Gastrointestinal injury following cardiopulmonary bypass

The gastrointestinal (GI) tract may be the source of a number of bacterial and non-bacterial mediators, which may contribute to the development of morbidity and mortality following episodes of gut hypoperfusion/ ischaemia. The aim of this thesis has been to identify the changes in gut blood flow, oxygenation and function following cardiopulmonary bypass (CPB) and their relationship to the development of post-CPB morbidity. The findings are summarised below: The retrospective study identified age (>65 yr) and CPB time as risk factors for the development of post-CPB intra-abdominal complications . Tonometrically determined values for intramucosal pH (pHi) need temperature correction to avoid calculation of erroneously high values during hypothermic CPB. Considerable hypoperfusion occurs during hypothermic CPB, with laser Doppler flowmetry (LDF) falling to approximately 45% of pre-CPB values. The gastric and colonic pHi becomes acidotic (<7.35) during the re-warming and immediate post-CPB period. Intramucosal acidosis occurs at a time when mucosal LDF blood flow is normal or supranormal. CPB increases gut permeability and reduces the absorption of the monosaccharides, 3-O-m-D-glucose, D-xylose & L-rhamnose. Post-CPB gut permeability has a temporal relationship with the CPB time. Pulsatile flow attenuates the increase in post-CPB gut permeability. Endotoxaemia occurs during CPB but is not associated with the production of TNFα; pulsatile flow attenuates this endotoxaemia. When examining perfusion and patient factors, the best predictor for a protracted ventilation & ICU stay for patients was a low gastric pHi (<7.35). A canine model of CPB supported the clinical findings, but also found that: (a) changes in large vessel blood flow do not indicate more dynamic alterations in small vessel blood flow (b) blood flow is prioritised to the mucosa at the expense of the serosal aspects of the bowel wall (c) in the re-warming phase of hypothermic CPB & the immediate post-CPB period, when intramucosal acidosis occurs, there is a disparity between gut oxygen consumption & delivery (b) increased expression of vasoactive intestinal peptide was found in the neural plexus of the submucosa post-CPB, which may indicate a role in preserving mucosal blood flow during periods of hypoperfusion

Surgical Treatment of Atrial Fibrillation

The concepts, techniques and evidence relating to surgical ablation of atrial fibrillation are discussed in detail. The historical background to surgical ablation is covered in brief, along with the electrophysiological basis underpinning its effective useage. The epidemiology of surgically treated atrial fibrillation and the current guidelines relating to its use are analysed. Safety aspects and perspectives on its ongoing future use are discussed. Modern surgical technologies and approaches are reviewed, along with the relevant advantages and disadvantages of each. The surgical techniques relating to left atrial appendage intervention are also reviewed, along with the relevant literature and evidence relating to reduction in thromboembolic risk and need for anticoagulation

Endogenous reference genes for gene expression studies on bicuspid aortic valve associated aortopathy in humans

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisposes patients to life-threatening aortic complications including aortic aneurysm. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most commonly used methods to investigate underlying molecular mechanisms involved in aortopathy. The accuracy of the gene expression data is dependent on normalization by appropriate housekeeping (HK) genes, whose expression should remain constant regardless of aortic valve morphology, aortic diameter and other factors associated with aortopathy. Here, we identified an appropriate set of HK genes to be used as endogenous reference for quantifying gene expression in ascending aortic tissue using a spin column-based RNA extraction method. Ascending aortic biopsies were collected intra-operatively from patients undergoing aortic valve and/or ascending aortic surgery. These patients had BAV or tricuspid aortic valve (TAV), and the aortas were either dilated (?4.5cm) or undilated. The cohort had an even distribution of gender, valve disease and hypertension. The expression stability of 12 reference genes were investigated (ATP5B, ACTB, B2M, CYC1, EIF4A2, GAPDH, SDHA, RPL13A, TOP1, UBC, YWHAZ, and 18S) using geNorm software. The most stable HK genes were found to be GAPDH, UBC and ACTB. Both GAPDH and UBC demonstrated relative stability regardless of valve morphology, aortic diameter, gender and age. The expression of B2M and SDHA were found to be the least stable HK genes. We propose the use of GAPDH, UBC and ACTB as reference genes for gene expression studies of BAV aortopathy using ascending aortic tissue

The Inflammatory Response to Miniaturised Extracorporeal Circulation: A Review of the Literature

Conventional cardiopulmonary bypass can trigger a systemic inflammatory response syndrome similar to sepsis. Aetiological factors include surgical trauma, reperfusion injury, and, most importantly, contact of the blood with the synthetic surfaces of the heart-lung machine. Recently, a new cardiopulmonary bypass system, mini-extracorporeal circulation (MECC), has been developed and has shown promising early results in terms of reducing this inflammatory response. It has no venous reservoir, a reduced priming volume, and less blood-synthetic interface. This review focuses on the inflammatory and clinical outcomes of using MECC and compares these to conventional cardio-pulmonary bypass (CCPB). MECC has been shown to reduce postoperative cytokines levels and other markers of inflammation. In addition, MECC reduces organ damage, postoperative complications and the need for blood transfusion. MECC is a safe and viable perfusion option and in certain circumstances it is superior to CCPB

