PubMed Posts

There is an urgent need for models that faithfully replicate heart failure with preserved ejection fraction (HFpEF), now recognized as the most common form of heart failure in the world. In vitro approaches have several shortcomings, most notably the immature nature of stem cell-derived human cardiomyocytes [induced pluripotent stem cells (iPSC)] and the relatively short lifespan of primary cardiomyocytes. Three-dimensional ‘organoids’ incorporating mature iPSCs with other cell types such as endothelial cells and fibroblasts are a significant advance, but lack the complexity of true myocardium. Animal models can replicate many features of human HFpEF, and rodent models are the most common, and recent attempts to incorporate haemodynamic, metabolic, and ageing contributions are encouraging. Differences relating to species, physiology, heart rate, and heart size are major limitations for rodent models. Porcine models mitigate many of these shortcomings and approximate human physiology more closely, but cost and time considerations limit their potential for widespread use. Ex vivo analysis of failing hearts from animal models offer intriguing possibilities regarding cardiac substrate utilisation, but are ultimately subject to the same constrains as the animal models from which the hearts are obtained. Ex vivo approaches using human myocardial biopsies can uncover new insights into pathobiology leveraging myocardial energetics, substrate turnover, molecular changes, and systolic/diastolic function. In collaboration with a skilled cardiothoracic surgeon, left ventricular endomyocardial biopsies can be obtained at the time of valvular surgery in HFpEF patients. Critically, these tissues maintain their disease phenotype, preserving inter-relationship of myocardial cells and extracellular matrix. This review highlights a novel approach, where ultra-thin myocardial tissue slices from human HFpEF hearts can be used to assess changes in myocardial structure and function. We discuss current approaches to modelling HFpEF, describe in detail the novel tissue slice model, expand on exciting opportunities this model provides, and outline ways to improve this model further.

Data from animal models is now available to initiate assessment of human safety and feasibility of wide-angle three-dimensional intracardiac echocardiography (3D ICE) to guide point-of-care implantation of percutaneous left ventricular assist devices in critical care settings. Assessment of these combined new technologies could be best achieved within a surgical institution with pre-existing expertise in separate utilization of ICE and Impella.

No abstract available

Objectives: Full sternotomy (FS) is the common surgical access for patients undergoing open aortic valve replacement (AVR) with concomitant supracommissural replacement of the tubular ascending aorta. Since minimally invasive approaches are being used with increasing frequency in cardiac surgery, the aim of this study was to compare outcomes of patients undergoing AVR with supracommissural replacement of the tubular ascending aorta via FS versus partial upper sternotomy (PS).

Methods: We included all patients who underwent elective AVR with concomitant supracommissural replacement of the tubular ascending aorta at our institution between 2000 and 2015. Exclusion criteria were emergency surgery, other major concomitant procedures and reoperations. After 2:1 propensity score matching, outcomes of patients with PS and FS were compared.

Results: A total of 652 consecutive patients were included, 117 patients operated via PS and 234 patients operated via FS. Cardiopulmonary bypass time and aortic cross-clamp time of the PS and FS groups were 89 vs 92 min (P = 0.2) and 65 vs 70 min (P = 0.3), respectively. Postoperative morbidity was low and there were no significant differences in postoperative outcomes between patient groups. In-hospital mortality was 1.7% in the PS vs 0.4% in the FS group (P = 0.3). Kaplan-Meier analysis revealed no difference in mid-term survival (P = 0.3). Reoperation rates for valve or aortic complications were very low with no significant difference between groups.

Conclusions: In a high-volume centre with extensive experience in minimally invasive cardiac surgery, AVR with concomitant supracommissural replacement of the tubular ascending aorta via PS results in similar outcomes with regard to safety and longevity when compared to conventional FS.

Background: Comparative costing studies using real-world data stratified by patient case-mix, are valuable to decision makers for making reimbursement decisions of new interventions. This study evaluated real-world hospital admissions and short-term costs of transcatheter aortic valve implantation (TAVI) and isolated surgical aortic valve replacement (SAVR) for patients with aortic stenosis, stratified by the Society of Thoracic Surgeons (STS) risk scores.

