A Large-Diameter Vascular Graft Replacing Animal-Derived Sealants With an Elastomeric Polymer.

INTRODUCTION: To assess the safety and efficacy of an experimental large-diameter vascular graft externally sealed with an elastomeric polymer when used as an interposition graft in the descending aorta of sheep. METHODS: The experimental vascular grafts as well as control gelatin sealed interposition grafts were inserted into the descending aorta of juvenile sheep. The grafts were assessed by time to hemostasis and blood loss during surgery and hematology and biochemistry panels at distinct time points. Magnetic resonance imaging (MRI) was performed at 3 and at 6 mo after surgery, after which the animals were euthanized and necropsies were carried out including macroscopic and microscopic examination of the grafts, anastomoses, and distal organs. RESULTS: All animals survived the study period. There was no perceivable difference in the surgical handling of the grafts. The median intraoperative blood loss was 27.5 mL (range 10.0-125.0 mL) in the experimental group and 50.0 mL (range 10.0-75.0 mL) in the control group. The median time to hemostasis was 5.0 min (range 2.0-16.0 min) minutes in the experimental group versus 6.0 min (range 4.0-6.0 min) in the control group. MRI showed normal flow and graft patency in both groups. Healing and perianastomotic endothelialization was similar in both groups. CONCLUSIONS: The experimental graft has a similar safety and performance profile and largely comparable necropsy results, in comparison to a commonly used prosthetic vascular graft, with the experimental grafts eliciting a nonadherent external fibrous capsule as the major difference compared to the control grafts that were incorporated into the periadventitia. Survival, hemostatic sealing, and hematologic and radiologic results were comparable between the study groups.

Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease.

BACKGROUND: Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. METHODS: We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. RESULTS: Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (ß = -0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. CONCLUSIONS: Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease.

Perioperative and long-term outcomes following aortic valve replacement: a population cohort study of 4124 consecutive patients.

OBJECTIVE: Because of increasing life expectancy, more patients require valve replacement for aortic stenosis. We aimed to determine perioperative and long-term outcomes, the factors associated with these and whether they have changed over time. METHODS: We undertook a retrospective cohort study of all 4124 patients, who underwent isolated, primary aortic valve replacement in Scotland between April 1996 and March 2009 inclusive. RESULTS: Annual operations increased by 68%, from 261 to 439. The overall risk of dying within 30 days, 5 years and 10 years was 3.4%, 19.9% and 38.5%, respectively. Over 10 years' follow-up, 4.4% underwent further valve surgery, 7.9% suffered a stroke and 5.3% a myocardial infarction. Age, renal impairment and urgency were predictors of both perioperative and long-term death. Perioperative death was associated with left-ventricular impairment and long-term death with respiratory disease, diabetes and deprivation. Over the 13 years, there was an increase in median age (from 66 to 69 years, p < 0.001), diabetes (from 1.9% to 12.6%, p < 0.001), hypertension (from 26.4% to 56.1%, p < 0.001), cerebrovascular disease (from 3.7% to 9.8%, p < 0.001), respiratory disease (from 6.6% to 9.7%, p = 0.020) and previous myocardial infarction (from 0.6% to 5.8%, p < 0.001), but the risk of perioperative death fell from 6.5% to 3.1% (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.83, 0.92, p < 0.001) per year. CONCLUSIONS: Patients undergoing aortic valve replacement have a poor risk profile. Over time, their numbers, age and co-morbidity have increased. In spite of these, there has been a significant reduction in the risk of perioperative death.

Reduced LDL-cholesterol levels in patients with coronary artery disease are paralleled by improved endothelial function: An observational study in patients from 2003 and 2007.

