technique of SVGs may
sing or flushing.9,18 After removal, the vein is stored in hepar- decrease early graft failure and also reduce postoperative
inized blood. Manual distension using a syringe is avoided, morbidity and mortality rate, contributing to improved graft
thus preventing pressure-induced trauma to the endothelium and patency rate in the long-term.26, p. 510
vessel wall. Although EVH decreases local wound complications and
improves cosmetic results, several authors have demonstrated
that the time required for completing the harvest and the need
Harvesting Technique and Vascular Damage to convert to an open technique or place external repair stitches
were higher, especially during early adoption of EVH, with the
Endothelium reported rate of conversion to OVH ranging from 5% to 7%.27
A number of histological studies have reported the effect of Despite an increased number of defects requiring suture repair
both EVH and OVH on the endothelium (Figure 3) with con- with EVH, patency rates up to 6 months appeared similar to
flicting results. Reports comparing EVH to traditional, OVH, OVH in prospective randomized studies.6,7,28
preparation showed no detrimental effect on vein morphology, Distension in OVH is performed using saline even though
endothelial structure, or function;20,21 better preservation;22,23 many reports emphasize its negative effect on endothelial
or no difference24,25 in endothelial integrity between these integrity and graft performance.29 Overdistension has long
grafts. However, Rousou et al showed that there is damage to been proven to have an adverse effect on graft patency, and the
the endothelium of EVH saphenous vein grafts and that cellular amount of time the saphenous vein is distended during harvest-
metabolic activity, viability, and membrane damage to the ing is directly correlated with an upregulation of innate inflam-
endothelium is less in OVH compared with EVH grafts.8 Also, matory biomarkers in conduits used in CABG.30 Data suggest
this is accompanied by attenuated cell viability and extensive that vein graft failure is a multifactorial process involving
membrane damage in intimal/medial layers of EVH compared neointimal hyperplasia and inflammation, although immediate
with OVH vein grafts. Consistent with these data, using optical vein graft failure is partially attributed to defects that originate
coherence tomography (OCT), Kiani and Poston described from intraoperative technical errors.31 Early graft failure may
regions of endothelial denudation in EVH saphenous veins and be attributed to endothelial damage and the involvement of
also abnormalities within the intima and deeper layers of these inflammatory cytokines, whereas late failure (>1 year after
grafts18 (Figure 4). Interestingly, the histological examples in CABG) may be attributed to neointimal hyperplasia. However,
this article also show marked damage to the adventitia of the underlying cause of both processes is quite likely exacer-
EVH saphenous vein grafts, a factor that seems to have been bated by high-pressure distension.
Kopjar and Dashwood 125

Figure 4. Structural damage to conventional OVH and EVH saphenous vein. Transverse sections of saphenous veins used in coronary artery
bypass surgery (CABG). No-touch saphenous vein graft (NTSVG): undamaged saphenous vein harvested by the no-touch technique with
adventitia and surrounding perivascular fat intact. The OVH: conventional, OVH, vein harvested with adventitia damaged or removed (Dash-
wood unpublished). The EVH: endoscopically harvested vein with adventitia damaged or removed. Republished with permission from Kiani and
Poston.18 Copyright Wolters Kluwer Health (2011). Large arrow indicates intimal tearing. Small arrows indicate position of the adventitia. Scale
bar 2 mm. EVH indicates endoscopic vein harvesting; OVH, open vein harvesting.

Perivascular Tissue remains intact, representing another mechanism underlying the