Methods: Retrospective analysis of consecutive patients with a principal diagnosis of aortic stenosis who underwent isolated valve replacement at a single tertiary hospital, January 2012-December 2017. Patients were followed-up for 30 days post-procedure or until hospital discharge if index hospitalisation was greater than 30 days. Intensive care unit (ICU) and hospital length of stay (days), and costs in 2018 Australian dollars for the index procedure and 30-day follow-up were assessed. Multivariable generalised linear and two-part models with gamma distribution and log link function adjusting for Society of Thoracic Surgeons (STS) risk group and key sociodemographic characteristics were used.

Results: Of 488 patients, 61% males, median age 78 years (IQR 14 years), 221 (45%) received transcatheter aortic valve replacement (TAVI) and 267 (55%) received surgical aortic valve replacement (SAVR). STS risk scores were low (28%), intermediate (46%) and high (26%) for TAVI patients, and low (85%), intermediate (12%) and high (3%) for SAVR patients. When adjusted, TAVI length of stay was 57% shorter than SAVR (95% CI 31-83%, p<0.001) for intensive care unit (ICU) admission, and 64% shorter (95% CI 47-81%, p<0.001) for hospital admissions. TAVI costs were 13% lower than SAVR (95% CI 4-22%, p=0.005).

Conclusion: This data suggests short-term health care costs are lower for patients with aortic stenosis undergoing TAVI than SAVR. A further roll-out of the TAVI program in hospitals across Australia may result in savings to the health system.

Background: Although preoperative immunotherapy (IT) is increasingly utilized for non-small-cell lung cancer (NSCLC), there remains a paucity of robust clinical data on its safety and long-term survival. Our objective was to evaluate the perioperative outcomes and survival associated with IT followed by surgery for patients with NSCLC.

Methods: Outcomes of patients with NSCLC who underwent lung resection after preoperative chemotherapy (PC)±radiation or IT (with or without chemotherapy or chemoradiation) in the National Cancer Data Base (2010-2017) were evaluated using Kaplan Meier analysis, multivariable logistic regression, multivariable Cox proportional hazards analysis, and propensity score-matched analysis.

Results: From 2010-2017, 236 patients (2.2%) received IT and 10,715 patients received PC followed by surgery. There were no significant differences between the IT and PC groups with regard to margin positivity (8.5%[n=20] vs 7.5%[n=715], P=0.98), 30-day readmission (4.2%[n=10] vs 4.1%[n=440], P=0.87), and 30-day mortality (0.4%[n=1] vs 2.4%[n=253], P=0.25). The IT and PC groups had similar overall survival (5-year survival: 63% [95% CI, 50-74] vs 51% [95% CI, 50-52]; log-rank P=0.06; multivariable adjusted hazard ratio 0.98 [95% CI, 0.67-1.41], P=0.90). A propensity score-matched analysis of 344 patients, well-matched by preoperative characteristics, showed no significant differences in short-term outcomes and overall survival (log-rank P=1.00) between the two groups.

Conclusions: In this national analysis, preoperative immunotherapy followed by surgery for NSCLC was found to be safe and feasible with similar short-term outcomes and overall survival when compared to preoperative chemotherapy followed by surgery.

Background: Although transcatheter aortic valve implantation (TAVI) has become the standard treatment for severe aortic stenosis in high-risk patients in Australia, there is still limited data on long term survival.

Methods: All patients undergoing TAVI at a single tertiary institution between September 2009 and December 2015 were included. The primary outcome was survival, by linkage of patients with the National Death Index of the Australian Institute of Health and Welfare. Post-procedure data and echocardiographic measurements were retrospectively analysed for all patients.

Results: A total of 186 patients were included. It was a high-risk patient population (mean EuroSCORE 31.5±20.5, mean age 83.0±8.2 years). Valve prostheses used were Edwards SAPIEN (ES) (Edwards, Irvine, CA, USA) in 16.1%, Edwards SAPIEN XT (ESXT) in 74.2%, and Medtronic CoreValve (MCV) (Medtronic, Minneapolis, MN, USA) in 9.7%. Median survival time for the entire cohort was 68.2 months (95% Confidence Interval [CI]; Lower Limit [LL] 58.0 months, Upper Limit [UL] not defined). The 2- and 5-year estimates of survival were 85% (LL 80%, UL 90%) and 56% (LL 48%, UL 66%), respectively. There was no statistically significant difference in median survival between the ES and ESXT valves, or implantation approach. Survival was greater in patients with creatinine <200 μmol/L compared to >200 μmol/L (68.8 months [LL 61.4, UL n/a] vs 48.0 months [LL 25.5, UL n/a]). Over the study period, there was a statistically significant trend in increasing mean transvalvular gradient (ES: 1.66 mmHg/yr, p=0.0058; ESXT: 2.50 mmHg/yr, p≤0.001) and maximum velocity (ESXT: 0.16 m/s/yr, p=0.004) and decreasing valve area (ESXT: -0.07 cm²/yr, p<0.001). There was substantial attrition of patient echocardiographic follow-up (number of echocardiograms followed up at 5 years=6, number at risk=41).

