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Background: There are limited economic evaluations comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multi-vessel coronary artery disease (MVCAD) in contemporary, routine clinical practice. Objective(s): The aim was to perform a cost-effectiveness analysis comparing CABG and PCI in patients with MVCAD, from the perspective of the Australian public hospital payer, using observational data sources. Method(s): Clinical data from the Melbourne Interventional Group (MIG) and the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registries were analysed for 1022 CABG (treatment) and 978 PCI (comparator) procedures performed between June 2009 and December 2013. Clinical records were linked to same-hospital admissions and national death index (NDI) data. The incremental cost-effectiveness ratios (ICERs) per major adverse cardiac and cerebrovascular event (MACCE) avoided were evaluated. The propensity score bin bootstrap (PSBB) approach was used to validate base-case results. Result(s): At mean follow-up of 2.7 years, CABG compared with PCI was associated with increased costs and greater all-cause mortality, but a significantly lower rate of MACCE. An ICER of $55,255 (Australian dollars)/MACCE avoided was observed for the overall cohort. The ICER varied across comparisons against bare metal stents (ICER $25,815/MACCE avoided), all drug-eluting stents (DES) ($56,861), second-generation DES ($42,925), and third-generation of DES ($88,535). Moderate-to-low ICERs were apparent for high-risk subgroups, including those with chronic kidney disease ($62,299), diabetes ($42,819), history of myocardial infarction ($30,431), left main coronary artery disease ($38,864), and heart failure ($36,966). Conclusion(s): At early follow-up, high-risk subgroups had lower ICERs than the overall cohort when CABG was compared with PCI. A personalised, multidisciplinary approach to treatment of patients may enhance cost cont

Current prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus. At 24 hours post-infection, 623 host genes were significantly upregulated, including the cell adhesion molecule CEACAM1. H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to influenza A PR8 (H1N1) virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity. Furthermore, silencing of endogenous CEACAM1 resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection. Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.

Background: We examined whether socioeconomic status and rurality influenced outcomes after coronary surgery. Method(s): We identified 14,150 patients undergoing isolated coronary surgery. Socioeconomic and rurality data was obtained from the Australian Bureau of Statistics and linked to patients' postcodes. Outcomes were compared between categories of socioeconomic disadvantage (highest versus lowest quintiles, n= 3150 vs. 2469) and rurality (major cities vs. remote, n=9598 vs. 839). Result(s): Patients from socioeconomically-disadvantaged areas experienced a greater burden of cardiovascular risk factors including diabetes, obesity and current smoking. Thirty-day mortality (disadvantaged 1.6% vs. advantaged 1.6%, p>0.99) was similar between groups as was late survival (7 years: 83+/-0.9% vs. 84+/-1.0%, p=0.79). Those from major cities were less likely to undergo urgent surgery. There was similar 30-day mortality (major cities: 1.6% vs. remote: 1.5%, p=0.89). Patients from major cities experienced improved survival at seven years (84+/-0.5% vs. 79+/-2.0%, p=0.010). Propensity-analysis did not show socioeconomic status or rurality to be associated with late outcomes. Conclusion(s): Patients presenting for coronary artery surgery from different socioeconomic and geographic backgrounds exhibit differences in their clinical profile. Patients from more rural and remote areas appear to experience poorer long-term survival, though this may be partially driven by the population's clinical profile. © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).

Introduction: Abnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5). Methods: Ultrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics. Results: In normal mouse fetuses between E14.5-18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here. Conclusion: Our EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels., NA

Objectives: Controversy continues over the optimal revascularisation strategy for patients with multi-vessel coronary artery disease. Clinical characteristics, risk profile, and mortality of patients undergoing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are thought to differ but there are limited contemporary comparative data. Method(s): We compared clinical characteristics, in-hospital and 30-day mortality of 3841 consecutive patients undergoing isolated CABG and 4417 undergoing PCI. Independent predictors of 30-day mortality were determined by multiple logistic regression analysis. Result(s): CABG patients were older (p < 0.01). The CABG group had a higher incidence of diabetes, heart failure, left ventricular ejection fraction <45%, multi-vessel coronary artery, peripheral vascular and cerebro-vascular disease (all p < 0.01). Patients undergoing PCI had a higher incidence of recent myocardial infarction (MI) as the indication for revascularisation (p < 0.01). In-hospital and 30-day mortality was 1.8% and 1.7% in the CABG group, and 1.4% and 1.8% in the PCI group, respectively. Independent predictors of 30-day mortality after CABG were age (odds ratio 1.1 per year, 95% confidence interval 1.0-1.1), cardiogenic shock (4.10, 1.7-10.5) and previous CABG (6.6, 2.4-17.7). Predictors after PCI were diabetes (2.7, 1.4-5.1), female gender (3.0, 1.6-5.5), renal failure (3.2, 1.2-8.0), MI < 24 h (4.0, 2.2-7.6), left main intervention (5.4, 1.0-27.7), heart failure (6.0, 2.6-14.0) and cardiogenic shock (11.7, 5.4-25.2). Conclusion(s): In contemporary clinical practice, CABG is preferred in patients with multi-vessel coronary and associated non-coronary vascular disease, while PCI is the dominant strategy for acute MI. Despite this, in-hospital and 30-day mortality rates were similar. Predictors of early mortality after CABG differ to those of PCI. © 2008 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of

