Kondyurina I, Wise SG, Ngo AKY, Filipe EC, Kondyurin A, Weiss AS, Bao S, Bilek MMM

Kondyurina I, Wise SG, Ngo AKY, Filipe EC, Kondyurin A, Weiss AS, Bao S, Bilek MMM

Biomed Mater 2017 Jul;12(4):045002

PMID: 28435148

Abstract

Polyurethanes are a diverse class of polymers, with independently tunable mechanical and biodegradation properties making them a versatile platform material for biomedical implants. Previous iterations have failed to adequately embody appropriate mechanical and biological properties, particularly for vascular medicine where strength, compliance and multifaceted biocompatibility are required. We have synthesized a new polyurethane formulation with finely tuned mechanical properties, combining high strength and extensibility with a low Young’s modulus. Additional cross-linking during synthesis enhanced stability and limits leaching. Under cyclic testing, hysteresis was minimal following completion of the initial cycles, indicating the robustness of the material. Building on this platform, we used plasma immersion ion implantation to activate the polymer surface and functionalized it with recombinant human tropoelastin. With tropoelastin covalently bound to the surface, human coronary endothelial cells showed improved attachment and proliferation. In the presence of heparinized whole blood, tropoelastin-coated polyurethane showed very low thrombogenicity in both static and flow conditions. Using this formulation, we synthesized robust, elastic prototype conduits which easily retained multiple sutures and were successfully implanted in a pilot rat aortic interposition model. We have thus created an elastic, strong biomaterial platform, functionalized with an important regulator of vascular biology, with the potential for further evaluation as a new synthetic graft material.

Chan AH, Tan RP, Michael PL, Lee BS, Vanags LZ, Ng MK, Bursill CA, Wise SG

PLoS ONE 2017;12(3):e0174773

PMID: 28355300

Abstract

Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM) analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP). This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days). We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.

Saxena A, Virk SA, Bowman S, Bannon PG

J Cardiovasc Surg (Torino) 2017 Mar;

PMID: 28322038

Abstract

BACKGROUND: This systematic review and meta-analysis was performed to evaluate the impact of preoperative atrial fibrillation (preAF) on early and late outcomes after aortic valve replacement (AVR).

METHODS: Medline, EMBASE, and CENTRAL were systematically searched for studies that reported AVR outcomes according to the presence or absence of preAF. Data were independently extracted by two investigators; a meta-analysis was conducted according to predefined clinical endpoints. Studies including patients undergoing concomitant atrial fibrillation surgery were excluded.

RESULTS: Six observational studies with 8 distinct AVR cohorts (AVR ± concomitant surgery) met criteria for inclusion, including a total of 6693 patients. Of these, 1014 (15%) presented with preAF. Overall, peri-operative mortality was increased in patients with preAF (odds ratio [OR] 2.33; 95% CI, 1.48 – 3.67; p<0.001). Subgroup analysis of patients undergoing isolated AVR also demonstrated preAF as a risk factor for peri-operative mortality (OR 2.49; 95% CI, 1.57-3.95; p<0.001). PreAF was also associated with acute renal failure (OR 1.42; 95% CI, 1.07-1.89; p=0.02) but not stroke (OR 1.11; 95% CI, 0.59 - 2.12; p=0.74). Late mortality was significantly higher in patients with preAF (hazard ratio [HR] 1.75; 95% CI, 1.33-2.30; p<0.001). This relationship remained true when only patients who underwent isolated AVR were analyzed (HR 1.97; 95% CI, 1.11-3.51; p=0.02).

CONCLUSIONS: PreAF is associated with an increased risk of early- and late-mortality after AVR. These data support the more widespread utilization of concomitant AF ablation.

Seco M, Zhao DF, Byrom MJ, Wilson MK, Vallely MP, Fraser JF, Bannon PG

Int. J. Cardiol. 2017 May;235:22-32

PMID: 28285802

Abstract

BACKGROUND: This systematic review aimed to evaluate the clinical outcomes and cost-effectiveness of left ventricular assist devices (LVADs) used as bridge to transplantation (BTT), compared to orthotopic heart transplantation (OHT) without a bridge.

METHOD: Systematic searches were performed in electronic databases with available data extracted from text and digitized figures. Meta-analysis of short and long-term term post-transplantation outcomes was performed with summation of cost-effectiveness analyses.

