Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning.

The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches. Applying this approach to a dataset of optical coherence tomography images, we demonstrate performance comparable to that of human experts in classifying age-related macular degeneration and diabetic macular edema. We also provide a more transparent and interpretable diagnosis by highlighting the regions recognized by the neural network. We further demonstrate the general applicability of our AI system for diagnosis of pediatric pneumonia using chest X-ray images. This tool may ultimately aid in expediting the diagnosis and referral of these treatable conditions, thereby facilitating earlier treatment, resulting in improved clinical outcomes. VIDEO ABSTRACT.

P16INK4a Upregulation Mediated by SIX6 Defines Retinal Ganglion Cell Pathogenesis in Glaucoma.

Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrate that the genetic effect of the SIX6 risk variant (rs33912345, His141Asn) is enhanced by another major POAG risk gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform INK4a). We further show that the upregulation of homozygous SIX6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence, as evidenced in a mouse model of elevated IOP and in human POAG eyes. Our data indicate that SIX6 and/or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult human retinas. Our study provides important insights linking genetic susceptibility to the underlying mechanism of RGC death and provides a unified theory of glaucoma pathogenesis.

Impact of prehospital opioid dose on angiographic and clinical outcomes in acute coronary syndromes.

BACKGROUND: An adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS. METHODS: Patients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not. RESULTS: 10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001). CONCLUSIONS: Opioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.

Lens regeneration using endogenous stem cells with gain of visual function.

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

Mitral Valve Regurgitation After Lung Transplantation: Aetiology, Management and Outcome.

BACKGROUND: Problematic mitral regurgitation (MR) may develop following lung transplantation (LTx). There is limited information on the management of MR in LTx patients, as such we sought to evaluate our centre's experience. METHODS: From 2000 to 2019, 1,054 patients underwent LTx at our centre (896 bilateral, 158 single). We identified patients in whom significant MR developed at any point post-LTx. The aetiology of MR, management and outcome were retrospectively analysed. RESULTS: Eight (8) patients developed severe MR post-LTx, six following bilateral LTx and two following single LTx. Lung transplantation indications included interstitial lung disease (n=5), chronic obstructive pulmonary disease (n=2) and pulmonary arterial hypertension (n=1). Severe MR occurred intraoperatively (n=1), postoperative day 1 (n=1) with the remaining six cases between 80 and 263 days post-LTx. The aetiology was noted to be due to severe left ventricular dysfunction following unmasking of a chronically pulmonary hypertension-related under-preloaded left ventricle in one case, and in the remaining seven patients causes included myxomatous degeneration, ischaemic MR, and functional MR due to annular dilatation. In the patient with intraoperative severe MR, the MR became mild with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and in the remaining seven patients a variety of procedures were used, including mitral valve repair, valve replacement and transcatheter edge-to-edge mitral valve repair. All patients survived the mitral procedure. Two (2) deaths occurred at 12.9 years (stroke) and 5 years (cancer) from mitral valve surgery. CONCLUSIONS: Development of significant mitral valve regurgitation is a rare but morbid complication after lung transplantation. This may represent the progressive natural history of pre-existing degenerative mitral valve disease and rarely, early after transplantation may be related to changes in ventricular geometry. Management of severe MR can follow the same management approach as in the non-transplant community, with the expectation of similarly good results.

Nanoparticle biointerfacing by platelet membrane cloaking.

Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.

Comparison of Variations Between Spectral Doppler and Gaussian Surface Integration Methods for Umbilical Vein Blood Volume Flow.