Objectives: To determine the association between previous percutaneous coronary intervention (PCI) and results after coronary artery bypass graft surgery (CABG). Background(s): Increasing numbers of patients undergoing CABG have previously undergone PCI. Method(s): We analyzed consecutive first-time isolated CABG procedures within the Australasian Society of Cardiac and Thoracic Surgeons Database from June 2001 to May 2008. Logistic regression and propensity score analyses were used to assess the risk-adjusted impact of prior PCI on in-hospital mortality and major adverse cardiac events. Cox regression model was used to assess the effect of prior PCI on mid-term survival. Result(s): Of 13,184 patients who underwent CABG, 11,727 had no prior PCI and 1,457 had prior PCI. Mean follow-up was 3.3 +/- 2.1 years. Patients without prior PCI had a higher EuroSCORE value (4.4 +/- 3.3 vs. 3.6 +/- 3.0, p < 0.001), were older, and more likely to have left main stem stenosis and recent myocardial infarction. There was no difference in unadjusted in-hospital mortality (1.65% vs. 1.55%, p = 0.78) or major adverse cardiac events (3.0% vs. 3.0%, p = 0.99) between patients with or without prior PCI. After adjustment, prior PCI was not a predictor of in-hospital (odds ratio: 1.22, 95% confidence interval [CI]: 0.76 to 2.0, p = 0.41) or mid-term mortality at 6-year follow-up (hazard ratio: 0.94, 95% CI: 0.75 to 1.18, p = 0.62). Conclusion(s): In this large registry study, prior PCI was not associated with increased short- or mid-term mortality after CABG. Good outcomes can be obtained in the group of patients undergoing CABG who have had previous PCI. © 2009 American College of Cardiology Foundation.

Objective: Mitral valve surgery may be regarded as less favourable for training, due to greater mortality risk, technical complexity, and difficulty for the supervisor to observe. We examined this perception by reviewing a multicentre experience. Method(s): We analysed a multicentre database over a 7-year period containing 2216 isolated and combined mitral procedures. Of these, 2048 were performed by consultants and 168 by trainees (92% vs 8%) of varying seniority. Preoperative characteristics, early postoperative outcomes and 6-year survival were compared between groups. Propensity-score matching was performed to correct for group differences. Result(s): Trainees were less likely to operate on patients, who had previously undergone coronary surgery (consultant 4.3% vs trainee 1.2%, p=0.043) and those with moderate to severe mitral regurgitation (86% vs 81%, p=0.012). There were no other statistically significant differences in preoperative variables, such as urgency, endocarditis and left-ventricular dysfunction. There were similar rates of mitral valve repair (48% vs 51%, p=0.48). Trainees were more likely to operate on rheumatic valve pathology (20% vs 28%, p=0.012). Intra-operatively, trainees had longer aortic cross-clamp times (119 +/- 52 vs 136 +/- 50. min, p=0.0001). At 30 days, mortality was comparable (4.5% vs 3.6%, p=0.56) with a trend towards higher any mortality/morbidity in consultant procedures (33% vs 26%, p=0.059). At 6 years, survival was similar (79 +/- 1.4% vs 78 +/- 4.0%, p=0.73). After derivation of 142 propensity-score-matched patient pairs, trainees cases still experienced longer cross-clamp times (121 +/- 58 vs 137 +/- 52. min, p=0.023), but there was similar 30-day mortality (4.2% vs 3.5%, p>0.99) and any mortality/morbidity (28% vs 24%, p=0.52). Six-year survival between matched pairs was also similar (74 +/- 7.2% vs 80 +/- 4.4%, p=0.64). Trainee status did not predict early or late adverse events after multivariate Cox regression with and

