Peripheral Arterial Bypass Research Articles

Nanomedicine-based strategies for the treatment of vein graft disease.

Autologous saphenous veins are the most frequently used conduits for coronary and peripheral artery bypass grafting. However, vein graft failure rates of 40-50% within 10 years of the implantation lead to poor long-term outcomes after bypass surgery. Currently, only a few therapeutic approaches for vein graft disease have been successfully translated into clinical practice. Building on the past two decades of advanced understanding of vein graft biology and the pathophysiological mechanisms underlying vein graft disease, nanomedicine-based strategies offer promising opportunities to address this important unmet clinical need. In this Review, we provide deep insight into the latest developments in the rational design and applications of nanoparticles that have the potential to target specific cells during various pathophysiological stages of vein graft disease, including early endothelial dysfunction, intermediate intimal hyperplasia and late-stage accelerated atherosclerosis. Additionally, we underscore the convergence of nanofabricated biomaterials, with a particular focus on hydrogels, external graft support devices and cell-based therapies, alongside bypass surgery to improve local delivery efficiency and therapeutic efficacy. Finally, we provide a specific discussion on the considerations, challenges and novel perspectives for the future clinical translation of nanomedicine for the treatment of vein graft disease.

Tissue‐engineered vascular grafts for cardiovascular disease management: Current strategies, challenges, and future perspectives

AbstractCardiovascular diseases are the leading cause of mortality which primarily occurs due to the blood vessel obstruction or narrowing. Surgical procedures such as, coronary artery and peripheral artery bypass grafting frequently require vascular grafts for long‐term revascularization. However, using autogenous vessels, such as the internal thoracic artery and saphenous vein, especially for vessels with diameters less than 6 mm, are associated with number of concerns due to limited availability, invasive retrieval procedures, and aptness. To overcome these limitations, the development of tissue‐engineered vascular grafts (TEVGs) is in continuous thrust. This review comprehensively provides the potentiality of a range of artificial and naturally occurring biopolymers and their fabrication techniques, cell sources and seeding techniques to realize the state‐of‐the‐art TEVGs. Moreover, this review article presents a synopsis of insights obtained from a variety of in vitro and in vivo studies, including human clinical trials. It underscores the need for further exploration into key areas such as optimal cell sources, seeding techniques, mechanical properties, hemodynamics, graft integration, the impact of patient conditions, optimum burst pressure, sufficient suture strength, hydrophilicity, biodegradability, and related factors. In summary, the review offers insights into the current strategies, challenges, and future perspectives of TEVG.

Safety and Feasibility of the BYCROSS® Atherectomy Device for the Treatment of Femoropopliteal Arterial Obstructions: Single-Center Short-Term Outcomes.

Background: Endovascular techniques have gained preference over peripheral arterial bypass surgery due to their minimally invasive nature; however, endovascular treatments often show limited efficacy in arterial segments with a high atherosclerotic load. The use of atherectomy devices enables the removal of calcified plaque material and may promote arterial wall remodeling. This study assessed the technical success, safety, and feasibility of the BYCROSS® atherectomy device in femoropopliteal lesions. Methods: This single-center, retrospective cohort study analyzed elective patients undergoing BYCROSS® atherectomy for chronic peripheral arterial disease from March 2022 to May 2023. Patient data, procedural details, and outcomes were retrospectively collected from electronic patient records. The primary performance endpoints of this study were technical success, complications, and patency rates. Primary safety endpoints included 30-day and short-term major adverse limb events (MALEs), major adverse cardiovascular events (MACEs), and mortality rate. Results: The study included 19 patients (median age, 71 years; 63% male) with Fontaine class IIb (26%), III (21%), or IV (53%). The BYCROSS® atherectomy device was used to treat 22 limbs in the femoropopliteal tract, of which 11 lesions (50%) were occlusions and 11 were stenoses, with a median length of 24 cm (interquartile range: 17-38). Technical success was achieved in all cases: 4.5% required atherectomy only, 50% required additional balloon angioplasties, 41% required balloon angioplasties and stenting, and 4.5% required segments only stenting. Additional treatment of below-the-knee arteries was performed in 12 patients. Procedurally related complications (not limited to the use of the BYCROSS® device) occurred in 23% of limbs, including distal embolization and laceration. At 30 days, mortality was 5%, the MACE rate was 11%, and the MALE rate was 0%. The observed mortality rate was not directly related to the procedure. Patency (<50% restenosis at duplex ultrasound) was 83% at 30 days. Conclusions: The use of the BYCROSS® atherectomy device for the treatment of femoropopliteal lesions appears to be safe and feasible, with high technical success and low MALE and MACE rates in a challenging population with long-segment femoropopliteal lesions. Long-term follow-up in larger patient series is needed to confirm these findings and to determine the durability of this technique.

