Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial.

Background: RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery. Methods: This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high-dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO-1, IL-10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833. Findings: Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high-dose, 42 low-dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high-dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low-dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug-related adverse event was dose-dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high-dose RBT-1 and in six (13%) of 45 patients treated with low-dose RBT-1 (safety population). Interpretation: RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned. Funding: Renibus Therapeutics, Inc.

Optimal Conduit Diameter Selection in Coronary Bypass Grafting Using Saphenous Vein.

BACKGROUND: Predictors of long-term saphenous vein graft (SVG) patency following coronary artery bypass grafting (CABG) include harvesting technique, degree of proximal coronary stenosis, and target vessel diameter and runoff. The objective of this study was to evaluate the association between vein graft diameter and long-term survival. METHODS: Patients undergoing primary CABG (2000-2017) at Flinders Medical Centre, Adelaide, Australia, were categorised into three groups according to average SVG diameter (<3.5 mm [small], 3.5-4 mm [medium], >4 mm [large]). Survival data was obtained from the Australian Institute of Health and Welfare National Death Index. To determine the association of SVG diameter with long-term survival we used Kaplan-Meier survival analysis and Cox proportional hazard models adjusted for preoperative variables associated with survival. RESULTS: Vein graft diameter was collected in 3,797 patients. Median follow-up time was 7.6 years (interquartile range, 3.9-11.8) with 1,377 deaths. SVG size >4 mm was associated with lower rates of adjusted survival up to 4 years postoperatively (hazard ratio 1.48; 95% confidence interval 1.05-2.1; p=0.026). CONCLUSIONS: Vein graft diameter >4mm was found to be associated with lower rates of survival following CABG.

Lost in Translation: The Impact of Language Barriers on the Outcomes of Patients Receiving Coronary Artery Revascularization.

INTRODUCTION: Clear and effective communication is vital in discussions regarding coronary revascularization. Language barriers may limit communication in healthcare settings. Previous studies on the influence of language barriers on the outcomes of patients receiving coronary revascularization have produced conflicting results. The aim of this systematic review was to evaluate and synthesise the existing evidence regarding the effects of language barrier on the outcomes of patients receiving coronary revascularization. METHODS: A systematic review was conducted, including a search of the PubMed, EMBASE, Cochrane, and Google Scholar databases on 01/10/2022. The review was conducted in accordance with PRISMA guidelines. This review was also prospectively registered on PROSPERO. RESULTS: Searches identified 3983 articles of which a total 12 studies were included in the review. Most studies describe that language barriers result in delayed presentation, but not delays in treatment following hospital arrival with respect to coronary revascularization. The findings with respect to the likelihood of receiving revascularization have varied significantly; however, some studies have indicated that those with language barriers may be less likely to receive revascularization. There have been some conflicting results with respect to the association between language barrier and mortality. However, most studies suggest that there is no association with increased mortality. In studies that evaluated length of stay variable results have been reported based on geographical location. Namely Australian studies have suggested no association between language barrier and length of stay, but Canadian studies support an association. Language barriers may also be associated with readmissions following discharge, and major adverse cardiovascular and cerebrovascular events (MACCE). CONCLUSION: This study demonstrates that patients with language barriers may have poorer outcomes from coronary revascularization. Future interventional studies will be required to consider the sociocultural context of patients with language barriers, and may be targeted at timepoints including prior to, during, or after hospitalisation for coronary revascularization. Further examination of the adverse health outcomes of those with language barriers in fields outside of coronary revascularization are required in view of the stark inequities identified in this field.

Surgery for rheumatic heart disease in the Northern Territory, Australia, 1997-2016: what have we gained?

BACKGROUND: Between 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival. METHODS: A retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis. FINDINGS: The cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18-42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4-12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p<0.001). Preoperative chronic kidney disease (HR 6.5 (95% CI: 3.0 to 14.0) p≤0.001)), coronary artery disease (HR 3.3 (95% CI: 1.3 to 8.4) p=0.012) and pulmonary artery systolic pressure>50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death. INTERPRETATION: Survival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes.

Obesity-induced vena cava compression syndrome: a case report of a rare precipitant of a type 2 myocardial infarction in a patient with critical aortic stenosis.

