The aortic paradox: a nationwide analysis of 523,994 individual echocardiograms exploring fatal aortic dissection.

BACKGROUND: Increasing aortic dilation increases the risk of aortic dissection. Nevertheless, dissection occurs at dimensions below guideline-directed cut-offs for prophylactic surgery. There is no current large-scale population imaging data assessing aortic dimensions before dissection. METHODS: Patients within the National Echo Database of Australia (NEDA) were stratified according to absolute, height-indexed and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM code I79) were identified via linkage with the National Death Index. RESULTS: 524,994 individuals were assessed, comprising patients with normal aortic dimensions (n = 460,992), mild dilation (n = 53,402), moderate dilation (n = 10,029) and severe dilation (n = 572). 274,992 (52.4%) were male, with median age 64 years and median follow-up time 6.9 years. 899 fatal aortic dissections occurred (normal diameter = 610, mildly-dilated aorta = 215, moderately-dilated =53 and severely-dilated = 21). Using normal aortas as the reference population, odds of fatal dissection increased with aortic diameter (mild = OR 3.05, 95% confidence interval (CI) 2.61-3.56; moderate = OR 4.0, 95% CI 3.02-5.30; severe = OR 28.72, 95% CI 18.44-44.72). Due to the much larger number of patients without severe aortic dilation, 97.7% of fatal aortic dissections occurred in non-severely dilated aortas. Following sensitivity analysis, severe aortic dilation was responsible for at most 24.4% of fatal aortic dissections. Results were robust for absolute, height-indexed or BSA-indexed aortic measurements. CONCLUSION: Although severe aortic dilatation is associated with a near-thirty-fold increase in fatal dissection, severely dilated aortas are implicated in only 2.3-24.4% of fatal dissections. This highlights the 'aortic paradox' and limitations of current guidelines. Future studies should seek to refine risk predictors in patients without severe aortic dilation.

Understanding Children's Accuracy in Recognizing Facial Expressions of Pain.

Facial expressions of pain have an adaptive function in informing others of the need of attention and care. The detection of these nonverbal cues is particularly important in children since they are not always capable of expressing their needs verbally. Nevertheless, research recurrently shows that distinguishing between genuine, suppressed, and simulated pain expressions produced by children is a difficult task for adults; even when their professions require such a skill (e.g. doctors or nurses). Only a few studies have explored the development of this specific ability amongst children's peers. The current study aims to fill this literature gap by exploring children's ability to recognize and judge genuine, simulated, and suppressed expressions of pain produced by other children their age. Seventy-nine children from kindergarten to fourth grade viewed videos in which children encoders expressed the three aforementioned types of pain while plunging their hand in cold or warm water. Participants were asked to select the type of pain that was expressed. They were also asked their level of confidence in their answer and the level of pain they thought the children were experiencing. Despite having a high level of confidence in their answers, kindergarteners had a significantly lower proportion of correct answers compared to children in third and fourth grade. Furthermore, regardless of their grade level, children were better at recognizing suppressed pain expressions and had lower performance rates for genuine pain recognition. Our overall findings revealed an improvement in children's performance with aging.

Characterizing the influence of cardiorespiratory fitness on left atrial size and function in the general population.

Increased left atrial (LA) size and reduced LA function have been associated with heart failure and atrial fibrillation (AF) in at-risk populations. However, atrial remodeling has also been associated with exercise training and the relationship between fitness, LA size, and function has not been defined across the fitness spectrum. In a cross-sectional study of 559 ostensibly healthy participants, comprising 304 males (mean age, 46 ± 20 yr) and 255 females (mean age, 47 ± 15 yr), we sought to define the relationship between cardiorespiratory fitness (CRF), LA size, and function. We also aimed to interrogate sex differences in atrial factors influencing CRF. Echocardiographic measures included biplane measures of LA volumes indexed to body surface area (LAVi) and atrial deformation using two-dimensional speckle tracking. CRF was measured as peak oxygen consumption (V̇o2peak) during cardiopulmonary exercise testing (CPET). Using multivariable regression, age, sex, weight, and LAVi (P < 0.001 for all) predicted V̇o2peak (P < 0.001, R2 = 0.66 for combined model). After accounting for these variables, heart rate reserve added strength to the model (P < 0.001, R2 = 0.74) but LA strain parameters did not predict V̇o2peak. These findings add important nuance to the perception that LA size is a marker of cardiac pathology. LA size should be considered in the context of fitness, and it is likely that the adverse prognostic associations of increased LA size may be confined to those with LA enlargement and low fitness.NEW & NOTEWORTHY Left atrial (LA) structure better predicts cardiorespiratory fitness (CRF) than LA function. LA function adds little statistical value to predictive models of peak oxygen uptake (V̇o2peak) in healthy individuals, suggesting limited discriminatory for CRF once LA size is factored. In the wider population of ostensibly healthy individuals, the association between increased LA volume and higher CRF provides an important counter to the association between atrial enlargement and heart failure symptoms in those with cardiac pathology.