Preoperative Chronic Steroid Use is Associated with Increased Incidence of Postoperative Mortality and Limb Loss following Peripheral Arterial Bypass Surgery for Chronic Limb Threatening Ischemia

Steroids are a commonly prescribed medication in the United States and have been associated with poor surgical and treatment outcomes. The objective of this study is to assess the relationship between chronic steroid use and surgical outcomes of femoropopliteal and femoral-distal bypasses in patients suffering from chronic limb threatening ischemia (CLTI). All adult patients undergoing femoropopliteal and femoral-distal bypasses with single segment autologous vein with an indication of CLTI in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) between 2012 and 2021 were stratified between chronic preoperative steroid use (Group I) and no preoperative use (Group II). Primary outcomes of the study included 30-day mortality, amputation, and combined outcome of mortality and/or limb loss. Secondary outcomes included specific bypass related, cardiovascular, respiratory and renal outcomes. A total of 8,324 patients (66.8% Male, 33.2% Females) underwent peripheral arterial bypass operations for the indication of chronic limb threatening ischemia. The median age was 68 years. Group I included 408 patients (4.9%) and Group II included 7,916 patients (95.1%). As compared to patients in Group II, those in Group I were more likely to be females (Group I: 42.2% vs. Group II: 32.8%), more likely to have co-existing COPD (Group I: 20.6% vs. Group II: 11.8%), less likely to be diabetic (Group I: 45.9% vs. Group II: 48%), less likely to be smokers (Group I: 30.6% vs. Group II: 45.4%) and more likely to be in ASA III or IV Classes (Group I: 98% vs. Group II: 96.5%) (all p<0.05). Primary outcomes were as follows: 30-day mortality (Group I: 3.3% vs. Group II: 1.7%), amputation (Group I: 5.9% vs. Group II: 2.8%), 30-day mortality and/or amputation (Group I: 9.1% vs. Group II: 4.5%) (all p<0.05). Among secondary outcomes, the following were found to be statistically significant: untreated loss of patency (Group I: 4.2% vs. Group II: 1.7%), significant bleeding (Group I: 26.2% Vs. Group II: 16.5%), wound infection/complication (Group I: 18.6% vs. Group II: 15%), and return to OR (Group I: 21.8% vs. Group II: 16.7%) (all p<0.05). As compared to patients with an indication of tissue loss (Rutherford's class V and VI), patients in Group I with an indication of rest pain (Rutherford's class IV) were more likely to experience 30-day mortality, major amputation and a composite of mortality and amputation. Risk adjusted analysis showed that chronic steroid use has a statistically significant effect on 30-day mortality (AOR 1.7, p=0.05), amputation (AOR 2.05, p<0.001), composite outcomes of mortality and amputation (AOR 1.959, p<0.001), untreated loss of patency (AOR 2.31, p=0.002), bleeding (AOR 1.33, p<0.011) and unplanned return to the OR (AOR 1.36, p=0.014). Chronic steroid use in patients undergoing femoropopliteal or femoral-distal bypass is associated with a higher risk of 30-day mortality, major amputation, readmission, bleeding, return to operating room, and untreated loss of patency. No significant difference in outcomes were appreciated in patients with chronic steroid use and with Rutherford class V or VI disease (tissue loss), suggesting that the effects of steroids may be less prominent in those with the most advanced peripheral arterial disease. These findings may aid physicians with risk stratification and preoperative discussions regarding open revascularization in patients receiving chronic steroid therapy. More studies including randomized trials are needed to guide perioperative management of steroids in this cohort.

Abstract 16822: Short Term Outcomes of Endovascular and Surgical Therapies for Critical Limb Ischemia: A Nationwide Analysis

