Clinical implications
The success of CABG is dependent on long-term graft patency because vein graft occlusion is associated with a return of cardiac symptoms, an increase in myocardial infarction and death.[5, 26] Aspirin therapy reduces early vein graft thrombosis, but no treatment, with the exception of aggressive lipid lowering has been shown to attenuate the incidence of vein graft atherosclerosis and improve long-term graft patency.[4, 5, 27] The E2F antisense oligonucleotide, Edifoligide, reduced neointima formation in pre-clinical experiments, showed clinical efficacy in a first in human study, but failed to benefit graft patency in a phase 2 study.[28] A method for external vein graft stenting also reduced wall thickness in pigs, but proved impractical in patients.[24, 29] These failures prompted us to re-evaluate simple surgical techniques for vein graft harvesting that might improve patency. Such interventions do not increase operative costs and require no laboratory or manufacturing resources.
Souza, in a RCT with veins harvested using the pedicled technique reported a superior patency compared to veins harvested conventionally (90% versus 76% at a mean of 8.5 years post-grafting, p=0.01).[30] Assessment of a subset of vein grafts using IVUS (18 patients) showed less intimal hyperplasia and atherogenesis in grafts harvested with the surrounding pedicle (mean intimal thickness 0.42±0.07mm versus 0.53±0.08mm, p<0.01).[16] Similar excellent long-term results were reported by this group in a comparison of pedicled vein grafts with radial artery grafts.[22] Although the improved graft patency with the pedicled technique is encouraging the results derive from a single surgeon study and have not been confirmed by others.
Compared to low pressure distention of conventionally harvested veins, pedicle grafting requires more extensive dissection (which led to a number of protocol deviations) and increases the frequency of leg wound morbidity.[11] Our data demonstrate that it is possible to achieve similar benefits in terms of reduced wall thickening to pedicled grafts by using low pressure distension of conventionally harvested veins.

Strengths and limitations

Strengths include the inclusive eligibility criteria, with few patients being ineligible and minimisation of bias through concealed allocation. Personnel conducting the analyses, participants and staff not involved in the surgical procedure were blinded to the group allocation. The factorial study design allows two interventions to be evaluated in one study.
Limitations include that participants were recruited from a single centre, limiting the generalizability of the findings. There were protocol deviations, mostly in the pedicle harvest group, which reduces the power of the study to detect differences between the interventions. Some patients withdrew and did not attend the follow-up at 12 months, although the impact of this missing data was minimised by estimating the missing data using multiple imputation.
In conclusion, conventional saphenous vein graft preparation with low pressure distension and harvesting the vein with a surrounding pedicle yielded similar graft wall thickness after 12 months, but low pressure distention was associated with fewer short and long-term adverse events.