improved patency of these grafts.36 Apart from the obvious dif-
Apart from preserving the endothelium of saphenous vein
ferences in the appearance of EVH, OVH, and NTVH, the pro-
grafts in patients with CABG, there is evidence that veins har-
tective properties of the saphenous veins outer cushion are
vested complete with surrounding cushion of tissue results in
striking when compared by both light (Figures 4 and 5) and
improved graft performance. The NTVH technique removes
electron microscopy.19,34 Histologically, EVH and conven-
the saphenous vein with its cushion of perivascular fat intact
tional OVH saphenous veins look very different than those pre-
and, using this procedure, the vein does not go into spasm,
pared by the no-touch technique (Figures 4 and 5). These
high-pressure saline distension is not required, and the vein
differences are not only seen at the light microscope level but
maintains its normal architecture (Figure 4).10,11,13 Short-term
also obvious at the ultrastructural level (Figure 3).
patency of NTSVG is improved compared with conventionally
prepared grafts that have been stripped of surrounding tissue and
distended.32 Mid-33 and long-term10 follow-up studies have Perivascular Fat
shown a dramatic improvement in NTSVG over conventional Adipose tissue is accepted as a source of inflammatory media-
grafts with a resulting patency rate comparable to the ITA. tors associated with coronary artery disease (CAD), such as
Various mechanisms have been described underlying the interleukin 6 and tumor necrosis factor a. Regarding the coron-
success of NTSVGs. Of particular relevance to OVH versus ary circulation, epicardial adipose tissue may represent a
EVH preparations is the suggestion that the pronounced cush- source of adipocyte-derived factors with cardioprotective prop-
ion surrounding the vein when using NTVH plays an important erties but also those associated with various aspects of CAD.37
mechanical role that protects the vein, not just at harvesting, Although the outer layers of OVH and EVH saphenous veins
but once implanted, where it buffers against arterial hemody- are removed or damaged, NTVH veins are harvested with a
namics. In support of this are data showing that the external pronounced cushion of perivascular adipose tissue (PVAT)
cushion protects against high pressure-induced damage to both intact (Figures 2, 4, and 5). The PVAT, surrounding most blood
vascular smooth muscle and endothelial cells as observed in vessels, is no longer thought of as merely having a support-
conventional vein grafts.11,12,19,34,35 Importantly, the outer ing role but is now recognized as a source of factors that
cushion possesses mechanical properties where it prevents potentially influences vascular tone and structure. There is
kinking of grafts of excessive length.15 Also, by preserving the experimental evidence that PVAT influences vascular tone38
cushion of perivascular surrounding tissue, the vasa vasorum via so-called adipocyte-derived relaxing factor (ADRF).39,40
126 Angiology 67(2)

Figure 5. Damaged vasa vasorum: no-touch saphenous vein graft (NTSVG) versus conventional OVH and EVH veins. Dark CD34 immu-
nostaining identifies endothelial cells lining the lumen (L) and the vasa vasorum. Left, Part of a transverse section of a no-touch harvested vein
with adventitia and vasa vasorum intact. Middle, Conventional OVH vein with adventitia and vasa vasorum damaged (both from Dashwood
unpublished). Right, Damaged adventitia and vasa vasorum in an EVH vein. Republished with permission from Nowicki et al.22 Copyright Elsevier
(2004). Large arrows adventitia; small arrows indicate vasa vasorum. Scale bar 0.5 mm. EVH indicates endoscopic vein harvesting; L, lumen;
OVH, open vein harvesting; PVAT, perivascular adipose tissue.

