Professor Doan Ngo

Background: The mechanisms contributing to impaired neurocognitive performance in adults born with congenital heart disease (ACHD) are incompletely defined. Objectives: The authors performed a pilot study measuring novel biomarkers of blood-brain barrier integrity, angiogenesis, and endothelial function in patients with ACHD. Methods: Adults with congenital heart disease underwent biomarker assessment. Plasma levels of asymmetric dimethyl arginine, as a marker of endothelial dysfunction, vascular endothelial growth factor A, as a measure of angiogenesis, and S100B, as a biomarker of the integrity of the blood-brain barrier, were assayed. Results: A total of 70 patients were recruited with the average age of 43.6 years with 54% patients female. The majority of patients were considered to have moderate severity ACHD (43/70). S100B levels were undetectable in patients with mild ACHD and highest in the cohort with severe ACHD (4,551.9 pg/mL; P = 0.24). Patients with Fontan palliation (1,383.89 pg/mL) and those having undergone atrial switch repair (14,845.78 pg/mL) had the highest mean levels of S100B. Mean asymmetric dimethyl arginine levels were particularly elevated in patients with aortic coarctation surgery (358.10 ng/UL). Mean vascular endothelial growth factor levels were elevated across the spectrum of patients with ACHD, most notably in patients with moderate severity ACHD incorporating repaired tetralogy of Fallot (306.2 pg/mL vs 177.9 pg/mL [severe] and 145.0 pg/mL [mild]; P = 0.01). Conclusions: In a pilot study across the spectrum of ACHD, we note elevated levels of biomarkers that may improve the ability to more accurately identify neurological injury and impaired vascular function, which in turn may have implications with respect to cognitive function and cardiovascular sequelae.

The Internet of Medical Things (IoMT) is a network of interconnected medical devices and applications aiming to facilitate real-time data sharing and personalised patient care. IoMT devices collect vast amounts of data, which are then analysed using advanced computational methods. Real-time patient monitoring is crucial, particularly for people with chronic diseases and older adults. Moreover, traditional in-person monitoring by healthcare providers can be resource-intensive and time-consuming. By leveraging IoMT technology for remote patient monitoring (RPM), healthcare providers can improve service quality, reduce costs and enhance patient care. To evaluate the current state of knowledge and address research gaps in IoMT adoption for RPM, we conducted a thorough systematic literature review (SLR). This SLR aims to provide a comprehensive overview of existing research, identify knowledge gaps, and analyse the factors that influence IoMT adoption. It follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol. PRISMA guidelines allow us to systematically evaluate and synthesise the current state of relevant literature. After analysing the theoretical models used in previous studies on IoMT adoption for RPM, UTAUT2 was identified as the most effective framework for technology adoption in this area. Additionally, this SLR has identified the key factors influencing the adoption of IoMT technology, including privacy, trust, security, and perceived risk, and suggested their inclusion in future studies by analysing and integrating the findings of other studies. As much of the current research focuses solely on patient viewpoints, our SLR points to the necessity of giving equal weight to the opinions of both patients and healthcare professionals. To create IoMT systems that are more effective and inclusive, these deficiencies must be filled. This study will benefit researchers, healthcare professionals, policymakers and technology developers by offering insights to inform decision-making, guide future research and aid the development of effective IoMT solutions for RPM.

