A New Current to The Armamentarium: Is the CHA2DS2-Vasc-HS Score Predictive of Low Left Internal Mammary Artery (LIMA) Flow in Patients Underwent Coronary Bypass Surgery?

INTRODUCTION: Left internal mammary artery (LIMA) grafts should be used in patients undergoing CABG. No other procedure results in patency equivalent to that of the left anterior descending coronary artery (LAD)-LIMA bypass graft. The CHA2DS2-Vasc-HS scoring system can be used to successfully predict CAD severity in stable CAD patients. We aimed to investigate the relationship between LIMA flow and the CHA2DS2-Vasc-HS score. METHODS: A total of 684 patients, who underwent CABG surgery, were included in this study. Previous history of bypass surgery, emergency operations, patients with Leriche syndrome and patients with severe obstructive pulmonary and subclavian artery disease were excluded from our study. Patients with a LIMA flow that was suitable for bypass grafting, as determined during the intraoperative evaluation, were included in the low LIMA flow group, and the CHA2DS2-Vasc-HS score was calculated for all patients. RESULTS: Patients in the low LIMA flow group (Group 1) were older. The CHA2DS2-Vasc-HS score (P < 0.001), presence of mild or moderate COPD (P = 0.022), number of severely diseased vessels (P = 0.036), and BMI (P < 0.001) were independent predictors of poor LIMA flow. The cutoff value of the CHA2DS2-VASc-HS score for the prediction of poor LIMA flow was >5.5, with a sensitivity of 92.9% and specificity of 83.4% (AUC: 0.938, 95% Cl: 0.906 - 0.970, P < 0.001). CONCLUSION: A preoperative high CHA2DS2-Vasc-HS score can be used to predict low intraoperative LIMA flow. The CHA2DS2-Vasc-HS score is an easy-to-use and reliable estimation method and can be used as an additional preoperative of LIMA flow in patients undergoing CABG due to severe CAD.

Resilience of the Internal Mammary Artery to Atherogenesis: Shifting From Risk to Resistance to Address Unmet Needs.

Fueled by the global surge in aging, atherosclerotic cardiovascular disease reached pandemic dimensions putting affected individuals at enhanced risk of myocardial infarction, stroke, and premature death. Atherosclerosis is a systemic disease driven by a wide spectrum of factors, including cholesterol, pressure, and disturbed flow. Although all arterial beds encounter a similar atherogenic milieu, the development of atheromatous lesions occurs discontinuously across the vascular system. Indeed, the internal mammary artery possesses unique biological properties that confer protection to intimal growth and atherosclerotic plaque formation, thus making it a conduit of choice for coronary artery bypass grafting. Its endothelium abundantly expresses nitric oxide synthase and shows accentuated nitric oxide release, while its vascular smooth muscle cells exhibit reduced tissue factor expression, high tPA (tissue-type plasminogen activator) production and blunted migration and proliferation, which may collectively mitigate intimal thickening and ultimately the evolution of atheromatous plaques. We aim here to provide insights into the anatomy, physiology, cellular, and molecular aspects of the internal mammary artery thereby elucidating its remarkable resistance to atherogenesis. We propose a change in perspective from risk to resilience to decipher mechanisms of atheroresistance and eventually identification of novel therapeutic targets presently not addressed by currently available remedies.

Angiographic Patency of Coronary Artery Bypass Conduits: A Network Meta-Analysis of Randomized Trials.