These factors are of particular interest in vessels used as con- that this poorly understood relationship is important for normal
duits in CABG such as the ITA41 and saphenous vein.42 vascular function and warrants further detailed studies.
Regarding the saphenous vein, we have shown that the PVAT These reports are of particular relevance to the saphenous
surrounding NTSVG exhibits immunostaining for endothelial vein when used in CABG, since removal of the perivascular
nitric oxide (eNOS) as well as NOS activity.43 In addition, lep- cushion of fat would be expected to affect graft performance.
tin expression and staining have been identified in PVAT of Since preservation of PVAT improves graft performance in
NTVH veins.44 Since PVAT is in direct contact with the adven- NTSVG the question arises, might perivascular damage to the
titia and possesses ADRF activity, there is the potential for this saphenous vein (as in OVH and EVH) influence certain
layer to influence vessel structure and tone. Also, within the receptor-mediated effects? For example, removal of PVAT and
PVAT is a network of capillaries that connect to the vasa subsequent loss of ADRFs (eg, adiponectin, leptin, and NO)
vasorum, microvessels providing the vessel wall with oxygen might be associated with vasospasm and early occlusion rates
and nutrients that are implicated in the superior patency rate that often occur in OVH47 and EVH vein grafts. Also, does
in NTSVG.36,45 The presence of ADRFs surrounding this capil- adventitial damage and removal of PVAT affect autonomic
lary network that connects to the vasa vasorum suggests that control of the saphenous vein as well as PVAT-derived
ADRFs may play a role in preserving a healthy graft by ADRFs? If reduced ADRF levels are associated with vein graft
maintaining blood flow through the vessel wall after its implan- failure, their receptors may represent potential therapeutic tar-
tation into the coronary circulation. Apart from influencing gets in CABG patients.
vascular tone ADRFs may also affect vessel structure, since The saphenous vein is under the influence of many neuro-
many may possess direct growth factor properties. transmitters and neuropeptides that, apart from affecting vascu-
lar tone, possess mitogenic properties that may contribute to
morphological changes caused by vascular injury. Such neuro-
Perivascular Innervation vascular actions may play a role in the altered vein reactivity
In addition to the ADRFs mentioned previously, the autonomic and structure involved in graft failure.48 The sympathetic inner-
innervation of fat should be considered. A recent review vation of NTSVG has been studied at both the light microscope
describes the interaction between autonomic nerves and and the ultrastructural level. Here, adrenergic nerves were iden-
PVAT.46 Here, the authors describe the expression of adreno- tified using tyrosine hydroxylase immunohistochemistry,
ceptors, purinoceptors, and receptors for neuropeptide Y, where nerve plexi were located in the adventitia, many being
receptors that can modulate both lipolysis and lipogenesis. A associated with microvessels (vasa vasorum). In conventional
mechanism is proposed whereby sympathetic neurotransmis- preparations of SV that had been stripped and distended,
sion can simultaneously activate smooth muscle cells in the degenerating tyrosine hydroxylase-positive axons were identi-
tunica media to cause vasoconstriction and alter free fatty acid fied as well varicosities with prominent swollen mitochondria
content and release from adjacent adipocytes in PVAT that can and other signs of nerve damage.49
then influence endothelial function. The authors hypothesize a Clearly, when harvesting the saphenous vein in patients
strong link between PVAT and autonomic fibers, suggesting undergoing CABG, any nerve fibers in the NTSVG will be
Kopjar and Dashwood 127