Background: Cancer and heart disease are the two most common health conditions in the world, associated with high morbidity and mortality, with even worse outcomes in regional areas. Cardiovascular disease is the leading cause of death in cancer survivors. We aimed to evaluate the cardiovascular outcomes of patients receiving cancer treatment (CT) in a regional hospital. Methods: This was an observational retrospective cohort study in a single rural hospital over a ten-year period (17th February 2010 to 19th March 2019). Outcomes of all patients receiving CT during this period were compared to those who were admitted to the hospital without a cancer diagnosis. Results: 268 patients received CT during the study period. High rates of cardiovascular risk factors: hypertension (52.2%), smoking (54.9%), and dyslipidaemia (38.4%) were observed in the CT group. Patients who had CT were more likely to be readmitted with ACS (5.9% vs. 2.8% p = 0.005) and AF (8.2% vs. 4.5% p = 0.006) when compared to the general admission cohort. There was a statistically significant difference observed for all cause cardiac readmission, with a higher rate observed in the CT group (17.1% vs. 13.2% p = 0.042). Patients undergoing CT had a higher rate of mortality (49.5% vs. 10.2%, p = 0.001) and shorter time (days) from first admission to death (401.06 vs. 994.91, p = 0.001) when compared to the general admission cohort, acknowledging this reduction in survival may be driven at least in part by the cancer itself. Conclusion: There is an increased incidence of adverse cardiovascular outcomes, including higher readmission rate, higher mortality rate and shorter survival in people undergoing cancer treatment in rural environments. Rural cancer patients demonstrated a high burden of cardiovascular risk factors.

Australia's First Nations Peoples, Aboriginal and Torres Strait Islanders, have reduced life expectancy compared to the wider community. Cardiovascular diseases, mainly driven by ischaemic heart disease, are the leading contributors to this disparity. Despite over a third of First Nations Peoples living in New South Wales, the bulk of the peer-reviewed literature is from Central Australia and Far North Queensland. Regardless of the site of publication, First Nations Peoples are significantly younger at disease onset and have higher rates of comorbidities, in turn driving adverse health events. On top of this, very few First Nations Peoples specific cardiovascular interventions or programs have been shown to improve outcomes. The traditional biomedical model of care is less efficacious and non-traditional models of communication such as clinical yarning may benefit both clinicians and patients. The key purpose of this review is to highlight the deficiencies of our knowledge of cardiovascular burden of disease for First Nations Peoples; and to serve as a catalyst for more dedicated research. We need to have relationships with communities and concentrate on community improvement and partnerships. By involving First Nations Peoples researchers in collaboration with local communities in all levels of health care design and intervention will improve outcomes.

Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1 -/-) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3¿6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.

Aims This study aims to (1) define the characteristics of patients with a first admission for heart failure (HF), stratified by type (reduced (HFrEF) vs preserved (HFpEF) ejection fraction) in a regional Australian setting; (2) compare the outcomes in terms of mortality and rehospitalisation and (3) assess adherence to the treatment guidelines. Methods We identified all index hospitalisations with HF to John Hunter Hospital and Tamworth Rural Referral Hospital in the Hunter New England Local Health District over a 12 months. We used the recent Australian HF guidelines to classify HFrEF and HFpEF and assess adherence to guideline-directed therapy. The primary outcome of the study was to compare short-term (1 year) and long-term all-cause mortality and the composite of all-cause hospitalisation or all-cause mortality of patients with HFrEF and HFpEF. Results There were 664 patients who had an index HF admission to John Hunter and Tamworth hospitals in 2014. The median age was 80 years, 47% were female and 22 (3%) were Aboriginal. In terms of HF type, 29% had HFrEF, 37% had HFpEF, while the remainder (34%) did not have an echocardiogram within 1 year of admission and could not be classified. The median follow-up was 3.3 years. HFrEF patients were predominantly male (64%) and in 48% the aetiology was ischaemic heart disease. The 1-year all-cause mortality was 23% in HFpEF subgroup and 29% in HFrEF subgroup (p=0.15). Five-year mortality was 61% in HFpEF and HFrEF patients. Of the HFrEF patients, only 61% were on renin-angiotensin-aldosterone blockers, 74% were on ß-blockers and 39% were on aldosterone antagonist. Conclusion HF patients are elderly and about evenly split between HFrEF and HFpEF. In this regional cohort, both HF types are associated with similar 1-year and 5-year mortality following incident HF hospitalisation. Echocardiography and guideline-directed therapies were underused.

