Transitioning to high-sensitivity troponin: 1-year mortality outcomes in patients with suspected acute coronary syndrome presenting to emergency departments.

Background: Switching from a conventional to a high-sensitivity cardiac troponin (hs-cTn) assay enables detection of smaller amounts of myocardial damage, but the clinical benefit is unclear. We investigated whether switching to a hs-cTnI assay with a sex-specific 99th centile diagnostic threshold was associated with lower 1-year death or new myocardial infarction (MI) in patients with suspected acute coronary syndrome (ACS).

Methods: This pre-post study included nine tertiary hospitals in Australia.

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.

Comparative Algorithms for Identifying and Counting Hospitalisation Episodes of Care for Coronary Heart Disease Using Administrative Data.

Purpose: Measures of disease burden using hospital administrative data are susceptible to over-inflation if the patient is transferred during their episode of care. We aimed to identify and compare measures of coronary heart disease (CHD) and myocardial infarction (MI) episodes using six algorithms that account for transfers.

Patient And Methods: We used person-linked hospitalisations for CHD and MI for 2000-2016 in Western Australia based on the interval between discharge and subsequent admission (date, datetime algorithms), pathway (admission source, discharge destination) and any combination to generate machine learning models (random forest [RF], gradient boosting machine [GBM]).

Infiltrative Myocardial T-Cell Lymphoma.

We report a unique case involving cardiac manifestation of T-cell lymphoma and associated risk management of ventricular arrhythmia and sudden cardiac death. A 39-year-old woman presented with a syndrome consistent with fever in a returned traveler, ultimately diagnosed with stage IV peripheral T-cell lymphoma involving the myocardium with ventricular tachycardia. Management of risk of sudden cardiac death was complicated by hematological management with an antibody-drug conjugate chemotherapy regimen and later autologous stem cell transplant.

Genetics, Fitness and Left Ventricular Remodeling: The Current State of Play.

Cardiorespiratory fitness (CRF) exists on a spectrum and is driven by a constellation of factors including genetic and environmental differences. This results in wide inter-individual variation in baseline CRF and the ability to improve CRF with regular endurance exercise training. As opposed to monogenic conditions, CRF is described as a complex genetic trait as it is believed to be influenced by multiple common genetic variants in addition to exogenous factors.

Integration of validated functional evidence to support the pathogenicity of variants.

Functional investigation of genetic variants found in long QT syndrome can provide evidence that is needed to confirm the genetic diagnosis and establish the cause of the condition. We performed functional assessment to determine the -score, using a clinically calibrated automated patch clamp assay, for 2 missense variants found in 2 families that have been diagnosed with long QT syndrome. These variants are currently classified as variant of uncertain significance in ClinVar.

A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship.

Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD).

Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS.

Subaortic pannus causing complete outlet obstruction after bioprosthetic aortic valve replacement in a patient with left ventricular assist device: a case report.

Background: Subaortic pannus formation complicates bioprosthetic aortic valve (AV) replacement. We report an extreme case in a continuous-flow left ventricular assist device (LVAD) patient.

Case Summary: A 49-year-old Caucasian female with dilated cardiomyopathy was bridged to transplant with a HeartWare Ventricular Assist Device (Medtronic).

Australian outcomes from heart transplantation in the machine perfusion era.

Background: In the current era of heart transplantation, machine perfusion strategies are emerging as potential additions to the armamentarium of a transplant unit. Donation after circulatory death (DCD) donor hearts assessed through normothermic machine perfusion (NMP) has helped expand the donor pool. Hypothermic machine perfusion (HMP) is emerging as an alternative strategy to traditional static cold storage (SCS) when a prolonged ischemic time is anticipated in brain dead (BD) donors, this is important in Australia where long distant procurement is vital.

Clinical and Genomic Prediction of Coronary Artery Disease Subtypes.

Background: Coronary artery disease (CAD) is a complex, heterogeneous disease with distinct etiological mechanisms. These different etiologies may give rise to multiple subtypes of CAD that could benefit from alternative preventions and treatments. However, so far, there have been no systematic efforts to predict CAD subtypes using clinical and genetic factors.

Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis.

Ageing is associated with a decline in the number and fitness of adult stem cells. Ageing-associated loss of stemness is posited to suppress tumorigenesis, but this hypothesis has not been tested in vivo. Here we use physiologically aged autochthonous genetically engineered mouse models and primary cells to demonstrate that ageing suppresses lung cancer initiation and progression by degrading the stemness of the alveolar cell of origin.

On the long-term storage of tissue for fluorescence and electron microscopy: lessons learned from rat liver samples.

Occasionally, tissue samples cannot be processed completely and are stored under varying conditions for extended periods. This is particularly beneficial in interinstitutional studies where a given research setting may lack the expertise or infrastructure for sample processing, imaging and data analysis. Currently, there is limited literature available on the controlled storage of biological tissues in primary fixatives for fluorescence and electron microscopy.

Epilepsy and Cardiac Arrhythmias: A State-of-the-Art Review.

Epilepsy is an important cause of disability and mortality worldwide. It can be frequently misdiagnosed, and detailed history and relevant investigations are needed to differentiate epilepsy from syncope. Electroencephalogram is a key noninvasive assessment of neurological function, and the diagnostic yield is increased when performed for an extended period in the ambulatory setting with concurrent electrocardiogram and video monitoring.

Cardiovascular Risk Factors and Genetic Risk in Transthyretin V142I Carriers.

Background: Nearly 3% to 4% of Black individuals in the United States carry the transthyretin V142I variant, which increases their risk of heart failure. However, the role of cardiovascular (CV) risk factors (RFs) in influencing the risk of clinical outcomes among V142I variant carriers is unknown.

Objectives: This study aimed to assess the impact of CV RFs on the risk of heart failure in V142I carriers.

Using an Isolated Working Rat Heart Model to Test Donor Heart Preservation Strategies.

Optimization of donor heart preservation solutions has played a key role in reducing ischemia-reperfusion injury in donor hearts during organ retrieval, transportation, and transplantation. Previous work from our laboratory showed that the addition of glyceryl trinitrate and erythropoietin to donor heart preservation solutions could significantly improve cardiac functional recovery after prolonged cold storage and in donation after circulatory death hearts. This supplementation protocol has been implemented in clinical use in transplant units around Australia, Belgium, and the United Kingdom.