Sex disparities in bystander defibrillation for out-of-hospital cardiac arrest.

Background: Previous studies have suggested that females experiencing out-of-hospital cardiac arrest (OHCA) receive lower rates of both bystander cardiopulmonary resuscitation (CPR) and defibrillation compared to males. Whether this disparity has improved over time is unknown. Methods: A state-wide OHCA registry in Victoria, Australia collected data over twenty years (2002-2021) regarding rates of bystander interventions in OHCA. Characteristics and outcomes of each OHCA were compared with logistic regression according to sex and time (defined in two-year periods). Results: 32,502 OHCAs were included (69.7% male). Both bystander CPR and defibrillation rates increased for females over time (p < 0.0001). There was no sex disparity in receipt of bystander CPR after adjustment for baseline differences. Females were less likely than males to receive bystander defibrillation, with sex disparity increasing from 2010 onwards (adjOR 0.26 (95%CI 0.09-0.80) in 2020-21 for females compared to males). Conclusion: Initiatives to increase bystander CPR and defibrillation have resulted in higher overall rates of bystander interventions in the last two decades and no significant sex differences in provision of bystander CPR. However, females receive less bystander defibrillation than males, and sex disparity is increasing. Strategies to promote bystander defibrillation in females experiencing OHCA with a shockable rhythm should be a priority.

Prevalence of atrial septal defects and patent foramen ovale in a cohort of sudden cardiac death patients undergoing autopsy.

BACKGROUND: Patent foramen ovale (PFO) and atrial septal defects (ASD) have been described in up to 30 % of subjects in autopsy series but contemporary data are scarce. It is important to confirm the prevalence of ASD/PFO in the general population given the potential associated stroke risk and the increasing availability of intervention via PFO closure. METHODS: A state-wide prospective out-of-hospital cardiac arrest registry (OHCA) identified all patients aged 1 to 50 years who experienced OHCA in Victoria, Australia from April 2019 to April 2022 and subsequently underwent autopsy with a cardiac cause of death identified. Autopsy was performed including visual description of any ASD and identification of probe patency of foramen ovale. RESULTS: A total of 517 patients underwent autopsy in the setting of sudden cardiac death; 36 patients (6.9 %) had a probe-patent foramen ovale, 2 patients (0.4 %) had secundum ASD, and 2 patients (0.4 %) had both a PFO and ASD (1 of whom had undergone percutaneous repair of both lesions). Twelve patients (2.3 %) had a prior history of cerebrovascular accident either recorded on medical history or detected on neuropathological examination; however none of these patients had a PFO or ASD. CONCLUSIONS: The combined rate of PFO and ASD in a cohort of 517 patients undergoing autopsy was 7.9 %. None of these patients had experienced a cerebrovascular accident. This rate of PFOs appears lower than earlier reports and raises the possibility that the relative risk of an associated stroke could be higher than previously estimated.

Gene Therapy in Cardiology: Is a Cure for Hypertrophic Cardiomyopathy on the Horizon?

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy worldwide, affecting approximately 1 in 500 individuals. Current therapeutic interventions include lifestyle optimisation, medications, septal reduction therapies, and, rarely, cardiac transplantation. Advances in our understanding of disease-causing genetic variants in HCM and their associated molecular mechanisms have led to the potential for targeted therapeutics and implementation of precision and personalised medicine. Results from preclinical research are promising and raise the question of whether cure of some subtypes of HCM may be possible in the future. This review provides an overview of current genetic therapy platforms, including 1) genome editing, 2) gene replacement, 3) allelic-specific silencing, and 4) signalling pathway modulation. The current applicability of each of these platforms within the paradigm of HCM is examined, with updates on current and emerging trials in each domain. Barriers and limitations within the current landscape are also highlighted. Despite recent advances, translation of genetic therapy for HCM to clinical practice is still in early development. In realising the promises of genetic HCM therapies, ethical and equitable access to safe gene therapy must be prioritised.

