Aortocoronary Saphenous Vein Bypass Grafts Research Articles

Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial

Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions. Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50-99% stenosis of a 2·25-4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224. Between Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63-1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached. In patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy. US Department of Veterans Affairs Cooperative Studies Program.

Potentially positive ageing-related variations of medial smooth muscle cells in the saphenous veins used as aortocoronary bypass grafts.

Currently, elderly people constitute a large proportion of patients undergoing coronary artery bypass grafting (CABG). Activated smooth muscle cells in the tunica media of saphenous vein (SV) grafts are thought to play a key role in the formation of neointima and development of occluding atherosclerotic plaques. The aim of this study was to identify ageing-related variations in the expression of the smooth muscle cells pro-teins that may impact on patency rate of the grafts and the CABG outcomes. The study involved 216 consecutive patients with the mean of 62.7 ± 8.4 years who underwent isolated CABG with at least one SV aortocoronary bypass graft. Expression of a-smooth muscle actin (a-SM actin), smooth muscle-myosin heavy chain (SM-MHC), calponin (CALP), cytokeratin 8 (CK-8), metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 and -3 (TIMP-2, TIMP-3) in the SV wall was assessed by immunohistochemistry and correlated with the age of patients. Calponin and a-SM actin were expressed in all studied SV transplants. SM-MHC immunoreactivity was observed in SV segments in 68.5% of patients, whereas MMP-2a and TIMPs expression was found in 75% of cases. In more than 50% of analyzed SV transplants, no expression of cytokeratin-8 was found. Moderate correlations between preexisting expressions of either cytoskeletal or hemostatic proteins in the tunica media of the SV grafts and the age of CABG patients were demonstrated. They were positive for SM-MHC (r = 0.494), CALP (r = 0.548), TIMP-2 (r = 0.413) and TIMP-3 (r = 0.406) whereas negative for CK-8 (r = -0.528) and MMP-2 (r = -0.417). Age-dependent decreases in the expression of MMP-2 and CK-8 accompanied by increases in expression of SM-MHC, TIMP-2 and TIMP-3 may promote SV graft patency and, thus, suggest a rationale for common use of SV grafts in the elderly.

Downregulation of the glucocorticoid-induced leucine zipper (GILZ) promotes vascular inflammation

ObjectiveGlucocorticoid-induced leucine zipper (GILZ) represents an anti-inflammatory mediator, whose downregulation has been described in various inflammatory processes. Aim of our study was to decipher the regulation of GILZ in vascular inflammation. Approach and resultsDegenerated aortocoronary saphenous vein bypass grafts (n = 15), which exhibited inflammatory cell activation as determined by enhanced monocyte chemoattractrant protein 1 (MCP-1, CCL2) and Toll-like receptor 2 (TLR2) expression, showed significantly diminished GILZ protein and mRNA levels compared to healthy veins (n = 23). GILZ was also downregulated in human umbilical vein endothelial cells (HUVEC) and macrophages upon treatment with the inflammatory cytokine TNF-α in a tristetraprolin (ZFP36, TTP)- and p38 MAPK-dependent manner. To assess the functional implications of decreased GILZ expression, we determined NF-κB activation after GILZ knockdown by siRNA and found that NF-κB activity and inflammatory gene expression were significantly enhanced. Importantly, ZFP36 is induced in TNF-α-activated HUVEC as well as in degenerated vein bypasses. When atheroprotective laminar shear stress was employed, GILZ levels in HUVEC increased on mRNA and protein level. Laminar flow also counteracted TNF-α-induced ZFP36 expression and GILZ downregulation. MAP kinase phosphatase 1 (MKP-1, DUSP1), a negative regulator of ZFP36 expression, was distinctly upregulated under laminar shear stress conditions and downregulated in degenerated vein bypasses. ConclusionOur data show a diminished expression of the anti-inflammatory mediator GILZ in the inflamed vasculature and indicate that GILZ downregulation requires the mRNA binding protein ZFP36. We suggest that reduced GILZ levels play a role in cardiovascular disease.

