Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass.

OBJECTIVES: Cardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6). MATERIALS AND METHODS: The role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model. RESULTS: In the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB). CONCLUSION: CPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflammatory response to cardiac surgery may be manipulated to improve clinical outcomes.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction.

Tissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG), human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM), and erythropoietin (EPO) therapy in a rat model of myocardial infarction. PEG with/out iPSC-CMs and EPO; iPSC-CMs in saline; or saline alone was injected into infarcted hearts shortly after infarction. Injection of almost any combination of the therapeutics limited acute elevations in chamber volumes. After 10 weeks, attenuation of ventricular remodeling was identified in all groups that received PEG injections, while ejection fractions were significantly increased in the gel-EPO, cell, and gel-cell-EPO groups. In all treatment groups, infarct thickness was increased and regions of muscle were identified within the scar. However, no grafted cells were detected. Hence, iPSC-CM-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment.

A systematic review of left ventricular cardio-endoscopic surgery.

Better visualisation, accurate resection and avoidance of ventriculotomy associated with use of endoscopic devices during intracardiac surgery has led to increasing interest in their use. The possibility of combining a cardio-endoscopic technique with either minimally invasive or totally endoscopic cardiac surgery provides an incentive for its further development. Several devices have been used, however their uptake has been limited due to uncertainty around their impact on patient outcomes. A systematic review of the literature identified 34 studies, incorporating 54 subjects undergoing treatment of left ventricular tumours, thrombus or hypertrophic myocardium using a cardio-endoscopic technique. There were no mortalities (0%; 0/47). In 12 studies, the follow-up period was longer than 30 days. There were no post-operative complications apart from one case of atrial fibrillation (2.2%; 1/46). Complete resection of left ventricular lesion was achieved in all cases (100%; 50/50). These successful results demonstrate that the cardio-endoscopic technique is a useful adjunct in resection of left ventricular tumours, thrombus and hypertrophic myocardium. This approach facilitates accurate resection of pathological tissue from left ventricle whilst avoiding exposure related valvular damage and adverse effects associated with ventriculotomy. Future research should focus on designing adequately powered comparative randomised trials focusing on major cardiac and cerebrovascular morbidity outcomes in both the short and long-term. In this way, we may have a more comprehensive picture of both the safety and efficacy of this technique and determine whether such devices could be safely adopted for routine use in minimal access or robotic intra-cardiac surgery.

Quality of life after mitral valve intervention.

Advancements in surgical technique and understanding of the pathophysiology of mitral valve (MV) dysfunction have led to improved outcomes. Seen as a development beyond measures of morbidity and mortality, health-related quality-of-life (HRQOL) outcome measures are becoming increasingly popular. These measures are important because complications following routine (i.e. low-risk) operations on the MV are uncommon and further markers of outcome are needed. Surgeons are increasingly operating earlier on asymptomatic patients and will need to prove that HRQOL is not impacted. Novel minimally invasive and transcatheter technologies will also need to demonstrate satisfactory HRQOL outcomes prior to widespread use. This systematic review provides an overview of all available literature detailing HRQOL in patients receiving MV interventions. In the 43 studies included, 6865 patients underwent procedures ranging from open replacement to percutaneous repair using devices such as the Mitraclip Clip Delivery System (MitraClip) (Abbott Vascular, Santa Clara, CA, USA). Most studies performed baseline HRQOL assessment, allowing postinterventional comparison. While the underlying literature had deficiencies, most studies report acceptable postintervention HRQOL that was comparable to that of matched general populations. Patient-specific (e.g. female gender, renal dysfunction) and surgical-specific factors (e.g. replacement instead of repair, elevated transmitral gradient) were identified that predispose patients to poorer long-term HRQOL outcomes. These factors are important for clinicians developing strategies to maximize their HRQOL outcomes. Future randomized studies would benefit from HRQOL measurements at specific time points to allow large-scale comparisons. Establishing a common HRQOL instrument for use in MV intervention studies may support detailed comparisons between specific techniques. Physical activity monitors, physiological biomarkers and radiological markers could also be used as innovative indicators of functional outcome.