Background Several randomized trials have compared the patency of coronary artery bypass conduits. All of the published studies, however, have performed pairwise comparisons and a comprehensive evaluation of the patency rates of all conduits has yet to be published. We set out to investigate the angiographic patency rates of all conduits used in coronary bypass surgery by performing a network meta-analysis of the current available randomized evidence. Methods and Results A systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the conventionally harvested saphenous vein, the no-touch saphenous vein, the radial artery (RA), the right internal thoracic artery, or the gastroepiploic artery. The primary outcome was graft occlusion. A total of 4160 studies were retrieved of which 14 were included with 3651 grafts analyzed. The weighted mean angiographic follow-up was 5.1 years. Compared with the conventionally harvested saphenous vein, both the RA (incidence rate ratio [IRR] 0.54; 95% CI, 0.35-0.82) and the no-touch saphenous vein (IRR 0.55; 95% CI, 0.39-0.78) were associated with lower graft occlusion. The RA ranked as the best conduit (rank score for RA 0.87 versus 0.85 for no-touch saphenous vein, 0.23 for right internal thoracic artery, 0.29 for gastroepiploic artery, and 0.25 for the conventionally harvested saphenous vein). Conclusions Compared with the conventionally harvested saphenous vein, only the RA and no-touch saphenous vein grafts are associated with significantly lower graft occlusion rates. The RA ranks as the best conduit. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020164492.

The Growth Potential and Patency of Free Right Internal Thoracic Arteries Verified by Computed Tomography Angiography.

BACKGROUND: The use of the left internal thoracic artery (LITA) is the gold standard in coronary artery bypass graft surgery (CABG). Multiarterial grafting for CABG is being increasingly emphasized. This study aimed to resolve the utility of the right internal thoracic artery (RITA) for multiple CABG as "free" RITA and described new evidence. METHODS: One hundred sixty-three patients received solo CABG with bilateral internal thoracic arteries between 2005 and 2018. The RITA was used as in situ RITA, group A (n = 62), and the composite graft created with saphenous vein graft (SVG), group B (n = 101). The patency rate and graft size of the composite free RITA and SVG were examined by coronary computed tomography angiography. RESULTS: The average number of distal anastomoses per patient was 3.4 ± 1.0 in group A, and 4.2 ± 1.1 in group B (P < .001). The sequential grafting with free RITA was in 86 patients. The patency rate of both LITA and RITA was similar in both groups. In group B, 40 patients received late computed tomography angiography at a mean of 46 months (range, 17 to 175). The late patency rate was 95.1% in LITA and 96.9% in free RITA. The diameter of free RITA increased from 2.06 ± 0.34 mm to 2.37 ± 0.23 mm (P = .036); that of in situ LITA increased from 2.08 ± 0.51 mm to 2.44 ± 0.49 mm (P = .047); and that of composite SVG decreased from 4.1 ± 0.9 mm to 2.6 ± 0.7 mm (P < .001). CONCLUSIONS: Multiple bypass grafting can be sufficiently achieved with LITA and free RITA. The growth potential of free RITA and in situ LITA might play the important role of expected long-term patency.

Equivalent 10-year angiographic and long-term clinical outcomes with saphenous vein composite grafts and arterial composite grafts.

OBJECTIVES: We compared 10-year graft patency rates and long-term clinical outcomes after off-pump coronary artery bypass grafting using the saphenous vein composite grafts based on the left internal thoracic artery with those using total arterial composite grafts. METHODS: A total of 483 patients who underwent off-pump coronary artery bypass grafting using composite grafts based on the left internal thoracic artery were included. The saphenous vein was used as a second (connected to the left internal thoracic artery; n = 63) or a third (connected to the second arterial graft; n = 40) composite graft in 103 patients (SV group); total arterial composite grafting was performed in 380 patients (ART group). A propensity score-matched analysis was used to match the SV group to the ART group (n = 103 patients in each). The median follow-up duration was 128 (97-139) months. RESULTS: There were no differences in operative mortality and postoperative complication rates between the 2 matched groups. Propensity score-matched analyses showed no differences in the overall survival and freedom from cardiac death rates between the 2 groups (P = .369 and P = .206, respectively) up to 12 years after surgery. Freedom rates from reintervention and major adverse cardiac and cerebrovascular events were also similar between the 2 matched groups (P = .695 and P = .758, respectively) up to 12 years after surgery. Generalized mixed-effects models showed that the 2 matched groups demonstrated no differences in overall and composite graft patency rates during 10 years after surgery (P = .568 and P = .702, respectively). CONCLUSIONS: The saphenous vein composite grafts were equivalent to arterial composite grafts in terms of 10-year graft patency and long-term clinical outcomes.