OBJECTIVE: Recent guidelines recommend more aggressive lipid-lowering in secondary prevention protocols. We examined whether this resulted in improved endothelial function. METHODS: We studied saphenous vein specimens of patients undergoing surgical coronary revascularisation in 2007 and compared results with those of patients examined in 2003. Endothelium-dependent vasodilation was assessed by relaxation to calcium ionophore A23187, and vascular superoxide production by lucigenin enhanced chemiluminescence. RESULTS: Statin dose increased from 26+/-16 mg/d in 2003 to 37+/-17 mg/d in 2007 (P<0.001), and total (4.0+/-0.9 mmol/L vs 4.8+/-1.0 mmol/L) and LDL-cholesterol levels (2.0+/-0.7 mmol/L vs 3.0+/-0.9 mmol/L) were lower in 2007 compared to 2003 (P<0.001; n=90 each). Endothelium-dependent vasodilation was greater in 2007 (44+/-15%) compared to 2003 (28+/-12%; n=36 each; P<0.001). Vascular superoxide derived from endothelial NO synthase (eNOS) was lower in 2007 than in 2003 (reduction by NG-nitro-L-arginine-methyl ester, 0.29+/-0.21 nmol/(mg min) vs 0.09+/-0.20 nmol/(mg min); P=0.002). In linear regression analysis, LDL-cholesterol levels have been shown to be the major determinant of endothelial function in the combined 2003 and 2007 cohort. CONCLUSION: Intensive lipid-lowering is associated with improved endothelial function and reduced superoxide production from eNOS. Further improvement in vascular function could be achieved by targeting other sources of superoxide including xanthine oxidase.

Cardiac magnetic resonance findings predict increased resource utilization in elective coronary artery bypass grafting.

Morbidity following CABG (coronary artery bypass grafting) is difficult to predict and leads to increased healthcare costs. We hypothesized that pre-operative CMR (cardiac magnetic resonance) findings would predict resource utilization in elective CABG. Over a 12-month period, patients requiring elective CABG were invited to undergo CMR 1 day prior to CABG. Gadolinium-enhanced CMR was performed using a trueFISP inversion recovery sequence on a 1.5 tesla scanner (Sonata; Siemens). Clinical data were collected prospectively. Admission costs were quantified based on standardized actual cost/day. Admission cost greater than the median was defined as 'increased'. Of 458 elective CABG cases, 45 (10%) underwent pre-operative CMR. Pre-operative characteristics [mean (S.D.) age, 64 (9) years, mortality (1%) and median (interquartile range) admission duration, 7 (6-8) days] were similar in patients who did or did not undergo CMR. In the patients undergoing CMR, eight (18%) and 11 (24%) patients had reduced LV (left ventricular) systolic function by CMR [LVEF (LV ejection fraction) <55%] and echocardiography respectively. LE (late enhancement) with gadolinium was detected in 17 (38%) patients. The average cost/day was $2723. The median (interquartile range) admission cost was $19059 ($10891-157917). CMR LVEF {OR (odds ratio), 0.93 [95% CI (confidence interval), 0.87-0.99]; P=0.03} and SV (stroke volume) index [OR 1.07 (95% CI, 1.00-1.14); P=0.02] predicted increased admission cost. CMR LVEF (P=0.08) and EuroScore tended to predict actual admission cost (P=0.09), but SV by CMR (P=0.16) and LV function by echocardiography (P=0.95) did not. In conclusion, in this exploratory investigation, pre-operative CMR findings predicted admission duration and increased admission cost in elective CABG surgery. The cost-effectiveness of CMR in risk stratification in elective CABG surgery merits prospective assessment.

Impact of off-pump coronary artery bypass surgery on systemic inflammation: current best available evidence.

The systemic inflammatory response after coronary artery bypass grafting using cardiopulmonary bypass (CPB) contributes substantially to postoperative organ dysfunction and coagulation disorders. Important features of this inflammatory reaction include the activation of complement and leukocytes, the release of proinflammatory cytokines, alterations in the metabolism of nitric oxide, and an increase in the production of oxygen-free radicals, which in some cases may lead to oxidant stress injury. Several strategies including the use of steroids, use of aprotinin, heparin-coated CPB circuits, and hemofiltration have been reported to reduce the inflammatory reaction induced by CPB and its consequences. A more radical and effective way of counteracting the effects of the inflammatory reaction and oxidative stress may be the omission of CPB itself. The development and application of off-pump coronary artery bypass (OPCAB) technology has largely been driven by this theme of avoiding systemic inflammatory reaction to decrease the incidence and/or severity of adverse outcomes. This review article discusses the influence of cardiopulmonary bypass on systemic inflammation and attempts to evaluate the current best available evidence on the impact of OPCAB on systemic inflammation.

