Improved Graft Patency Rates Research Articles

Identification of a subpopulation of highly adherent endothelial cells for seeding synthetic vascular grafts

ObjectiveThere is an unmet clinical need for alternatives to autologous vessel grafts. Small-diameter (<6 mm) synthetic vascular grafts are not suitable because of unacceptable patency rates. This mainly occurs due to the lack of an endothelial cell (EC) monolayer to prevent platelet activation, thrombosis, and intimal hyperplasia. There are no reliable methods to endothelialize small-diameter grafts because most seeded ECs are lost due to exposure to fluid shear stress after implantation. The goal of this work is to determine if EC loss is a random process or if it is possible to predict which cells are more likely to remain adherent. MethodsIn initial studies, we sorted ECs using fluid shear stress and identified a subpopulation of ECs that are more likely to resist detachment. We use RNA sequencing to examine gene expression of adherent ECs compared with the whole population. Using fluorescence activated cell sorting, we sorted ECs based on the expression level of a candidate marker and studied their retention in small-diameter vascular grafts in vitro. ResultsTranscriptomic analysis revealed that fibronectin leucine rich transmembrane protein 2 (FLRT2), encoding protein FLRT2, is downregulated in the ECs that are more likely to resist detachment. When seeded onto vascular grafts and exposed to shear stress, ECs expressing low levels of FLRT2 exhibit 59.2% ± 7.4% retention compared with 24.5% ± 6.1% retention for the remainder of the EC population. ConclusionsFor the first time, we show EC detachment is not an entirely random process. This provides validation for the concept that we can seed small-diameter vascular grafts only with highly adherent ECs to maintain a stable endothelium and improve graft patency rates.

Secondary prevention after coronary artery bypass grafting: Anticoagulation and antiplatelet therapy is only one factor.

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel/ticagrelor/prasugrel does not lead to improved graft patency rates or clinical outcomes after coronary artery bypass grafting (CABG) over aspirin monotherapy, at least for on pump CABG. The protective effects of DAPT tended to be observed to be greater extent in patients undergoing off pump CABG. In general, the addition of the potent thienopyridines increased the risk of major bleeding, although the incidence of major bleeding is relatively low after either on pump or off pump surgical revascularization. There is a lack of evidence that anticoagulation post-CABG provides any protection against graft failure, but it may decrease the incidence of major adverse cardiovascular events. However, antiplatelet and anti thrombotic therapy after CABG is only one component of secondary prevention that needs to be taken into consideration when optimizing the long-term outcomes of patients after CABG.

Abstract 16197: Pedicled Vein Grafts in Coronary Surgery Exhibit Reduced Intimal Hyperplasia at 6 Months

Introduction: Less-than-optimal long-term patency of the saphenous vein is one of the main obstacles for the success of CABG. Harvesting saphenous veins including a pedicle of perivascular tissue has been proposed to improve graft patency rates and endothelial function. Hypothesis: We hypothesized that pedicled vein grafts would show less intimal hyperplasia at 6-month angiographic follow-up. Method: Sixty patients scheduled for first time elective on-pump CABG were randomized to conventional or pedicled vein harvesting. Exclusion criteria were insulin dependent diabetes mellitus, recent smoking or renal failure. Pedicled veins were harvested with perivascular tissue and conventional veins were skeletonized. All veins were distended manually to check for leakage and stored in heparinized blood and saline. At 6 months vein grafts were examined with Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT). Imaging analysis was performed by an external blinded Core-lab. Results: Fifty-four patients were available for follow-up. There were no significant differences in occlusion rates between the two groups. IVUS showed no significant difference in intima-media complex thickness (pedicled: n=28, mean 0.229 mm, SEM 0.011; conventional: n = 26, mean 0.235 mm, SEM 0.017). However, using OCT pedicled veins showed significantly less intimal thickness than conventional veins (pedicled: mean 0.270 mm, SEM 0.012; conventional: mean 0.358 mm, SEM 0.021; p&lt;0.001). In conventional veins higher perioperative flow was positively correlated to increased intimal thickness. Such a correlation was not found in pedicled grafts. The difference in response to flow was significant using a general linear model including an interaction term (adjusted R squared = 0.254, p&lt;0.018). Conclusion: Performing CABG using saphenous vein grafts harvested with a pedicle of perivascular tissue provides significantly less vein graft intimal hyperplasia at 6 months.

The Role of Oral Vitamin K Antagonists in the Outcome of Infrainguinal Bypass Procedures

We investigated the role of oral vitamin K antagonists (VKAs) in graft patency, limb salvage, major and minor bleeding rates in patients undergoing infrainguinal bypass surgery. Five randomized-controlled trials (RCTs; n = 3746 patients) comparing VKA versus non-VKA treatment outcomes in patients undergoing infrainguinal bypass surgery were analyzed. The VKA treatment was associated with improved graft patency rates when a vein graft was used (risk ratio [RR]: 0.74; P = .0004), while there was no difference with prosthetic grafts (RR: 1.07; P = .39). The VKA treatment was also associated with improved limb salvage rates (RR: 0.33; P = .0008). Major and minor bleeding complications were higher in the VKA group. In conclusion, VKA treatment is associated with improved graft patency and limb salvage rates when a vein graft is used at the price of an increased risk of bleeding. Due to the inconsistent results, further well-designed RCTs are needed.