CD68 expression in aortocoronary saphenous vein bypass grafts

Atherosclerosis commonly affects the arteries harvested from patients 70 years of age or older. Saphenous vein grafts appear to maintain a higher patency rate after coronary artery bypass grafting in these subjects. The infiltration of macrophages is an early step in saphenous vein graft atherosclerosis; however, little is known regarding the underlying mechanisms of infiltration. The objective of the present report is to evaluate the presence of CD68-positive cells in the saphenous vein wall and correlate initial CD68-positive infiltration to specific clinical and biochemical parameters and the graft patency rate as estimated in patients undergoing coronary artery bypass grafting. A total of 309 patients were allocated into two groups: A1 patients, who were between 50 and 70 years of age, and A2 patients, who were 70 years or older at the time of vein harvesting. CD68 expression was evaluated by immunohistochemistry. There were no significant differences between A1 and A2 patients regarding macrophage expression within any of the analyzed vascular regions. Saphenous vein macrophages were never present in the tunica intima unless they were also expressed in the media or the adventitia. The patients with CD68-positive cells in the tunica intima had a significantly higher number of bypass stenoses when compared with the subjects who did not have CD68-positive cells in this layer. These findings suggest that the CD68-positive cells (those that have not yet developed into foam cells) present in the intima of saphenous vein grafts might serve as a very early marker of graft occlusion.

A simple method for eliminating strain on aortocoronary saphenous vein bypass grafts: The suspension of the right atrial appendage and plication of the right atrium

Strain on saphenous vein grafts may compromise the blood flow in the bypass graft. This may result in early postoperative ischemic complications as well as a decrease in early and late graft patency rates. In this article, we present two simple techniques to eliminate the excessive strain on the saphenous grafts when the patient is weaned off the cardiopulmonary bypass.

Forthcoming Issues

We sought to identify soluble vasoconstrictor substances that are released during stent implantation into saphenous vein aortocoronary bypass grafts.Atherosclerotic saphenous vein aortocoronary bypass grafts are particularly vulnerable to plaque rupture. Protection devices prevent particulate debris from being embolized. Additional soluble vasoconstrictor substances possibly also contribute to impaired microvascular perfusion.Peripheral venous blood (VB) and aspirate (AS) were obtained from 14 patients with a significant stenosis in a saphenous vein graft during stent implantation under protection with a distal balloon occlusion device. In five additional patients, arterial blood (AB) was also taken distal to the stented lesion before intervention. Vasomotor substances in VB, AB, and AS plasma were identified in a bioassay of rat mesenteric arteries with intact (+E) and denuded endothelium (−E). Vasoconstriction was normalized to that induced by potassium chloride depolarization (100%).Venous blood, AB, and AS plasma induced maximum vasoconstriction within six minutes. The AS plasma induced a vasoconstriction of 138 ± 13% (−E) and 87 ± 14% (+E); VB, of 70 ± 14% (−E) and 23 ± 4% (+E); and AB plasma obtained before intervention, of 49 ± 9% (−E) and 36 ± 8% (+E). The vasoconstrictor potency of AS plasma in endothelium-denuded vessels was related to the severity of anginal symptoms, angiographic stenosis severity, plaque volume, and plaque burden as determined by intravascular ultrasound. The AS plasma-induced vasoconstriction was largely attenuated by combined serotonin/5-hydroxytryptamine (5-HT)2A/2C- and 5-HT1A/1B-receptor blockade and eliminated by additional thromboxane A2 thromboxane-prostanoid (TP)-receptor blockade.Stent implantation releases, apart from and in addition to particulate debris, soluble vasoconstrictor substances that possibly contribute to impaired microvascular perfusion.

