Endoscopic Vein-Graft Harvesting Balancing the Risk and Benefits

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EDITORIAL
Endoscopic Vein-Graft Harvesting
Balancing the Risk and Benefits
Davy C. H. Cheng, MD,* Janet Martin, PharmD, MSc (HTA),*† Francis D. Ferdinand, MD,‡
John D. Puskas, MD,§ Anno Diegeler, MD, PhD,¶ and Keith B. Allen, MD储
In a retrospective post hoc analysis of the previously published PREVENT IV trial,
Lopes et al
1
found significantly higher rates of mortality, myocardial infarction, or repeat
revascularization 3 years after primary coronary artery bypass grafting when an endo-
scopic approach was compared with an open approach for harvesting the vein graft. These
are important findings, but this study should be considered in the context of all available
evidence in the field of technology assessment. Multiple randomized trials of patients who
are prognostically similar at baseline have demonstrated that endoscopic vein-graft
harvesting (EVH) significantly reduces perioperative complications and need for surgical
reintervention, all without adverse effects on graft failure, survival, or major coronary
adverse events in the near term.
2
In our recent meta-analysis (13 randomized; 23
nonrandomized) in 36 trials of 9632 patients undergoing saphenous vein harvest,
2
the risk
of wound complications was significantly reduced by EVH compared with open vein-graft
harvesting (OVH) (OVH; Odds Ratio [OR] 0.31, 95% CI 0.23– 0.41; Fig. 1). Similarly,
the risk of wound infections was significantly reduced (OR 0.23, 95% CI 0.20 – 0.53; P⬍
0.0001). Need for surgical wound intervention was also significantly reduced (OR 0.16,
95% CI 0.08 – 0.29; Fig. 2). The incidence of pain (23.1% versus 6.7%), neuralgia (24.3%
versus 7.1%), and patient satisfaction (49% versus 75%) was significantly improved with
EVH compared with OVH. Postoperative myocardial infarction, stroke, reintervention for
ischemia or angina recurrence, and mortality were similar between patients having OVH or
EVH. (Table 1) Although time to harvest the vein was significantly increased (weighted mean
differences [WMD] 15.26 minutes, 95% CI 0.01–30.51), overall operative times were similar,
hospital length of stay was reduced (WMD ⫺0.85 days, 95% CI ⫺1.55 to ⫺0.15), and
readmissions were reduced (OR 0.53, 95% CI 0.29 – 0.98).
2,3
One randomized trial of 110
patients using clinical event free survival at 5-years as a surrogate marker for graft failure
reported no difference between groups (75% vs. 74%)
4
Indeed, pooled analysis of all
observational and randomized trials of short- to midterm follow-up showed no difference in
survival (Fig. 3).
2
The difference in conclusions by Lopes et al,
1
suggesting that EVH has a negative
impact on graft patency in contrast to the meta-analyses of all comparative studies,
2
highlights the risk of focusing only on one single retrospective post hoc analysis, which
have important prognostic differences between groups unaccounted for.
5
In particular,
there was no accounting for the proportion of patients undergoing on-pump versus
off-pump bypass in the analysis by Lopes et al
1
In another publication comparing
off-pump and on-pump coronary artery bypass grafting from the same dataset, Magee
Accepted for publication January 11, 2010.
From the *Department of Anesthesia and Perioperative Medicine, Evidence-Based Perioperative Clinical Outcomes Research Group (EPiCOR), University of
Western Ontario, London, ON, Canada; †High Impact Technology Evaluation Centre, London Health Sciences Centre, London, ON, Canada; ‡Department
of Cardiothoracic Surgery, The Lankenau Hospital and the Lankenau Institute for Medical Research, Wynnewood, PA USA; §Division of Cardiothoracic
Surgery, Emory University, Atlanta, GA USA; ¶Division of Cardiothoracic Surgery, Herz-und Gefasse Klinik Bad Neustadt, Bad Neustadt, Germany; and
储Department of Cardiothoracic Surgery, Mid America Heart Institute, St. Luke’s Hospital, Kansas City, MO USA.
Disclosure: John D. Puskas, MD, is a consultant for MAQUET, Inc, Wayne, NJ USA and Medtronic, Inc., Minneapolis, MN USA.