Background: Obesity is a global health problem of increasing prevalence with a broad range of multisystem complications. An under-recognized complication of severe obesity is the potential haemodynamic compromise that may arise due to pathological external compression of the inferior vena cava whilst lying in the supine position, a phenomenon known as obesity-induced vena cava compression syndrome. Case summary: A 56-year-old independent woman presented to a rural Australian hospital for routine dressing care for bilateral lymphoedema on a background of class III morbid obesity (weight 197 kg, body mass index 68.55 kg/m3) and aortic stenosis. Whilst laid in the supine position with both legs elevated to aid lower limb venous return, the patient developed angina with associated troponin rise (15 to 75 to 332 ng/L) and inferolateral territory ischaemic changes on electrocardiogram. The pain then resolved shortly after restoring the patient to the upright position. A transthoracic echocardiogram showed critical bicuspid aortic stenosis. Computerized tomography coronary angiogram showed no significant coronary artery disease. Following multidisciplinary discussions, a transcatheter aortic valve insertion was performed via a transfemoral approach. Post-procedure, she went into atrial fibrillation, she was cardioverted into a sinus rhythm with new left bundle branch block. There were no complications otherwise, and the patient was discharged home following a brief period of convalescence. Discussion: We describe a case of suspected obesity-induced vena cava compression syndrome precipitating a type 2 myocardial infarction in a pre-load dependent patient with critical bicuspid valve aortic stenosis. This case highlights a potential haemodynamic consequence of morbid obesity in the supine position.

Quantification of the internal mammary artery size in Aboriginal and Torres Strait islanders.

BACKGROUND: Variation in size of the internal mammary artery has been demonstrated in ethnic groups, but not reported in Aboriginal patients. We hypothesised that the left internal mammary artery is smaller in Aboriginal patients compared to non-Aboriginal patients and aimed to determine the impact on survival following coronary artery bypass graft (CABG) surgery. METHODS: Left internal mammary artery size was compared between Aboriginal (n = 345) and non-Aboriginal (n = 1819) in 2343 patients undergoing CABG at Flinders Medical Centre from January 2010 to June 2021. To determine the association with-survival we used Kaplan-Meier survival analysis and Cox proportional hazard models adjusted for preoperative variables. RESULTS: There was a significant difference in left internal mammary artery (LIMA) size-Aboriginal 1.8 ± 0.4 mm; non-Aboriginal 2.1 ± 0.4 mm (P < 0.001)-and left anterior descending (LAD) artery size-Aboriginal 1.7 ± 0.3 mm; non-Aboriginal 1.9 ± 0.3 mm (P < 0.001). Aboriginal patients were more likely to have the LIMA discarded (9.3% vs. 0.4%) and to receive a LAD vein graft (17% versus 3%) (P < 0.001). There was no difference in 30-day mortality or survival <5 years. CONCLUSION: This study supports the hypothesis that the left internal mammary artery is smaller in Aboriginal patients compared to non-Aboriginal patients. Although Aboriginal patients were more likely to receive a venous conduit to the LAD, we observed no difference in survival up to 5 years. This data contrasts with reported outcomes of other ethnic groups.

Endovascular thrombectomy for large vessel occlusion acute ischemic stroke after cardiac surgery.

INTRODUCTION: Acute ischemic stroke (AIS) can be a catastrophic complication of cardiac surgery previously without effective treatment. Endovascular thrombectomy (EVT) is a potentially life-saving intervention. We examined patients at our institution who had EVT to treat AIS post cardiac surgery. METHODS: We retrospectively reviewed a stroke database from January 1, 2016 to October 31, 2021 to identify patients who had undergone EVT to treat AIS following cardiac surgery. Demographic data, operation type, stroke severity, imaging features, management and outcomes (mortality and modified Rankin Score (mRS)) were assessed. RESULTS: Of 5022 consecutive patients with AIS, 870 underwent EVT. Seven patients (0.8%) had EVT following cardiac surgery. Operations varied: two coronary artery bypass grafting (CABG), two transcatheter AVR, one redo surgical aortic valve replacement (AVR), one mitral valve repair and one patient with combined aortic and mitral valve replacements and CABG. Meantime postsurgery to stroke symptoms onset was 3 days (range 0-9 days). Median NIHSS was 26 (range 10-32). Five patients had middle cerebral artery occlusion and two internal carotid artery (n = 2). Median time between onset of symptoms and recanalization was 157 min (range 97-263). Two patients received Intra-arterial Thrombolysis. All patients survived and were discharged to another hospital (n = 3), home (n = 2), or rehabilitation facility (n = 2). Median 3-month mRS was 3 (range 0-6). CONCLUSION: We report the largest case series of EVT after cardiac surgery. EVT can be associated with excellent outcomes in these patients. Close neurological monitoring postoperatively to identify patients who may benefit from intervention is key.