Conclusions: This study has demonstrated acceptable survival in a high-risk cohort of patients undergoing TAVI, with comparable results to larger international experiences. There was a trend for worsening haemodynamics that needs to be monitored. Future studies need to examine patient quality of life and the performance of newer generation prostheses.

Background: Patients with bicuspid aortic valve (BAV) with zero or two raphes have been under-represented in previous studies. Whether these patients have unique clinical courses remains unclear. We describe the indications for and types of surgery in patients with BAV, and describe differences between valve morphotypes.

Methods: Adults who had undergone aortic and/or aortic valve surgery for BAV disease at our centres were identified and classified according to the Sievers definitions.

Results: 317 patients were included (74.4% male, median age at surgery 62 years). Of these, 187 (59.0%) had aortic valve surgery, 7 (2.2%) aortic surgery, 120 (37.9%) combined valve and aortic surgery and 3 had a Ross procedure. Most patients had aortic stenosis (71.9%), followed by aortic regurgitation (16.7%). 30-day mortality was low (1.6%).The commonest valve morphology was type-1 (one raphe) in 89.6%; type-0 (no raphes) occurred in 7.9% and type-2 (two raphes) in 2.5%. Patients with type-2 valves were substantially younger at time of surgery than type-1 patients (median 36 vs 63 years, p = 0.008). A higher proportion of patients with type-0 valves required aortic surgery than those with type-1 (68.0% vs 37.3%, p = 0.007). There were no differences between groups for the indication for surgery, valvular abnormality or 30-day mortality.

Conclusions: The number of BAV raphes was independently and significantly associated with age at surgery and the need for aortic intervention. Patients with type 0 and type 2 valves are a small but important proportion of the BAV population, potentially requiring different clinical surveillance and management.

Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand’s activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500-24000] versus VV 28,800 IU [IQR 17,300-40,800.00]; < 0.001. Twenty-eight patients (72%) survived to hospital discharge; comprising 53% of VA patients and 77% of VV patients. Significant differences between the coagulation profiles of VA and VV patients exist, and anticoagulation strategies for patients of these modalities should be different. Further research into the development of tailored anticoagulation strategies that include the mode of ECMO support need to be completed.

Objective: To assess the association between having a serious mental illness and surgical outcomes for adults, including in-hospital and 30-day mortality, post-operative complications, and hospital length of stay.

Study design: Systematic review and meta-analysis of publications in English to 30 July 2018 of studies that examined associations between having a serious mental illness and surgical outcomes for adults who underwent elective surgery. Primary outcomes were in-hospital and 30-day mortality, post-operative complications, and length of hospital stay. Risk of bias was assessed with the Quality in Prognosis Studies (QUIPS) tool. Studies were grouped by serious mental illness diagnosis and outcome measures. Odds ratios (ORs) or mean differences (MDs), with 95% confidence intervals (CIs), were calculated in random effects models to provide pooled effect estimates.

Data sources: MEDLINE, EMBASE, PsychINFO, and the Cochrane Library.

Data synthesis: Of the 3824 publications identified by our search, 26 (including 6 129 806 unique patients) were included in our analysis. The associations between having any serious mental illness diagnosis and having any post-operative complication (ten studies, 125 624 patients; pooled effect: OR, 1.44; 95% CI, 1.15-1.79) and a longer stay in hospital (ten studies, 5 385 970 patients; MD, 2.6 days; 95% CI, 0.8-4.4 days) were statistically significant, but not those for in-hospital mortality (three studies, 42 926 patients; OR, 1.21; 95% CI, 0.69-2.12) or 30-day mortality (six studies, 83 013 patients; OR, 1.85; 95% CI, 0.86-3.99).

Conclusions: Having a serious mental illness is associated with higher rates of post-operative complications and longer stays in hospital, but not with higher in-hospital or 30-day mortality. Targeted pre-operative interventions may improve surgical outcomes for these vulnerable patients.

Systematic review registration: PROSPERO, CRD42018080114 (prospective).