Background: Endovascular therapy (EVT) and peripheral arterial bypass surgery (PABS) are established revascularization modalities in patients with critical limb ischemia (CLI). However, there is limited data regarding the short term outcomes of both procedures. Research question: Is there a difference between the in-hospital outcomes of EVT and PABS for patients with CLI? Methods: Patients with a diagnosis of CLI in the National Inpatient Sample database were reviewed from 2018 to 2020, and stratified into EVT and PABS groups. The primary outcome was in-hospital mortality and secondary outcomes included in-hospital complications. Multivariate logistic regression was used to adjust for confounders. Results: A total of 14,015 adult patients with CLI were identified (EVT:11,970; PABS: 2045). There was no significant difference in the in-hospital mortality between the two groups (adjusted odds ratio [aOR] 0.43, 95%CI 0.10-1.89 p=0.264). Furthermore, there was no significant difference in the rates of in-hospital complications: septic shock (aOR 0.67, 95%CI 0.18-2.36, p=0.529), acute stroke (aOR 0.54, 95%CI 0.12-2.36, p=0.413), cardiogenic shock (aOR 0.89, 95%CI 0.14-7.84, p=0.973), vascular complications, (aOR 1.66, 95%CI 0.67-4.11, p=0.278), compartment syndrome (aOR 0.24, 95%CI 0.03-1.90, p=0.177), and acute kidney injury (aOR 1.30, 95%CI 0.88-1.90, p=0.184) between the two groups fig 1 . In addition, the mean length of stay was comparable between the groups 5.95 vs 6.14 days (adjusted mean difference[aMD] 0.23, 95%CI -0.31-0.78, p=0.298. However, the mean hospital costs were significantly lower for the PABS group compared to the EVT group ($24,463 vs $29,400, aMD 0.87 $-3,684, 95%CI $-5,813-$-1,554, p=0.001). Conclusion: Endovascular therapy and bypass surgery for CLI had comparable in-hospital mortality and in-hospital complications, although, the hospital cost was significantly higher with endovascular therapy.

Patients living farther from a tertiary care center are more likely to undergo peripheral arterial bypass for acute and chronic limb-threatening ischemia

ObjectiveThe aim of this study was to assess the association between the proximity to the tertiary care hospital and the severity of peripheral arterial disease (PAD) at the time of lower extremity bypass (LEB) in a rural-urban mix region. MethodsPatients undergoing LEB from 2010 to 2020 at Penn State Milton S. Hershey Medical Center were reviewed and stratified into two study groups based on a median distance from hospital (ie, Group I: ≥34 miles and Group II: <34 miles). Patients’ demographic features, preoperative data including comorbidities, and medications were analyzed. A univariate analysis for the patient characteristics between the two study groups, along with evaluation of postoperative outcomes, and a multivariate predictive modeling to study the PAD stage as the indication of LEB was performed. A P-value of < .05 was set as a significant difference between the groups for all the analyses. ResultsThere were 175 patients (49.9%) in Group I and 176 patients (50.1%) in Group II with a mean age of 65 ± 11.92 years (median, 64.61 years). No significant difference was observed in gender (P = .530), age (P = .906), and functional status (P = .830) between study groups. It was observed that patients in Group I were more likely to be overweight or obese (71.3% vs 57%; P = .007) and had a prior history of myocardial infarction (24.3% vs 15.3%; P = .036) in comparison to Group II. No postoperative outcomes were found to be statistically different between the study groups. The multivariate analyses based on various confounders displayed that patients in Group I had 56% higher likelihood of LEB for chronic limb-threatening ischemia (adjusted odds ratio, 1.56; 95% confidence interval, 0.92-2.62; P = .042). Group I patients also had five times higher odds of LEB for acute limb ischemia (adjusted odds ratio, 5.07; 95% confidence interval, 1.42-18.13; P = .012) as compared with those in the Group II. ConclusionsPatients’ proximity to a major tertiary hospital may have implications on the disease progression for patients with PAD and could also be related to inadequate vascular services in primary and secondary hospitals. Lack of preventive care and disease management in regions afar from a tertiary hospital could be other implicating factors and highlights the need for outreach programs, along with distribution of vascular specialists, to reduce geographical disparities and ensure equity in access to care.

The Human Acellular Vessel (HAV) as a vascular conduit for infrainguinal arterial bypass.

Autologous vein is the optimal conduit for peripheral arterial bypass surgery, a standard recently highlighted by findings from the BEST-CLI trial. The Human Acellular Vessel is a novel biologic conduit produced using regenerative medicine technologies with structural and mechanical properties like a human blood vessel. Not yet approved by the United States Food and Drug Administration, the Human Acellular Vessel is being studied as an alternative bypass conduit in patients with peripheral arterial disease, vascular injury, and those in need of arteriovenous access for hemodialysis. This report describes and illustrates the technical aspects of intraoperative handling specific to the use of this new and innovative technology.

Peripheral Artery Bypass Graft for the Treatment of Ischemic Ulcer or Severe Pain of Hand in Connective Tissue Diseases.