separated from their respective cell bodies and thus not be under had EVH.5 Patients who had EVH had about 20% reduced risk
full autonomic control. As far as we are aware, there are no data of mortality at 4 years and a nonsignificant increased risk of
to show whether, postimplantation, these fibers remain discon- repeat revascularization when compared to OVH.5 In the same
nected or are reconnected. However, neural reorganization year, Zenati et al published the results of 1471 Veteran Admin-
has been previously described in a porcine saphenous veincar- istration patients and found no significant differences in 1-year
otid artery interposition grafting model using NF200 immunos- mortality, although EVH patency was lower and repeat revas-
taining (a nerve marker). Here, a significant time-dependent cularization rate was significantly higher (Table 1).53 And
(1 and 6 months) reduction in perivascular nerves located in finally, following on the safety concerns of EVH, the US Food
the media was observed. In contrast, there was a highly signifi- and Drug Administration issued a request to analyze the Soci-
cant increase in paravascular nerves in the adventitia accom- ety of Thoracic Surgeons Adult Cardiac Surgery Database for
panied by the appearance of large paravascular nerve bundles EVH- and OVH-related outcomes. A retrospective analysis
at 1 month that diminished at 6 months. Based on these findings, of 235 394 Medicare patients who underwent isolated CABG
it was concluded that there is a reorganization of neural tissue in surgery in 934 centers between 2003 and 2008 were exam-
this porcine vein graft model. Whether these alterations consti- ined and published in 2012 by Williams et al51 where 52%
tute an adaptation to arterial conditions and grafting per se or of patients received EVH. In a propensity score-adjusted
whether they influence graft thickening and subsequent patholo- analysis, there were no significant differences in 3-year mor-
gical consequences remains to be established.50 tality, or a composite of death, myocardial infarction, and
revascularization. The EVH was associated with a 13% lower
harvest wound infection rate.
Graft Patency: OVH Versus EVH Considering these new data and the number of patients
Dacey et al recently reported on the increasing use of EVH in included in the subsequent analyses, the NICE interventional
the United States (34% in 2001, 75% in 2004, and 80% by procedure guidance Committee judged that current evidence
2005).5 Although many studies support the use of EVH,5,51 on the efficacy and safety of EVH for CABG is adequate to
other studies show that saphenous veins prepared by EVH support the use of this procedure, although the importance of
provide a graft with inferior patency to those harvested by training and regular experience for any clinician doing this pro-
OVH.52-54 Protagonists of EVH raise the benefits of this tech- cedure was noted (NICE interventional procedure guidance
nique being reduced local wound complications, infection rate, 494, issued June 2014).
and pain and improved cosmetic outcome while those favoring The difference between the findings from more recent
OVH highlight the reduced patency rate of EVH veins compared studies,5,51 and the study by Lopes et al,52 regarding increased
with those harvested conventionally by OVH.52-54 risk of death and adverse cardiac events highlights the poten-
Previous guidance in the United Kingdom advised that EVH tial bias from unaccounted confounding variables, since the
should only be used with special arrangements (NICE Interven- vein-harvesting technique was not the basis for randomiza-
tional procedures guidance 343, Issued: May 2010).14 This tion. In this era of percutaneous coronary stenting, it is diffi-
decision was based on data from the Project of Ex Vivo Vein cult to explain how impaired saphenous vein patency might
Graft Engineering via Transfection IV (PREVENT IV) trial lead to mortality, particularly when veins are frequently used
undergoing protocol-mandated follow-up angiography 12- to for bypassing worse targets, while the second arterial graft is
18-month post-CABG or earlier clinically driven angiography, placed on the better target after the left anterior descending
where EVH grafts showed higher failure rates than OVH grafts territory. From a recent review regarding graft quality,64 it
and, at 3 years, a higher death rate, myocardial infarction, or appears that suture repairs of saphenous vein grafts are more
revascularization in EVH versus OVH grafts.52 This landmark often necessary in EVH than OVH, presumably since EVH
study by Lopes et al52 showed that EVH is independently veins are subjected to greater vascular trauma than those pre-
associated with graft failure and adverse clinical outcomes pared by OVH.
in a secondary analysis of 3000 patients undergoing CABG Overall patency rate does not solely depend on harvesting
(EVH: 1753 patients and OVH: 1247 patients). The finding method but on target and vein-related variables and patient
of this study resulted in a debate and apprehension among sur- characteristics.55 So far, there are only a few short- and mid-
geons to use EVH grafts for coronary artery surgery. More term follow-up trials (listed in Table 1) comparing EVH and
recently, yet another post hoc analysis of the PREVENT IV OVH patency, with the general consensus being that patency
trial revealed a high prevalence of vein graft failure following of EVH grafts is, at best, comparable to OVH grafts. Lack of
CABG (12.1%-63.6%) and multiple patient- and surgery- long-term follow-up EVH patency data forces one to draw con-
specific factors associated with vein graft failure, including clusions about contemporary saphenous vein patency from
EVH.55 trials comparing it with arterial conduits. It seems difficult to
Data published subsequently to the study by Lopes et al in justify EVH use in favor of NTVH, given the potential benefit
2009 provided more definitive answers regarding hard clinical to patients with CABG. It is interesting that, while 1 major
outcome of patients undergoing EVH for CABG. In 2011, advantage of EVH is cosmetic outcome, differences in
Dacey et al published a retrospective analysis of 8542 patients appreciation of scarring are mostly notable during the early
in Northern New England, in which about a half of the patients postoperative period whereas, after 6 weeks, cosmetic outcome
128 Angiology 67(2)

Table 1. Early Saphenous Vein Graft Patency to Non-left Anterior Descending Territory.