A completely fractured zotarolimus-eluting stent in an aortocoronary saphenous vein bypass graft

Drug-eluting stents (DES) have significantly improved the rate of target vessel revascularization in comparison with bare metal stents. DES fracture was not reported in multicenter randomized clinical trials, but several case reports of DES fracture have been published, mostly with sirolimus-eluting stents. DES fracture is associated with stent restenosis and thrombosis. We report a zotarolimus-eluting stent fracture in an aortocoronary saphenous vein graft (SVG) bypass. The patient presented with chest pain and a non-ST-elevation myocardial infarction. He underwent cardiac catheterization that showed a complete fracture of a zotarolimus-eluting stent in the ostium of a sequential SVG to the diagonal and obtuse coronary arteries. His management included coronary angioplasty and retrieval of the proximal fractured segment. We discuss the potential causes for this stent fracture and suggest caution when using a DES in an ostial location of a SVG bypass, especially in a highly mobile vessel.

The Role of Embolic Protection in Peripheral Arterial Atherectomy

Embolic protection devices were initially developed for use in the treatment of saphenous vein aortocoronary bypass graft stenosis as well as in carotid artery stenting because of the significant risk of atheroembolism and their use is well accepted. The use of these devices for lower-extremity arterial interventions is becoming well accepted because of the significant consequences of embolization in patients with limited circulatory runoff. This is especially true in the use of mechanical atherectomy devices for femoropopliteal arterial lesions.

Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation

Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion. To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action. Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B(2), and tumor necrosis factor (TNF)α was measured. The response of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21±5% and the aspirate plasma after stenting induced 95±8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B(2), and TNFα release into aspirate plasma increased by 1.9±0.2 μmol/L, 25.6±3.1 pg/mL, and 19.7±6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNFα did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries +E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside (+E, 3.3×10(-8); -E, 1.9×10(-8) mol/L) and verapamil (+E, 8.3×10(-8); -E, 7.8×10(-8) mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker. Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNFα somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium.

Pathophysiology of Aortocoronary Saphenous Vein Bypass Graft Disease

Aortocoronary saphenous vein bypass grafting relieves anginal pain in patients with coronary artery disease. However, its effectiveness is limited due to graft failure; the 10-year patency rate is 50%-60%. Early, 1-year and late graft failure may be due to thrombosis, fibrointimal hyperplasia and atherosclerosis, respectively. There is general agreement that vein graft atherosclerosis differs from arterial lesions in terms of temporal and histological changes. Vein graft atherosclerosis is more rapid, with diffuse concentric changes and a less noticeable fibrous cap, making venous plaques more vulnerable to rupture and subsequent thrombus formation. Despite progress in understanding the pathophysiology, some aspects of vein graft atherosclerosis need to be clarified. This review focuses on the pathophysiologic aspects of this widespread, costly and disabling disease, with emphasis on late graft occlusion and distinctions between arterial and venous atherosclerosis in terms of histology, pathophysiology and risk factors.

Radial Artery Versus Saphenous Vein Patency Randomized Trial

Graft patency is a fundamental predictor of long-term survival after coronary artery bypass surgery. Left and right internal thoracic artery (arterial) graft patency has been shown to be superior to that of saphenous vein grafts. More recently, the radial artery has been used as an aortocoronary graft, but little is known about the midterm and long-term patency of this conduit. We performed a single-center prospective randomized trial comparing the angiographic patency of radial artery and saphenous vein aortocoronary bypass grafts at 5 years after surgery. We enrolled 142 patients randomized at a single center to have either the radial artery or saphenous vein grafted to a stenosed branch of the native left circumflex coronary artery. The primary end point was angiographic graft patency 5 years postoperatively. At 5 years, 134 patients were alive and eligible for reangiography (5-year survival, 94.4%). Angiography was performed in 103 patients (77%); 98.3% of radial artery grafts and 86.4% of saphenous vein grafts were patent (P=0.04). Graft narrowing occurred in 10% of patent radial artery grafts and 23% of patent saphenous vein grafts (P=0.01). Radial artery aortocoronary bypass grafts to a stenosed branch of the circumflex coronary artery have an excellent patency rate at 5 years. This was significantly better than the patency rate for saphenous vein grafts and comparable to reported patency rates for internal thoracic artery grafts.

Invited Commentary

Invited Commentary

Expanding Use of Embolic Protection Devices

Embolic protection devices were initially developed for the treatment of saphenous vein aorto-coronary bypass graft stenosis due to the significant risk of atheroembolism, and their use is well accepted. The use of these devices for carotid arterial interventions is also well accepted due to the significant consequences of embolization in the cerebral circulation. The use of these devices is extending to other vascular beds to include the renal arteries and lower extremities. We review the basic principles of these devices and their uses in various vascular beds based on our own experience as well as that in the literature.