Nonautologous Grafts in Coronary Artery Bypass Surgery: A Systematic Review.

BACKGROUND: Suitable autologous conduits may be lacking when performing coronary artery bypass grafting. The aim of this review is to determine the status of nonautologous grafts in coronary artery bypass grafting. METHODS: We conducted a literature search on MEDLINE All, Embase Classic, and Embase through Ovid from 1960 to April 2020. RESULTS: Of the 1579 records identified, 21 studies were included in the review. The following grafts were assessed for patency: 109 homologous saphenous veins (patency rates ranged from 66.7% at a median follow-up of 8.5 months to 0% at 6-12 months and 7-18 months, respectively), 29 expanded polytetrafluoroethylene grafts (from 80% at a median follow-up of 5 months to 14.3% at 45 months), 12 human umbilical veins (50% at a median follow-up of 6 months), 50 Bioflow bovine internal mammary arteries (from 15.8% to 0% at a mean follow-up of 9.5 months and 19 months, respectively), 39 Perma-Flow grafts (80% and 76.9% at 1-3 months and 12 months, respectively), 20 No-React bovine internal mammary arteries (57.1% at a median follow-up of 28 months and 23.1% at a mean follow-up of 7 months), 40 autologous venous endothelial cell-seeded expanded polytetrafluoroethylene grafts (94.7% and 81% at a mean follow-up of 27 months and 60 months, respectively), and 12 autologous venous endothelial cell-seeded cryopreserved homologous veins (83.3% at a mean follow-up of 8.5 months). CONCLUSIONS: The goal of an alternative conduit with patency and attributes that match those of autografts remains elusive. Autologous endothelial cell-seeded synthetic grafts have demonstrated promising results but require further investigation.

Computational fluid dynamics of internal mammary artery-left anterior descending artery anastomoses.

OBJECTIVES: The aim of this study was to elucidate the remodelling of the internal mammary artery (IMA)-left anterior descending artery anastomosis and compare 2 different anastomosis techniques (end-to-side versus side-to-side) using computational fluid dynamics. METHODS: This study included 9 patients. Computed tomography (CT) angiography was performed immediately after coronary artery bypass grafting (CABG) and at 3-6 months later. The computational fluid dynamics models were made using the CT data. The pulsatile 3-dimensional blood flow was achieved with the finite volume method to evaluate the postoperative morphological and haemodynamic changes at the anastomosis in each patient. Flow velocity distribution, wall shear stress (WSS) and its fluctuation oscillatory shear index were measured. RESULTS: No early or mid-term graft occlusion was observed in the study series. In the side-to-side anastomosis, pouch formation at the distal end of IMA caused a vortex flow with low WSS immediately after CABG. However, at 3-6 months after surgery, this pouch disappeared. As a result, the laminar straight flow with uniform WSS distribution was achieved inside the anastomosis. In the end-to-side anastomosis, the anastomosis shape was remodelled, resulting in a laminar flow pattern with uniform WSS distribution. A patchy high oscillatory shear index was detected at the IMA wall on the top of anastomosis in either anastomosis techniques immediately after the surgery, but it disappeared at 3-6 months after surgery. CONCLUSIONS: Regardless of the anastomosis technique used, a successful remodelling of the IMA-left anterior descending artery anastomosis shape was achieved a few months after surgery, resulting in a straightforward flow streamline, with uniform WSS distribution and minimal oscillatory shear index.

Can the Wall Shear Stress Values of Left Internal Mammary Artery Grafts during the Perioperative Period Reflect the One-Year Patency?