Chronic ischemia of the hands and feet is a rare medical condition that requires surgical revascularization. In particular, digital ischemia resulting from connective tissue diseases (CTDs) is among the most important manifestations that negatively affect patients' quality of life. Here, we describe a bypass graft technique for treating digital ischemia. This study aimed to share the considerable benefits of surgical intervention for CTD and present a treatment algorithm. From 2009 to 2020, bypass graft surgery was performed on 10 patients with CTD to relieve their ischemic symptoms or ulceration. Preoperative angiography was performed, and blood distribution patterns were analyzed in detail. Based on the angiographic 4-level analysis, bypass graft surgeries were performed accordingly. The postoperative follow-up was 15 to 72 months. Pain in the hands that underwent the bypass graft surgery improved immediately after surgery. All ulcerations healed and the mean time recorded for ulceration healing was 45.7 days. Here, we propose an appropriate surgical treatment algorithm for managing CTD using arterial bypass graft surgery, and its positive long-term results demonstrate that it is an appropriate option for treating digital ischemia. In conclusion, strict measures with precise preoperative planning can provide satisfactory long-term results in patients with CTD.

Popliteal access for endovascular procedures in femoropopliteal artery occlusive disease.

Even though it has been reported that femoropopliteal artery endovascular revascularization is often performed with antegrade femoral artery interventions, which are technically relatively challenging, having the advantage of better control, it has also been reported that recanalization failure may occur in approximately 20% of patients and some materials have been developed for this reason. To evaluate the safety of retrograde popliteal artery intervention and our procedural success rate for symptomatic femoropopliteal artery occlusive disease. A total of 95 endovascular revascularization procedures were performed for treating symptomatic occlusive peripheral artery disease in the study period. Inclusion criteria were defined as patients who underwent endovascular revascularization procedures for symptomatic femoropopliteal artery occlusive disease. Patients who underwent a percutaneous endovascular procedure for iliac artery or below-knee arterial occlusive disease in the same session and patients who had previously undergone peripheral arterial bypass grafting or endovascular treatment for existing femoropopliteal artery disease were excluded. We evaluated 45 peripheral endovascular procedures performed on 39 patients with a mean age of 62.49 ±11.38 years in our hospital for chronic femoropopliteal artery occlusive disease. Twelve (26.7%) of the endovascular treatment procedures were performed with retrograde access through the popliteal artery (Group 2). In neither group were any complications of arterial rupture, distal embolism, early thrombosis, or pseudoaneurysms observed. We are of the opinion that the retrograde popliteal artery technique is an effective and safe intervention option in endovascular revascularization, particularly in the revascularization of the long segment and complex femoropopliteal artery occlusions.

Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass

ObjectiveThe human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years. MethodsIn the present report, we have described the 6-year results of a prospective, open-label, single-treatment arm, multicenter study. Patients with advanced peripheral artery disease (PAD) requiring above-the-knee femoropopliteal bypass surgery without available autologous graft options had undergone implantation with the HAV, a bioengineered human tissue replacement blood vessel. The patients who completed the 24-month primary portion of the study will be evaluated for ≤10 years after implantation. The present mid-term analysis was performed at the 6-year milestone (72 months) for patients followed up for 24 to 72 months. ResultsHAVs were implanted in 20 patients at three sites in Poland. Seven patients had discontinued the study before completing the 2-year portion of the study: four after graft occlusion had occurred and three who had died of causes deemed unrelated to the conduit, with the HAV reported as functional at their last visit. The primary results at 24 months showed primary, primary assisted, and secondary patency rates of 58%, 58%, and 74%, respectively. One vessel had developed a pseudoaneurysm deemed possibly iatrogenic; no other signs of structural failure were reported. No rejections or infections of the HAV occurred, and no patient had required amputation of the implanted limb. Of the 20 patients, 13 had completed the primary portion of the study; however, 1 patient had died shortly after 24 months. Of the remaining 12 patients, 3 died of causes unrelated to the HAV. One patient had required thrombectomy twice, with secondary patency achieved. No other interventions were recorded between 24 and 72 months. At 72 months, five patients had a patent HAV, including four patients with primary patency. For the entire study population from day 1 to month 72, the overall primary, primary assisted, and secondary patency rate estimated using Kaplan-Meier analysis was 44%, 45%, and 60% respectively, with censoring for death. No patient had experienced rejection or infection of the HAV, and no patient had required amputation of the implanted limb. ConclusionsThe infection-resistant, off-the-shelf HAV could provide a durable alternative conduit in the arterial circuit setting to restore the lower extremity blood supply in patients with PAD, with remodeling into the recipient’s own vessel over time. The HAV is currently being evaluated in seven clinical trials to treat PAD, vascular trauma, and as a hemodialysis access conduit.