Inferior vena cava filter limb embolization to the right ventricle: a case report.

Background: Inferior vena cava (IVC) filters are used to prevent pulmonary embolism (PE) in patients at a high risk for venous thromboembolism with a contraindication to anticoagulation. Inferior vena cava filters are associated with rare but significant long-term complications such as filter fracture and embolization. Case summary: We report the case of a 53-year-old female with an IVC filter inserted 8 years back for the management of recurrent bilateral PE resistant to anticoagulation. Imaging revealed an incidental finding of IVC filter limb fracture and migration to the right heart and the hepatic and renal veins. The patient remained asymptomatic with no impairment in cardiac, liver, or renal function. Due to a high operative risk, the broken IVC filter and embolized filter limbs were not retrieved. Discussion: There is no consensus on the management of intracardiac embolization of IVC filters. Intravascular fragments may be removed by endovascular or surgical approaches, depending on the anatomical location. Following IVC filter insertion, an appropriate follow-up must be put in place to ensure removal and limit clinical sequelae that are otherwise avoidable. A multidisciplinary approach to the management of IVC filter fracture and embolization is recommended.

Transcatheter mitral valve-in-valve: treatment of rheumatic heart disease in young patients.

BACKGROUND: Rheumatic heart disease (RHD) in young people presents a complex management problem. In Australia a significant proportion of those affected are Aboriginal and Torres Strait Islanders. Transcatheter mitral valve-in-valve (TMViV) replacement has emerged as an alternative to redo surgery in high-risk patients with degenerated mitral bioprostheses. The aim of this study is to review outcomes of TMViV replacement in young patients with RHD. METHODS: A single-centre, retrospective review of prospectively collected data on patients undergoing TMViV from December 2017 to June 2021. Primary outcome was major adverse cardiovascular events. Secondary outcome was post-operative trans-thoracic echocardiogram (TTE) results. RESULTS: There were seven patients with a mean age of 33 years and predominantly female (n = 5). Pre-operative comorbidities included diabetes (29%), chronic obstructive pulmonary disease (43%), left ventricular dysfunction (43%) and current smoking status (80%). Post-operative median length of hospital stay was 4 days with no post-operative renal failure, stroke, return to theatre, valve embolization or in hospital mortality. Post-operative TTE showed either nil or trivial central mitral regurgitation, no paravalvular leak and a median gradient of 5 mmHg (IQR 4.5, 7) across the new bioprosthesis; sustained at median follow-up of 22 months. CONCLUSION: Current literature of TMViV replacement is focused on an older population with concurrent comorbidities. This study provides a unique insight into TMViV replacement in a young cohort of patients with complex social and geographical factors which sometimes prohibits the use of a mechanical valve. The prevalence of RHD remains high for Aboriginal and Torres Strait Islanders, planning for future repeat valve operations should be considered from the outset. We consider TMViV as a part of a staged procedural journey for young patients with RHD.

Brian Fowell Buxton (15/04/1940-20/05/2022)-Outstanding Achievements and Personal Memories.

Brian F. Buxton, one of Australia's greatest cardiac surgeons, died in May 2022, aged 82 years. In June 2022, a memorial celebration of Brian's life was held in Melbourne, Australia, attended by 550 colleagues and friends from many walks of life-not only "medical people" but also friends involved in Brian's sailing and hiking activities. This Special Article includes an introduction from Professor Jayme Bennetts, President of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS), an abridged version of a memorial address by Professor James Tatoulis and contributions from two other long-term professional colleagues and personal friends of Buxton, Professor Jaishankar Raman and Professor Franklin Rosenfeldt, founding editor of Heart, Lung and Circulation. Buxton was an outstanding and pioneering surgeon, clinical leader, and good friend to many. The Brian F. Buxton Cardiac and Thoracic Aortic Surgery Unit in Melbourne, Australia, is now so named in honour of his outstanding achievements and as a legacy. Vale Brian F. Buxton.

The long-term mortality of an Aboriginal and Torres Strait Islander Australian population after isolated coronary artery bypass graft surgery.