Assessment of Hemodynamic Conditions in the Aorta Following Root Replacement with Composite Valve-Conduit Graft.

This paper presents the analysis of detailed hemodynamics in the aortas of four patients following replacement with a composite bio-prosthetic valve-conduit. Magnetic resonance image-based computational models were set up for each patient with boundary conditions comprising subject-specific three-dimensional inflow velocity profiles at the aortic root and central pressure waveform at the model outlet. Two normal subjects were also included for comparison. The purpose of the study was to investigate the effects of the valve-conduit on flow in the proximal and distal aorta. The results suggested that following the composite valve-conduit implantation, the vortical flow structure and hemodynamic parameters in the aorta were altered, with slightly reduced helical flow index, elevated wall shear stress and higher non-uniformity in wall shear compared to normal aortas. Inter-individual analysis revealed different hemodynamic conditions among the patients depending on the conduit configuration in the ascending aorta, which is a key factor in determining post-operative aortic flow. Introducing a natural curvature in the conduit to create a smooth transition between the conduit and native aorta may help prevent the occurrence of retrograde and recirculating flow in the aortic arch, which is particularly important when a large portion or the entire ascending aorta needs to be replaced.

How revascularization on the beating heart with cardiopulmonary bypass compares to off-pump? A meta-analysis of observational studies.

Off-pump coronary artery bypass surgery has been a controversial area of debate and the outcome profile of the technique has been thoroughly investigated. Scepticism regarding the reported outcomes and the conduct of the randomized trials comparing this technique with conventional on-pump coronary artery bypass surgery has been widely voiced, and the technique of off-pump surgery remains as an infrequently adopted approach to myocardial revascularization worldwide. Criticisms of the technique are related to lower rates of complete revascularization and its unknown long-term consequences, the significant detrimental effects on mortality and major adverse events when emergency conversion is required, and the significant lack of long-term survival and morbidity data. The hybrid technique of myocardial revascularization on the beating heart with the use of cardiopulmonary bypass may theoretically provide the beneficial effects of off-pump surgery in terms of myocardial protection and organ protection, while providing the safety and stability of on-pump surgery to allow complete revascularization. Large randomized comparison to support evidence-based choices is currently lacking. In this article, we have meta-analysed the outcomes of on-pump beating heart surgery in comparison with off-pump surgery focusing on major adverse cardiovascular and cerebrovascular adverse events (MACCE) including mortality, stroke and myocardial infarction and the degree of revascularization and number of bypass grafts performed. It was demonstrated that the beating heart on-pump technique allows a significantly higher number of bypass grafts to be performed, resulting in significantly higher degree of revascularization. We have also demonstrated a slightly higher rate of 30-day mortality and MACCE with the technique although not at a statistically significant level. These results should be considered alongside the population risk profile, where a significantly higher risk cohort had undergone the beating heart on-pump technique. Long-term survival and morbidity figures are required to assess the impact of these findings in the coronary surgery patient population.

Quality of life after intervention on the thoracic aorta.

Surgery on the thoracic aorta is challenging and historically associated with significant mortality and morbidity. In recent times, there has been increased emphasis on the importance of health-related quality of life (HRQOL) measures. It is seen as a development beyond isolated markers of outcome such as operative mortality and is particularly applicable to aortic surgery given the number of asymptomatic patients operated on (for prognostic grounds), and rapidly advancing endovascular technologies which require proper assessment. This systematic review provides an outline of all available literature detailing HRQOL in patients receiving intervention (both open and endovascular) on the thoracic aorta. In total, 30 studies were identified encompassing 4746 patients undergoing a variety of procedures from aortic root replacement to thoracoabdominal aortic aneurysm repair. While there were deficiencies in the underlying literature such as lack of baseline HRQOL assessment, the majority of the studies confirm that HRQOL after major aortic surgery (including on the elderly and in emergency situations) is acceptable and compares well to matched general populations. Strategies for improving the HRQOL in aortic surgery are summarized and include the need for surgeons to plan cerebral protection methods more carefully and to develop operative strategies to avoid reoperation or reintervention, as this is associated with deterioration of long-term HRQOL. Randomized studies measuring baseline and follow-up HRQOL at specific set points are needed. Innovative research methods could be employed in future studies with the aim of correlating HRQOL with imaging or physiological/inflammation biomarkers, or other end points such as aortic stiffness or wall shear stress to characterize disease progression and prognosis.