Elevated Lipoprotein(a) levels increase Major Adverse Limb Event

Abstract Background High lipoprotein(a) levels are involved in the development of cardiovascular events, as particularly in myocardial infarction, stroke, and peripheral artery disease. Studies assessing prognostic values of lipoprotein(a) levels on the lower limbs are lacking. Purpose The aim of our study was to look after a relationship between the lipoprotein(a) level and the incidence of major adverse limb events (MALE) defined as major amputation, peripheral artery endovascular revascularization or peripheral artery bypass. Methods We included 16,513 patients with lipoprotein(a) measurements from our clinical information system. Normal lipoprotein(a) level was under 50 mg/dL and we defined: high lipoprotein(a) level as a lipoprotein(a) level between 50 mg/dL and 134 mg/dL and very high lipoprotein(a) level as a lipoprotein(a) levels over 134 mg/dL, i.e the 95th percentile in this cohort. Accelerated Failure Time models were used to assess the relationship between the lipoprotein(a) level and the incidence of MALE retrieved from the patient's electronic record during a median (interquartile range) follow-up of 3.74 (1.07; 7.30) years after the lipoprotein(a) measurement. MALE was defined as the occurrence of one of the following during follow-up: aortofemoral bypass surgery, limb bypass surgery, percutaneous transluminal angioplasty revascularization of the iliac, or infrainguinal arteries; or major amputation above the forefoot. Secondary outcomes included individual components of the primary Results Median lipoprotein(a) level was 24 mg/dL (10; 60), with 70.3%; 24.7%; and 5.0% within normal; high and very high lipoprotein(a) level respectively. The 1-year MALE incidence was 2.2% [95% CI: 1.96; 2.51]; 2.60% [95% CI: 2.09; 3.10] and 4.54% [95% CI: 3.08; 5.98] among the normal, high and very high lipoprotein(a) level patients respectively. High and very high lipoprotein(a) levels were independently associated with an increased risk of MALE (adjusted Accelerated Failure Time Exponential Estimate) 0.43 [95% CI: 0.24; 0.78], p=0.01 and 0.17 [95% CI: 0.07; 0.40], p&amp;lt;0.001, respectively. Conclusion In this large cohort of unselected real-world hospital inpatients, higher lipoprotein(a) levels were independently associated with an increased risk of MALE. Though, lipoprotein(a) measurement shall be taken into account not only to refine the cardiovascular risk but also the lower limb risk of revascularization or amputation. Funding Acknowledgement Type of funding sources: None.

Development and Preliminary Testing of Porcine Blood-Derived Endothelial-like Cells for Vascular Tissue Engineering Applications: Protocol Optimisation and Seeding of Decellularised Human Saphenous Veins.

Functional endothelial cells (EC) are a critical interface between blood vessels and the thrombogenic flowing blood. Disruption of this layer can lead to early thrombosis, inflammation, vessel restenosis, and, following coronary (CABG) or peripheral (PABG) artery bypass graft surgery, vein graft failure. Blood-derived ECs have shown potential for vascular tissue engineering applications. Here, we show the development and preliminary testing of a method for deriving porcine endothelial-like cells from blood obtained under clinical conditions for use in translational research. The derived cells show cobblestone morphology and expression of EC markers, similar to those seen in isolated porcine aortic ECs (PAEC), and when exposed to increasing shear stress, they remain viable and show mRNA expression of EC markers similar to PAEC. In addition, we confirm the feasibility of seeding endothelial-like cells onto a decellularised human vein scaffold with approximately 90% lumen coverage at lower passages, and show that increasing cell passage results in reduced endothelial coverage.

Graphene Oxide Coating Improves the Mechanical and Biological Properties of Decellularized Umbilical Cord Arteries.

The lack of small-diameter vascular grafts (inner diameter <5 mm) to substitute autologous grafts in arterial bypass surgeries has a massive impact on the prognosis and progression of cardiovascular diseases, the leading cause of death globally. Decellularized arteries from different sources have been proposed as an alternative, but their poor mechanical performance and high collagen exposure, which promotes platelet and bacteria adhesion, limit their successful application. In this study, these limitations were surpassed for decellularized umbilical cord arteries through the coating of their lumen with graphene oxide (GO). Placental and umbilical cord arteries were decellularized and perfused with a suspension of GO (C/O ratio 2:1) with ∼1.5 μm lateral size. A homogeneous GO coating that completely covered the collagen fibers was obtained for both arteries, with improvement of mechanical properties being achieved for umbilical cord decellularized arteries. GO coating increased the maximum force in 27%, the burst pressure in 29%, the strain in 25%, and the compliance in 10%, compared to umbilical cord decellularized arteries. The achieved theoretical burst pressure (1960 mmHg) and compliance (13.9%/100 mmHg) are similar to the human saphenous vein and mammary artery, respectively, which are used nowadays as the gold standard in coronary and peripheral artery bypass surgeries. Furthermore, and very importantly, coatings with GO did not compromise the endothelial cell adhesion but decreased platelet and bacteria adhesion to decellularized arteries, which will impact on the prevention of thrombosis and infection, until full re-endothetialization is achieved. Overall, our results reveal that GO coating has an effective role in the improvement of decellularized umbilical cord artery performance, which is a huge step toward their application as a small-diameter vascular graft.