Should vacuum-assisted closure therapy be routinely used for management of deep sternal wound infection after cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether vacuum-assisted closure (VAC) should be routinely used for management of deep sternal wound infection after cardiac surgery. Altogether, 198 papers were identified using the reported search. A further three relevant papers were identified by hand searching reference lists. Thirteen papers represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that VAC provides a viable and efficacious adjunctive method by which to treat postoperative wound infection after cardiac surgery. It is especially useful for managing sternal osteomyelitis in high-risk patients and is an attractive option as a first-line therapy in this group of patients. However, currently the evidence to endorse its routine use for management of deep sternal wound infection after cardiac surgery is weak. A randomised controlled trial comparing VAC therapy with the conventional treatment is mandatory to validate its safety, efficacy, and cost effectiveness as a routine first-line therapy for management of deep sternal wound infection after cardiac surgery.

Moderate ischemic mitral regurgitation: to treat or not to treat?

There is consensus of opinion that patients with moderately severe to severe (grade 3+ or 4+) ischemic mitral regurgitation (IMR) should undergo mitral valve surgery at the time of coronary artery bypass grafting (CABG), while trace to mild (grade 1+) IMR can probably be left alone. However, the management of moderate (grade 2+) IMR continues to be a subject of constant debate and controversy. In particular, as techniques of valvular repair continue to be refined; many surgeons have advocated mitral valve repair and concomitant CABG for these patients. Others, however, have continued to treat these patients with revascularization alone and close postoperative observation of the mitral valve. In their opinion, degree of concomitant mitral valve dysfunction in this group of patients does not justify the increased operative risks associated with simultaneous mitral valve correction. We are currently practicing in an era of evidence-based medicine (EBM) in which clinical decision-making has to be guided by current best available evidence from scientific, clinical studies. This review article attempts to tackle this controversial issue and find the best approach of dealing with moderate IMR at the time of CABG by evaluating current best available evidence.

Outcomes of off-pump coronary artery bypass surgery: current best available evidence.

In the last decade, there has been an upsurge of interest in less invasive alternatives to standard coronary artery bypass grafting performed with cardiopulmonary bypass. Off-pump coronary artery bypass grafting is one such less invasive alternative that has seen a resurgence in the last 10 years. The development and application of the technology required has largely been driven by the hope of decreasing the incidence and/or severity of the adverse outcomes associated with cardiopulmonary bypass, the idea being to perform coronary artery bypass grafting without cardiopulmonary bypass. A number of studies that have reported the safety and efficacy of off-pump coronary artery bypass surgery have provided the impetus for the development of this technology over the last decade. Despite tremendous enthusiasm on the part of cardiac surgeons, patients, industry and the media, skepticism still exists about the actual impact of off-pump coronary artery bypass grafting on the outcomes after coronary artery bypass grafting. The only means of countering this skepticism is to validate the safety and efficacy of off-pump coronary artery bypass surgery through the explicit and conscientious assessment of current best evidence. This review article attempts to evaluate the current best evidence available from randomized, controlled trials in order to compare the outcomes of off-pump coronary artery bypass surgery and conventional coronary artery bypass grafting.

Safety of drug eluting stents: current concerns and controversies.