NR2 antibody is associated with quality of life in aortic valve replacement.

BACKGROUND: The relationship between the potential brain injury biomarker N-methyl-D-aspartate receptor antibody and quality of life has never been assessed. METHODS: We measured serum N-methyl-D-aspartate receptor antibody levels preoperatively in patients undergoing aortic valve replacement. Quality of life was scored using the Short Form-36 and European Quality of Life 5-Dimensions questionnaires pre- and postoperatively. We analyzed the antibody levels as a continuous variable and as a dichotomous variable with 1.8 ng mL(-1) as the cutoff. RESULTS: Fifty-two patients (15 females) with a mean age of 71 ± 8.4 years were recruited for this study. Forty-eight (92%) patients attended the follow-up visit (405 ± 161 days). No mortality or severe neurological event was recorded. In both quality-of-life instruments, the low antibody level group (n = 35) had significantly better scores than the high antibody level group (n = 17) preoperatively. Postoperatively, the scores for both groups improved; however, the low antibody level group continued to score significantly better in most of the physical and mental health domains (p = 0.04 to <0.001). Multiple regression analyses revealed that antibody level and the 1.8 ng mL(-1) cutoff were independently related to quality of life (pre- and postoperatively). CONCLUSIONS: Higher N-methyl-D-aspartate receptor antibody levels in aortic valve replacement patients are independently related to poorer quality of life pre- and postoperatively.

In-vivo assessment of the morphology and hemodynamic functions of the BioValsalva™ composite valve-conduit graft using cardiac magnetic resonance imaging and computational modelling technology.

BACKGROUND: The evaluation of any new cardiac valvular prosthesis should go beyond the classical morbidity and mortality rates and involve hemodynamic assessment. As a proof of concept, the objective of this study was to characterise for the first time the hemodynamics and the blood flow profiles at the aortic root in patients implanted with BioValsalva™ composite valve-conduit using comprehensive MRI and computer technologies. METHODS: Four male patients implanted with BioValsalva™ and 2 age-matched normal controls (NC) underwent cardiac magnetic resonance imaging (MRI). Phase-contrast imaging with velocity-mapping in 3 orthogonal directions was performed at the level of the aortic root and descending thoracic aorta. Computational fluid dynamic (CFD) simulations were performed for all the subjects with patient-specific flow information derived from phase-contrast MR data. RESULTS: The maximum and mean flow rates throughout the cardiac cycle at the aortic root level were very comparable between NC and BioValsalva™ patients (541 ± 199 vs. 567 ± 75 ml/s) and (95 ± 46 vs. 96 ± 10 ml/s), respectively. The maximum velocity (cm/s) was higher in patients (314 ± 49 vs. 223 ± 20; P = 0.06) due to relatively smaller effective orifice area (EOA), 2.99 ± 0.47 vs. 4.40 ± 0.24 cm2 (P = 0.06), however, the BioValsalva™ EOA was comparable to other reported prosthesis. The cross-sectional area and maximum diameter at the root were comparable between the two groups. BioValsalva™ conduit was stiffer than the native aortic wall, compliance (mm2 • mmHg(-1) • 10(-3)) values were (12.6 ± 4.2 vs 25.3 ± 0.4.; P = 0.06). The maximum time-averaged wall shear stress (Pa), at the ascending aorta was equivalent between the two groups, 17.17 ± 2.7 (NC) vs. 17.33 ± 4.7 (BioValsalva™ ). Flow streamlines at the root and ascending aorta were also similar between the two groups apart from a degree of helical flow that occurs at the outer curvature at the angle developed near the suture line. CONCLUSIONS: BioValsalva™ composite valve-conduit prosthesis is potentially comparable to native aortic root in structural design and in many hemodynamic parameters, although it is stiffer. Surgeons should pay more attention to the surgical technique to maximise the reestablishment of normal smooth aortic curvature geometry to prevent unfavourable flow characteristics.

