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Prof. Nawwar Al-Attar
To achieve complete myocardial revascularisation, coronary artery bypass grafting offers the best option. Agressive insulinotherapy reduces the complication rate in the peri-operative period while use of both internal thoracic arteries gives excellent long term results and are especially adapted to the coronary tree. Vigourous secondary prevention must be provided regardless of the strategy with tight blood glucose control and modification of cardiovascular risk factors.
Cardiovascular disease is a major cause of death in diabetic patients (1), and more particularly in type 2 diabetic patients (2). Diabetic Mellitus (DM) is the seventh reported cause of death in the United States. Furthermore, diabetes has been shown to be an independent predictor of morbidity and/or mortality in patients admitted with myocardial infarction or acute ischemic syndromes (3). Likewise, revascularisation of diabetic patients poses a challenge as diabetes has been found to be a significant risk factor for poorer outcomes after both percutaneous coronary interventions (PCI) and surgical revascularisation (4,5). Indeed, diabetics tend to have more diffuse, multivessel coronary artery disease (CAD) with less run-off from distal involvement, smaller reference vessels, poorer collateral circulation, and more frequent left main stem disease (6,7). The GUSTO-II study demonstrated that once CAD develops, DM doubles the risk for acute coronary syndromes, with an additional doubling of risk for new events once these events occur (8). Recent progress in anaesthetic management, surgical procedures and postoperative care has helped to thoroughly reduce the operative risk of coronary artery surgery. Current diabetic population makes up approximately 30% of total coronary patient load. However, increased comorbidites associated with their coronary involvement and with the diffuse character of their vascular involvement, causes the surgical risk of diabetics to be considered higher to non diabetics’ both in regards to short and long term outcomes (9,10).
In a triple vessel diseased diabetic patient, greater mid and long term benefits have been demonstrated with surgical myocardial revascularisation strategy over percutaneous angioplasty both in terms of functional amelioration of quality of life and survival. Subgroup analysis from the BARI study has also shown that surgery was the choice revascularisation method in diabetic patients Its results were confirmed in subsequent clinical trials (11).
1 - The internal thoracic artery (ITA) is the best graft to use Choice of graft for myocardial revascularisation will influence the short and long term prognosis of the surgical procedure. The internal thoracic artery (ITA) is the first choice in diabetics as it :
2 - The ITA produces beneficial nitric oxide
The ITA is a natural nitric oxide (NO) producing graft. The bioavailability of NO is a key marker in vascular health since it causes vasodilation by activating guanylyl cyclase on subjacent vascular smooth muscle cells (12). Additionally, many clinical studies have found that endothelium-dependent vasodilation is abnormal in patients with type 1 or type 2 DM (13,14). Consequently, decreased levels of nitric oxide in diabetes may underlie its atherogenic predisposition. Considering its natural NO producing properties there is valuable gain of employing ITA, in diabetic patients.
3 - Using both ITAs improves prognosis
Furthermore an arterial myocardial revascularisation procedure using both ITAs improves immediate and long term prognosis of diabetic patients. The series of 1124 patients reported by Lytle showed a significant reduction in reoperation at 10 years whenever both ITAs were used (8% vs. 40%. Odds ratio: 0.27; 95% IC 0.19-.37). This difference is equally significant when only the subgroup of diabetic patients is included (15).
4 - Skeletonised harvesting of the ITA had demonstrated reduced infection
Skeletonisation of the ITA aims to preserve sternal blood flow by limiting tissue aggression and in turn reduces the incidence of sternal and wound complications. Skeletonisation allows to obtain longer graft length, larger graft calibre, and greater graft flow. Calafiore et al. performed 304 pedicled bilateral ITA anastomoses and then changed to skeletonised bilateral ITA and performed an additional 842 operations. They reported a decreased sternal wound infection rate in the skeletonised group (2.5% vs. 1.7%, P<0.005) whereas for diabetics the pedicled harvest caused a sternal infection rate of 10%.
On the other hand, angiographic patency was similar at one year while event-free survival was similar or superior with skeletonised grafts. However, with the skeletonised technique, an extra 4 cm was gained for each graft (16). Skeletonised harvesting has repeatedly demonstrated reduced infection rates when compared to traditional harvesting technique. A meta-analysis of studies comparing pedicled ITA harvest with skeletonised harvest identified a significantly increased level of free flow down skeletonised ITAs and good evidence for improved sternal vascularity (17).