Statins and noncardiac vascular disease

To discuss the beneficial effects of statin treatment in patients with peripheral arterial disease (PAD), abdominal aortic aneurysms (AAAs), atherosclerotic renal artery stenosis (ARAS) and carotid artery disease. Evidence suggests that statins may reduce the progression (or even reverse the development) of carotid artery stenosis and AAAs. Statins also improve several indices (e.g. serum creatinine) and preserve renal function in ARAS. In patients with PAD, statins are associated with improved claudication distance and time, reduced cardiovascular events, and improved graft patency rates should these patients undergo surgery. Finally, statins are associated with improved perioperative and long-term morbidity and mortality rates in all vascular patients whether they undergo surgery or endovascular procedures. Routine statin treatment should be implemented for all vascular patients to ensure a reduced progression of their disease, as well as a reduction in cardiovascular events.

Modified Prosthetic Vascular Conduits

Atherosclerosis in the form of peripheral arterial disease results in significant morbidity. Surgical treatment options for peripheral arterial disease include angioplasty, endarterectomy, and bypass grafting. For bypass grafting, vein remains the conduit of choice; however, poor quality and limited availability have led to the use of prosthetic materials. Unfortunately, because of a lack of endothelium and compliance mismatch, neointimal hyperplasia develops aggressively, resulting in high failure rates. To improve graft patency, investigators have developed surgical, chemical, and biological graft modifications. This review describes common prosthetic materials, as well as approaches currently in use and under investigation to modify and improve prosthetic conduits for bypass grafting in an effort to improve graft patency rates.

Improved graft patency rates and mid-term outcome of diabetic patients undergoing total arterial myocardial revascularization.

Objectives:Diabetes negatively affects the outcome of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary surgery. However, data are lacking with respect to the impact of arterial revascularization in the diabetic population.Methods:Between 1999 and 2003, 100 of 491 diabetics underwent coronary artery bypass graft surgery (CABG) with total arterial grafting (Group 1, G1); these patients were compared with 100 diabetics undergoing conventional CABG with saphenous veins (Group 2, G2), who were matched for Euroscore and other risk factors such as age, obesity, hypertension, left ventricular ejection fraction (LVEF), previous myocardial infarction and chronic obstructive pulmonary disease (COPD).Results:Both groups had a similar number of diseased coronary vessels (G1=2.6 vs G2= 2.7) and received a similar degree of myocardial revascularization (grafted vessels: G1=2.2 vs G2=2.4). Early outcome was comparable between the groups in terms of ventilatory support (G1=10.8±6 vs G2=10.4±5 hours), intensive care unit (ICU) stay (G1=24±12 vs G2=25±14 hours) and major post-operative complications such as atrial fibrillation (G1=26% vs G2=28%), peri-operative myocardial infarction (G1=1% vs G2=2%)and prolonged ventilatory support (G1=6% vs G2=5%). Hospital mortality was 2% in G1 and 3% in G2. Angiography was performed at a mean follow-up of 34 months in 65.9% and 71.1% of hospital survivors of G1 and G2 respectively: patients of G1 showed a significantly higher patency rate (G1=96% vs G2=83.6%, p=0.02). Additionally, patients of G1 showed a significantly lower incidence of recurrent myocardial ischemia (G1=7 pts. vs G2=18 pts., p=0.03), late myocardial infarction (G1=2 pts. vs G2=10 pts., p=0.03) and need for coronary reintervention (G1=1 pt. vs G2=12 pts, p=0.004).Conclusions:Total arterial grafting in diabetic patients significantly improved the benefits of coronary surgery providing at mid term a higher graft patency rate with a lower incidence of cardiac related events.

Improved Graft Patency Rates and Mid-Term Outcome of Diabetic Patients Undergoing Total Arterial Myocardial Revascularization

Improved Graft Patency Rates and Mid-Term Outcome of Diabetic Patients Undergoing Total Arterial Myocardial Revascularization

Effect of Warfarin Anticoagulation on Below-Knee Polytetrafluoroethylene Graft Patency