REFERENCES

1. The Society of Cardiothoracic Surgeons of Great Britain and Ireland National Adult Cardiac Surgical Database Report: Dendrite Clinical Systems, Oxforshire, United Kingdom;2003.
2. Goldman S, Zadina K, Moritz T, Ovitt T, Sethi G, Copeland JG, et al. Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study. J Am Coll Cardiol. 2004;44(11):2149-56. Epub 2004/12/08.
3. Sabik JF, 3rd, Lytle BW, Blackstone EH, Houghtaling PL, Cosgrove DM. Comparison of saphenous vein and internal thoracic artery graft patency by coronary system. Ann Thorac Surg. 2005;79(2):544-51; discussion -51. Epub 2005/02/01.
4. Rosenfeldt FL, He GW, Buxton BF, Angus JA. Pharmacology of coronary artery bypass grafts. Ann Thorac Surg. 1999;67(3):878-88. Epub 1999/04/24.
5. Guida G, Ward AO, Bruno VD, George SJ, Caputo M, Angelini GD, et al. Saphenous vein graft disease, pathophysiology, prevention, and treatment. A review of the literature. J Card Surg. 2020;35(6):1314-21. Epub 2020/05/01.
6. Angelini GD, Bryan AJ, Williams HM, Morgan R, Newby AC. Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts. J Thorac Cardiovasc Surg. 1990;99(3):433-9. Epub 1990/03/01.
7. Angelini GD, Passani SL, Breckenridge IM, Newby AC. Nature and Pressure-Dependence of Damage Induced by Distension of Human Saphenous-Vein Coronary-Artery Bypass Grafts. Cardiovasc Res. 1987;21(12):902-7.
8. Angelini GD, Breckenridge IM, Williams HM, Newby AC. A Surgical Preparative Technique for Coronary-Bypass Grafts of Human Saphenous-Vein Which Preserves Medial and Endothelial Functional Integrity. J Thorac Cardiov Sur. 1987;94(3):393-8.
9. Soyombo AA, Angelini GD, Bryan AJ, Newby AC. Surgical Preparation Induces Injury and Promotes Smooth-Muscle Cell-Proliferation in a Culture of Human Saphenous-Vein. Cardiovasc Res. 1993;27(11):1961-7.
10. Angelini GD, Bryan AJ, Williams HMJ, Soyombo AA, Williams A, Tovey J, et al. Time-Course of Medial and Intimal Thickening in Pig Venous Arterial Grafts - Relationship to Endothelial Injury and Cholesterol Accumulation. J Thorac Cardiov Sur. 1992;103(6):1093-103.
11. Souza DSR, Dashwood MR, Tsui JCS, Filbey D, Bodin L, Johansson B, et al. Improved patency in vein grafts harvested with surrounding tissue: Results of a randomized study using three harvesting techniques. Annals of Thoracic Surgery. 2002;73(4):1189-95.
12. Ahmed SR, Johansson BL, Karlsson MG, Souza DSR, Dashwood MR, Loesch A. Human saphenous vein and coronary bypass surgery: ultrastructural aspects of conventional and ”no-touch” vein graft preparations. Histol Histopathol. 2004;19(2):421-33.
13. Dashwood MR, Dooley A, Xu SW, Abraham DJ, Souza DSR. Does periadventitial fat-derived nitric oxide play a role in improved saphenous vein graft patency in patients undergoing coronary artery bypass surgery? J Vasc Res. 2007;44(3):175-81.
14. Dashwood MR, Anand R, Loesch A, Souza DSR. Hypothesis: A potential role for the vasa vasorum in the maintenance of vein graft patency. Angiology. 2004;55(4):385-95.
15. Hong MK, Mintz GS, Hong MK, Abizaid AS, Pichard AD, Satler LF, et al. Intravascular ultrasound assessment of the presence of vascular remodeling in diseased human saphenous vein bypass grafts. Am J Cardiol. 1999;84(9):992-8.
16. Johansson BL, Souza DS, Geijer H, Loesch A, Allared M, Wennerblom B. Improved long-term coronary bypass results with a new ”no touch” vein graft preparation technique: Preliminary results from an angiographic and IVUS follow-up study. Circulation. 2004;110(17):630-.
17. Willard JE, Netto D, Demian SE, Haagen DR, Brickner ME, Eichhorn EJ, et al. Intravascular ultrasound imaging of saphenous vein grafts in vitro: comparison with histologic and quantitative angiographic findings. J Am Coll Cardiol. 1992;19(4):759-64. Epub 1992/03/15.
18. Angelini GD, Culliford L, Smith DK, Hamilton MCK, Murphy GJ, Ascione R, et al. Effects of on-and off-pump coronary artery surgery on graft patency, survival, and health-related quality of life: Long-term follow-up of 2 randomized controlled trials. J Thorac Cardiov Sur. 2009;137(2):295-303.
19. Calafiore AM, Teodori G, Mezzetti A, Bosco G, Verna AM, Di Giammarco G, et al. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg. 1995;59(2):398-402. Epub 1995/02/01.
20. Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, et al. Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004;108(3):248-57. Epub 2004/03/20.
21. Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. A scoring method (ASEPSIS) for postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet. 1986;1(8476):311-3. Epub 1986/02/08.
22. Dreifaldt M, Mannion JD, Geijer H, Liden M, Bodin L, Souza D. The no-touch saphenous vein is an excellent alternative conduit to the radial artery 8 years after coronary artery bypass grafting: A randomized trial. J Thorac Cardiovasc Surg. 2019. Epub 2019/12/14.
23. Higuchi Y, Hirayama A, Shimizu M, Sakakibara T, Kodama K. Postoperative changes in angiographically normal saphenous vein coronary bypass grafts using intravascular ultrasound. Heart Vessels. 2002;17(2):57-60.
24. Murphy GJ, Newby AC, Jeremy JY, Baumbach A, Angelini GD. A randomized trial of an external Dacron sheath for the prevention of vein graft disease: The Extent study. J Thorac Cardiov Sur. 2007;134(2):504-5.
25. Weglarz P, Krejca M, Trusz-Gluza M, Bochenek K, Konarska-Kuszewska E, Szydlo K, et al. Neointima development in externally stented saphenous vein grafts. Postepy Kardiol Interwencyjnej. 2016;12(4):334-9. Epub 2016/12/17.
26. Harskamp RE, Williams JB, Hill RC, de Winter RJ, Alexander JH, Lopes RD. Saphenous vein graft failure and clinical outcomes: toward a surrogate end point in patients following coronary artery bypass surgery? Am Heart J. 2013;165(5):639-43. Epub 2013/04/30.
27. Campeau L, Hunninghake DB, Knatterud GL, White CW, Domanski M, Forman SA, et al. Aggressive cholesterol lowering delays saphenous vein graft atherosclerosis in women, the elderly, and patients with associated risk factors. NHLBI post coronary artery bypass graft clinical trial. Post CABG Trial Investigators. Circulation. 1999;99(25):3241-7. Epub 1999/06/29.
28. Alexander JH, Hafley G, Harrington R, Peterson ED, Ferguson TB, Lorenz TJ, et al. Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery - PREVENT IV: A randomized controlled trial. Jama-J Am Med Assoc. 2005;294(19):2446-54.
29. Angelini GD, Izzat MB, Bryan AJ, Newby AC. External stenting reduces early medial and neointimal thickening in a pig model of arteriovenous bypass grafting. J Thorac Cardiovasc Surg. 1996;112(1):79-84. Epub 1996/07/01.
30. Souza DSR, Johansson B, Bojo L, Karlsson R, Geijer H, Filbey D, et al. Harvesting the saphenous vein with surrounding tissue for CABG provides long-term graft patency comparable to the left internal thoracic artery: Results of a randomized longitudinal trial. J Thorac Cardiov Sur. 2006;132(2):373-U75.