Aortic Stiffness Is Related to the Ischemic Brain Injury Biomarker N-Methyl-D-aspartate Receptor Antibody Levels in Aortic Valve Replacement.

Background. Aortic stiffness changes the flow pattern of circulating blood causing microvascular damage to different end-organ tissues, such as brain cells. The relationship between aortic stiffness measured by pulse wave velocity (PWV) and serum ischemic brain injury biomarker N-methyl-D-aspartate receptor antibody (NR2Ab) levels in aortic valve replacement has not been assessed. Methods. Patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS) had their PWV and NR2Ab serum levels measured preoperatively. We analyzed PWV and NR2Ab in two ways: (1) as continuous variables using the actual value and (2) as dichotomous variables (PWV-norm and PWV-high groups) and (NR2Ab-low and NR2Ab-high groups). Results. Fifty-six patients (71 ± 8.4 years) were included in this study. The NR2Ab level (ng/mL) was significantly higher in the PWV-high group (n = 21) than in PWV-norm group (n = 35; median 1.8 ± 1.2 versus 1.2 ± 0.7, resp., P = 0.003). NR2Ab level was positively associated with PWV and negatively associated with male gender. Multiple regression revealed PWV independently related to NR2Ab level, and PWV cut-off was associated with a 7.23 times increase in the likelihood of having high NR2Ab (>1.8 ng/mL). Conclusion. Higher PWV in patients with surgical aortic stenosis is associated with higher levels of the ischemic brain biomarker NR2Ab.

Pulse wave velocity and neutrophil gelatinase-associated lipocalin as predictors of acute kidney injury following aortic valve replacement.

BACKGROUND: Accurate prediction, early detection and treatment of acute kidney injury (AKI) are essential for improving post-operative outcomes. This study aimed to examine the role of aortic stiffness and neutrophil gelatinase-associated lipocalin (NGAL) as predictors of AKI or need for early medical renal intervention following aortic valve replacement (AVR). METHODS: Aortic pulse wave velocity and plasma NGAL were measured pre-operatively in recruited patients undergoing AVR for aortic stenosis (AS). Plasma NGAL was also measured at 3 and 18-24 hours after cardiopulmonary bypass (CPB). AKI was defined using RIFLE criteria. Early medical renal intervention included diuretics or dopamine infusion exclusively for renal causes. RESULTS: Fifty-three patients aged 71 ± 9 years were included. Sixteen (30%) developed AKI (AKI-Yes) and 24 patients (45%) received early medical intervention (Intervention-Yes). There was no significant difference in the demographic, clinical or operative characteristics between the two groups for either outcome. PWV did not significantly correlate with AKI (r = 0.12, P = 0.13) or early intervention (r = 0.18, P = 0.18). At 3 h post-CPB, plasma NGAL was a much stronger predictor of both AKI and the need for early medical intervention than conventional markers such as creatinine (AKI: AUC 83%, 95% CI 0.70-0.95 vs. AUC 65%, 95% CI 0.47- 0.82; Medical intervention: AUC 84%, 95% CI 0.72-0.96 vs. AUC 56%, 95% CI 0.38-0.73). Post-CPB (3 hr) plasma NGAL was also significantly associated with AKI (r = 0.68, P < 0.001) at levels above 150 ng/ml; and significantly associated with early intervention (r = 0.64, P < 0.001) above 136 ng/ml. Simple linear regression showed no relationship between PWV and NGAL levels. CONCLUSION: Aortic PWV does not correlate significantly with post-operative AKI or plasma NGAL levels in surgical AS patients. Post-operative NGAL is however an early and powerful predictive biomarker of both post-operative AKI and the need for early medical renal intervention and should consequently be considered in prediction models for AKI after cardiac surgery.

Aortic stiffness is an indicator of cognitive dysfunction before and after aortic valve replacement for aortic stenosis.