Objective: There is an important role for accurate risk prediction models in current cardiac surgical practice. Such models enable benchmarking and allow surgeons and institutions to compare outcomes in a meaningful way. They can also be useful in the areas of surgical decision-making, preoperative informed consent, quality assurance and healthcare management. The aim of this study was to assess the performance of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) model on the Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) patient database. Method(s): The additive and logistic EuroSCORE models were applied to all patients undergoing cardiac surgery at six institutions in the state of Victoria between 1st July 2001 and 4th July 2005 within the ASCTS database who have complete data. The entire cohort and a subgroup of patients undergoing coronary artery bypass grafting (CABG) only were analysed. Observed and predicted mortalities were compared. Model discrimination was tested by determining the area under the receiver operating characteristic (ROC) curve. Model calibration was tested by the Hosmer-Lemeshow chi-square test. Result(s): Eight thousand three hundred and thirty-one patients with complete data were analysed. There were significant differences in the prevalence of risk factors between the ASCTS and European cardiac surgical populations. Observed mortality was 3.20% overall and 2.00% for the CABG only group. The EuroSCORE models over estimated mortality (entire cohort: additive predicted 5.31%, logistic predicted 8.76%; CABG only: additive predicted 4.25%, logistic predicted 6.19%). Discriminative power of both models was very good. Area under ROC curve was 0.83 overall and 0.82 for the CABG only group. Calibration of both models was poor as mortality was over predicted at nearly all risk deciles. Hosmer-Lemeshow chi-square test returned P-values less than 0.05. Conclusion(s): The additive and logistic EuroSCORE does not accu

Background: The proportion of elderly (<80 years) patients undergoing coronary artery bypass surgery (CABG) is increasing. Method(s): A retrospective analysis of data, collected by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program between June 2001 and December 2009 was performed. Isolated CABG was performed in 21,534 patients; of these, 1,664 (7.7%) were at least 80 years old (group 1). Patient characteristics, morbidity, and short-term mortality of these patients were compared with those aged less than 80 years (group 2). The long-term outcome of group 1 patients after CABG surgery was compared with an age and sex-matched Australian population. Result(s): Patients over 80 years old were more likely to be female (36.6% vs 17.3%, p < 0.001) and presented significantly more often with heart failure, hypertension, and triple-vessel disease (all p < 0.05). The 30-day mortality was higher in group 1 patients (4.2% vs 1.5%, p < 0.001). Group 1 patients also had an increased risk of complications, including prolonged (>24 hours) ventilation (14.2% vs 8.2%, p < 0.001), renal failure (7.3% vs 3.4%, p < 0.001), and mean intensive care unit stay (60.7 vs 42.5 hours, p < 0.001). The 5-year survival of elderly patients (73%) was comparable with the age-matched Australian population. Independent risk factors for 30-day mortality in group 1 patients included preoperative renal failure (p = 0.010), congestive heart failure (p = 0.014), and a nonelective procedure (p = 0.016). Conclusion(s): Elderly patients who undergo isolated CABG have significantly lower perioperative risks than have been previously reported. The long-term survival of these patients is comparable with an age-adjusted population. © 2011 The Society of Thoracic Surgeons.

Objective: The effect of training on outcomes in cardiac surgery is poorly studied. We aimed to study the results of coronary artery bypass grafting procedures performed by surgeons in training across our state with respect to short- and midterm postoperative outcomes. Method(s): All coronary artery bypass grafting surgeries performed by trainee surgeons between July 2001 and December 2006 were compared with those performed by consultant surgeons using mandatory prospectively collected statewide data. Early mortality; prolonged ventilation or intensive care unit stay; return to operating theater for bleeding, stroke, myocardial infarction, or renal failure; and 5-year survival were compared using propensity score analysis. Result(s): A total of 7745 surgeries were included in this study. Trainees performed 983 (13%) surgeries. Trainee surgeries had longer perfusion and crossclamp times. Crude early postoperative outcomes were similar between trainee and consultant surgeries. After propensity score adjustment, early outcomes remained similar, with the exception of myocardial infarction (0.8% in trainee surgeries vs 0.4% in consultant surgeries, P = .046). Adjusted 1-, 3-, and 5-year survivals were similar between trainee and consultant surgeries: 95.3% versus 95.5%, 90.8% versus 92.0%, and 86.3% versus 87.1%, respectively. Conclusion(s): Coronary artery bypass grafting performed by trainee surgeons within a supervised program is safe with acceptable short- and midterm outcomes. © 2009 The American Association for Thoracic Surgery.