PURPOSE: The left internal mammary artery (LIMA) is the preferred graft for coronary artery bypass grafting, but the reasoning for LIMA occlusion is unclear. We sought to examine whether the wall shear stress (WSS) values of LIMA grafts during the perioperative period reflected the 1-year patency by using combining computational fluid dynamics (CFD) and coronary computed tomography angiography (CCTA) images. METHODS: CCTA was performed in 233 patients with LIMA graft perioperatively and 1 year later from October 2014 to May 2017. LIMA occlusion was detected in six patients at the 1-year follow-up CCTA. Two patients were excluded due to poor imaging quality. The remaining four patients were enrolled as occlusive (OCC) group, and eight patients with patent LIMA were recruited as patent (PAT) group. The WSS values of LIMA during perioperative period were calculated. LIMA graft was artificially divided into three even segments, proximal (pLIMA), middle (mLIMA) and distal (dLIMA) segments. The independent samples t-test and the Student-Newman-Keuls test were used. RESULTS: The WSS values of dLIMA were significantly higher in the PAT group than in the OCC group (4.43 vs. 2.56, p < 0.05). The WSS values of dLIMA in the PAT group were significantly higher than pLIMA, which was absent in the OCC group. CONCLUSIONS: A higher WSS value of the distal segment of LIMA and a higher WSS value of the distal segment compared with the proximal segment of LIMA in the PAT were observed; this tendency might be helpful in predicting the 1-year patency of LIMA.

Patient and haemodynamic factors affecting intraoperative graft flow during coronary artery bypass grafting: an observational pilot study.

Transit-time flow measurement (TTFM) is frequently used to evaluate intraoperative quality control during coronary artery bypass grafting (CABG) and has the ability to assess graft failure intraoperatively. However, perioperative factors affecting TTFM during CABG remain poorly understood. Patients who underwent CABG at a single institution between July 2016 and May 2018 were prospectively evaluated. TTFM and blood viscosity were measured haemodynamically, while mean flow (mL/min), pulsatility index, and diastolic filling were recorded. Arterial blood gas was analysed immediately after left internal mammary artery to left descending artery anastomosis and before sternal closure. Factors associated with TTFM were assessed using multiple linear regression analysis. We evaluated 57 of the 62 patients who underwent CABG during the study period, including 49 who underwent off-pump and 8 who underwent on-pump surgeries. Blood viscosity was not significantly associated with TTFM (p > 0.05). However, TTFM was significantly associated with body mass index, systolic blood pressure, and cardiac index (p < 0.05 each). In conclusion, maintaining the SBP in the perioperative period and maintaining the CI with inotropic support or fluid resuscitation can be important in improving blood flow of graft vessels after surgery.

Coronary-coronary bypass grafting: artery or vein?

BACKGROUND: The method of coronary-coronary bypass grafting was described in 1987 but has not been widely used, and there are only a few studies that report good short-term and mid-term results as well as some individual cases of long-term follow-up. In our medical institution, we carried out an analysis of the long-term results of coronary-coronary bypass grafting, which are presented in this study. METHODS: This was a retrospective single-center study on 95 patients who underwent coronary-coronary bypass grafting as a supplement to the standard coronary bypass grafting procedure. All patients underwent angiographic assessment of the coronary bypass grafts during the long-term follow-up period. The observation period was up to 123 months. Angiographic assessment of 109 coronary-coronary grafts was carried out. RESULTS: Twelve (7.6%) arterial and 11 (19.3%) venous conduits were found to be occluded, and 8 (10.3%) arterial and 10 (31.3%) venous coronary-coronary grafts were occluded during the observation period. CONCLUSION: Arterial coronary-coronary artery bypass grafting represents an alternative technique that allows complete myocardial revascularization.

Patency of conduits in patients who received internal mammary artery, radial artery and saphenous vein grafts.

