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Page 2 of 14 Heng et al. Vessel Plus 2023;7:31 https://dx.doi.org/10.20517/2574-1209.2023.97

[2,3]
form of repeat revascularization, with failure rates approaching 50% at 10 years postoperatively . The
pathophysiology of vein graft failure is complex and multifactorial, involving the interplay between multiple
biological and mechanical changes stemming from the transposition of vein grafts from low-pressure
venous systems to pulsatile high-pressure arterial systems during bypass surgery. In particular, the
constellation of early endothelial and smooth muscle cell proliferation, later extracellular matrix (ECM)
deposition, and eventual atherosclerotic degeneration, collectively known as neointimal hyperplasia, has
been identified as a therapeutic target in technologies aimed at preventing vein graft failure. Over the years,
special attention has been given to extravascular stenting as a method of reducing neointimal hyperplasia by
offloading vein graft wall stress, with several devices now being implemented in ongoing human clinical
trials. In this review, we will aim to provide a comprehensive overview of the biology and prevention of
SVG failure, with a focus on the role of external stenting. We will examine the underlying mechanisms of
SVG failure, the current understanding of disturbed flow and its impact on graft biology, and the evidence
supporting the use of external stenting as a preventive strategy. Additionally, we will discuss historical
perspectives, modern approaches, and emerging strategies for studying SVG failure and its prevention in
patients undergoing CABG.

NATURAL HISTORY OF VEIN GRAFT FAILURE
Ever since Favorolo et al. pioneered its use in the 1960s, autologous saphenous vein has long been a
conduit of choice in coronary bypass surgery due to its ready availability and ease of use . SVGs are utilized
[4]
[5]
in over 90% of patients undergoing CABG , but they are associated with a high incidence of graft failure,
which can, in turn, lead to adverse clinical outcomes. Historically, it has been estimated that 5%-10% of
SVGs fail within 1 month of surgery, 10%-25% within 12-18 months, and 40%-50% within 10 years [2,3,6] .
Various risk factors for SVG failure have been identified, including patient-related factors such as age,
diabetes, and smoking, as well as surgical factors related to harvesting technique, graft storage solutions, and
[6]
target coronary anatomy .
Since the advent of CABG, the use of the left internal mammary artery (LIMA) has been recognized to
confer significant prognostic benefit owing to its superior patency of up to 90% at 10 years [2,7,8] , particularly
when associated with the left anterior descending (LAD) coronary artery territory. Likewise, multiple
arterial grafting using radial artery (RA) and right internal mammary artery (RIMA) as second conduits has
seen increasing adoption in the contemporary practice of coronary revascularization, supported by
numerous studies consistently demonstrating significant improvements in event-free survival [9,10,11] .
Nonetheless, total arterial grafting is not always feasible, and less than 10% of CABGs in North America
utilize more than one arterial graft . Therefore, SVG remains the most widely used conduit in CABG, with
[5,6]
the prevention of SVG failure remaining a significant unmet clinical need.

The clinical significance of SVG failure in the setting of CABG is underscored by its impact on patient
morbidity and mortality. Early studies, such as that by Lytle et al., reported significant mortality associated
with SVG failure in the LAD territory, with only 50% survival at 5 years following catheterization
demonstrating > 50% SVG stenosis . In a large single-center cohort review of 1,388 patients undergoing
[12]
CABG over a 25-year span, Fitzgibbon et al. reported that vein grafts to the LAD occluded early less often
than grafts to other vessels; however, high profile lesions of > 50% stenosis were present even in 37% of all
[8]
patent grafts by 12.5 years following surgery . Analysis of data from the Duke Cardiovascular Databank by
Halabi et al. has further corroborated the relationship between critical but non-occlusive SVG disease and
[13]
adverse clinical outcomes of death, myocardial infarction, and repeat revascularization . Because
angiography in these early cases series was driven by the presence of clinical symptoms, it is likely they
underestimated the true incidence of vein graft failure, and it is possible that vein graft failure accompanied