Prevalence of Multiple Causes of Death Within Young and Middle-Aged People Experiencing Sudden Cardiac Arrest.

BACKGROUND: Multiple causes of death are increasingly reported, particularly in older populations. Rates of multiple causes of young sudden death have not been quantified. METHOD: The End Unexplained Cardiac Death (EndUCD) registry was utilised to identify cases of young sudden death (aged 1-50 years) referred for forensic assessment from April 2019 to April 2022. Causes of death were coded according to whether one or more underlying causes of death were identified. Patients were compared according to the number of causes of death, with significant predictors assessed using logistic regression analysis. RESULTS: 1,085 cases of sudden death were identified. 263 (24.2%) cases had more than one competing cause of their sudden death. The most common multi-causal associations identified were dual non-cardiac causes of the sudden death (n=68), cardiomyopathy with non-cardiac event (n=64) and coronary artery disease with non-cardiac cause (n=63). Multi-causal death was more common in those undergoing comprehensive autopsy examination (95.8% vs 77.6%, p<0.0001), and in the setting of higher body mass index (median 31.3 kg/m2 vs 29.9 kg/m2, p=0.01), older age (44.3 years vs 41.4 years, p<0.0001), non-ventricular cardiac arrest rhythm (93.2% vs 87.3%, p=0.009), and smoking (22.8% vs 14.2%, p=0.001). The strongest predictor of multiple pathologies was comprehensive autopsy examination compared with external inspection, full-body post-mortem computed tomography and review of ancillary documentation and investigations (odds ratio 6.49, 95% confidence interval 3.47-12.14). CONCLUSIONS: One-quarter of young sudden deaths have more than one underlying cause, highlighting the value of comprehensive investigations including autopsy. Awareness of the complexity of young sudden death is important, along with multidisciplinary involvement to ensure all contributors to death are identified.

A two-point strategy to clarify prognosis in >80 year olds experiencing out of hospital cardiac arrest.

BACKGROUND: The global population is aging, with the number of ≥80-year-olds projected to triple over the next 30 years. Rates of out-of-hospital cardiac arrest (OHCA) are also increasing within this age group. METHODS: The Victorian Ambulance Cardiac Arrest Registry was utilised to identify OHCAs in patients aged ≥80 years between 2002-2021. Predictors of survival to discharge were defined and a prognostic score derived from this cohort. RESULTS: 77,628 patients experienced OHCA of whom 25,269 (32.6%) were ≥80 years (80-90 years = 18,956; 90-100 years = 6,148; >100 years = 209). The number of patients ≥80 years increased over time both absolutely (p = 0.002) and proportionally (p = 0.028). 619 (2.4%) patients survived to discharge without change over time. Older ages had no difference in witnessed OHCA status but were less likely to have shockable rhythm (OR 0.50 (95% CI 0.44-0.57) for 90-100-year-olds, OR 0.28 (95% CI 0.12-0.63) for 90-100-year-olds). If OHCA was witnessed and there was a shockable rhythm then survival was 14%; if one factor was present survival was 5-6% and if neither factor was present, survival was 0.09%. These survival rates enabled derivation of a simplified prognostic assessment score - the '15/5/0' score - highly comparable to a previously-published American cohort. CONCLUSIONS: Elderly OHCA rates have increased to one-third of caseload. The most important factors predicting survival were whether the OHCA was witnessed and there was a shockable rhythm. We present a simple two-point '15/5/0' prognostic score defining which patients will gain most from advanced resuscitative measures.

Understanding Exercise Capacity: From Elite Athlete to HFpEF.

Exercise capacity is a spectrum that reflects an individual's functional capacity and the dynamic nature of cardiac remodelling along with respiratory and skeletal muscle systems. The relationship of increasing physical activity, increased cardiac mass and volumes, and improved cardiorespiratory fitness (CRF) is well established in the endurance athlete. However, less emphasis has been placed on the other end of the spectrum, which includes individuals with a more sedentary lifestyle and small hearts who are at increased risk of functional disability and poor clinical outcomes. Reduced CRF is an independent predictor of all-cause mortality and cardiovascular events determined by multiple inter-related exogenous and endogenous factors. In this review, we explore the relationship of physical activity, cardiac remodelling, and CRF across the exercise spectrum, emphasising the critical role of cardiac size in determining exercise capacity. In contrast to the large compliant left ventricle of the endurance athlete, an individual with a lifetime of physical inactivity is likely to have a small, stiff heart with reduced cardiac reserve. We propose that this might contribute to the development of heart failure with preserved ejection fraction in certain individuals, and is key to understanding the link between low CRF and increased risk of heart failure.

