2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

Inflammation risk before cardiac surgery and the treatment effect of intraoperative dexamethasone.

Patients who exhibit high systemic inflammation after cardiac surgery may benefit most from pre-emptive anti-inflammatory treatments. In this secondary analysis (n = 813) of the randomised, double-blind Intraoperative High-Dose Dexamethasone for Cardiac Surgery trial, we set out to develop an inflammation risk prediction model and assess whether patients at higher risk benefit from a single intraoperative dose of dexamethasone (1 mg/kg). Inflammation risk before surgery was quantified from a linear regression model developed in the placebo arm, relating preoperatively available covariates to peak postoperative C-reactive protein. The primary endpoint was the interaction between inflammation risk and the peak postoperative C-reactive protein reduction associated with dexamethasone treatment. The impact of dexamethasone on the main clinical outcome (a composite of death, myocardial infarction, stroke, renal failure, or respiratory failure within 30 days) was also explored in relation to inflammation risk. Preoperatively available covariates explained a minority of peak postoperative C-reactive protein variation and were not suitable for clinical application (R2 = 0.058, P = 0.012); C-reactive protein before surgery (excluded above 10 mg/L) was the most predictive covariate (P < 0.001). The anti-inflammatory effect of dexamethasone increased as the inflammation risk increased (-0.689 mg/L per unit predicted peak C-reactive protein, P = 0.002 for interaction). No treatment-effect heterogeneity was detected for the main clinical outcome (P = 0.167 for interaction). Overall, risk predictions from a model of inflammation after cardiac surgery were associated with the degree of peak postoperative C-reactive protein reduction derived from dexamethasone treatment. Future work should explore the impact of this phenomenon on clinical outcomes in larger surgical populations.

Methylomic and transcriptomic characterization of postoperative systemic inflammatory dysregulation.

In this study, we define and validate a state of postoperative systemic inflammatory dysregulation (PSID) based on postoperative phenotypic extremes of plasma C-reactive protein concentration following major abdominal surgery. PSID manifested clinically with significantly higher rates of sepsis, complications, longer hospital stays and poorer short, and long-term outcomes. We hypothesized that PSID will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression suggests that dysregulation is mediated at multiple levels within specific gene sets and hence, nonspecific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.

DNA methylation patterns from peripheral blood separate coronary artery disease patients with and without heart failure.

AIMS: Natriuretic peptides are useful for diagnosis and prognostication of heart failure of any cause. Now, research aims to discover novel biomarkers that will more specifically define the heart failure phenotype. DNA methylation plays a critical role in the development of cardiovascular disease with the potential to predict fundamental pathogenic processes. There is a lack of data relating DNA methylation in heart failure that specifically focuses on patients with severe multi-vessel coronary artery disease. To begin to address this, we conducted a pilot study uniquely exploring the utility of powerful whole-genome methyl-binding domain-capture sequencing in a cohort of cardiac surgery patients, matched for the severity of their coronary artery disease, aiming to identify candidate peripheral blood DNA methylation markers of ischaemic cardiomyopathy and heart failure. METHODS AND RESULTS: We recruited a cohort of 20 male patients presenting for coronary artery bypass graft surgery with phenotypic extremes of heart failure but who otherwise share a similar coronary ischaemic burden, age, sex, and ethnicity. Methylation profiling in patient blood samples was performed using methyl-binding domain-capture sequencing. Differentially methylated regions were validated using targeted bisulfite sequencing. Gene set enrichment analysis was performed to identify differences in methylation at or near gene promoters in certain known Reactome pathways. We detected 567 188 methylation peaks of which our general linear model identified 68 significantly differentially methylated regions in heart failure with a false discovery rate <0.05. Of these regions, 48 occurred within gene bodies and 25 were located near enhancer elements, some within coding genes and some in non-coding genes. Gene set enrichment analyses identified 103 significantly enriched gene sets (false discovery rate <0.05) in heart failure. Validation analysis of regions with the strongest differential methylation data was performed for two genes: HDAC9 and the uncharacterized miRNA gene MIR3675. Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2. CONCLUSIONS: We demonstrate the utility of methyl-binding domain-capture sequencing to evaluate peripheral blood DNA methylation markers in a cohort of cardiac surgical patients with severe multi-vessel coronary artery disease and phenotypic extremes of heart failure. The differential methylation status of specific coding genes identified are candidates for larger longitudinal studies. We have further demonstrated the value and feasibility of examining DNA methylation during the perioperative period to highlight biological pathways and processes contributing to complex phenotypes.

Genetics and epigenetics in perioperative medicine.

PURPOSE OF REVIEW: To summarize is to review recent progress in 'genomic' science and how this may be applied to the perioperative environment. Although investigations that relate genetic variation to perioperative outcomes continue, it is increasingly apparent that epigenetic mechanisms may contribute to much of the observed variation in complex outcomes not otherwise explained by differences in genetic sequence. RECENT FINDINGS: Examples of recent findings relating to the role of epigenetic modifications in complex disease and outcomes are derived from research into type 1 diabetes, pain, and the hypoxic response. These studies provide models for future cohort study design, potential perioperative drug targets, and hypothesis development. Genetic and epigenetic factors combine to alter both gene expression and drug responses at both pharmacokinetic and pharmacodynamic levels. These factors impact on the efficacy and safety of multiple drug classes used in perioperative medicine. SUMMARY: Enhancing our understanding of the way in which patients as genomic organisms interact with the perioperative environment requires a more sophisticated appreciation of the factors governing gene expression than has been the case to date. Epigenetic mechanisms are sure to play a pivotal role in what is essentially an acquired phenotype.