The abdominal waist circumference and 4-year outcomes following peripheral bypass grafting.

Current literature evaluating the relationship between obesity, utilizing measures other than the Body Mass Index (BMI), and postoperative outcomes following vascular surgery are sparse. This study aimed to investigate any association between abdominal waist circumference (AWC) and waist-hip ratio (WHR) in relation to postoperative morbidity and mortality following peripheral artery bypass graft (PABG) surgery. AWC and hip circumference (HC) were measured from pre-intervention magnetic resonance (MR) and computed tomography (CT) scans of patients undergoing elective and nonelective PABG. The AWC and WHR were assessed in relation to: the need for higher level care (i.e. level 2/3), the duration of higher level care, postoperative limb ischemia, postoperative hospital stay, graft patency on discharge and 30 day readmission, using logistic and linear regression analysis. Mortality was assessed using cox-regression analysis with calculation of hazard ratios at 30 days and 4 years. In total, 177 patient images performed between January 2014 to January 2017 were analyzed. There were no significant intra-observer and interobserver differences in measurements of AWC and HC. Pre-intervention AWC was predictive of the need for higher level care following non-elective PABG (adjusted OR 1.1 [95% CI: 1.0-1.1, P=0.026]). An inverse relationship between AWC and mortality at 4 years was also observed (adjusted HR=0.9, 95% CI: 0.9-1.0, P=0.028). However, pre-intervention WHR failed to predict mortality and morbidity. AWC may potentially be a suitable risk stratification tool in patients undergoing non-elective PABG. The association of AWC with long-term mortality outcomes require further investigation so that suitable cut-off values may be determined.

Extracellular signal-regulated kinase inhibition prevents venous adaptive remodeling via regulation of Eph-B4.

Vein graft adaptation (VGA) is a process that vein as a vascular graft conduits in arterial reconstructive surgery; VGA can lead to postoperative vein graft stenosis (VGS) and complications after coronary artery bypass graft and other peripheral artery bypass surgeries. VGA is characterized by vein graft loss the venous features without exhibiting arterial features; furthermore, the activation of ERK inhibited the maintenance of venous properties of the vein graft. We hypothesized that ERK inhibition can affect vein VGS through regulating the expression of EphB4. Rat vein transplantation model was established using wild-type and EphB4+/- Sprague-Dawley rats. Hematoxylin-eosin, Masson, Verhoeff, actin staining, and immunohistochemistry were applied to observe the structure of the vein grafts. Vascular smooth muscle cells (VSMCs) were isolated from the vein and vein grafts. Western blotting was used to determine the expression of p-ERK1/2 and EphB4, and immunofluorescence was applied to detect the expression and location of EphB4. Cell wound scratch assay and CCK8 assay were used to determine the migration and proliferation of VSMCs. Real-time polymerase chain reaction was used to determine the mRNA expression of EphB4. Western blotting in vein sample and vein graft sample detected p-ERK1/2 and ERK1/2 expression in both EphB4+/+ and EphB4+/- rats. The expression of p-ERK was increased in vein graft compared to vein. Immunofluorescence in VSMCs form EphB4+/+ and EphB4+/- rats detected EphB4 expression in both cells, and the expression of EphB4 was increased in VSMCs form EphB4+/+ rats. SCH772984 reduces the proliferation and migration of VSMCs. Inhibition of ERK suppressed the increase of vein graft wall thickness, and the expression of collagen fibers, elastic fibers, and α-actin was decreased. Vein graft from EphB4+/- rats reduces the expression of EphB4, and SCH772984 suppressed the decrease of EphB4 in vivo. Vein graft from EphB4+/- rats increased the expression of EphB4, and SCH772984 suppressed the increase of EphB4 in vivo. The inhibition of ERK1/2 suppressed the process of VGS by decreasing the proliferation of VSMCs. The ERK-inhibitor SCH772984 suppressed the level of VGS by extending the time of EphB4 expression during the process of VGA, thus maintaining the venousization of vein graft. The mechanism may be that the inhibitor SCH772984 suppresses the level of VGS by extending the time of EphB4 expression during the process of VGA. Therefore, our research provides a new target of VGS treatment by inhibiting the expression of ERK1/2 through the process of VGA.