Epidemiology of pediatric out-of-hospital cardiac arrest compared with adults.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with ∼90% mortality rate. In the pediatric population, this would equate to a large number of years of life lost, posing a heavy medical and economic burden to society. OBJECTIVE: The purpose of this study was to outline the characteristics and causes of pediatric OHCA (pOHCA) and associations with survival until discharge in patients enrolled in the End Unexplained Cardiac Death Registry. METHODS: A prospective statewide multisource registry identified all pOHCAs cases in patients aged 1-18 years in Victoria, Australia (population 6.5 million), from April 2019 to April 2021. Cases were adjudicated using ambulance, hospital, and forensic records; clinic assessments; and interviews of survivors and family members. RESULTS: The analysis included 106 cases after adjudication (62, 58.5% male), 45 (42.5%) of which were due to cardiac causes of OHCA, with unascertained (n = 33 [31.1%]) being the most common cardiac cause reported. Respiratory events (n = 28 [26.4%]) were the most common noncardiac cause of pOHCA. Noncardiac causes were more likely to present with asystole or pulseless electrical activity (P = .007). The overall survival to hospital discharge rate was 11.3% and associated with increasing age, witnessed cardiac arrest, and initial ventricular arrhythmias (P < .05). CONCLUSION: The incidence of pOHCA in the study population was 3.69 per 100,000 child-years. In contrast to young adults with OHCA, the most common etiology was noncardiac in pediatric patients. Prognostic factors associated with survival to discharge included increasing age, witnessed arrest, and initial ventricular arrhythmias. Rates of cardiopulmonary resuscitation and defibrillation were suboptimal.

A systematic review of global autopsy rates in all-cause mortality and young sudden death.

Autopsy is the gold standard method for determining cause of death. Young sudden death (SD) is a prototype condition in which autopsy is universally recommended. The aim of this review was to quantify real-world global rates of autopsy in either all-cause death or young SD. A systematic review was conducted. Rates of autopsy in all-cause death and in young SD were determined in each country using scientific and commercial search engines. In total, 59 of 195 countries (30.3%) reported autopsy rates in all-cause death, with rates varying from 0.01%-83.9%. Almost all of these figures derived from academic publications rather than governmental statistics. Only 16 of 195 countries (8.2%) reported autopsy rates in the context of young SD, with reported rates ranging from 5%-100%. The definition of "young" was heterogeneous. No governmental statistics reported autopsy rates in young SD. Risks of bias included inability to verify reported figures, heterogeneity in reporting of clinical vs medicolegal autopsies, and the small number of studies identified overall, resulting in the consistent exclusion of low- and middle-income countries. In conclusion, most countries globally do not report autopsy rates in either all-cause death (69.7%) or in SD (92.8%). Without transparent reporting of autopsy rates, global burdens of disease and rates of sudden cardiac death cannot be reliably calculated.

Dedicated Next Day Discharge Post Minimalist TAVI: The Tasmanian Experience.

OBJECTIVES: To assess the safety, feasibility and independent predictors of next day discharge (NDD) in patients undergoing minimalist transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) in a real-world Australian population. METHODS: This single centre study reviewed 135 consecutive patients who underwent minimalist transfemoral TAVI from June 2020 to February 2022. Baseline demographics, procedural characteristic and outcomes were obtained. All patients were assessed by the local protocol for NDD. Patients were then divided into two groups: those who achieved next day discharge (NDD) and those requiring >1 overnight hospital stay. Univariate, bivariate and stepwise multivariate logistic regression modelling was used to identify the predictors of successful next day discharge. RESULTS: The mean age of the cohort was 82.9±5.7 years with 62.3% patients male, the average STS score was 4.1±2.4. All 135 patients underwent a successful transfemoral TAVI procedure, with 131 (97%) receiving a balloon-expandable valve. Ninety-seven (97) (71.9%) patients achieved NDD. Thirty (30)-day outcomes were excellent with a 30-day mortality of 0.7%, transient ischaemic attack/cardiovascular accident (TIA/CVA) 1.5%, major vascular complication 1.5% and 11.4% need for permanent pacemaker (PPM). In patients not achieving NDD, the average length of stay (LOS) was 3.0 days. Baseline characteristics demonstrated pre-existing first degree atrioventricular (AV) block and right bundle branch block (RBBB) as statistically significant negative predictors of NDD on univariate analysis. Next day discharge was achievable in only 50% of patients who suffered any minor or major procedural complication (15/30). Stepwise multivariate logistic regression modelling demonstrated female gender (OR 3.094, 95% CI 1.141-8.391, p=0.026), smaller aortic valve area (AVA) (OR 48.265, 95% CI 2.269-102.6, p=0.013), the presence of diabetes mellitus (OR 0.594, 95% CI 0.356-0.991, p=0.046) and a longer procedure time (OR 0.960, 95% CI 0.935-0.986, p=0.002) as statistically significant negative predictors of NDD. In addition, there was no difference in 30-day readmission rates between the NDD and non-NDD cohort (7.2% vs 10.5%, p=0.386). CONCLUSION: Next day discharge is safe and feasible in almost three quarters of patients undergoing minimalist TAVI for severe AS in a predominantly balloon expandable valve cohort, with a very low rate of 30-day readmission. NDD provides advantages for hospital efficiency and improved cost-effectiveness. Female gender, smaller AVA, the presence of diabetes mellitus and a longer procedure time were independent negative predictors of successful NDD.