OBJECTIVES: Post-cardiac surgical cognitive dysfunction occurs more commonly following valvular procedures. Cognitive function has been related to vascular health status; however, the relation between pre-existent arterial stiffness and perioperative cognitive dysfunction is yet to be defined. The objective of this study was to assess whether aortic stiffness is related to cognitive dysfunction in surgical aortic stenosis (AS) pre- and postoperatively. METHODS: Between June 2010 and August 2012, patients undergoing aortic valve replacement (AVR) for AS were recruited for inclusion in this prospective observational study. Aortic pulse wave velocity (PWV) was used as a measure of aortic stiffness and cognitive function was assessed using the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) preoperatively and (409 ± 159 days) post-AVR. RESULTS: Fifty-six patients (age 71 ± 8.4 years) were recruited. Of the total, 50 (89%) completed postoperative follow-up. Pre- and postoperatively, patients with normal PWV (PWV-norm) had significantly superior delayed memory, sustained visual attention and executive function compared with those with high PWV (PWV-high). Immediate memory and decision-making were similar between groups. Postoperatively, improvement in cognitive function was more marked in PWV-high compared with PWV-norm patients. In two models of multiple regression analysis, PWV as a continuous variable was independently related to all preoperative main cognitive components as well as postoperative executive function. PWV as a dichotomous variable was independently related to all pre- and postoperative main cognitive function components. CONCLUSIONS: AVR may not be associated with an independent or homogeneous effect on cognitive decline. Aortic PWV might be useful as an additional indicator for cognitive dysfunction before and after surgical intervention for AS.

Aortic stiffness as a marker of cardiac function and myocardial strain in patients undergoing aortic valve replacement.

BACKGROUND: Cardiac function and myocardial strain are affected by cardiac afterload, which is in part due to the stiffness of the aortic wall. In this study, we hypothesize that aortic pulse wave velocity (PWV) as a marker of aortic stiffness correlates with conventional clinical and biochemical markers of cardiac function and perioperative myocardial strain in aortic valve replacement (AVR). METHODS: Patients undergoing AVR for aortic stenosis between June 2010 and August 2012 were recruited for inclusion in this study. PWV, NYHA class and left ventricular (LV) function were assessed pre-operatively. PWV was analysed both as a continuous and dichotomous variable according to age-standardized reference values. B-type natriuretic peptide (BNP) was measured pre-operatively, and at 3 h and 18-24 h after cardiopulmonary bypass (CPB). NYHA class, leg edema, and LV function were recorded at follow-up (409 ± 159 days). RESULTS: Fifty-six patients (16 females) with a mean age of 71 ± 8.4 years were included, with 50 (89%) patients completing follow-up. The NYHA class of PWV-norm patients was significantly lower than PWV-high patients both pre- and post-operatively. Multiple logistic regression also highlighted PWV-cut off as an independent predictor of NYHA class pre- and post-operatively (OR 8.3, 95% CI [2.27,33.33] and OR 14.44, 95% CI [1.49,139.31] respectively). No significant relationship was observed between PWV and either LV function or plasma BNP. CONCLUSION: In patients undergoing AVR for aortic stenosis, PWV is independently related to pre- and post-operative NYHA class but not to LV function or BNP. These findings provisionally support the use of perioperative PWV as a non-invasive marker of clinical functional status, which when used in conjunction with biomarkers of myocardial strain such as BNP, may provide a holistic functional assessment of patients undergoing aortic valve surgery. However, in order for PWV assessment to be translated into clinical practice and utilised as more than simply a research tool, further validation is required in the form of larger prospective studies specifically designed to assess the relationship between PWV and these functional clinical outcomes.

High aortic pulse wave velocity is associated with poor quality of life in surgical aortic valve stenosis patients.