Background: Prosthesis - patient mismatch (PPM) is characterised by the effects of inadequate prosthesis size relative to body surface area (BSA). It is uncertain whether PPM after mitral valve replacement impacts upon clinical outcome. This was examined in an Australian population. Method(s): From 2001 to 2009, 1006 mechanical and bioprosthetic mitral valves were implanted across 10 institutions. Effective orifice areas (EOA) were obtained from a literature review of in vivo echocardiographic data. Absent, moderate and severe PPM was defined as an indexed EOA (EOA/BSA) of >1.20 cm2/m2, >0.90 to <=1.20 cm2/m2 and <=0.9 cm 2/m2, respectively. Early outcomes and 7-year survival were compared between these three groups. Result(s): PPM was absent in 34%, moderate in 53% and severe in 13% of patients. Patients with PPM were more likely to be male (42% vs 52% vs 62%, p<0.0001) and obese (14% vs 20% vs 56%, p<0.0001). Postoperatively there was similar 30-day mortality (5% vs 5% vs 6%, p=0.83) and early any mortality/morbidity (24% vs 27% vs 29%, p=0.40). Seven-year survival was similar between groups (72+/-4.1% vs 76+/-3.2% vs 69+/-10.3%, p=0.76). PPM did not predict adverse events after logistic and Cox regressions with and without propensity score adjustment. Subgroup analyses of those with isolated mitral valve surgery, patients with preoperative congestive heart failure and non-obese patients failed to show an association between PPM and mid-term mortality. Conclusion(s): Overall, PPM was not associated with poorer early outcomes or mid-term survival. Oversizing valves may be technically hazardous and do not yield superior outcomes. Easier implantation by appropriate sizing appears justified.

Objective: To develop a multivariable logistic risk model for predicting early mortality following aortic valve replacement (AVR) in adults, and to compare its performance against existing AVR-dedicated models. Method(s): Prospectively collected data from the Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) database project were used. Thirty-five preoperative variables from AVR literature were considered for analysis by chi-square method and multiple logistic regression. Using the bootstrap re-sampling technique for variable selection, five plausible models were identified. Based on models' calibration, discrimination and predictive capacity during n-fold validation, a final model, the AVR-Score, was chosen. An additive score, derived from the final model, was also validated externally in a consecutive cohort. The performance of AVR-dedicated risk models from the North West Quality Improvement Program (NWQIP) and the Northern New England Cardiovascular Study (NNE) groups were also assessed using the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow (H-L) chi-square test. Result(s): Between July 2001 and June 2008, a total of 3544 AVR procedures were performed. Early mortality was 4.15%. The AVR-Score contained the following predictors: age, New York Heart Association class, left main disease, infective endocarditis, cerebrovascular disease, renal dysfunction, previous cardiac surgery and estimated ejection fraction. Our final model (AVR-Score) obtained an average area under ROC curve of 0.78 (95% confidence interval (CI): 0.76, 0.80) and an H-L p-value of 0.41 (p> 0.05) during internal validation, indicating good discrimination and calibration capacity. External validation of the additive score on a consecutive cohort of 1268 procedures produced an ROC of 0.73 (0.62, 0.84) and an H-L p-value of 0.48 (p> 0.05). The NWQIP and NNE risk models achieved acceptable discrimination of ROC of 0.77 (0.73, 0.81). However, both models obtained H

Background: Reoperative coronary artery bypass grafting (redo CABG) shows improving outcomes, but with varying degrees of improvement. We assessed contemporary outcomes after redo CABG to determine if redo status is still a risk factor for early postoperative complications and midterm survival. Method(s): Isolated CABG procedures (June 1, 2001 to May 31, 2008) within the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database were included. Redo status as a predictor for early outcomes was assessed with logistic regression analysis. Midterm survival was determined from the National Death Index. Effect of redo status on midterm survival was assessed using a Cox proportional hazards model. Result(s): Inclusion criteria were met by 13,436 patients, and 458 (3.4%) underwent redo CABG. Operative mortality was 4.8% for redo CABG and 1.8% for first-time CABG (p < 0.001). After adjustment, redo status remained a predictor for operative mortality (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3 to 3.6), myocardial infarction (OR, 2.8; 95% CI, 1.6 to 6.0), and prolonged ventilation (OR, 1.5; 95% CI, 1.1 to 2.0). Unadjusted survival was lower for the redo CABG group vs the first-time CABG group at up to 6 years (p = 0.01, log-rank test. After adjusting for differences in patient variables, redo status was not a predictor of midterm survival (OR, 1.03; 95% CI, 0.78 to 1.35; p = 0.85). Conclusion(s): Early postoperative outcomes of redo CABG are encouraging. Midterm survival is excellent; however, redo remains a significant risk factor for operative mortality in contemporary practice. © 2009 The Society of Thoracic Surgeons.