Purpose of Review: Breast cancer survival rate has greatly improved in the last two decades due to the emergence of next-generation anti-cancer agents. However, cardiotoxicity remains a significant adverse effect arising from traditional and emerging chemotherapies as well as targeted therapies for breast cancer patients. In this review, we will discuss cardiotoxicities of both traditional and emerging therapies for breast cancer. We will discuss current practices to detect cardiotoxicity of these therapies with the focus on new and emerging biomarkers. We will then focus on 'omics approaches, especially the use of epigenetics to discover novel biomarkers and therapeutics to mitigate cardiotoxicity. Recent Findings: Significant cardiotoxicities of conventional chemotherapies remain and new and unpredictable new forms of cardiac and/or vascular toxicity emerge with the surge in novel and targeted therapies. Yet, there is no clear guidance on detection of cardiotoxicity, except for significant left ventricular systolic dysfunction, and even then, there is no uniform definition of what constitutes cardiotoxicity. The gold standard for detection of cardiotoxicity involves a serial echocardiography in conjunction with blood-based biomarkers to detect early subclinical cardiac dysfunction. However, the ability of these tests to detect early disease remains limited and not all forms of toxicity are detectable with these modalities. Summary: There is an unprecedented need to discover novel biomarkers that are sensitive and specific for early detection of subclinical cardiotoxicity. In that space, novel echocardiographic techniques, such as strain, are becoming more common-place and new biomarkers, discovered by epigenetic approaches, seem to become promising alternatives or adjuncts to conventional non-specific cardiac biomarkers.

Radiation therapy is a key component of modern-day cancer therapy and can reduce the rates of recurrence and death from cancer. However, it can increase risk of cardiovascular (CV) events, and our understanding of the timeline associated with that risk is shorter than previously thought. Risk mitigation strategies, such as different positioning techniques, and breath hold acquisitions as well as baseline cardiovascular risk stratification that can be undertaken at the time of radiotherapy planning should be implemented, particularly for patients receiving chest radiation therapy. Primary and secondary prevention of cardiovascular disease (CVD), as appropriate, should be used before, during, and after radiation treatment in order to minimize the risks. Opportunistic screening for subclinical coronary disease provides an attractive possibility for primary/secondary CVD prevention and thus mitigation of long-term CV risk. More data on long-term clinical usefulness of this strategy and development of appropriate management pathways would further strengthen the evidence for the implementation of such screening. Clear guidelines in initial cardiovascular screening and cardiac aftercare following radiotherapy need to be formulated in order to integrate these measures into everyday clinical practice and policy and subsequently improve post-treatment morbidity and mortality for these patients.

Background: Ibrutinib increases the risk of atrial fibrillation (AF) and is associated with bleeding tendencies. Reported rates of arrhythmia are variable in different studies. The aim of the current analysis was to evaluate the incidence of AF in a single-center cohort of patients. Methods: This analysis was conducted at Hunter New England Local Health District, Australia between April 1, 2015 and June 30, 2017. We included all consecutive patients commenced on ibrutinib for hematological malignancies. Patients with a history of paroxysmal AF were excluded. The primary end point was incidence of AF. Time to diagnosis and management were secondary outcomes of interest. Results: A total of 24 patients (age 73¿±¿9 years, males n¿=¿16 [67%]) were commenced on ibrutinib treatment during the study period with chronic lymphocytic leukemia (n¿=¿21, 88%) as the main indication. During a median follow-up of 12 months, four (17%) patients were diagnosed with AF with increasing age, duration of ibrutinib treatment as associations. The median time to AF diagnosis was 9 (interquartile range [IQR]: 7-18) months. All patients were managed with a rate control strategy with beta blockers as the preferred agents. Three (75%) patients were commenced on anticoagulation for stroke prevention. During a follow-up of 18 (IQR: 17-23) months following AF onset, one patient required hospitalization for AF. There were no bleeding complications reported. Conclusions: In conclusion, this series noted a higher incidence of AF than previously reported. Oncologists and cardiologists need to be aware of the increased risk of AF in patients receiving ibrutinib.