RESULTS: Twenty studies reported clinical outcomes of 4575 patients (1083 LVAD BTT and 3492 OHT). Five studies reported cost-effectiveness data on 837 patients (339 VAD BTT and 498 OHT). There was no difference in long-term post-transplantation survival (HR 1.24, 95% CI 1.00-1.54), acute rejection (HR 1.10, 95% CI 0.93-1.30), or chronic rejection and cardiac allograft vasculopathy (HR 0.99, 95% CI 0.73-1.36). No differences were found in 30-day post-operative mortality (OR 0.91, 95% CI 0.42-2.00), stroke (OR 1.64, 95% CI 0.43-6.27), renal failure (OR 1.43, 95% CI 0.58-3.54), bleeding (OR 1.56, 95% CI 0.78-3.13), or infection (OR 2.44, 95% CI 0.81-7.38). Three of the five studies demonstrated incremental cost-effectiveness ratios below the acceptable maximum threshold. The total cost of VAD BTT ranged from $316,078 to $1,025,500, and OHT ranged from $179,051 to $802,200.

CONCLUSION: LVADs used as BTT did not significantly alter post-transplantation long-term survival, rejection, and post-operative morbidity. LVAD BTT may be cost-effective, particularly in medium and high-risk patients with expected prolonged waiting times, renal dysfunction, and young patients.

Ramponi F, Jeremy RW, Wilson MK

J Card Surg 2017 Apr;32(4):259-261

PMID: 28271560

Abstract

We present a patient with Takayasu arteritis and severe aortic valve regurgitation and bilateral carotid artery occlusions, who underwent aortic valve replacement and aorto-bicarotid bypass. The management of the cardiovascular manifestations of Takayasu arteritis is reviewed.

Stevens MC, Callaghan FM, Forrest P, Bannon PG, Grieve SM

J Biomech 2017 Apr;55:64-70

PMID: 28262284

Abstract

Peripheral veno-arterial extra-corporeal membrane oxygenation (ECMO) is an artificial circulation that supports patients with severe cardiac and respiratory failure. Differential hypoxia during ECMO support has been reported, and it has been suggested that it is due to the mixing of well-perfused retrograde ECMO flow and poorly-perfused antegrade left ventricle (LV) flow in the aorta. This study aims to quantify the relationship between ECMO support level and location of the mixing zone (MZ) of the ECMO and LV flows. Steady-state and transient computational fluid dynamics (CFD) simulations were performed using a patient-specific geometrical model of the aorta. A range of ECMO support levels (from 5% to 95% of total cardiac output) were evaluated. For ECMO support levels above 70%, the MZ was located in the aortic arch, resulting in perfusion of the arch branches with poorly perfused LV flow. The MZ location was stable over the cardiac cycle for high ECMO flows (>70%), but moved 5cm between systole and diastole for ECMO support level of 60%. This CFD approach has potential to improve individual patient care and ECMO design.

Indja B, Seco M, Seamark R, Kaplan J, Bannon PG, Grieve SM, Vallely MP

Heart Lung Circ 2017 Feb;

PMID: 28237537

Abstract

Neurocognitive and psychiatric complications are common following cardiac surgery and impact on patient quality of life, recovery from surgery, participation in rehabilitation and long-term mortality. Postoperative cognitive decline, depressive disorders, post-traumatic stress disorder and neurocognitive impairment related to silent brain infarcts have all been linked to the perioperative period of cardiac surgery, and potentially have serious consequences. The accurate assessment of these conditions, particularly in determining the aetiology, and impact on patients is difficult due to the poorly recognised nature of these complications as well as similarities in presentation with postoperative delirium. This review aims to summarise current understanding surrounding psychiatric disturbances following cardiac surgery including the impact on patient quality of life and long-term outcomes.

Fung R, Stellios J, Bannon PG, Ananda A, Forrest P

Anaesth Intensive Care 2017 01;45(1):88-91

PMID: 28072940

Abstract

We describe the use of peripheral veno-venous extracorporeal membrane oxygenation (VV ECMO) and high-flow nasal oxygen as procedural support in a patient undergoing debulking of a malignant tumour of the lower airway. Due to the significant risk of complete airway obstruction upon induction of anaesthesia, ECMO was established while the patient was awake, and was maintained without systemic anticoagulation to minimise the risk of intraoperative bleeding. This case illustrates that ECMO support with high-flow nasal oxygen can be considered as part of the algorithm for airway management during surgery for subtotal lower airway obstruction, as it may be the only viable option for maintaining adequate gas exchange.