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.

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.

The challenge of risk stratification in hypertrophic cardiomyopathy: Clinical, genetic and imaging insights from a quaternary referral centre.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD). METHODS: Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest. RESULTS: 380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p = 0.0041), unexplained syncope (33.3% vs 9.4%, p = 0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p < 0.0001), increased septal thickness (21.5 vs 17.5 mm, p = 0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p = 0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most >60-year-olds having a non-cardiac cause of death (p = 0.0223). CONCLUSION: This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Incorporating newer risk markers such as HCM genotyping and myocardial fibrosis quantification by cardiac MRI may assist future risk refinement.

Right ventricular pneumatosis and extensive multi-territory air emboli in an intravenous drug user: a case report.

Background: Air emboli are a life-threatening diagnosis, which may form through a range of mechanisms. In this case, we describe the case of extensive multi-territory air emboli in a patient with a history of intravenous drug abuse. Case summary: This case describes a 41-year-old male who presented with confusion following fall with long lie. He was diagnosed with hyperkalaemia, renal failure, rhabdomyolysis, and compartment syndrome, and he developed extensive multi-territory air emboli. Air embolism was identified in arterial, venous, subcutaneous, and mediastinal territories. Echocardiography demonstrated right ventricular dilation and dysfunction, consistent with air visualized in the right coronary artery on computed tomography. The patient was transferred to the intensive care unit for close cardiac and neurological monitoring and supportive organ care, and ultimately made an uneventful recovery by 6 weeks without apparent complications from the air emboli. Discussion: The presence of multi-territory air emboli has previously been described in the setting of surgery, manipulation of intravascular catheters, pulmonary barotrauma, and in sepsis with gas-forming organisms. It has not previously been reported in intravenous drug use or sterile rhabdomyolysis. Computed tomography imaging and echocardiography are useful to diagnose air emboli and their haemodynamic impact. Our patient's case provides a novel example of multi-territory air emboli in a unique scenario.

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.

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.

Sudden Cardiac Death in People With Schizophrenia: Higher Risk, Poorer Resuscitation Profiles, and Differing Pathologies.

BACKGROUND: People with schizophrenia account for approximately 1.0% of the population and seem to experience increased rates of sudden cardiac death (SCD). OBJECTIVES: This study sought to determine characteristics of increased SCD in people with schizophrenia. METHODS: The End Unexplained Cardiac Death (EndUCD) prospective state-wide registry compared people aged 15 to 50 years with and without schizophrenia who experienced SCD within a 2-year time period and were referred for forensic evaluation. RESULTS: We identified 579 individuals, of whom 65 (11.2%) had schizophrenia. Patients with schizophrenia were more commonly smokers (46.2% vs 23.0%; P < 0.0001), consumed excess alcohol (32.3% vs 21.4%; P = 0.05), and used QTc-prolonging medications (69.2% vs 17.9%; P < 0.0001). They were less likely to arrest while exercising (0.0% vs 6.4%; P = 0.04). Unfavorable arrest-related factors included lower rates of witnessed arrest (6.2% vs 23.5%; P < 0.0001), more likely to be found in asystole (92.3% vs 73.3%; P < 0.0001), and being more likely to be found as part of a welfare check after a prolonged period of time (median 42 hours vs 12 hours; P = 0.003). There was more frequent evidence of decomposition, and they more commonly underwent autopsy (41.2% vs 26.4%; P = 0.04 and 93.8% vs 82.5%; P = 0.05), with a diagnosis of nonischemic cardiomyopathy being more common (29.2% vs 18.1%; P = 0.04). CONCLUSIONS: People with schizophrenia account for 11% of young SCD patients referred for forensic investigations, exceeding population rates by 11-fold. They have a higher preexisting cardiac risk factor burden, unfavorable resuscitation profiles, and higher rates of nonischemic cardiomyopathy. Strategies targeting biopsychosocial support may deliver not only psychological benefits, but also help to decrease unwitnessed cardiac arrest.

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.

Prevalence of illicit drug use in young patients with sudden cardiac death.