BACKGROUND: Where each patient has all three conduits of internal mammary artery (IMA), saphenous vein graft (SVG) and radial artery (RA), most confounders affecting comparison between conduits can be mitigated. Additionally, since SVG progressively fails over time, restricting patient angiography to the late period only can mitigate against early SVG patency that may have occluded in the late period. METHODS: Research protocol driven conventional angiography was performed for patients with at least one of each conduit of IMA, RA and SVG and a minimum of 7 years postoperative. The primary analysis was perfect patency and secondary analysis was overall patency including angiographic evidence of conduit lumen irregularity from conduit atheroma. Multivariable generalized linear mixed model (GLMM) was used. Patency excluded occluded or "string sign" conduits. Perfect patency was present in patent grafts if there was no lumen irregularity. RESULTS: Fifty patients underwent coronary angiography at overall duration postoperative 13.1 ± 2.9, and age 74.3 ± 7.0 years. Of 196 anastomoses, IMA 62, RA 77 and SVG 57. Most IMA were to the left anterior descending territory and most RA and SVG were to the circumflex and right coronary territories. Perfect patency RA 92.2% was not different to IMA 96.8%, P = 0.309; and both were significantly better than SVG 17.5%, P < 0.001. Patency RA 93.5% was also not different to IMA 96.8%, P = 0.169, and both arterial conduits were significantly higher than SVG 82.5%, P = 0.029. Grafting according to coronary territory was not significant for perfect patency, P = 0.997 and patency P = 0.289. Coronary stenosis predicted perfect patency for RA only, P = 0.030 and for patency, RA, P = 0.007, and SVG, P = 0.032. When both arterial conduits were combined, perfect patency, P < 0.001, and patency, P = 0.017, were superior to SVG. CONCLUSIONS: All but one patent internal mammary artery or radial artery grafts had perfect patency and had superior perfect patency and overall patency compared to saphenous vein grafts.

Preventing treatment failures in coronary artery disease: what can we learn from the biology of in-stent restenosis, vein graft failure, and internal thoracic arteries?

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent restenosis (ISR) is a major drawback for intracoronary stenting, while graft failure is the limiting factor for coronary artery bypass graft surgery (CABG), especially using veins. Conversely, internal thoracic artery (ITA) is known to maintain long-term patency in CABG. Understanding the biology and pathophysiology of ISR and vein graft failure (VGF) and mechanisms behind ITA resistance to failure is crucial to combat these complications in CAD treatment. This review intends to provide an overview of the biological mechanisms underlying stent and VGF and of the potential therapeutic strategy to prevent these complications. Interestingly, despite being different modalities of revascularization, mechanisms of failure of stent and saphenous vein grafts are very similar from the biological standpoint.

Patency When Grafted to Coronary Stenosis More Than 50% in LIMA-RA-Y Grafts.

BACKGROUND: Recent coronary surgery practice is to graft arterial conduits to more severely stenosed coronary targets than in the past. We aimed to investigate postoperative arterial graft patency with native coronary stenosis at the time of surgery, using the left internal mammary artery and radial artery (RA) as a composite Y graft (LIMA-RA-Y). In the study timeframe, it was routine clinical practice to graft coronary arteries with >50% stenosis. METHODS: Of 464 patients previously reported 1996-1999, 346 who underwent LIMA-RA-Y at the Royal Melbourne Hospital, 76 had postoperative angiograms at the same institution. Each anastomosis was considered separately. For arterial grafts a "string sign" was analysed as being occluded. Predictor of patency was performed with a generalised linear mixed model (GLMM). RESULTS: Seventy-six (76) patients had postoperative angiograms at 5.8±5.4 years (range 0.23-19.4; interquartile range 1.7-10.0) years postoperative; with age at operation 62.5±10.7 years and 3.4±0.8 grafts per patient, 82% were male. Of 256 anastomoses, 230 were to coronary targets >50% stenosis. Overall patency was 84.0% (214/256). For coronary stenosis >50%, patency was 88% (201/230) and varied by coronary territory left anterior descending (LAD) 94% (87/93), circumflex 90% (71/79) and right coronary artery (RCA) 74% (43/58). Interaction for coronary territory was significant (p=0.022). Higher preoperative coronary stenosis predicted higher patency; with odds ratio for improved patency of 1.83 (95% CI 1.51, 2.22), p<0.001 for each 10% increase in stenosis. CONCLUSIONS: Late patency of composite arterial grafts is acceptable when grafted to coronary arteries of greater than 50% stenosis.