Telehealth in Australian cardiology: insight into factors predicting the use of telephone versus video during the COVID-19 pandemic.

BACKGROUND: The use of telehealth has increased dramatically in Australia in 2020 as a pragmatic response to the COVID-19 pandemic; however, differences between telehealth modalities have not been established. AIM: To identify characteristics contributing to choosing telephone (TP) versus video consultation (VC) and assess patient outcomes between telehealth modalities. METHODS: We conducted an observational study of cardiology outpatients at a tertiary hospital with appointments from 17 March 2020 to 12 August 2020. Demographic variables and appointment modality were compared between each group. Outcomes assessed were mortality, emergency department (ED) presentations and cross over between appointment modalities. RESULTS: There were 1754 telemedicine encounters with 1188 patients seen by TP and 327 patients by VC. Consulting volume increased from previous years. Cardiac mortality was low (0.3%). There were no differences in mortality or ED presentations between telehealth modalities. Patients choosing TP over VC were older (P < 0.001), more likely to be female (P = 0.005), non-English-speaking (P = 0.041), living in metropolitan Melbourne (P < 0.0001), undertaking a first appointment (P = 0.002) and seeing particular cardiologists (P < 0.001). VC patients were more likely to have early review (P = 0.015), and this was likely to be TP (P < 0.0001). TP patients were more likely to follow up in person (P < 0.0001). CONCLUSION: During COVID-19, we increased consultation volumes without adverse patient outcomes. We identified factors influencing the choice of telemedicine modality which did not translate into differences in mortality or ED presentations. Telemedicine is a growing platform with an important role of facilitating access to healthcare for diverse patient groups.

Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8(+) T cell differentiation.

The molecular mechanisms that regulate the rapid transcriptional changes that occur during cytotoxic T lymphocyte (CTL) proliferation and differentiation in response to infection are poorly understood. We have utilized ChIP-seq to assess histone H3 methylation dynamics within naive, effector, and memory virus-specific T cells isolated directly ex vivo after influenza A virus infection. Our results show that within naive T cells, codeposition of the permissive H3K4me3 and repressive H3K27me3 modifications is a signature of gene loci associated with gene transcription, replication, and cellular differentiation. Upon differentiation into effector and/or memory CTLs, the majority of these gene loci lose repressive H3K27me3 while retaining the permissive H3K4me3 modification. In contrast, immune-related effector gene promoters within naive T cells lacked the permissive H3K4me3 modification, with acquisition of this modification occurring upon differentiation into effector/memory CTLs. Thus, coordinate transcriptional regulation of CTL genes with related functions is achieved via distinct epigenetic mechanisms.

Creation and implementation of standardised craniofacial views for the Institute Of Medical Illustrators National Guidelines.

Vetter (1) states, "Standardisation is the key word in all discussions of clinical photography". As part of clinical photography standardised guidelines form an integral part of providing a basis to obtaining standardised images. The Institute of Medical Illustrators (IMI) provides sets of standardised guidelines that have been developed in consultation with relevant clinicians, providing theory and standardised images that are to be considered as guides to good clinical photography practice. At the time of the study there were no official standardised IMI guidelines for craniofacial photography, for this reason, the primary objective of this project was to produce a set of standardised craniofacial guidelines that could be utilised by other clinical photographers for guidance on taking craniofacial images. This paper describes the development, evaluation and implementation of the guidelines.