5 - Operative risk is higher in diabetic patients Operative risk is considered significantly higher in diabetics because of the severity of coronary involvement, and also to diffuse lesions on fine arteries which are technically more difficult to graft. Comorbidities associated with diabetes increase the risk of infectious, neurological, pulmonary, vascular and renal complications and are equally a determinant post-operative prognostic factor.
Various studies have studied coronary surgery in the diabetic patient in order to assess morbidity and mortality, predictive factors of operative risk and potential long term benefit in terms of functional improvement after survival. The reported results vary but they all concord on a superior operative risk. In a series of 1,805 CABG patients in-hospital mortality rate was 4.99% in diabetics while it was only 0.36% in non-diabetics (P<0.0001) (18) . The progress accomplished in the fields of myocardial protection, microsurgical techniques, choice of grafts and postoperative care, have improved the prognosis of coronary surgery. Likewise, changes in the profile of candidates for surgery has been an added factor explaining the heterogeneity of the results described.
6 - Using two internal thoracic arteries is better Use of 2 internal thoracic arteries can thus improve results. In a recent series of 515 diabetic patients who underwent CABG, Lev-Ran et al confirmed the advantage of this technique. The results in patients bypassed with both ITAs as a Y graft was compared to revascularisation with 2 in-situ ITAs. The operative mortality was respectively in type 2 DM 2.4% and 1.9% and in type 1 DM 6.3% and 4.3%. The risk factors for mediastinal infection were respiratory insufficiency (OR:10) obesity (OR:7), reoperations (OR:22) and elevated creatinine levels (OR:8). Survival at 5 years was 82%. Absence of death from cardiac causes at 6.5 years was 95.6% and 87.6% (p=NS) and absence of iterative revascularisation was 91.5% and 92.7% (p=NS). The choice regarding which ITA and the configuration chosen for the ITAs did not influence the prognosis and gave satisfactory results.
7 - Pure ITA grafting can perform complet revascularisation.
In our own series, skeletonised harvesting of the ITA allowed complete revascularisation by Y grafting of the free right ITA to the in-situ left ITA in 98% of cases. Since skeletonised harvesting carries the additional benefit of obtaining long ITA, the distal segment of the left internal mammary artery (LIMA) was sectioned and reanastomosed to the in-situ left ITA permitting CABG of the diagonal, ramus intermedius or high marginal artery; or reanatomosed to the in-situ right ITA for CABG of a distal marginal or posterior descending artery. Segmentation of the left ITA thus offers an “additional” mammary graft for performing exclusive internal mammary artery (IMA) bypass grafting.
This technique carries the inherent advantage of enabling end to side coronary anastomosis which is easier to perform in an off-pump context. Another important advantage of pure ITA grafting is avoiding wound complications related to harvesting of venous or radial artery grafts, otherwise a source of associated morbidity. Moreover there is preservation of the venous reserve which is an important capital to protect in these multi-vascular patients.
8 - Insulinotherapy through electric syringes reduces risk of deep sternal infection
The risk of mediastinal infection following cardiac surgery is nevertheless known to be raised in poorly controlled diabetes. Furnary et al show that protocols achieving blood glucose control using continuous insulinotherapy through electric syringes in the perioperative period reduces infectious morbidity. On a prospective series of 2467 consecutive diabetic patient, a significant reduction (p=0.01) in the incidence of mediastinitis was observed in a group of patients treated with intravenous insulin as compared to the group treated with subcutaneous injections (2%). The multivariate analysis showed that IV insulin significantly reduced the risk of deep sternal infection (p=0.005, RR: 0.34) (22).
Despite a real risk related to bilateral harvesting of the ITAs, the incidence of sternal wound infection was similar in diabetics suffering a 1.1% deep infection rate compared to a 1.2% rate in non-diabetics in patients under 70 years old with skeletonised harvesting technique (23). 9 - Long-term outcome of diabetic patients is lower The long-term outcome of diabetic patients compared to non-diabetic patients following CABG is compromised with significant reduction in both 5-year (78% vs. 88%) and 10-year survival (50% vs. 71%; p<0.05) respectively (15). Factors include: 1) progression of native CAD, 2) left ventricular dysfunction from repeated silent ischemia and 3) added morbidity from co-existing diabetic complications.
CABG remains in view of all the above factors the gold standard for revascularisation strategy in diabetic patients. This is even more true for patients with multivessel disease.
Despite a higher operative risk as compared to non diabetic patients, surgery remains the only reliable alternative for complete myocardial revascularisation. The use of both ITAs associated with aggressive management of blood sugar in the peri-operative period allows the application of techniques adapted to the quality of the coronary tree and gives very satisfactory results. Regardless of the treatment strategy, vigorous secondary prevention must be provided with tight blood glucose control and modification of cardiovascular risk factors.