BACKGROUND: Illicit drug use may accelerate coronary disease and cardiac hypertrophy or stimulate arrhythmias. Rates of illicit drug use in young patients with sudden cardiac death (SCD) are uncertain. OBJECTIVE: The purpose of this study was to identify rates of illicit drug use in young patients with SCD. METHODS: A prospective statewide registry identified out-of-hospital patients with cardiac arrest aged 18-50 years from April 2019 to April 2021. Clinical characteristics were compared between patients with and without illicit drug use (defined by toxicological results or reported regular use). Illicit drugs included amphetamine-type substances, cocaine, heroin, cannabis, and other drugs. RESULTS: A total of 554 (40.2%) of 1378 patients had confirmed cardiac cause of out-of-hospital cardiac arrest, with 523 undergoing toxicological assessment. There were 170 patients (32.5%) having either positive toxicology for illicit drugs (n = 138) or negative toxicology but reported regular drug use (n = 32). Patients with SCD and illicit drug use were more commonly male (81.2% vs 72.3%; P = .028), smokers (38.8% vs 19.8%; P ≤ .0001), and excess alcohol drinkers (30.6% vs 20.6%; P = .012) and had a psychiatric diagnosis (38.8% vs 25.7%; P = .002), lower body mass index (29.4 kg/m2 vs 31.7 kg/m2; P = .0063), and lower rates of hypertension (10.6% vs 18.6%; P = .019). Death commonly occurred while sedentary (47.5%) or during sleep (45.8%). Accounting for these baseline differences, there were no differences in rates of coronary disease or cardiomyopathy. Cannabis (n = 106) was the most common illicit drug identified and polysubstance abuse occurred frequently (n = 25). CONCLUSION: Approximately one-third of young patients with SCD have positive toxicology at the time of death or reported frequent use of illicit drugs, with high rates of polysubstance abuse.

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.

Inconsistent discharge diagnoses for young cardiac arrest episodes: insights from a statewide registry.

BACKGROUND: Administrative coding of out-of-hospital cardiac arrest (OHCA) is heterogeneous, with the prevalence of noninformative diagnoses uncertain. AIM: To characterize the prevalence and type of non-informative diagnoses in a young cardiac arrest population. METHODS: Hospital discharge diagnoses provided to a statewide OHCA registry were characterised as either 'informative' or 'noninformative.' Informative diagnoses stated an OHCA had occurred or defined OHCA as occurring due to coronary artery disease, cardiomyopathy, channelopathy, definite noncardiac cause, or no known cause. Noninformative diagnoses were blank, stated presenting cardiac rhythm only, provided irrelevant information or presented a complication of the OHCA as the main diagnosis. Characteristics of patients receiving informative versus noninformative diagnoses were compared. RESULTS: Of 1479 patients with OHCA aged 1 to 50 years, 290 patients were admitted to 15 hospitals. Ninety diagnoses (31.0%) were noninformative (arrest rhythm = 50, blank = 21, complication = 10 and irrelevant = 9). Two hundred diagnoses (69.0%) were informative (cardiac arrest = 84, coronary artery disease = 54, noncardiac diagnosis = 48, cardiomyopathy = 8, arrhythmia disorder = 4 and unascertained = 2). Only 10 diagnoses (3.5%) included both OHCA and an underlying cause. Patients receiving a noninformative diagnosis were more likely to have survived OHCA or been referred for forensic assessment (P = 0.011) and had longer median length of stay (9 vs 5 days, P = 0.0019). CONCLUSION: Almost one third of diagnoses for young patients discharged after an OHCA included neither OHCA nor any underlying cause. Underestimating the burden of OHCA impacts ongoing patient and at-risk family care, data sampling strategies, international statistics and research funding.

Causes, circumstances, and potential preventability of cardiac arrest in the young: insights from a state-wide clinical and forensic registry.

AIMS: The causes, circumstances, and preventability of young sudden cardiac arrest remain uncertain. METHODS AND RESULTS: A prospective state-wide multi-source registry identified all out-of-hospital cardiac arrests (OHCAs) in 1-50 year olds in Victoria, Australia, from 2019 to 2021. Cases were adjudicated using hospital and forensic records, clinic assessments and interviews of survivors and family members. For confirmed cardiac causes of OHCA, circumstances and cardiac history were collected. National time-use data was used to contextualize circumstances. 1319 OHCAs were included. 725 (55.0%) cases had a cardiac aetiology of OHCA, with coronary disease (n = 314, 23.8%) the most common pathology. Drug toxicity (n = 226, 17.1%) was the most common non-cardiac cause of OHCA and the second-most common cause overall. OHCAs were most likely to occur in sleep (n = 233, 41.2%). However, when compared to the typical Australian day, OHCAs occurred disproportionately more commonly during exercise (9% of patients vs. 1.3% of typical day, P = 0.018) and less commonly while sedentary (39.6 vs. 54.6%, P = 0.047). 38.2% of patients had known standard modifiable cardiovascular risk factors. 77% of patients with a cardiac cause of OHCA had not reported cardiac symptoms nor been evaluated by a cardiologist prior to their OHCA. CONCLUSION: Approximately half of OHCAs in the young have a cardiac cause, with coronary disease and drug toxicity dominant aetiologies. OHCAs disproportionately occur during exercise. Of patients with cardiac cause of OHCA, almost two-thirds have no standard modifiable cardiovascular risk factors, and more than three-quarters had no prior warning symptoms or interaction with a cardiologist.