Address correspondence and reprint requests to Davy C. H. Cheng, Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre-UH,
339 Windermere Road, C3-172, London, ON, Canada N6A 5A5. Email: davy.cheng@lhsc.on.ca.
Copyright © 2010 by the International Society for Minimally Invasive Cardiothoracic Surgery
ISSN: 1556-9845/10/0502-0070
Copyright © 2010 by the International Society for Minimally Invasive Cardiothoracic Surgery70

et al
6
demonstrated that with EVH, the probability of graft
failure was significantly higher in the off-pump group than in
the on-pump group (OR 0.82, 95% CI 1.78 - 0.67–1.00).
The results in Lopes et al
1
were also significantly
different across institutions, suggesting that there may have
been important differences in surgical technique, experiences,
and/or devices used, which were represented in an imbal-
anced way between groups. More important, vein harvest
technique was not the basis for randomization. Thus, unrec-
ognized confounding variables could have been unaccounted
for, such as significantly more clopidogrel use during fol-
low-up in the traditional than in EVH patients.
Another important point to consider is whether EVH
devices may have differential effects on outcomes. During
the PREVENT IV trial, there were only two EVH devices in
use (Guidant and Ethicon), which differ in both their appli-
FIGURE 2. Readmission for wound complications: EVH vs OVH.
FIGURE 1. Wound complications: EVH vs OVH.
Innovations • Volume 5, Number 2, March/April 2010 Editorial
Copyright © 2010 by the International Society for Minimally Invasive Cardiothoracic Surgery 71

cation for the dissection technique and in the use of CO
2
.
Guidant (now Maquet Cardiovascular, LLC, Wayne, NJ) is a
closed CO
2
system using blunt circumferential dissection
with a documented tendency to form clots within the vein if
heparin is not given before dissection.
7
And, heparin was not
being used during the time of the PREVENT IV trial. The
Ethicon system (now Sorin, Milano, Italy) was an open
system that used blunt anterior dissection only, and at the
time of PREVENT IV trial, CO
2
was being infrequently used.
In the PREVENT IV trial, ⬃80% of cases were performed
with Guidant and only 20% with Ethicon, which reflected the
market share that those devices had at the time. Although
there may be device differences with regard to clinical out-
come, these remain undocumented to date because no clinical
trials have tested the devices head-to-head to determine their
relative benefit-to-risk profiles. The possibility that the out-
comes in PREVENT IV could be device related cannot be
ruled out at this time and should be considered in future
investigations.
In our meta-analysis, there were only three long-term
follow-up randomized controlled trials (RCTs) in which two
provided angiographic outcomes up to 9 months (both using
Guidant, now Maquet)
8,9
and one (using Ethicon, now Sorin)
provided with 5-year follow-up of clinical outcomes includ-
ing major adverse cardiac events (MACE).
4
The RCT that
used the Ethicon system showed no difference in MACE,
whereas the two studies, which used the Guidant system and
which incorporated angiographic follow– up, showed non-
significant trends in worse patency following EVH com-
pared with traditional open harvest. The fact that the subset
data of the recent PAS-Port proximal anastomosis system
trial primarily using Guidant also show worse vein-graft
patency with EVH is worrisome.
10
Again, further research
is required to confirm whether these worrisome trends are
device related. It raises the importance of considering
device-related differences in clinical outcomes in trials
where device-dependent procedures are studied and when
a variety of devices are available. Unfortunately, as with
the Lopez et al article,
1
randomization was not based on
harvest technique, and potential confounding variables
may not have been accounted for. This raises the impor-
tance of taking into consideration when designing random-
ized trials the possibility that clinical outcomes may be
device related, particularly when a variety of devices are
available.
Currently, the available evidence suggests that EVH
has significant short-term benefits in reducing infections and
operative complications while improving patient mobility and
satisfaction.
2,3
The study by Lopes et al
1
highlights the
potential risk on medium-term vein-graft patency, which
should be further defined by additional long-term prospective
RCTs. Therefore, until further RCTs with longer term angio-
graphic, clinical, and resource utilization follow-up are con-
ducted, which take into account device-specific consider-
ations, surgeons should weight the unequivocal short-term
patient benefits of EVH, particularly in patients with comor-
FIGURE 3. Death: EVH vs OVH.