Coronary artery stenting is currently the most frequently performed percutaneous coronary intervention for the treatment of coronary artery disease. Recently, drug- eluting stents, loaded with anti-inflammatory, anti-migratory, anti-proliferative or pro-healing drugs, have revolutionized the management of coronary artery disease by markedly reducing in-stent restenosis. Despite the excellent short- and mid-term results of randomized controlled trials observed with drug-eluting stents, there remain a number of unresolved issues and valid concerns about long-term safety and efficacy of this revolutionary technology. Important safety issues such as thrombosis, late stent malapposition, aneurysm formation, edge effect, late inflammation due to choice of polymer used to bind the drug, the release of toxins, and potential interactions with brachytherapy and drugs have not been completely addressed. This review article evaluates current available scientific evidence on the various safety issues related to the use of drug-eluting stents.

Low-density lipoprotein cholesterol determines oxidative stress and endothelial dysfunction in saphenous veins from patients with coronary artery disease.

OBJECTIVE: There is evidence for a relationship between endothelial dysfunction and cardiovascular disease, but a causative role for oxidative stress remains to be determined. METHODS AND RESULTS: We studied 188 patients with severe coronary artery disease (CAD), of whom 51 were age and sex matched with 51 healthy controls undergoing varicose vein surgery. Relaxation of saphenous vein to calcium ionophore, apocynin, and allopurinol was studied together with the markers of oxidative stress, total antioxidant capacity and reduced/oxidized glutathione ratio. Vascular superoxide levels were measured using lucigenin chemiluminescence and hydroethidine. Relaxation to calcium ionophore was decreased in CAD compared with control patients (maximum relaxation 26+/-2% versus 60+/-1%; P<0.001). Total superoxide production was increased (0.89+/-0.09 versus 0.56+/-0.06 nmol/mg per min; P=0.008), whereas superoxide inhibition with apocynin or allopurinol had a greater effect on vasorelaxation in CAD patients. Low-density lipoprotein (LDL) cholesterol predicted relaxation to calcium ionophore (P<0.001) and oxidative stress markers (P<0.001) in CAD patients. CONCLUSIONS: Endothelial dysfunction is associated with raised levels of superoxide and biomarkers of oxidative stress in saphenous veins from CAD patients. LDL cholesterol is a major determinant of endothelial dysfunction and oxidative stress in these patients. These results support intensive LDL cholesterol-lowering therapy as suggested by recent clinical trials.

Duroflo II heparin bonding does not attenuate cytokine release or improve pulmonary function.

BACKGROUND: Comparison of the cytokine generation and leukocyte activation properties of Duroflo II heparin bonded bypass circuit (Baxter Healthcare Corp, Compton, UK) and the conventional cardiopulmonary bypass circuit. Attempt to correlate these to pulmonary dysfunction postoperatively. METHODS: Forty patients undergoing elective, isolated coronary artery bypass grafting were randomly allocated to have either plain extracorporeal circuits (group C) or heparin bonded extracorporeal circuits (group H). Full systemic heparinization was used in all patients. The inflammatory response was assessed by measuring plasma levels of interleukin-6, interleukin-8, interleukin-10, and polymorphonuclear elastase. Gas exchange was assessed by measuring the PaO2/FIO2 ratio. RESULTS: Significant impairment of oxygenation was seen in both groups with the lowest values at the end of the operation before a gradual return to normal during the next 6 hours. There were no differences between the groups in gas exchange or times to extubation. There were significant elevations in all the cytokines, with interleukin-6 levels peaking at 4 hours in group H and 24 hours in group C, before starting to return to normal at 48 hours. The patterns of interleukin-8 and interleukin-10 rise were identical in the two groups. Polymorphonuclear elastase reached a peak at the end of the operation in group H and remained elevated up to 24 hours, whereas levels continued to rise in group C up to 4 hours. There were no significant differences in levels between groups at any time. There were no differences between the groups in blood loss or blood product usage. CONCLUSIONS: Cardiopulmonary bypass induces a systemic inflammatory response with release of cytokines and activation of leukocytes. This correlates with the severe deterioration in pulmonary gas exchange from preoperative levels up to 6 hours postoperatively (p < 0.05). In the presence of systemic heparinization, Duroflo II heparin bondingtf the circuits has minor effects on the pattern of evolution of this inflammatory response.