BACKGROUND: Aboriginal and Torres Strait Islander (Indigenous) Australians have an increased prevalence of coronary artery disease and present at a younger age for coronary artery bypass graft surgery (CABG) when compared to non-Indigenous Australians. Studies have reported postoperative outcomes in Indigenous people to be less favourable. Therefore, the aim of this study is to evaluate long term mortality between Indigenous and non-Indigenous people post-CABG. METHODS: We analysed data on all patients who underwent isolated CABG, with and without cardiopulmonary bypass, at our institution between January 1998 to September 2008. There were 33 395 person-years of survival for analysis with a median follow-up of 13 years (Interquartile range (IQR): 8-16 years). We analysed all-cause mortality with the Kaplan-Meier graph and log-rank test. Univariate and multivariate analysis was performed using a Cox proportional hazards model. RESULTS: The mean age at presentation for Indigenous people was 52 years compared to 65 yr for non-indigenous people. There were 1431 (52.1%) deaths by the study census date, with the overall mortality for Indigenous patients at 49.8% (n = 147) and 52.4% for non-Aboriginal patients (n = 1284). The age and comorbidities adjusted hazard ratio (HR) for all-cause late mortality (median years) was HR = 1.712 (95% CI: 1.288-2.277, p < 0.001). CONCLUSION: Indigenous patients present for CABG at a younger age and have a higher prevalence of comorbidities. Our study demonstrates they have a higher risk of propensity adjusted all-cause long term mortality. Primary and secondary prevention strategies, tailored to Indigenous people, may improve health outcomes in the long-term post-CABG.

Development of an organ procurement team in South Australia in response to COVID-19.

BACKGROUND: Due to the nature of border closures and quarantine requirements in Australia during the COVID-19 pandemic, the feasibility of interstate travel for organ retrieval created complex logistics. An organ procurement service in South Australia, to procure heart and lungs of local donors, was commenced to mitigate the impact of the travel restrictions imposed due to COVID-19. The purpose of this review was to examine the initial data and feasibility of the service. METHODS: A single unit, multi-site retrospective review from April 2020-August 2021 of all organ retrievals undertaken by the Flinders Medical Centre cardiothoracic service across Adelaide metropolitan area. Data was prospectively collected and analysed from the DonateLife South Australian centralized database. All data was de identified. RESULTS: A total of 25 organ procurements had been undertaken across 17 months since commencing the program. Total of 9 hearts and 16 bilateral lungs were procured with median age of donor of hearts 49 years (IQR 35.5-51. 5) and 60 years (IQR 44-72) for lung donation. Six organs were donated after determination of circulatory death and 19 after neurological determination of death. Median ischaemic time for heart donation was 4.4 h (IQR 3.0-5.8) and lung donation 4.4 h (IQR 3.4-6.1). All organs procured by the local South Australian team were successfully transplanted at the recipient site. Recipient sites included 8 in Victoria, 10 in New South Wales, 4 in Western Australia and 3 in Queensland. CONCLUSIONS: The necessity of flexibility within the field of cardiothoracic surgery is evident during the COVID-19 pandemic. The implementation of an organ retrieval service in South Australia has been successful with no apparent increased risk to successful transplant outcomes.

Institutional variation in early mortality following isolated coronary artery bypass graft surgery.

BACKGROUND: Thirty-day mortality following coronary artery bypass grafting (CABG) is a widely accepted marker for quality of care. Although surgical mortality has declined, the utility of this measure to profile quality has not been questioned. We assessed the institutional variation in risk-standardised mortality rates (RSMR) following isolated CABG within Australia and New Zealand (ANZ). METHODS: We used an administrative dataset from all public and most private hospitals across ANZ to capture all isolated CABG procedures recorded between 2010 and 2015. The primary outcome was all-cause death occurring in-hospital or within 30-days of discharge. Hospital-specific RSMRs and 95% CI were estimated using a hierarchical generalised linear model accounting for differences in patient characteristics. RESULTS: Overall, 60,953 patients (mean age 66.1 ± 10.1y, 18.7% female) underwent an isolated CABG across 47 hospitals. The observed early mortality rate was 1.69% (n = 1029) with 81.8% of deaths recorded in-hospital. The risk-adjustment model was developed with good discrimination (C-statistic = 0.81). Following risk-adjustment, a 3.9-fold variation was observed in RSMRs among hospitals (median:1.72%, range:0.84-3.29%). Four hospitals had RSMRs significantly higher than average, and one hospital had RSMR lower than average. When in-hospital mortality alone was considered, the median in-hospital RSMR was 1.40% with a 5.6-fold variation across institutions (range:0.57-3.19%). CONCLUSIONS: Average mortality following isolated CABG is low across ANZ. Nevertheless, in-hospital and 30-day mortality vary among hospitals, highlighting potential disparities in care quality and the enduring usefulness of 30-day mortality as an outcome measure. Clinical and policy interventions, including participating in clinical quality registries, are needed to standardise CABG care.