OBJECTIVES: We are studying a new method for estimating blood volume flow that uses 3-dimensional ultrasound to measure the total integrated flux through an ultrasound-generated Gaussian surface that intersects the umbilical cord. This method makes none of the assumptions typically required with standard 1-dimensional spectral Doppler volume flow estimates. We compared the variations in volume flow estimates between techniques in the umbilical vein. METHODS: The study was Institutional Review Board approved, and all 12 patients gave informed consent. Because we had no reference standard for the true umbilical vein volume flow, we compared the variations of the measurements for the flow measurement techniques. At least 3 separate spectral Doppler and 3 separate Gaussian surface measurements were made along the umbilical vein. Means, standard deviations, and coefficients of variation (standard deviation/mean) for the flow estimation techniques were calculated for each patient. P < .05 was considered significant. RESULTS: The ranges of the mean volume flow estimates were 174 to 577 mL/min for the spectral Doppler method and 100 to 341 mL/min for the Gaussian surface integration (GSI) method. The mean standard deviations (mean ± SD) were 161 ± 95 and 45 ± 48 mL/min for the spectral Doppler and GSI methods, respectively (P < .003). The mean coefficients of variation were 0.46 ± 0.17 and 0.18 ± 0.14 for the spectral Doppler and GSI methods respectively (P < 0.002). CONCLUSIONS: The new volume flow estimation method using 3-dimensional ultrasound appears to have significantly less variation in estimates than the standard 1-dimensional spectral Doppler method.

DNA methylation markers for diagnosis and prognosis of common cancers.

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis.

Long-Term Outcomes of Childhood Left Ventricular Noncompaction Cardiomyopathy: Results From a National Population-Based Study.

BACKGROUND: Long-term outcomes for childhood left ventricular noncompaction (LVNC) are uncertain. We examined late outcomes for children with LVNC enrolled in a national population-based study. METHODS: The National Australian Childhood Cardiomyopathy Study includes all children in Australia with primary cardiomyopathy diagnosed before 10 years of age between 1987 and 1996. Outcomes for subjects with LVNC with a dilated phenotype (LVNC-D) were compared with outcomes for those with dilated cardiomyopathy. Propensity-score analysis was used for risk factor adjustment. RESULTS: There were 29 subjects with LVNC (9.2% of all cardiomyopathy subjects), with a mean annual incidence of newly diagnosed cases of 0.11 per 100 000 at-risk individuals. Congestive heart failure was the initial symptom in 24 of 29 subjects (83%), and 27 (93%) had LVNC-D. The median age at diagnosis was 0.3 (interquartile interval, 0.08-1.3) years. The median duration of follow-up was 6.8 (interquartile interval, 0.7-24.0) years for all subjects and 24.7 (interquartile interval, 23.3 - 27.7) years for surviving subjects. Freedom from death or transplantation was 48% (95% confidence interval [CI], 30-65) at 10 years after diagnosis and 45% (95% CI, 27-63) at 15 years. In competing-risk analysis, 21% of subjects with LVNC were alive with normal left ventricular systolic function, and 31% were alive with abnormal function at 15 years. Propensity-score matching between subjects with LVNC-D and those with dilated cardiomyopathy suggested a lower freedom from death/transplantation at 15 years after diagnosis in the subjects with LVNC-D (LVNC-D, 46% [95% CI, 26-66] versus dilated cardiomyopathy, 70% [95% CI, 42-97]; P=0.08). Using propensity-score inverse probability of treatment-weighted Cox regression, we found evidence that LVNC-D was associated with a greater risk of death or transplantation (hazard ratio, 2.3; 95% CI, 1.4-3.8; P=0.0012). CONCLUSIONS: Symptomatic children with LVNC usually present in early infancy with a predominant dilated phenotype. Long-term outcomes are worse than for matched children with dilated cardiomyopathy.

Hypothyroidism associated with therapy for multi-drug-resistant tuberculosis in Australia.

BACKGROUND: Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multi-drug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. AIM: To identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia. METHODS: Retrospective multicentre study of MDR-TB patients from five academic centres covering tuberculosis (TB) services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if the thyroid-stimulating hormone was elevated and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions. Our main outcome measured was the cumulative proportion of hypothyroidism (at 5 years from treatment initiation). RESULTS: Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% confidence interval (CI): 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (P = 0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication. CONCLUSIONS: Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement, if initiated, may not need to be continued after MDR-TB treatment is completed.

Identifying low-grade cellular rejection after heart transplantation in children by using gene expression profiling.

Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection after heart transplantation but is costly and invasive. This study aims to distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart transplantation in children by using global gene expression profiling in blood. A total of 106 blood samples with corresponding EMB from 18 children who underwent heart transplantation from 2011 to 2014 were analyzed (18 baseline/pretransplantation samples, 88 EMB samples). Corresponding rejection grades for each blood sample were 0R in 39% (34/88), 1R in 51% (45/88), and 2R in 10% (9/88). mRNA from each sample was sequenced. Differential expression analysis was performed at the gene level. A k-nearest neighbor (kNN) analysis was applied to the most differentially expressed (DE) genes to identify rejection after transplantation. Mean age at transplantation was 10.0 ± 5.4 yr. Expression of B cell and T cell receptor sequences was used to measure the effect of posttransplantation immunosuppression. Follow-up samples had lower levels of immunoglobulin gene families compared with pretransplantation ( P < 3E-5) (lower numbers of activated B cells). T cell receptor alpha and beta gene families had decreased expression in 0R samples compared with pretransplantation ( P < 4E-5) but recovered to near baseline levels in 1R/2R samples. kNN using the most DE gene (MKS1) and k = 9 nearest neighbors correctly identified 83% (73/88) of 1R/2R compared with 0R by leave-one-out cross validation. Using a genomic approach we can distinguish low-grade cellular allograft rejection (1R/2R) from no rejection (0R) after heart transplantation in children despite a wide age range.

Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma.

An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive 'liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (P < 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (P < 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.

Manual Braiding of GoreTex Neochords to Ensure Correct Length in Mitral Valve Repair.

Ascertaining the correct length of neochords during mitral valve repair is challenging. We describe a modified technique of chordal replacement where a GoreTex (W.L. Gore and Assoc, Inc, Flagstaff, AZ, USA) sutures are repeatedly tied so as to braid the suture to the optimal length before sutures are passed through the mitral leaflet. The length of the braided chord remains fixed when tying on the atrial side. For bileaflet repairs, a second suture is incorporated into the initial chord to create a "Y" braided neo-chord configuration. This technique facilitates precision in mitral repair.

Rapid-Deployment Versus Conventional Bio-Prosthetic Aortic Valve Replacement.

BACKGROUND: The use of rapid-deployment aortic valve replacement (RD-AVR) has burgeoned in recent years. There are few studies comparing RD-AVR to conventional aortic valve replacement (cAVR) and no studies where both were inserted via full sternotomy. As such, we reviewed our experience and compared the two approaches. METHODS: From 2008 to 2015, 597 patients underwent isolated aortic valve replacement ± coronary artery bypass grafting (CABG) at a single centre. During this period, 41 (7%) patients received RD-AVR and 556 (93%) received cAVR. Of those receiving RD-AVR, surgical access was via full median sternotomy in 40 (98%). Propensity score matching yielded 41 matched pairs. Perioperative outcomes were compared. RESULTS: After propensity score matching, the RD-AVR group had shorter aortic cross clamp (X-clamp) (RD-AVR: 71±33min vs. cAVR: 106±42min, p<0.01) and cardiopulmonary bypass (CPB) times (95±42min vs. 134±47min, p<0.01). There was no difference in 30-day mortality (RD-AVR: 2% vs. cAVR: 2%, p>0.99). RD-AVR patients required shorter mean ventilation (17±25 vs. 63±131hrs, p<0.01) and intensive care unit (ICU) stay (51±45 vs. 108±157hrs, p=0.03) times. RD-AVR also had reduced rates of new postoperative atrial arrhythmias (8% vs. 20%, p=0.02). Total length of postoperative hospital stay was similar. Haemodynamic performance for the RD-AVR was within acceptable limits. CONCLUSIONS: The use of RD-AVR results in shorter X-clamp and CPB times and is associated with reductions in perioperative morbidity. RD-AVR is becoming a valuable component of the surgeon's armamentarium in selected patients. Long-term follow-up will reveal the full potential of these devices.

Joint Antiangiogenic Effect of ATN-161 and Anti-VEGF Antibody in a Rat Model of Early Wet Age-Related Macular Degeneration.