Author, Year, Graft No. Patency


Reference, Study F/u, Study Size F/u (EVH, OVH, or Failure P Patency or
Type Months (Patients) Angio, % NTVH, RA) Rate, % Value Failure Definition Comment

Perrault et al, 3 40 80.0 32, 27, 0, 0 84.4, 85.2 .99 No graft Standard EVH and OVH
2004,7 RCT occlusion intraoperative graft management
Yun et al, 2005,6 6 200 72.0 166, 170, 0, 0 68.1, 70.0 .58 <50% stenosis All veins were gently distended
RCT with autologous heparinized
blood
Zenati et al, 12 1471 60.8 689, 1118, 0, 0 74.5, 85.2 .00 FitzGibbon A, B Prior to 2003, the SV harvesting
2011,53 R technique was not noted
Goldman et al, 12 733 72.7 51, 218, 0, 266 78.4, 91.3 .01a Opacification of SV was dilated with heparinized
2011,54 RCT 88.8, 89.5 .82b distal target by cold (4 C) saline solution and
graft injection stored in this cold solution until
used
Lopes et al, 13 2400 75.7 2321, 1969, 0, 0 27.2, 22.6 .00 >75% stenosis SV were treated with edifoligide or
2009,52 R placebo in a pressure-mediated
system
Souza et al, 18 156 84.6 0, 107, 109, 0 88.9, 95.4 .03 No graft SV harvested by NTVH or the
2002,32RCT occlusion conventional OVH as described
Mannion et al, 15 210 9.5 22, 0, 16, 00 27.3, 93.8 .02 <80% stenosis SV harvested by NTVH or the
2014,65 R standard EVH as described
Dreifaldt et al, 36 108 91.7 0, 0, 99, 99 93.9, 81.8 .01 <70% stenosis RA grafts were prepared with
2013,33 RCT similar technique as the NTVH
grafts
Abbreviations: EVH, endoscopic vein harvesting; F/u, mean follow-up duration; F/u angio, follow-up angiography completion; NTVH, no-touch vein harvesting;
OVH, open vein harvesting; R, retrospective observational trial; RA, radial artery; RCT, randomized controlled trial; SV, saphenous vein.
a
EVH versus OVH.
b
EVH OVH versus RA.

Table 2. Beyond 5-Year Saphenous Vein Graft Patency to Non-left Anterior Descending Territory.

Author, Year, Graft No. Patency Patency


Reference, Study F/u, Study Size F/u (EVH, OVH, or Failure P or Failure
Type Months (Patients) Angio, % NTVH, RA) Rate, % Value Definition Comment

Tranbaugh et al, 60 1851 15.0 0, 364, 0, 420 47.0, 82.0 .00 <50% stenosis SV harvesting technique was not
2012,56 R described
Athanasiou et al, >60 1200 100 0, 848, 0, 309 75.2, 89.6 .00 <50% stenosis Moderate heterogeneity
2011,57 MA I2 25%, P .24
Hadinata et al, 65 416 61.3 0, 197, 0, 68 81.2, 86.9 .26 <70% stenosis SV harvesting was performed by OVH
2009,58 RCT with minimal conduit handling or
distention
Hayward et al, 66 225 50.2 0, 60, 0, 53 87.0, 90.0 .29 <80% stenosis 2008 AATS Meeting Dr Hayward: These
2010,59 RCT veins were all taken in a shamelessly
open no-touch manner.
Collins et al, 68 142 72.5 0, 44, 0, 59 86.4, 98.3 .04 No graft The SV was harvested in a routine fashion
2008,60 RCT occlusion and gently distended
Deb et al, 92 510 52.7 0, 234, 0, 234 19.7, 12.0 .03 TIMI 0-2 SV harvesting included OVH and EVH,62
2012,61 RCT although data not reported
Souza et al, 102 104 71.2 0, 101, 101, 0 76.2, 90.1 .01 No graft SV harvested by NTVH or the
2006,10 RCT occlusion conventional OVH as described
Goldman et al, 120 1254 29.4 56, 58a No graft Data from patients operated prior to the
2004,63 P occlusion introduction of EVH
Abbreviations: EVH, endoscopic vein harvesting; F/u, mean follow-up duration; F/u angio, follow-up angiography completion; MA, meta-analysis; NTVH, no-
touch vein harvesting; OVH, open vein harvesting; P, prospective observational trial; R, retrospective observational trial; RA, radial artery; RCT, randomized
controlled trial; SV, saphenous vein; TIMI, Thrombolysis In Myocardial Infarction flow grade.
a
Patency rates for OVH when bypassing the right (56%) and the circumflex (58%) coronary artery.
Kopjar and Dashwood 129

