Physiological Insights From Asymptomatic Severe Valvular Disease in a Highly Trained Athlete.

Parameters relied on as tools for prognostication in valvular disease can be confounded by athletic physiological remodeling. This case describes how cardiopulmonary exercise testing and multimodality imaging may be helpful in assessment of a 46-year-old female athlete with bicuspid aortic valve and subaortic membrane with associated asymptomatic severe mixed aortic valve disease.

Evaluation of research co-design in health: a systematic overview of reviews and development of a framework.

BACKGROUND: Co-design with consumers and healthcare professionals is widely used in applied health research. While this approach appears to be ethically the right thing to do, a rigorous evaluation of its process and impact is frequently missing. Evaluation of research co-design is important to identify areas of improvement in the methods and processes, as well as to determine whether research co-design leads to better outcomes. We aimed to build on current literature to develop a framework to assist researchers with the evaluation of co-design processes and impacts. METHODS: A multifaceted, iterative approach, including three steps, was undertaken to develop a Co-design Evaluation Framework: 1) A systematic overview of reviews; 2) Stakeholder panel meetings to discuss and debate findings from the overview of reviews and 3) Consensus meeting with stakeholder panel. The systematic overview of reviews included relevant papers published between 2000 and 2022. OVID (Medline, Embase, PsycINFO), EBSCOhost (Cinahl) and the Cochrane Database of Systematic reviews were searched for papers that reported co-design evaluation or outcomes in health research. Extracted data was inductively analysed and evaluation themes were identified. Review findings were presented to a stakeholder panel, including consumers, healthcare professionals and researchers, to interpret and critique. A consensus meeting, including a nominal group technique, was applied to agree upon the Co-design Evaluation Framework. RESULTS: A total of 51 reviews were included in the systematic overview of reviews. Fifteen evaluation themes were identified and grouped into the following seven clusters: People (within co-design group), group processes, research processes, co-design context, people (outside co-design group), system and sustainment. If evaluation methods were mentioned, they mainly included qualitative data, informal consumer feedback and researchers' reflections. The Co-Design Evaluation Framework used a tree metaphor to represent the processes and people in the co-design group (below-ground), underpinning system- and people-level outcomes beyond the co-design group (above-ground). To evaluate research co-design, researchers may wish to consider any or all components in the tree. CONCLUSIONS: The Co-Design Evaluation Framework has been collaboratively developed with various stakeholders to be used prospectively (planning for evaluation), concurrently (making adjustments during the co-design process) and retrospectively (reviewing past co-design efforts to inform future activities).

Blood pressure response to graded bicycle exercise in males and females across the age and fitness spectrum.

AIM: Blood pressure (BP) responses to exercise are frequently measured, with the concern that greater increases are a marker of disease. We sought to characterize the normal exercise BP response in healthy adults and its relationships with age, sex, and fitness. METHODS: 589 participants (median age 46 [IQR 24-56] years, 81% male) underwent cardiopulmonary exercise testing with repeated, automated BP measures. An exaggerated maximal systolic BP (SBPmax) was defined from current guidelines as ≥210 mmHg in males and ≥190 mmHg in females. Individual linear regression analyses defined the relationship between BP and workload (SBP/W-slope and DBP/W-slope). Participants with or without an exaggerated SBPmax and above or below median SBP/W-slope were compared. RESULTS: An exaggerated SBPmax was found in 51% of males and 64% of females and was more prevalent in endurance-trained athletes (males 58%, females 72%, p<0.001). The mean SBP/W-slope was lower in males (0.24±0.10 mmHg/W) than females (0.27±0.12 mmHg/W), p=0.031. In both sexes, peak oxygen uptake (VO2peak) was inversely correlated with SBP/W-slope (p<0.01). Those with an exaggerated SBPmax and below-median SBP/W-slope were 10 years younger and had a 20% higher VO2peak, on average (p<0.001). A non-exaggerated SBPmax and above-median SBP/W-slope was observed in older individuals with the lowest VO2peak. CONCLUSION: In a large cohort of healthy individuals, an exaggerated SBPmax was common and associated with higher fitness. In contrast, higher SBP indexed to workload was associated with older age, lower fitness, and female sex. Thus, sex, age and fitness should be considered when evaluating BP response to exercise.

We evaluated the predictors of blood pressure responses to exercise in 589 healthy individuals. We showed that there is a strong, positive relationship between the increase in systolic blood pressure during exercise with cardiorespiratory fitness and exercise workload.During intensive exercise, high maximal systolic blood pressures are more prevalent in young fit individuals than older, less fit individuals. Systolic blood pressure measures are higher in females than males when indexed to workload.Previous diagnostic cut-offs for peak exercise blood pressure are frequently exceeded in healthy individuals and are likely to have poor disease specificity. Workload-indexed exercise blood pressure is therefore a more informative metric than peak exercise blood pressure.

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

AIMS: Increasing aortic dilation increases the risk of aortic dissection. Nevertheless, dissection occurs at dimensions below guideline-directed cut-offs for prophylactic surgery. Currently, there are no large-scale population imaging data assessing aortic dimensions before dissection. METHODS AND RESULTS: Patients within the National Echo Database of Australia were stratified according to absolute, height-indexed, and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM Code I71) were identified via linkage with the National Death Index. A total of 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). A total of 274 992 (52.4%) were males, with a median age of 64 years and a median follow-up time of 6.9 years. Eight hundred and ninety-nine 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 = odds ratio (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. The results were robust for absolute, height-indexed, or BSA-indexed aortic measurements. CONCLUSION: Although severe aortic dilatation is associated with a near-30-fold increase in fatal dissections, 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.

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.

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.