Ruxolitinib withdrawal complicating emergency aortic root replacement.

Ruxolitinib, a Janus kinase inhibitor, is associated with severe withdrawal phenomena. Adequate tapering is often underemphasized in surgical emergencies and can complicate the postoperative course. We present a case of acute ruxolitinib withdrawal in a gentleman undergoing emergency cardiac surgery.

Impact of Surgical and Transcatheter Aortic Valve Replacement on Frailty Score.

OBJECTIVE: Frailty is common in the aortic stenosis (AS) population and impacts outcomes after both transcatheter and surgical aortic valve replacement (TAVR and sAVR, respectively). Frailty can significantly impact the decision regarding the suitability of a patient for aortic valve intervention, with frail patients often excluded. Since many frailty tools use indicators which may be influenced by AS itself, some of which are subjectively symptom driven, we sought to determine the impact of intervention on frailty scores. METHODS: A prospective, observational cohort study included patients being assessed for aortic valve (AV) intervention with either TAVR or sAVR due to severe aortic stenosis. Patients were assessed for symptoms at baseline, and 1- and 6-months post intervention subjectively, using the New York Heart Association (NYHA) class and the Kansas City Cardiomyopathy Questionnaire (KCCQ), and objectively, using a 6-minute walk test (6MWT). These were compared with frailty at baseline and final review using the Fried Frailty Scale (FFS). RESULTS AND CONCLUSIONS: Sixty-six (66) patients completed pre- and post-intervention reviews. The mean FFS score was significantly lower, indicating less frailty, at 6 months relative to pre procedure (1.18 vs 1.73, p=0.002). This correlated with the change in symptoms (p<0.001). Between intervention groups, the final mean FFS of both groups decreased significantly, with TAVR to 1.33 (p=0.030) and sAVR to 0.8 (p=0.015). There was no difference in the degree of improvement between interventions (p=0.517). Aortic valve intervention improves frailty scores in both TAVR and sAVR treated patients.

2021 CSANZ and ANZSCTS Position Statement on the Operator and Institutional Requirements for a Transcatheter Aortic Valve Implantation (TAVI) Program in Australia.

This document establishes the minimum standard for accreditation of institutions and operators as endorsed by the Cardiac Society of Australia and New Zealand (CSANZ) and the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS). The original Joint Society Position Statement was ratified in August 2014. This 2021 update replaces the original and serves as a consensus within which the Conjoint Committee for Trancatheter Aortic Valve Implantation (TAVI) Accreditation will function, as recommended by Medical Services Advisory Committee (MSAC) Determination for TAVI. This is not a Guideline Statement but takes into consideration regional, legislative, and health system factors important to establishing requirements for TAVI accreditation in Australia.

Self-inflicted penetrating chest trauma from solar powered garden light: a case report.

Penetrating chest trauma is associated with significant morbidity and mortality due to direct injury to vital organs located within the thorax. This is a case of a 53-year-old man who presented with a self-inflicted penetrating chest trauma using a solar powered garden light. The light penetrated the left side of his chest resulting in a haemopneumothorax, diaphragmatic perforation and pericardial haematoma. The patient underwent an urgent explorative thoracotomy for the removal of the garden light, repair of the diaphragmatic perforation and wedge resections of the perforated lung parenchyma. Postoperatively, the patient recovered in the intensive care before being transferred to the psychiatric department.

Operator and Institutional Requirements for Transcatheter Mitral Valve Therapies in Australia: a CSANZ and ANZSCTS Position Statement.

This expert Position Statement is a description of the requirements for Accreditation for transcatheter mitral valve therapy (TMVT) in Australia. The requirements include the need for a multidisciplinary Heart Team review of individual cases, mandatory reporting of outcome data to a national TMVT Registry, and accreditation of individuals and institutions by the Conjoint Accreditation Committee, the assigned accreditation authority.