1) Harris MI, Hadden WC, Knowler WC, Bennett PH. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20-74 yr. Diabetes. 1987 Apr;36(4):523-34 2) Ramsey S, Summers KH, Leong SA, Birnbaum HG, Kemner JE, Greenberg P. Productivity and medical costs of diabetes in a large employer population. Diabetes Care. 2002 Jan;25(1):23-9 3) Malmberg K, Yusuf S, Gerstein HC, Brown J, Zhao F, Hunt D, Piegas L, Calvin J, Keltai M, Budaj A: Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS Registry. Circulation 102:1014-1019, 2000 4) Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH: Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol 40:418-423, 2002 5) Herlitz J, Wognsen G, Emanuelsson H, Haglid M, Karlson BW, Karlsson T, Albertsson P, Westberg S: Mortality and morbidity in diabetic and nondiabetic patients during a 2-year period after coronary artery bypass grafting. Diabetes Care 19:698-703, 1996 6) Moussa I., Moses J. and Wang X. et al. Why do the coronary vessels in diabetics appear to be angiographically small? J Am Coll Cardiol 1999;33: (Suppl A). 7) Abaci A. , Oguzhan A. and Kahraman S. et al. Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation 1999;99:2239-2242. 8) McGuire DK, Emanuelsson H, Granger CB, Magnus Ohman E, Moliterno DJ, White HD, Ardissino D, Box JW, Califf RM, Topol EJ. Influence of diabetes mellitus on clinical outcomes across the spectrum of acute coronary syndromes. Findings from the GUSTO-IIb study. GUSTO IIb Investigators. Eur Heart J. 2000;21:1750-8. 9) Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH. Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol. 2002;40(3):418-23. 10) Thourani VH, Weintraub WS, Stein B, Gebhart SS, Craver JM, Jones EL, Guyton RA. Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting. Ann Thorac Surg. 1999;67(4):1045-52. 11) Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. N Engl J Med. 1996;335(4):217-25. 12) Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993;329:2002-12. 13) Williams SB, Cusco JA, Roddy MA, Johnstone MT, Creager MA. Impaired nitric oxide-mediated vasodilation in patients with non- insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1996;27:567-74. 14) Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA. Impaired endothelium-dependent vasodilation in patients with insulin- dependent diabetes mellitus. Circulation. 1993;88:2510-6. 15) Lytle BW, Blackstone EH, Loop FD, Houghtaling PL, Arnold JH, Akhrass R, McCarthy PM, Cosgrove DM. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg. 1999;117(5):855-72. 16) Calafiore AM, Vitolla G, Iaco AL, Fino C, Di Giammarco G, Marchesani F, Teodori G, D'Addario G, Mazzei V. Bilateral internal mammary artery grafting: midterm results of pedicled vs. skeletonised conduits. Ann Thorac Surg 1999;67:1637–1642. 17) Athanasiou T, Crossman MC, Asimakopoulos G, Cherian A, Weerasinghe A, Glenville B, Casula R. Should the internal thoracic artery be skeletonised? [Review] [51 refs]. Ann Thorac Surg 2004;77:2238–2246. 18) Weintraub WS, Stein B, Kosinski A, Douglas JS Jr, Ghazzal ZM, Jones EL, Morris DC, Guyton RA, Craver JM, King SB 3rd. Outcome of coronary bypass surgery versus coronary angioplasty in diabetic patients with multivessel coronary artery disease. J Am Coll Cardiol. 1998;31(1):10-9. http://www.ncbi.nlm.nih.gov/pubmed/9426011 19) Lev-Ran O, Mohr R, Pevni D, Nesher N, Weissman Y, Loberman D, Uretzky G. Bilateral internal thoracic artery grafting in diabetic patients: short-term and long-term results of a 515-patient series. J Thorac Cardiovasc Surg. 2004;127(4):1145-50. 20) Ramadan R, Al Attar N, Nappi F, Raffoul R, Nataf P. Segmentation of the left internal thoracic artery: a new technique for maximal arterial grafting. Heart Surg Forum. 2003;6(6):E146-7. 21) Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;125(5):1007-21. 22) Bical OM, Khoury W, Fromes Y, Fischer M, Sousa UM, Boccara G, Deleuze PH. Routine use of bilateral skeletonised internal thoracic artery grafts in middle-aged diabetic patients. Ann Thorac Surg 2004;78:2050–2053.
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