TRAIL Stimulates Proliferation of Vascular Smooth Muscle Cells via Activation of NF-κB and Induction of Insulin-like Growth Factor-1 Receptor

TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) is a multifunctional protein regulating homeostasis of the immune system, infection, autoimmune diseases, and apoptosis. However, its function in normal, nontransformed tissues is not clear. Here we show that TRAIL increases vascular smooth muscle cell (VSMC) proliferation in vitro, effects that can be blocked with neutralizing antibodies to TRAIL receptors DR4 and DcR1. In aortocoronary saphenous vein bypass grafts in vivo, TRAIL co-localizes with VSMC, proliferating cell nuclear antigen, and insulin-like growth factor type 1 receptor (IGF1R) expression but not active caspase-3. TRAIL is required for serum-inducible IGF1R expression, and antisense IGF1R inhibits TRAIL-induced VSMC proliferation. At 1 ng/ml, TRAIL stimulates IGF1R mRNA expression greater than insulin-like growth factor-1 and also activates the IGF1R promoter 7-fold. TRAIL-inducible IGF1R expression requires NF-kappaB activation. Consistent with this, ammonium pyrrolidine dithiocarbamate, a pharmacological inhibitor of NF-kappaB, blocks TRAIL-induced IGF1R expression, and p65 overexpression increases IGF1R protein levels. In addition, NF-kappaB binds a novel TRAIL-responsive element on the IGF1R promoter. Our findings suggest that the biological functions of TRAIL in VSMC extend beyond its role in promoting apoptosis. Thus, TRAIL may play an important role in atherosclerosis by regulating IGF1R expression in VSMC in an NF-kappaB-dependent manner.

Use of Drug‐Eluting Stents in Saphenous Vein Aortocoronary Bypass Graft Lesions: A Critical Appraisal

The use of drug-eluting stents (DES) in aortocoronary saphenous vein bypass grafts (SVGs) remains controversial. We reviewed 14 published studies that examined the outcomes after DES implantation in SVG lesions. All studies, except two, were retrospective, and reported follow-up for approximately 1 year or less. Ten of the 14 studies were single-center. Six studies (5 retrospective and 1 prospective), including a total of 711 patients, compared DES with bare metal stents: 2 studies included paclitaxel-eluting stents, 2 studies included sirolimus-eluting stents, and 2 studies included both. Four of five retrospective comparative studies showed lower incidence of major adverse cardiac events in the DES group during short-term follow-up (6-12 months), mainly due to a reduction in target vessel revascularization (TVR) (3 of 4 studies had high rates of follow-up angiography). In the only published prospective, randomized controlled study, patients receiving DES had lower incidence of TVR at 6 months, but during longer follow-up (median 32 months), they had similar incidence of TVR and higher mortality. A large, multicenter, randomized controlled clinical trial is needed to clarify the role of DES in the percutaneous treatment of SVG lesions.

Release of TNF-α during stent implantation into saphenous vein aortocoronary bypass grafts and its relation to plaque extrusion and restenosis

The reduction in plaque volume during stent implantation is associated with the release of particulate debris and plaque-derived soluble substances. We studied the potential release of the proinflammatory cytokine TNF-alpha into the coronary circulation and whether such release is related to the reduction in plaque volume and, possibly, a predictor for restenosis. In 18 male patients (n = 24 stents) with severe stenosis in a saphenous vein aortocoronary bypass graft (SVG), we used a distal balloon occlusion-aspiration device during stent implantation. The aspirate TNF-alpha levels were determined before and after stent implantation and related to the angiographic and intravascular ultrasound-assessed severity of stenosis and restenosis. We found that TNF-alpha is, indeed, released into the aspirate of stented SVG (9 +/- 1 and 28 +/- 3 pg/ml before and after stent implantation, respectively, P < 0.0001) and that such release is related to the reduction in plaque volume (r = 0.88, P < 0.0001) and associated with restenosis after 5 mo (r = 0.71, P = 0.001). The periprocedural release of plaque-derived TNF-alpha possibly represents the amount and activity of the atherosclerotic process and might be a predictor for restenosis.