Valve-in-Valve Transcatheter Aortic Valve Replacement: Challenges for Now and the Future

The recent years have seen a huge expansion in the number of bioprostheses implanted, and this number is likely to increase further in the future. This is likely to lead to a pandemic of patients requiring reoperation/re-intervention for structural deterioration of the valve. Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has become a safe and effective alternative to redo aortic valve surgery and has gained approval for use in high-risk patients with prohibitive operative risk. ViV-TAVR is a complex procedure requiring rigorous planning, technical expertise and patient anatomical appreciation. In this chapter, we examine the evidence supporting the use of ViV-TAVR along with the primary technical issues surrounding this procedure such as: elevated postprocedural gradients, coronary obstruction and valve-related thrombosis. TAVR use is also expanding towards an increasingly young patient profile with extended life expectancy, likely to outlive the implanted bioprosthesis. We therefore also examine the huge current challenge of establishing what is the best lifetime strategy for the management of aortic valve disease in younger patients

Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease.

BACKGROUND: Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. METHODS: Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter ≥ 45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify proteins demonstrating low abundance variability in the aneurysmal patients (consistent expression in disease), and high variability in the non-aneurysmal patients (differential expression between 'at risk' and not 'at risk' patients). RESULTS: Fifteen plasma samples were collected (seven non-aneurysmal and 8 aneurysmal BAV patients). The mean age of the patients was 55.5 years and the majority were female (10/15, 67%). Four proteins (haemoglobin subunits alpha, beta and delta and mannan-binding lectin serine protease) correlated significantly with maximal ascending aortic diameter (p < 0.05, r = 0.5-0.6). Five plasma proteins demonstrated significantly lower variability in the aneurysmal group and may indicate increased risk of aneurysm in non-aneurysmal patients (DNA-dependent protein kinase catalytic subunit, lumican, tetranectin, gelsolin and cartilage acidic protein 1). A further 7 proteins were identified only in the aneurysmal group (matrin-3, glucose-6-phosphate isomerase, coactosin-like protein, peptidyl-prolyl cis-trans isomerase A, golgin subfamily B member 1, myeloperoxidase and 2'-deoxynucleoside 5'-phosphate N-hydrolase 1). CONCLUSIONS: This study is the first to identify candidate plasma biomarkers for predicting aortic diameter and risk of future aneurysm in BAV patients. It provides valuable pilot data and proof of principle that could be used to design a large-scale prospective investigation. Ultimately, a more affordable 'off-the-shelf' follow-on blood assay could then be developed in place of SWATH-MS, for use in the healthcare setting

Disparity in clinical outcomes after cardiac surgery between private and public (NHS) payers in England

Background: there is little known about how payer status impacts clinical outcomes in a universal single-payer system such as the UK National Health Service (NHS). The aim of this study was to evaluate the relationship between payer status (private or public) and clinical outcomes following cardiac surgery from NHS providers in England. Methods: the National Adult Cardiac Surgery Audit (NACSA) registry was interrogated for patients who underwent adult cardiac surgery in England from 2009 to 2018. Information on socioeconomic status were provided by linkage with the Iteration of the English Indices of Deprivation (IoD). The primary outcome was in-hospital mortality. Secondary outcomes included incidence of in-hospital postoperative cerebrovascular accident (CVA), renal dialysis, sternal wound infection, and re-exploration. To assess whether payer status was an independent predictor of in-hospital mortality, binomial generalized linear mixed models (GLMM) were fitted along with 17 items forming the EuroSCORE and the IoD domains. Findings: the final sample consisted of 280,209 patients who underwent surgery in 31 NHS hospitals in England from 2009 to 2018. Of them, 5,967 (2.1%) and 274,242 (97.9%) were private and NHS payers respectively. Private payer status was associated with a lower risk of in-hospital mortality (OR 0.79; 95%CI 0.65 – 0.97;P = 0.026), CVA (OR 0.77; 95%CI 0.60 – 0.99; P = 0.039), need for re-exploration (OR 0.84; 95%CI 0.72 – 0.97; P = 0.017) and with non-significant lower risk of dialysis (OR 0.84; 95%CI 0.69 – 1.02; P = 0.074). Private payer status was found to be independently associated with lower risk of in-hospital mortality in the elective subgroup (OR 0.76; 95%CI 0.61 – 0.96; P = 0.020) but not in the non-elective subgroup (OR 1.01; 95%CI 0.64 – 1.58; P = 0.976). Interpretation: In conclusion, using a national database, we have found evidence of significant beneficial effect of payer status on hospital outcomes following cardiac surgery in favour of private payers regardless their socioeconomic factors.</p