OBJECTIVES: Aortic stiffness is an emerging risk factor for cardiovascular disease. The predictive value of aortic pulse wave velocity (PWV) for quality of life (QoL) and severity of surgical aortic valve stenosis (AS) have not been examined. METHODS: PWV was measured in patients undergoing aortic valve replacement (AVR) for AS. QoL [SF-36 and European QoL 5-dimensions (EQ-5D) questionnaires] was assessed pre- and postoperatively (409 ± 159 days). PWV was analysed: (i) as a continuous variable and (ii) as a dichotomous variable (PWV-norm and PWV-high groups) according to the published normal reference value. RESULTS: Fifty-six patients (16 females), mean age of 71 ± 8.4 years, were included, and 50 (89%) patients completed follow-up. The two groups were matched for age, gender and classical haemodynamic measurements. There was no significant relation between AS severity and PWV. PWV-norm patients (n = 35) scored significantly better than PWV-high (n = 21) patients in the EQ-5D visual analogue scale and the EQ-5D index pre- (P < 0.001 and P = 0.03, respectively) and postoperatively (P < 0.001 for both). In SF-36, PWV-norm group scored better than PWV-high group in physical health domains preoperatively and in all domains postoperatively. Spearman's correlation was significant between PWV and QoL component summaries pre- and postoperatively. Among PWV, age and gender, multiple regression analysis demonstrated PWV to be independently related to QoL pre- and postoperatively (P-values ranged from <0.01 to <0.05). CONCLUSIONS: PWV does not correlate with AS severity, but is associated with QoL before and after AVR. The published European PWV reference values can be used to categorise preoperative AS patients for QoL risk stratification.

The effect of off-pump coronary artery bypass on mortality after acute coronary syndrome: a meta-analysis.

BACKGROUND: Patients requiring surgical revascularisation for acute coronary syndrome (ACS) form a clinically heterogeneous group ranging from haemodynamic stability to cardiogenic shock. Whilst 'off-pump' revascularisation (OPCAB) is often considered, patient selection and operative timing remain controversial. This study aims to identify whether OPCAB may confer a mortality benefit over ONCAB in revascularisation for ACS. Secondly, we review the impact of OPCAB on completeness of revascularisation (CR) and long-term re-intervention. METHODS: A systematic literature review identified 9 studies (1 randomised controlled trial) of which 8 fulfilled criteria for meta-analysis. Outcomes for a total of 3001 patients (n=817 OPCAB, 2184 'on-pump' (ONCAB)) were meta-analysed using random effects modelling. Heterogeneity, subgroup analysis and quality scoring were assessed. Primary endpoints were 30-day and mid-term mortality. Secondary endpoints were CR, revascularisation index and re-intervention. RESULTS: OPCAB conferred comparable mortality to ONCAB at both 30-days and mid-term follow up (p=0.08 and p=0.46 respectively). OPCAB was also associated with less CR (WMD -0.60, 95% CI [-0.82, -0.38], p<0.00001) and a lower revascularisation index (WMD -0.25, 95% CI [-0.30, -0.19], p<0.00001), although no difference was observed in re-intervention rate (OR 1.33; 95% CI [0.99, 2.07], p=0.99). CONCLUSIONS: We conclude that OPCAB may be a safe and comparable alternative to ONCAB in clinically stable ACS patients requiring urgent/emergent revascularisation. However, in order to finally determine whether OPCAB may provide any more than just comparability to ONCAB in the setting of ACS, further research must clearly define selection criteria, better characterize this heterogeneous patient group and assess the effects of incomplete revascularisation on long-term outcomes.

An interesting collection of paraneoplastic syndromes in a patient with a malignant thymoma.

Paraneoplastic neurological syndromes are conditions that manifest as the remote effects of cancer. These are very rare, occurring in 1/10000 patients with a malignancy, and include Lambert-Eaton myasthenic syndrome, limbic encephalitis, subacute cerebellar ataxia, opsoclonus-myoclonus, Stiff-Person Syndrome, retinopathies, chronic gastrointestinal pseudo-obstruction and sensory neuropathy. This report describes a case of 41-year-old man who presented with elements of multiple paraneoplastic syndromes, including chronic gastrointestinal pseudo-obstruction, myasthenia gravis-Lambert-Eaton overlap syndrome and polymyositis, and who was subsequently found to have a malignant thymoma. There are only three reported cases in the literature describing cases of Lambert-Eaton myasthenic syndrome in association with a thymoma, and only one case of a myasthenia gravis-Lambert-Eaton overlap syndrome in a patient with thymoma. However, there are no documented cases in the literature of this constellation of syndromes in a patient with a malignant thymoma.