is equally appreciated.28 Long-term NTSVGs have a patency allow recommendations on the resource implications of the 2
rate of 90% compared with 76% for conventionally, OVH vein (OVH vs EVH) techniques.
grafts at mean time 8.5 years.10 These results were produced To date, no studies have analyzed the cost-effectiveness of
from a single-center randomized longitudinal trial. Initially, the NTVH technique. If we consider the no-touch technique,
52 patients were enrolled in each group. Angiographic it is clear that there are no additional equipment costs when
follow-up was performed at 18 months and at 8.5 years when compared to conventional OVH. Also, wound complication
37 patients in each group completed angiographic follow-up. and infection rates for NTSVH would be expected to be higher
At 18 months, NTSVG patency was 95%, while conventional than EVH but comparable with OVH. A very recent study,
OVH was 89%.32 Others have also emphasized the impor- focusing on vascular smooth muscle cell activation, showed
tance of no-touch graft handling on long-term saphenous vein worse leg wound assessment scores at 3 months but similar
patency (eg, The Radial Artery Patency and Clinical Out- scores at 12 months when comparing NTVH with OVH.35 This
comes [RAPCO] trial). Beyond 5 years, patency of conven- suggests that the cost-effectiveness of NTVH is more likely
tionally harvested vein grafts is about 75%, ranging from comparable with conventional OVH than EVH.
47% to 87% in the most recent literature (Table 2). Since the
majority of studies suggest that saphenous veins prepared by
both EVH and OVH have similar patency rates, it seems rea-
Conclusion/Discussion
sonable to assume that NTSVG would be superior to those Despite the benefits shown to date, the use of NTVH in CABG is
prepared by EVH. limited to a few centers. Poor conduit quality, as a sequel of the
learning curve for EVH, is a predictor of early graft failure as well
Learning Curve as an underrecognized public health issue.18 Recent supporting
data have shown NTSVG patency rate to be comparable to ITA,
Using OCT it has been proven that technicians inexperienced
giving it the advantage in the battle for the graft of second choice
with EVH are more likely to cause deep vessel injury to the
in CABG.33 When considering that EVH saphenous vein graft
saphenous vein graft than those with more experience.
patency is, at best, comparable to OVH, it seems reasonable to
Although prior studies suggest that only 20 cases of experience
assume that NTSVG would be superior to those prepared by
are required to complete the learning curve of EVH, a more
recent study showed that performing even 100 cases is insuffi- EVH, as confirmed by a recent small, short-term, study.65
It is surprising that while both EVH and NTVH techniques
cient to attain the beneficial results of more experienced har-
were introduced almost 20 years ago, EVH was so readily
vesters.18 Acquiring EVH experience and maintaining this
accepted, particularly in the United States.5 The improved cos-
skill presents a more complex challenge than previously
metic outcome and patient satisfaction may explain one of
assumed.66 Importantly, those CABG studies reporting adverse
the main reasons for the large take-up rate of EVH, despite the
outcomes after EVH had enrolled patients during the early
high initial equipment costs and lack of cost-effectiveness data.
phase of its adoption. To date no studies have specifically eval-
A number of studies into mechanisms underlying the improved
uated the learning curve of NTVH. Considering that EVH,
when compared to OVH or NTVH, is mostly associated with performance of NTSVGs have identified various features con-
tributing to its success from the advantages of reducing vascu-
increased intrinsic difficulties, from a surgeons perspective
lar damage and preservation of the vasa vasorum to preserving
(Tomislav Kopjar), the learning curve for EVH is longer than
the perivascular fat and various tissue factors beneficial to the
NTVH, which is comparable to that for OVH.
maintenance of a healthy graft.12,13,36
Here, an opportunity for patient selection arises when con-
sidering the emerging data on the improved patency of NTSVG
Cost-Effectiveness (Wound Infection) and concerns over EVH graft quality. Based on risk factors for
Despite the saphenous vein being the most commonly used harvest site wound morbidity, target characteristics, patient
graft in CABG and EVH, the preferred method in the United age, and preference, one technique may be considered over the
States, data regarding cost-effectiveness are unclear. Wound other.69 The optimal principle for saphenous vein conduit har-
infection rate is a crucial factor when determining cost- vesting is one causing minimal vascular trauma, as with
effectiveness of saphenous vein harvesting technique. Post- NTVH, and minimal wound complication rate, as with EVH.
operative costs show EVH not to be cost effective within 35 Until such a technique is developed, NTVH can and should
days whether effect is shown as purulent infections avoided be considered for those in whom the risk of harvest site wound
or as an estimate of quality-adjusted life years gained.67 How- morbidity is justified and tolerable. Multicenter randomized
ever, results suggest that conclusions may shift when the controlled clinical trials, such as the on-going Surgical and
follow-up period is increased. Although it has been suggested Pharmacological Novel Interventions to Improve Overall
that EVH is the most cost-effective method of harvesting the Results of Saphenous Vein Graft Patency in Coronary Artery
great saphenous vein and can significantly improve a patients Bypass Grafting Surgery: An International Multi-Center Ran-
quality of life,68 the Consensus Statement of the International domized Controlled Clinical (SUPERIOR SVG) trial (clinical-
Society of Minimally Invasive Cardiothoracic Surgery (ISMICS) trials.gov identifier: NCT01047449), comparing graft patency
2005 concluded there was inadequate cost-effectiveness data to and hard clinical outcome of OVH/EVH versus NTVH are
130 Angiology 67(2)