TABLE 1. Quality of Graft-Related Outcomes
Quality of Graft Related Outcomes
n, Patients
(N, Studies)
EVH
(%)
OVH
(%) OR (95% CI)
Heterogeneity Pfor
Overall EffectPI
2
(%)
Grafts with ⬎50% stenosis at 3–6 mo 446 (3) 10.3 12.6 0.79 (0.44–1.45) 1.0 0 0.5
Myocardial infarction 3233 (11) 2.0 2.2 1.02 (0.58–1.78) 1.0 0 1.0
Reexploration for bleeding 132 (3) 0 0 0.91 (0.09–8.89) 0.9 0 0.9
Stroke, 30 d 341 (3) 1.2 1.2 1.01 (0.17–5.97) 0.9 0 1.0
Death 1615 (8) 1.4 2.2 0.71 (0.34–1.48) 1.0 0 0.4
Angina recurrence or reintervention for ischemia 1257 (5) 0.9 1.1 1.06 (0.38–2.96) 0.8 0 0.9
Adopted from Innovations. 2005;1:61–74.
Cheng et al Innovations • Volume 5, Number 2, March/April 2010
Copyright © 2010 by the International Society for Minimally Invasive Cardiothoracic Surgery72

bidities such as obesity, diabetes, or peripheral vascular
disease, against the potential risk of reduced graft patency.
3,11
REFERENCES
1. Lopes RD, Hafley GE, Allen KB, et al. Endoscopic versus open
vein-graft harvesting in coronary-artery bypass surgery. N Engl J Med.
2009;361:235–244.
2. Cheng D, Allen K, Cohn W, et al. Endoscopic vascular harvest in
coronary artery bypass grafting surgery: a meta-analysis of randomized
trials and controlled trials. Innovations. 2005;1:61–74.
3. Allen KB, Cheng D, Cohn W, et al. Endoscopic vascular harvest in
coronary bypass grafting surgery: a consensus statement of the Inter-
nationally Society of Minimally Invasive Cardiothoracic Surgery
(ISMICS). Innovations. 2005;1:51– 60.
4. Allen KB, Griffith GL, Heimansohn DA, et al. The influence of
endoscopic versus traditional saphenous vein harvest on event free
survival: five year follow-up of a prospective RCT. Heart Surg Forum.
2003;6:E143–E145.
5. Cheng D, Martin J, Ferdinand FD. Endoscopic versus open vein-graft
harvesting [letter]. N Engl J Med. 2009;361:1908 –1909.
6. Magee MJ, Alexander JH, Hafley G, et al. Coronary artery bypass graft
failure after on-pump and off-pump coronary artery bypass: findings
from PREVENT IV. Ann Thorac Surg. 2008;85:494 –500.
7. Brown EN, Kon ZN, Tran R, et al. Strategies to reduce intraluminal
clot formation in endoscopically harvested saphenous veins. J Thorac
Cardiovasc Surg. 2007;134:1259 –1265.
8. Yun KL, Wu Y, Aharonian V, et al. Randomized trial of endoscopic
versus open vein harvest for coronary artery bypass grafting: six-month
patency rates. J Thorac Cardiovasc Surg. 2005;129:496 –503.
9. Perrault LP, Jeanmart H, Bilodeaul L, et al. Early quantitative coronary
angiography of saphenous vein grafts for coronary artery bypass
grafting harvested by means of open versus endoscopic saphenectomy:
a prospective randomized trial. J Thorac Cardiovasc Surg. 2004;127:
1402–1407.
10. Puskas JD, Halkos ME, Balkhy H, et al. Evaluation of the PAS-Port
proximal anastomosis system in coronary artery bypass surgery (the
EPIC trial). J Thorac Cardiovasc Surg. 2009;138:125–132.
11. Allen KB, Heimansohn DA, Robison JR, et al. Risk factors for leg
wound complications following endoscopic versus traditional saphe-
nous vein harvesting. Heart Surg Forum. 2000;3:325–330.
Innovations • Volume 5, Number 2, March/April 2010 Editorial
Copyright © 2010 by the International Society for Minimally Invasive Cardiothoracic Surgery 73