The wet form of age-related macular degeneration (AMD) is a leading cause of blindness among elderly Americans and is characterized by abnormal vessel growth, termed choroidal neovascularization (CNV). Integrin α5ß1 is a transmembrane receptor that binds matrix macromolecules and proteinases to stimulate angiogenesis. We recently demonstrated that integrin α5ß1 plays a critical role in the development of choroidal neovascularization. In this study, we determined the role and underlying mechanisms of integrin α5ß1 in angiogenesis in human choroidal endothelial cells and evaluated the antiangiogenic effects of delivering a combination therapy of ATN-161, an integrin α5ß1 inhibitor, and an anti-VEGF monoclonal antibody to rats with laser-induced CNV. Vascular endothelial growth factor (VEGF) is a signaling protein that stimulates vasculogenesis and angiogenesis through a pathway that is distinct from the integrin α5ß1 signaling pathway. Our results indicate that fibronectin binds to integrin α5ß1 and synergizes VEGF-induced angiogenesis via two independent signaling pathways, FN/integrin α5ß1/FAK/ERK1/2 and FN/integrin α5ß1/FAK/AKT. Integrin α5 knockdown by shRNA inhibits endothelial cell migration, tube formation, and proliferation, while ATN-161 only partially decreases integrin α5 function. Treatment with ATN-161 combined with anti-VEGF antibody showed joint effects in attenuating angiogenesis. In summary, our results provide the first evidence for the mechanisms by which integrin α5ß1 is involved in ocular pathological neovascularization in vivo, suggesting that dual inhibition of integrin α5ß1 and VEGF may be a promising novel therapeutic strategy for CNV in wet AMD.

Transcatheter versus Surgical Aortic Valve Replacement in High-risk Patients: A propensity-score matched analysis.

BACKGROUND: There is limited data from Australia and New Zealand comparing transcatheter aortic valve implantation (TAVI) with conventional surgical aortic valve replacement (sAVR). METHODS: Between 2009 and 2015, 64 patients underwent TAVI and 669 underwent sAVR at a single centre. Patients' peri-operative details were analysed and compared between groups. Propensity-score matching was performed for risk adjustment. RESULTS: Patients receiving TAVI were older (mean age in years TAVI: 83.9±4.6 vs. sAVR: 71±9.9, P<0.001), and were more likely to be female (TAVI: 67%, 43/64, vs. sAVR: 32%, 217/669, P <0.001). Unadjusted 30-day mortality was comparable between groups (2/64, 3% vs. 22/669, 3%, P >0.99). The matched analysis revealed comparable 30-day mortality (TAVI: 2/44, 5% vs. sAVR: 2/44, 5%, P > 0.99). New atrial arrhythmia occurred more frequently within the sAVR cohort (TAVI: 1/44, 2% vs. sAVR 18/44, 41%, P <0.001). Complete heart block requiring permanent pacemaker was more frequent amongst the TAVI cohort (TAVI: 10/44, 23% vs. sAVR 2/44, 5%, P=0.039). At two years, survival was comparable between groups (TAVI: 74±1.7 vs. sAVR: 80±0.1%, P=0.65). CONCLUSION: This single centre experience suggests that TAVI is a valuable treatment option for high-risk surgical patients with comparable survival.

Peri-operative Levosimendan in Patients Undergoing Cardiac Surgery: An Overview of the Evidence.

Levosimendan, a calcium sensitiser, has recently emerged as a valuable agent in the peri-operative management of cardiac surgery patients. Levosimendan is a calcium-sensitising ionodilator. By binding to cardiac troponin C and reducing its calcium-binding co-efficient, it enhances myofilament responsiveness to calcium and thus enhances myocardial contractility without increasing oxygen demand. Current evidence suggests that levosimendan enhances cardiac function after cardiopulmonary bypass in patients with both normal and reduced left ventricular function. In addition to being used as post-operative rescue therapy for low cardiac output syndrome, a pre-operative levosimendan infusion in high risk patients with poor cardiac function may reduce inotropic requirements, the need for mechanical support, the duration of intensive care admissions as well as post-operative mortality. Indeed, it is these higher-risk patients who may experience a greater degree of benefit. Larger, multicentre randomised trials in cardiac surgery will help to elucidate the full potential of this agent.

Impact of socioeconomic status and rurality on early outcomes and mid-term survival after CABG: insights from a multicentre registry.

BACKGROUND: We examined whether socioeconomic status and rurality influenced outcomes after coronary surgery. METHODS: 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). RESULTS: 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: 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.