Below Radar

Below Radar

Right Hemothorax from Leaking Aortocoronary Vein Graft Giant Aneurysm

Aneurysm of the saphenous vein aortocoronary bypass graft is a rare but potentially fatal complication of coronary artery bypass grafting (CABG). We report a case of an aneurysm of the saphenous vein aortocoronary bypass graft presented 7 years after redo CABG, with features of right atrial compression and right hemothorax. The patient was successfully treated surgically.

Intense Vasoconstriction in Response to Aspirate From Stented Saphenous Vein Aortocoronary Bypass Grafts

We sought to identify soluble vasoconstrictor substances that are released during stent implantation into saphenous vein aortocoronary bypass grafts. Atherosclerotic saphenous vein aortocoronary bypass grafts are particularly vulnerable to plaque rupture. Protection devices prevent particulate debris from being embolized. Additional soluble vasoconstrictor substances possibly also contribute to impaired microvascular perfusion. Peripheral venous blood (VB) and aspirate (AS) were obtained from 14 patients with a significant stenosis in a saphenous vein graft during stent implantation under protection with a distal balloon occlusion device. In five additional patients, arterial blood (AB) was also taken distal to the stented lesion before intervention. Vasomotor substances in VB, AB, and AS plasma were identified in a bioassay of rat mesenteric arteries with intact (+E) and denuded endothelium (-E). Vasoconstriction was normalized to that induced by potassium chloride depolarization (100%). Venous blood, AB, and AS plasma induced maximum vasoconstriction within six minutes. The AS plasma induced a vasoconstriction of 138 +/- 13% (-E) and 87 +/- 14% (+E); VB, of 70 +/- 14% (-E) and 23 +/- 4% (+E); and AB plasma obtained before intervention, of 49 +/- 9% (-E) and 36 +/- 8% (+E). The vasoconstrictor potency of AS plasma in endothelium-denuded vessels was related to the severity of anginal symptoms, angiographic stenosis severity, plaque volume, and plaque burden as determined by intravascular ultrasound. The AS plasma-induced vasoconstriction was largely attenuated by combined serotonin/5-hydroxytryptamine (5-HT)(2A/2C)- and 5-HT(1A/1B)-receptor blockade and eliminated by additional thromboxane A2 thromboxane-prostanoid (TP)-receptor blockade. Stent implantation releases, apart from and in addition to particulate debris, soluble vasoconstrictor substances that possibly contribute to impaired microvascular perfusion.

Evaluation of serum levels of solubilized adhesion molecules in patients with aortocoronary saphenous vein grafts

To assess the diagnostic importance of serum-solubilized adhesion molecules, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, sE-selectin and sP-selectin in aortocoronary saphenous vein graft disease. The study population was composed of two groups consisting of 41 patients with saphenous vein graft stenosis (stenosis group) and 43 patients without saphenous vein graft stenosis (no-stenosis group) based on the results of coronary angiography. All patients underwent coronary artery bypass graft operation involving the use of at least one saphenous vein graft for bypass. At the time of cardiac catheterization, it had been more than 1 year since the operation. Serum level of sP-selectin was significantly higher in the stenosis group than in the no-stenosis group (72.9+/-21.7 versus 48.7+/-18.6 ng/ml, P<0.001). No differences were found between the two groups with respect to serum levels of sE-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Multivariate analysis revealed that only serum levels of sP-selectin, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were independently correlated with the stenosis of saphenous vein grafts. A cutoff value of serum sP-selectin >57.5 ng/ml yields a specificity of 79.5%, a sensitivity of 73.3% and a positive predictive value of 80.5% for saphenous vein graft stenosis. In this study, sP-selectin level was found to be significantly higher in the group that had late aortocoronary saphenous vein bypass graft disease. This result suggests that platelet activation may play a causal role in late graft disease.