Does the use of an in situ or Y-configuration for bilateral internal thoracic arteries influence long-term survival, patency or repeat revascularization in coronary bypass surgery?

A best evidence topic was constructed according to a structured protocol. The question addressed was whether the configuration of bilateral internal thoracic arteries (BITAs) influences survival, patency or repeat revascularization in patients undergoing coronary artery bypass grafting. Five hundred and seventy-one papers were found using the reported searches, of which 8 represented the best evidence to answer the clinical question. One systematic review, 4 randomized trials and 3 observational studies were selected. The authors, date, journal, study type, population, main outcome measures and results are tabulated. All 4 prospective randomized trials found no significant difference in graft patency or mortality when comparing Y-graft and in situ configurations. Three of the 4 randomized trials found no difference in major adverse cardiovascular and cerebrovascular events or repeat revascularization at follow-up. An exception was Glineur et al. (Bilateral internal thoracic artery configuration for coronary artery bypass surgery: a prospective randomized trial. Circ Cardiovasc Interv 2016;9:7), who found that the Y-configuration resulted in lower rates of major adverse cardiovascular and cerebrovascular events. All 3 observational studies reviewed found no alteration in survival, cardiac events or repeat revascularization between in situ and Y-graft BITA configurations. One systematic review found similar outcomes with respect to mortality, cardiac events and repeat revascularization with in situ and composite BITA. In summary, existing literature demonstrates no difference in clinical outcomes between composite and in situ graft configurations. Furthermore, the configuration of BITA does not affect mortality, graft patency or repeat revascularization.

Long-Term Patency of Individual Segments of Different Internal Thoracic Artery Graft Configurations.

BACKGROUND: Internal thoracic artery (ITA) grafts are the most durable conduits available for coronary artery bypass grafting (CABG). However, little is known about long-term angiographic outcomes of ITA grafts used in different configurations and whether sequential or Y grafting compromises patency of the inflow ITA graft. METHODS: From January 1972 to August 2016, 60,500 patients underwent primary isolated CABG, of whom 326 received ITA grafts placed in sequential or Y configuration and were studied angiographically (median 4.8 years to first follow-up angiogram). Each sequential or Y segment was studied individually using a mixed-effects longitudinal model with the patient as the random effect. RESULTS: At 15 years, patency of the proximal ITA segment (n = 331) was 99%; of a sequential segment (n = 222), 97%; and of the segment beyond anastomosis of a Y graft (n = 109), 99%. Patency of the Y grafts (n = 109) was 92% at 5 years, 91% at 10 years, and 90% at 15 years. After adjusting for proximal stenosis and graft location, Y grafts were associated with greater occlusion than the inflow segment of ITA grafts (odds ratio; 51, 95% confidence interval, 6.1 to 422; p = 0.003) and of sequential grafts (odds ratio, 12; 95% confidence interval, 1.14 to 120; p = 0.04). CONCLUSIONS: Long-term patency of ITA grafts in sequential or Y configuration is similar qualitatively, but not quantitatively, to the known patency of single ITA-to-left anterior descending grafts. Sequential or Y grafting does not compromise patency of the inflow portion of an ITA graft. Y-graft patency is lower than sequential graft patency but is still better than known patency of saphenous vein grafts.

AFM Characterization of the Internal Mammary Artery as a Novel Target for Arterial Stiffening.

Using the atomic force microscopy- (AFM-) PeakForce quantitative nanomechanical mapping (QNM) technique, we have previously shown that the adventitia of the human internal mammary artery (IMA), tested under dehydrated conditions, is altered in patients with a high degree of arterial stiffening. In this study, we explored the nanoscale elastic modulus of the tunica media of the IMA in hydrated and dehydrated conditions from the patients with low and high arterial stiffening, as assessed in vivo by carotid-femoral pulse wave velocity (PWV). In both hydrated and dehydrated conditions, the medial layer was significantly stiffer in the high PWV group. The elastic modulus of the hydrated and dehydrated tunica media was significantly correlated with PWV. In the hydrated condition, the expression activity of certain small leucine-rich repeat proteoglycans (SLRPs), which are associated with arterial stiffening, were found to be negatively correlated to the medial elastic modulus. We also compared the data with our previous work on the IMA adventitia. We found that the hydrated media and dehydrated adventitia are both suitable for reflecting the development of arterial stiffening and SLRP expression. This comprehensive study of the nanomechanical properties integrated with the proteomic analysis in the IMAs demonstrates the possibility of linking structural properties and function in small biological samples with novel AFM methods. The IMA is a suitable target for predicting arterial stiffening.