Preoperative status and in-hospital complications of coronary artery surgery in patients with pre-diabetes and type 2 diabetes mellitus

Abstract Aim To assess the preoperative status and the rate of in-hospital complications of coronary artery surgery (CABG) in patients with pre-diabetes compared to patients with type 2 diabetes mellitus (type 2 DM) and normoglycemia. Materials and methods 708 consecutive patients who underwent CABG between 2011 to 2012 were included in the study. All patients without positive history of diabetes underwent an oral glucose tolerance test (OGTT). The lab findings were interpreted in accordance with the recommended diagnostic criteria for diabetes and other glycemic disorders. Results DM screening before coronary artery bypass grafting allowed to diagnose type 2 diabetes in 8.9% (n=63) and prediabetes in 10.4% (n=74) of the study population. The preoperative screening increased the number of patients with DM from 15.2% (n=108) to 24.1% (n=171), and with prediabetes from 3.0% (n=21) to 13.4% (n=95). The total number of patients with carbohydrate metabolism disorders increased from 18.2% (n=129) to 37.5% (n=266). All patients were enrolled into 3 groups based on their glycemic status: Group 1 - without carbohydrate metabolism disorders (n=442), Group 2 - pre-diabetes (n=95), Group 3 - type 2 DM (n=171). The analysis of in-hospital complications reported that patients with pre-diabetes more often underwent urgent peripheral artery bypass compared to the other two groups (p1–2=0.002 vs. p1–3=0.023). The highest rate of wound complications was found in patients with pre-diabetes (p1–2=0.012). In addition, a clear trend towards the rate of other in-hospital complications of CABG in the groups with pre-diabetes and diabetes was found. The regression analysis shows that type 2 DM was associated with the total number of significant complications (odds ratio (OR) 1.731, 95% confidence interval (CI) 1.131–2.626, p=0.012), prolonged in-hospital stay (OR 2.2229, 95% CI 1.412- 3.519, p&amp;lt;0.001), the risk of urgent peripheral artery bypass (OR 1.638, 95% CI 1.009–15.213, p=0.020), multiple organ dysfunction syndrome (OR 2.911, 95% CI 1.072–7.901, p=0.039) and the need for hemostasis correction using the extracorporeal methods (OR 3.472, 95% CI 1.042–11.556, p=0.044). All the associations described above remained significant when pre-diabetes was introduced into the regression model and any carbohydrate metabolism disorder was considered as a potential predictor of in-hospital complications. Additionally, an association between pre-diabetes and diabetes and the risk of acute renal damage (OR 1.700, 95% CI 1.067–2.612, p=0.024) and wound complications (OR 1.547, 95% CI 1.073–2.231, p=0.019) was observed. Conclusion Pre-diabetes affects the in-hospital outcomes after CABG as well as diabetes mellitus. Our findings emphasizes the relevance of active preoperative detection of carbohydrate metabolism disorders. Funding Acknowledgement Type of funding source: None

Alternative Venous Conduits for Below Knee Bypass in the Absence of Ipsilateral Great Saphenous Vein

Vein is regarded superior to artificial graft in peripheral arterial bypass surgery. However, this option is often limited owing to previous use or removal of the ipsilateral greater saphenous vein (iGSV). In this case, the contralateral great saphenous vein (cGSV), the small saphenous vein (SSV), or arm veins (AV) are possible alternatives. Experience with all three grafts for below knee vein bypass is reported.

Immediate postoperative hyperglycemia after peripheral arterial bypass is associated with short-term and long-term poor outcomes