required to inform and encourage trainee and established car- 11. Dashwood MR, Savage K, Tsui JCS, et al. Retaining perivascular
diac surgeons to adopt what is likely to be the best practice tissue of human saphenous vein grafts protects against surgical
principle in saphenous vein harvesting. and distension-induced damage and preserves endothelial nitric
oxide synthase and nitric oxide synthase activity. J Thorac Cardi-
Acknowledgments ovasc Surg. 2009;138(2):334-340.
We thank Dr Janice Tsui for comments on earlier versions of this 12. Tsui JCS, Souza DSR, Filbey D, Karlsson MG, Dashwood MR.
manuscript and Drs Sugam Bhatnagar and Robert Poston for the Localization of nitric oxide synthase in saphenous vein grafts har-
example of an EVH saphenous vein graft shown in Figure 2. vested with a novel no-touch technique: potential role of nitric
oxide contribution to improved early graft patency rates. J Vasc
Declaration of Conflicting Interests Surg. 2002;35(2):356-362.
13. Dashwood MR, Tsui JC. No-touch saphenous vein harvesting
The author(s) declared no potential conflicts of interest with respect to
improves graft performance in patients undergoing coronary
the research, authorship, and/or publication of this article.
artery bypass surgery: a journey from bedside to bench. Vascul
Pharmacol. 2013;58(3):240-250.
Funding
14. Barnard JB, Keenan DJM. Endoscopic saphenous vein harvesting
The author(s) received no financial support for the research, author- for coronary artery bypass grafts: NICE guidance. Heart. 2011;
ship, and/or publication of this article. 97(4):327-329.
15. Souza DSR, Arbeus M, Botelho Pinheiro B, Filbey D. The no-
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