Long-term graft patency after coronary artery bypass grafting: Effects of morphological and pathophysiological factors.

OBJECTIVE: The aim of the present study was to identify morphological and pathophysiological factors associated with long-term patency of grafts used in coronary artery bypass grafting (CABG). METHODS: A total of 127 patients who underwent CABG between 2000 and 2006 and presented for computed tomography evaluation of graft patency at 139.78±36.64 months post-CABG were analyzed. Patients received 340 grafts (2.68 grafts/patient), 399 distal anastomoses (3.14 anastomoses/ patient), 220 (55.14%) performed using arterial grafts, and 179 (44.86%) using saphenous vein grafts (SVGs). RESULTS: Graft patency varied according to vessel type and coronary territory. Overall graft patency was 90.16% for the left internal thoracic artery (LITA), 75.55% for the right internal thoracic artery (RITA), 79.25% for the radial artery (RA), and 74.3% for the SVG. The maximum patency rate was obtained with the RA (80.65%) for the right coronary territory, RITA (92.86%) for the anterolateral territory, and SVG (82.54%) for the circumflex territory. The LITA-left anterior descending artery graft occluded in 13 (7.93%) cases, 7 due to competitive flow. The influence of graft length on patency rates after indexing to height was not significant. The target vessel degree of stenosis influenced arterial graft patency rates with an occlusion odds ratio (OR) of 3.02 when anastomosed to target vessels with <90% stenosis. Target vessel caliber also influenced patency rates with occlusion ORs of 2.63 for SVGs and 2.31 for arterial grafts when anastomosed to ≤1.5 mm target vessels. CONCLUSION: Morphological parameters, such as graft type, target territory, target vessel caliber, and degree of stenosis, are important factors conditioning long-term graft patency.

Endothelial nitric oxide synthase enhancer AVE3085 reverses endothelial dysfunction induced by homocysteine in human internal mammary arteries.

Homocysteine (Hcy) is an independent risk factor for endothelial dysfunction in cardiovascular diseases. We hypothesized that the eNOS transcription enhancer AVE3085 may protect the endothelial function damaged by Hcy in the human internal mammary artery (IMA). Cumulative concentration-relaxation curves to acetylcholine (-10 to -4.5 log mol/L) or sodium nitroprusside were established in IMA from patients undergoing coronary artery surgery precontracted by U46619 (-8 log mol/L) in the absence/presence of Hcy (100 µmol/L) with/without AVE3085 (30 µmol/L) in vitro in a myograph. RT-qPCR and ELISA were used to quantify the mRNA and protein levels of eNOS. Colorimetric assay method was used to detect the production of nitric oxide (NO). Maximal relaxation was significantly attenuated by Hcy in human IMA. Co-incubation with AVE3085 protected endothelium from the impairment by Hcy and increased the production of NO. Exposure to Hcy for 24 h downregulated eNOS protein expression (P < 0.05) whereas it upregulated the expression of eNOS at mRNA levels (P < 0.05). The presence of AVE3085 in addition to Hcy significantly increased the eNOS protein (P < 0.05) and slightly decreased the mRNA level. The study for the first time revealed that in the human blood vessels (IMA) the clinically-relevant high concentration of Hcy directly causes endothelial dysfunction by downregulating eNOS protein that may be reversed by AVE3085. These findings not only provide new direction for protecting endothelium during coronary artery bypass grafting and improving long-term patency of the grafts, but also provide evidence to the use of eNOS enhancer in the patients with endothelial dysfunction in various pathological conditions.