When polytetrafluoroethylene (PTFE) must be used for below-knee bypass to achieve limb salvage, effective anticoagulation with warfarin may improve graft survival. We analyzed our practice of routinely using oral anticoagulation to improve graft patency rates for PTFE grafts to below-knee popliteal and crural vessels in limb salvage procedures. We reviewed our established vascular database from February 1999 through April 2003 to identify those patients who required below-knee and tibial artery bypass with PTFE for critical limb ischemia. All patients were initiated on warfarin anticoagulation postoperatively, with an international normalized ratio (INR) of 2.0-3.0 considered therapeutic. All patients were discharged in the therapeutic range. Life-table analysis and Kaplan-Meier estimates were used to compare primary patency rates with regard to INR and position of distal anastomosis. Cox proportional hazards analysis was performed to compare the patency rates for grafts with therapeutic versus subtherapeutic anticoagulation while correcting for variability in distal runoff. Between February 1999 and April 2003, 74 patients (mean age, 69.2 years; 58% men) had 77 below-knee PTFE bypasses. Indications for operation included rest pain (43), ischemic ulcer (27), and gangrene (7). Patients presenting with occluded grafts more often had a subtherapeutic INR. Patients with a subtherapeutic INR (< or = 1.9) had a median primary graft patency of 6.8 months and those with a therapeutic INR (> or = 2.0) had a median primary graft patency of 29.9 months (p = 0.0007). Analysis by Cox proportional hazards model demonstrated a significantly better graft patency rate in patients with a therapeutic INR regardless of outflow vessel. The patency rates of PTFE grafts to infrageniculate vessels may be improved by effective anticoagulation with warfarin. This improved patency rate may also result in improved limb salvage and further support the use of PTFE grafts for critical limb ischemia when autogenous vein is not available. Predictably, the best results are seen with an INR therapeutic range of 2.0 to 3.0.

Is there a haemodynamic advantage associated with cuffed arterial anastomoses?

The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of PTFE grafts, results in an altered distribution of intimal hyperplasia and improved graft patency rates, especially for below-knee grafts. Numerical simulations have been conducted under physiological conditions to identify the flow behaviour in a typical cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flow patterns at the cuffed anastomosis are significantly different to those at the conventional end-to-side anastomosis. In the former case, the flow is characterised by an expansive, low momentum recirculation within the cuff. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act on the artery floor during systole. In contrast, a less disturbed flow prevails and the floor shear stress distribution is less adverse in the conventional model. In conclusion, aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The benefits associated with the cuffed grafts may be related primarily to the presence of venous material at the anastomosis. Therefore, caution is advised with regard to the use of PTFE grafts, pre-shaped to resemble a cuffed geometry.

Angioscopy.

Over the last year, research using flexible, ultrathin fiberoptics for vascular imaging (angioscopy) has continued to demonstrate its clinical potential. Vascular surgeons, thus far angioscopy's strongest advocates, have repeatedly demonstrated that the use of this procedure during peripheral vascular bypass surgery can improve graft patency rates. Although it is doubtful that angioscopy could ever replace angiography, the qualitative details of a vessel's surface disclosed by angioscopy are significant and not available by other means, including intravascular ultrasound. Investigators have used angioscopy to evaluate the burgeoning number of new, catheter-based vascular technologies. A combination of angioscopy and laser or atherectomy, however appealing, will require major technologic advances. One such advance has been the balloon-tipped catheter for blood-free imaging, which circumvents the need for potentially hazardous saline flush. Such an imaging system has provided new insights into the diseased myocardium of living patients.

Coronary Bypass Surgery for Stable Angina and Unstable Angina Pectoris

Large randomized trials have shown that surgical revascularization is more effective than medical therapy in relieving angina and improving exercise tolerance. Development of atherosclerosis in the vein grafts plus progression of disease in the native vessels, however, results in a return of angina in a substantial proportion of patients 5 to 10 years after the procedure. The better myocardial protection, more complete revascularization, and improved graft patency rates that have occurred in the last decade imply that survival following coronary artery bypass may be improved in a broader spectrum of coronary artery disease patients than documented in the randomized trials. Patients with unstable angina have higher operative mortality but clearly benefit symptomatically from revascularization. There is a need for randomized trials to compare the relative risks and benefits of angioplasty versus surgical revascularization.

Technical innovations in nonreversed translocated saphenous vein bypass.

Saphenous _vein grafts are usually used in the reversed or in situ position. Reversed vein grafts have the attributes of (1) not reqUiring valve disruption, (2) eliminating the risk of arteriovenous fiStulas, (3) transferability from one site to another incl\lding subfascial location remote from potential subcutaneous wound infection, and (4) reduced operative time. However, reversed vein grafts have the" limitations of (1) creating mismatch of graft-artery diameters at anastomoses; (2) providing reversed taper in the conduit; (3) retaining valve leaflets that, while reversed, may still" restrict blood flow; and (4) potential injury to endothelium by distending fluids or pressure as well as intermption of the vasa vasorum. '. In ~situ saphenous vein grafts have the advantages of(1) matching graft-artery diameter at anastomoses, (2) providing natural graft taper, (3) preserving venous endothelium, and (4) potentially allowing improved graft patency rates in distal anastomoses to small runoff vessels. However, in situ grafts suffer the disadvantages of (1) harboring residual competent valve leaflets that may restrict· blood flow or reduce graft patency, (2) not being movable, with resultant vulnerability to potential. subcutaneous wound infection, (3) the potential development of arteriovenous fistulas that may impair graft function or patency, and (4) requiring more operative time. In 1985 Batson and Sotturai described the method of nonreversed tran.slocated saphenous vein bypass (NTSVB), which combines some of the attributes of both reversed and in situ techniques. The procedure involves complete mobilization of the saphenous vein with ligation of all branches. The vein is not reversed and the proximal anastomosis is created to allow graft distension with heparinized ar-