ObjectiveAlthough the impact of poorly controlled diabetes on surgical outcomes of patients undergoing lower extremity revascularization is well-known, it is not clear if immediate postoperative hyperglycemia (IPH) itself can be used as a surrogate for poor outcomes after peripheral arterial bypass. We sought to examine the effect of IPH in this patient population with its impact on short-term and long-term outcomes. MethodsRetrospective review was completed for 505 patients who underwent either suprainguinal bypass surgery or infrainguinal bypass surgery between July 2002 and April 2018 for the treatment of peripheral arterial disease. All patients were undergoing first-time open bypass grafting. Patients were stratified into those who were normoglycemic or hyperglycemic (glucose ≥ 140 mg/dL) within 24 hours after surgery. A comparative analysis was performed on comorbidities and outcomes. ResultsOf 505 patients who underwent bypass grafting, 255 patients (50.5%) were hyperglycemic. The mean age of patients was 63.5 ± 14.1 years. The median follow-up was 5.2 years (range, 0.0-15.2 years). The distribution of procedures was as follows: femoral to popliteal bypasses (29%), femoral to femoral bypasses (17%), femoral to tibial bypasses (12%), aortobifemoral bypasses (10%), iliofemoral bypasses (9%), and axillofemoral bypasses (7%). At 30 days, hyperglycemic patients had an increased incidence of limb loss (8.3% vs 4.0%) and myocardial infarction (4.8% vs 0.8%) and incurred higher costs of hospital stay ($27,701 vs $22,990) (all P < .05). At 10 years, these patients had a higher incidence of needing major amputations (15.4% vs 9.4%; P = .025). Hyperglycemia after infrainguinal bypass was associated with nearly twice the risk of limb loss at 5 years (hazard ratio, 1.91; P = .034). Among the cohort of patients who required major amputations, the time duration between index revascularization and amputation was significantly shorter as compared with normoglycemic patients (P = .003). ConclusionsIn this single-institution study with long-term follow-up, IPH was associated with increased rates of 30-day amputation and myocardial infarction, as well as an increased cost of hospital stay. In the long term, postoperative hyperglycemia was associated with greater major limb loss. Among the cohort of patients who required major amputations, the time period between revascularization and amputation was shorter for those patients who had IPH. IPH is an independent marker for poor outcomes after lower extremity revascularization procedures.

Alternative Venous Conduits for Below Knee Bypass in the Absence of Ipsilateral Great Saphenous Vein

Vein is regarded superior to artificial graft in peripheral arterial bypass surgery. However, this option is often limited owing to previous use or removal of the ipsilateral greater saphenous vein (iGSV). In this case, the contralateral great saphenous vein (cGSV), the small saphenous vein (SSV), or arm veins (AV) are possible alternatives. Experience with all three grafts for below knee vein bypass is reported. Consecutive patients treated at an academic tertiary referral centre between January 1998 and July 2018 using the cGSV, SSV, or AV as the main peripheral bypass graft were analysed. Study end points were primary patency, secondary patency, limb salvage, and survival. Over the observed time period, 2642 bypass operations for treatment of peripheral artery disease with below knee target arteries were performed at the authors' institution: 1937 procedures using the iGSV; 644 bypass procedures using the cGSV (n=186; 28.9%), SSV (n=101; 15.7%), or AV (n=357; 55.4%); and 61 procedures using a prosthetic graft. The median follow up period was 2.3 years (range 9 days-18.5 years). Thirty day mortality was 1.9% for the whole group and similar between the three groups. After five years, primary and secondary patency rates were comparable between the three groups. Secondary patency was 75% (95% confidence interval [CI] 66-83) in the cGSV and SSV groups, and 65% (95% CI 57-73) in the AV group (p=.47). Limb salvage and survival after five years were, respectively, 73% (95% CI 65-81) and 89% (95% CI 82-95) in the cGSV group, 79% (95% CI 69-89) and 87% (95% CI 79-95) in the SSV group, and 74% (95% CI 68-80) and 83% (77-89) in the AV group (p=.46). All three types of alternative autologous vein graft are equal regarding outcome parameters. Vascular surgeons should consider all autologous options if their preferred choice is not available.

The use of innominate artery cannulation for antegrade cerebral perfusion in aortic dissection

BackgroundDirect cannulation of the innominate artery for selective antegrade cerebral perfusion has been shown to be safe in elective proximal aortic reconstructions. We sought to evaluate the safety of this technique in acute aortic dissection.MethodsA multi-institutional retrospective review was undertaken of patients who underwent proximal aortic reconstruction for Stanford type A dissection between 2006 and 2016. Those patients who had direct innominate artery cannulation for selective antegrade cerebral perfusion were selected for analysis.ResultsSeventy-five patients underwent innominate artery cannulation for ACP for Stanford Type A Dissections. Isolated replacement of the ascending aorta was performed in 36 patients (48.0%), concomitant aortic root replacement was required in 35 patients (46.7%), of whom 7 had a valve-sparing aortic root replacement, ascending aorta and arch replacement was required in 4 patients (5%). Other procedures included frozen elephant trunk (n = 11 (14.7%)), coronary artery bypass grafting (n = 20 (26.7%)), and peripheral arterial bypass (n = 4 (5.3%)). Mean hypothermic circulatory arrest time was 19 ± 13 min. Thirty-day mortality was 14.7% (n = 11). Perioperative stroke occurred in 7 patients (9.3%).ConclusionsThis study is the first comprehensive review of direct innominate artery cannulation through median sternotomy for selective antegrade cerebral perfusion in aortic dissection. Our experience suggests that this strategy is a safe and effective technique compared to other reported methods of cannulation and cerebral protection for delivering selective antegrade cerebral perfusion in these cases.