The effect of prehospital time related variables on mortality following severe thoracic trauma.

OBJECTIVES: The aims of this study is firstly to analyse the impact of prehospital time related variables on mortality, in a specific subset of HEMS patients and secondly to demonstrate any interactions between time related variables and factors taking place in the prehospital setting. METHODS: Retrospective analysis of 688 consecutive London HEMS transfers with severe thoracic trauma and mean injury severity score (ISS) of 35, during a 9-year period (1994-2002). We have analysed the effect of the following time related variables on mortality: activation time, arrival on scene time (AoS), stay on scene time (SoS), total time (ToT), rush-hour time (RhT) and leisure-hour time (LhT). We have also investigated the interaction of the above mentioned variables with observations and interventions taken place on scene and at accident and emergency department (A&E) following adjustment for type and severity of injury. For statistical analysis the time variables were grouped into quintiles. RESULTS: Six hundred eighty eight victims (510 males) with mean age of 38.5 ± 17.5 had total survival rate of 59.6%. The mean AoS and SoS were 11.6 ± 5.8 min and 36.6 ± 16.8 min, respectively. ToT>65 min, as in quintiles III, IV and V with mean ToT of 65.3 min, 74.9 min and 102.7 min respectively, had an influence on mortality with calculated adjusted OR of 1.37 (95%CI=0.47-3.94), 3.36 (95%CI = 1.22-9.23) and 1.43 (95%CI = 0.52-3.92) respectively with concomitant adjustment for type of injury, severity of injury, age, physiological variables on scene and on scene emergency thoracotomy (ET). ET on scene was an independent predictor for mortality (OR 3.94, 95%CI = 1.03-15.06). SoS of more than 34 min can lead to harmful changes on patients' pathophysiological status. ISS has no significant effect on AoS or SoS. RhT and LhT have no significant effect on mortality and they did not influence the AoS and SoS. CONCLUSION: This study suggests that time related variables have a complex and heterogeneous effect on mortality. Thoracic trauma victims usually have high ISS, in such population, ToT <65 min may be associated with lower possibility of death. Neither AoS nor SoS was influenced by time of incident or severity of injury.

Aortic valve replacement for aortic stenosis in patients with concomitant mitral regurgitation: should the mitral valve be dealt with?

Co-existent mitral regurgitation may adversely influence both morbidity and mortality in patients undergoing aortic valve replacement for severe aortic stenosis. Whilst it is accepted that concomitant mitral intervention is required in severe, symptomatic mitral regurgitation, in cases of mild-moderate non-structural mitral regurgitation, improvement may be seen following aortic valve replacement alone, avoiding the increased risk of double-valve surgery. The exact benefit of such a conservative approach is, however, yet to be adequately quantified. We performed a systematic literature review identifying 17 studies incorporating 3053 patients undergoing aortic valve replacement for aortic stenosis with co-existing mitral regurgitation. These were meta-analysed using random effects modelling. Heterogeneity and subgroup analysis were assessed. Primary end points were change in mitral regurgitation severity and 30-day, 3-, 5- and 10-year mortality. Secondary end points were end-organ dysfunction (neurovascular, renal and respiratory), and the extent of ventricular remodelling following aortic valve replacement. Our results revealed improvement in the severity of mitral regurgitation following aortic valve replacement in 55.5% of patients, whereas 37.7% remained unchanged, and 6.8% worsened. No significant difference was seen between overall data and either the functional or moderate subgroups. The overall 30-day mortality following aortic valve replacement was 5%. This was significantly higher in moderate-severe mitral regurgitation than nil-mild mitral regurgitation both overall (p=0.002) and in the functional subgroup (p=0.004). Improved long-term survival was seen at 3, 5 and 10 years in nil-mild mitral regurgitation when compared with moderate-severe mitral regurgitation in all groups (overall p<0.0001, p<0.00001 and p=0.02, respectively). The relative risk of respiratory, renal and neurovascular complications were 7%, 6% and 4%, respectively. Reverse remodelling was demonstrated by a significant reduction in left-ventricular end-diastolic diameter and left-ventricular mass (p=0.0007 and 0.01, respectively), without significant heterogeneity. No significant change was seen in left-ventricular end-systolic diameter (p=0.10), septal thickness (p=0.17) or left atrial area (p=0.23). We conclude that despite reverse remodelling, concomitant moderate-severe mitral regurgitation adversely affects both early and late mortality following aortic valve replacement. Concomitant mitral intervention should therefore be considered in the presence of moderate mitral regurgitation, independent of the aetiology.

