Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery:
Endoscopic Vein-Graft Harvesting: Balancing the Risk and Benefits
Cheng, Davy C. H. MD*; Martin, Janet PharmD, MSc (HTA)*†; Ferdinand, Francis D. MD‡; Puskas, John D. MD§; Diegeler, Anno MD, PhD¶; Allen, Keith B. MD∥
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 ∥Department of Cardiothoracic Surgery, Mid America Heart Institute, St. Luke's Hospital, Kansas City, MO USA.
Accepted for publication January 11, 2010.
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: email@example.com.
In a retrospective post hoc analysis of the previously published PREVENT IV trial, Lopes et al1 found significantly higher rates of mortality, myocardial infarction, or repeat revascularization 3 years after primary coronary artery bypass grafting when an endoscopic 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 al1 In another publication comparing off-pump and on-pump coronary artery bypass grafting from the same dataset, Magee et al6 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 al1 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 imbalanced way between groups. More important, vein harvest technique was not the basis for randomization. Thus, unrecognized confounding variables could have been unaccounted for, such as significantly more clopidogrel use during follow-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 application for the dissection technique and in the use of CO2. Guidant (now Maquet Cardiovascular, LLC, Wayne, NJ) is a closed CO2 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, CO2 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 outcome, 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 outcomes 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 including 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 nonsignificant trends in worse patency following EVH compared 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 importance of taking into consideration when designing randomized 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 al1 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 angiographic, clinical, and resource utilization follow-up are conducted, which take into account device-specific considerations, surgeons should weight the unequivocal short-term patient benefits of EVH, particularly in patients with comorbidities such as obesity, diabetes, or peripheral vascular disease, against the potential risk of reduced graft patency.3,11
1.Lopes RD, Hafley GE, Allen KB, et al. Endoscopic versus open vein-graft harvesting in coronary-artery bypass surgery. N Engl J Med
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
3.Allen KB, Cheng D, Cohn W, et al. Endoscopic vascular harvest in coronary bypass grafting surgery: a consensus statement of the Internationally Society of Minimally Invasive Cardiothoracic Surgery (ISMICS). Innovations
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
5.Cheng D, Martin J, Ferdinand FD. Endoscopic versus open vein-graft harvesting [letter]. N Engl J Med
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
7.Brown EN, Kon ZN, Tran R, et al. Strategies to reduce intraluminal clot formation in endoscopically harvested saphenous veins. J Thorac Cardiovasc Surg
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
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
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
11.Allen KB, Heimansohn DA, Robison JR, et al. Risk factors for leg wound complications following endoscopic versus traditional saphenous vein harvesting. Heart Surg Forum
© 2010 Lippincott Williams & Wilkins, Inc.