How to manage the left subclavian artery during endovascular stenting for thoracic aortic dissection? An assessment of the evidence.

BACKGROUND: Despite the publication of recent guidelines for management of the left subclavian artery (LSA) during endovascular stenting procedures of the thoracic aorta, specific management for those presenting with dissection remains unclear. This systematic review attempts to address this issue. METHODS: Systematic assessment of the published data on thoracic aorta dissection was performed identifying 46 studies, which incorporated 1,275 patients. Primary outcomes included the prevalence of left arm ischemia, stroke, spinal cord ischemia, endoleak, stent migration, and mortality. Outcomes were compared between patients with and without LSA coverage and revascularization incorporating factors such as the number of stents used, length of aorta covered, urgency of intervention, and type of dissection (acute or chronic). Statistical pooling techniques, χ(2) tests, and Fisher's exact testing were used for group comparisons. RESULTS: As compared with other outcomes, LSA coverage without revascularization in the presence of aortic dissection is much more likely to be complicated by left arm ischemia (prevalence increased from 0.0% to 4.0% [p = 0.021]), stroke (prevalence increased from 1.4% to 9.0% [p = 0.009]), and endoleak (prevalence increased from 4.0% to 29.3% [p = 0.001]). However, revascularization was not shown to reverse these effects. Longer aortic coverage (≥ 150 mm) was associated with an increased prevalence of spinal cord ischemia (from 1.3% to 12.5% [p = 0.011]) and mortality (from 1.3% to 15.6% [p = 0.003]). CONCLUSION: In patients undergoing endovascular stenting for thoracic aortic dissection, in cases where LSA coverage is necessary, revascularization should be considered before the procedure to avoid complications such as left arm ischemia, stroke, and endoleak, and where feasible, an appropriate preoperative assessment should be carried out.

Do bigger hospitals or busier surgeons do better adult aortic or mitral valve operations?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether there is a relationship between hospital or surgeon volume (SV) and postoperative outcome in adult aortic or mitral valve surgery. One hundred and sixty papers were found using the specified search strategy, of which seven papers represented the best evidence to answer this question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, methodology scores, study weaknesses and results are tabulated. Outcomes assessed by these studies were variable; four papers used mortality, one paper used morbidity, one paper used care processes and one paper examined all the above-mentioned outcomes. Six papers investigated the effect of hospital volume (HV) on outcome whilst only one paper assessed the effect of both HV and SV on outcome. The type of valve operated on was also mixed; two papers studied aortic valve only, one paper studied mitral valve only and four papers studied both valves. The methodological quality and validity of each study was assessed by a predefined scoring system. The median total quality score was modest and not strong enough to support the conclusions reported by these studies. In addition, volume-outcome relationship can be affected by several factors related to patient, surgeon and hospital. These factors have not been considered in depth by the mentioned papers. However, there may be a positive relationship between hospital procedural volume and mortality which is more likely to be mediated by SV, and there is also a potential relationship with the rate of mitral valve repair and the use of bio-prosthetic valves in elderly patients. We conclude that regionalisation of adult aortic or mitral valve surgery based on such a limited number of modest quality studies would be an indefensible policy. The implementation of such a scheme can have many clinical, practical, economical and political consequences which have not been examined prospectively until today. Furthermore, the relationship between volume and other outcomes rather than mortality needs further assessment.