COVID-19: The disease, the vaccine and the heart.

Coronavirus SARS-CoV-2 has fundamentally affected the health, healthcare delivery and daily life in all populations and age groups in Australia. The aim of this report is to summarise how it has affected the paediatric population with an emphasis on, but not limited to, the cardiac manifestations. A literature review and appraisal of data relating to SARS-CoV-2 cardiac manifestations and vaccination in the paediatric population was undertaken.The majority of children with SARS-CoV-2 infection recover well. However, a very small proportion may develop severe acute disease. In the sub-acute phase, children may also develop a Kawasaki like illness, Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2. Whilst not directly cardiac in nature, SARS-CoV-2 also affected children in other profound ways. Public health measures with widespread lockdowns appeared to disproportionately affect the paediatric population causing physical deconditioning and psychological harm. Vaccination against SARS-CoV-2 has proven to be safe and effective, but the small rate of complications did disproportionately affect teenage children with risks of myocarditis and pericarditis. The long term outcomes following myocarditis related to SARS-Cov-2 vaccination are yet to be clarified. When treating children in the era of SARS-CoV-2, Paediatricians need to be well aware of the risks of infection in the acute and sub-acute phases, have a good understanding of the well-established recommendations for vaccination, and also be cognisant of psychological impacts.

Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection.

Early host responses toward pathogens are essential for defense against infection. In Caenorhabditis elegans, the transcription factor, SKN-1, regulates cellular defenses during xenobiotic intoxication and bacterial infection. However, constitutive activation of SKN-1 results in pleiotropic outcomes, including a redistribution of somatic lipids to the germline, which impairs health and shortens lifespan. Here, we show that exposing C. elegans to Pseudomonas aeruginosa similarly drives the rapid depletion of somatic, but not germline, lipid stores. Modulating the epigenetic landscape refines SKN-1 activity away from innate immunity targets, which alleviates negative metabolic outcomes. Similarly, exposure to oxidative stress redirects SKN-1 activity away from pathogen response genes while restoring somatic lipid distribution. In addition, activating p38/MAPK signaling in the absence of pathogens, is sufficient to drive SKN-1-dependent loss of somatic fat. These data define a SKN-1- and p38-dependent axis for coordinating pathogen responses, lipid homeostasis, and survival and identify transcriptional redirection, rather than inactivation, as a mechanism for counteracting the pleiotropic consequences of aberrant transcriptional activity.

PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families.

PURPOSE: Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants. METHODS: Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. RESULTS: Among the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity. CONCLUSION: We expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.

Epidemiology and clinical characteristics of atrial fibrillation in patients with inherited heart diseases.

BACKGROUND: The prevalence and clinical course of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) is well described, though less so for other inherited cardiomyopathies (familial dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction); and inherited arrhythmia syndromes (long QT syndrome, Brugada syndrome or catecholaminergic polymorphic ventricular tachycardia [CPVT]). We examined the frequency, clinical characteristics and AF-related management and outcomes amongst this patient population. METHODS: We retrospectively studied consecutive probands with inherited cardiomyopathy (n = 962) and inherited arrhythmia syndromes (n = 195) evaluated between 2002 and 2018. RESULTS: AF was observed in 5% to 31% of patients, with the highest frequency in HCM. Age of AF onset was 45.8 ± 21.9 years in the inherited arrhythmia syndromes compared with 53.3 ± 15.3 years in the inherited cardiomyopathies, with four CPVT patients developing AF at a median age of 20 years. Overall, 11% of patients with AF had a transient ischemic attack or stroke of which a total of 80% were anticoagulated; with 48% of events occurring at a CHA2 DS2 -VASc < 2. Amongst sarcomere-positive HCM, AF was independently associated with age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.08; P = .0014), left atrial area (OR, 1.11; 95% CI, 1.05-1.17; P = .0005) and MYH7 variants (OR, 2.55; 95% CI, 1.16-5.61; P = .020). CONCLUSION: Up to one-third of inherited heart disease patients will develop AF. While common general population risk factors are key in patients with HCM, the genotype is independently associated with AF. Amongst inherited arrhythmia syndromes, AF is less common, though often occurs below the age of 50 years.

Clinical presentation and proteomic signature of patients with TANGO2 mutations.

Transport And Golgi Organization protein 2 (TANGO2) deficiency has recently been identified as a rare metabolic disorder with a distinct clinical and biochemical phenotype of recurrent metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias, and encephalopathy with cognitive decline. We report nine subjects from seven independent families, and we studied muscle histology, respiratory chain enzyme activities in skeletal muscle and proteomic signature of fibroblasts. All nine subjects carried autosomal recessive TANGO2 mutations. Two carried the reported deletion of exons 3 to 9, one homozygous, one heterozygous with a 22q11.21 microdeletion inherited in trans. The other subjects carried three novel homozygous (c.262C>T/p.Arg88*; c.220A>C/p.Thr74Pro; c.380+1G>A), and two further novel heterozygous (c.6_9del/p.Phe6del); c.11-13delTCT/p.Phe5del mutations. Immunoblot analysis detected a significant decrease of TANGO2 protein. Muscle histology showed mild variation of fiber diameter, no ragged-red/cytochrome c oxidase-negative fibers and a defect of multiple respiratory chain enzymes and coenzyme Q10 (CoQ10 ) in two cases, suggesting a possible secondary defect of oxidative phosphorylation. Proteomic analysis in fibroblasts revealed significant changes in components of the mitochondrial fatty acid oxidation, plasma membrane, endoplasmic reticulum-Golgi network and secretory pathways. Clinical presentation of TANGO2 mutations is homogeneous and clinically recognizable. The hemizygous mutations in two patients suggest that some mutations leading to allele loss are difficult to detect. A combined defect of the respiratory chain enzymes and CoQ10 with altered levels of several membrane proteins provides molecular insights into the underlying pathophysiology and may guide rational new therapeutic interventions.

Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood: Results From a National Population-Based Study.

BACKGROUND: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy. METHODS: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0-10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation. RESULTS: There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0-92.0) 1 year after presentation, 80% (95% CI, 69.0-87.0) at 10 years, and 78% (95% CI, 67.0-86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60-11.05; P=0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02-8.08; P=0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22-1.73; P<0.001), and lower fractional shortening z score (hazard ratio, 0.84; 95% CI, 0.74-0.95; P=0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with ß-blocker, and 13 (21%) had an implantable cardioverter-defibrillator. CONCLUSIONS: The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.

Long-Term Outcomes of Childhood Left Ventricular Noncompaction Cardiomyopathy: Results From a National Population-Based Study.

BACKGROUND: Long-term outcomes for childhood left ventricular noncompaction (LVNC) are uncertain. We examined late outcomes for children with LVNC enrolled in a national population-based study. METHODS: The National Australian Childhood Cardiomyopathy Study includes all children in Australia with primary cardiomyopathy diagnosed before 10 years of age between 1987 and 1996. Outcomes for subjects with LVNC with a dilated phenotype (LVNC-D) were compared with outcomes for those with dilated cardiomyopathy. Propensity-score analysis was used for risk factor adjustment. RESULTS: There were 29 subjects with LVNC (9.2% of all cardiomyopathy subjects), with a mean annual incidence of newly diagnosed cases of 0.11 per 100 000 at-risk individuals. Congestive heart failure was the initial symptom in 24 of 29 subjects (83%), and 27 (93%) had LVNC-D. The median age at diagnosis was 0.3 (interquartile interval, 0.08-1.3) years. The median duration of follow-up was 6.8 (interquartile interval, 0.7-24.0) years for all subjects and 24.7 (interquartile interval, 23.3 - 27.7) years for surviving subjects. Freedom from death or transplantation was 48% (95% confidence interval [CI], 30-65) at 10 years after diagnosis and 45% (95% CI, 27-63) at 15 years. In competing-risk analysis, 21% of subjects with LVNC were alive with normal left ventricular systolic function, and 31% were alive with abnormal function at 15 years. Propensity-score matching between subjects with LVNC-D and those with dilated cardiomyopathy suggested a lower freedom from death/transplantation at 15 years after diagnosis in the subjects with LVNC-D (LVNC-D, 46% [95% CI, 26-66] versus dilated cardiomyopathy, 70% [95% CI, 42-97]; P=0.08). Using propensity-score inverse probability of treatment-weighted Cox regression, we found evidence that LVNC-D was associated with a greater risk of death or transplantation (hazard ratio, 2.3; 95% CI, 1.4-3.8; P=0.0012). CONCLUSIONS: Symptomatic children with LVNC usually present in early infancy with a predominant dilated phenotype. Long-term outcomes are worse than for matched children with dilated cardiomyopathy.

A multicentre study of patients with Timothy syndrome.

Aims: Timothy syndrome (TS) is an extremely rare multisystem disorder characterized by marked QT prolongation, syndactyly, seizures, behavioural abnormalities, immunodeficiency, and hypoglycaemia. The aim of this study was to categorize the phenotypes and examine the outcomes of patients with TS. Methods and results: All patients diagnosed with TS in the United Kingdom over a 24-year period were reviewed. Fifteen centres in the British Congenital Arrhythmia Group network were contacted to partake in the study. Six patients with TS were identified over a 24-year period (4 boys and 2 girls). Five out of the six patients were confirmed to have a CACNA1C mutation (p.Gly406Arg) and the other patient was diagnosed clinically. Early presentation with heart block, due to QT prolongation was frequently seen. Four are still alive, two of these have a pacemaker and two have undergone defibrillator implantation. Five out of six patients have had a documented cardiac arrest with three occurring under general anaesthesia. Two patients suffered a cardiac arrest while in hospital and resuscitation was unsuccessful, despite immediate access to a defibrillator. Surviving patients seem to have mild developmental delay and learning difficulties. Conclusion: Timothy syndrome is a rare disorder with a high attrition rate if undiagnosed. Perioperative cardiac arrests are common and not always amenable to resuscitation. Longer-term survival is possible, however, patients invariably require pacemaker or defibrillator implantation.

Psychosocial Implications of Living with Catecholaminergic Polymorphic Ventricular Tachycardia in Adulthood.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmogenic disease with a high risk of sudden cardiac death. The impact on health-related quality of life (HR-QoL) and psychosocial outcomes is not known. We sought to provide the first description of HR-QoL and psychosocial wellbeing of adults with CPVT, parents of affected children and at-risk relatives. Participants were recruited through the Australian Genetic Heart Disease Registry and invited to complete a cross-sectional survey comprising a number of validated scales and open-ended questions. Thirty-five participants completed surveys (response rate 65%), including 19 with CPVT, 10 unaffected parents of a child with CPVT, and 7 at-risk relatives (one participant considered patient and parent). Young patients <40 years were significantly more likely to report anxiety (p = 0.04), depression (p = 0.03) and posttraumatic stress symptoms (p = 0.02) compared to older CPVT patients. Further, young patients with an implantable cardioverter defibrillator (ICD) reported significantly worse device-related distress (p = 0.04) and shock anxiety (p = 0.003). Patients with a genetic diagnosis had worse psychological adaptation than those patients without a gene result. Parents perceived their affected children to have poor quality of life across all subdomains compared to healthy age-matched children, however quality of life of parents and at-risk relatives was comparable to population norms. Ongoing psychosocial care is required for young people with CPVT. Those with an ICD and/or undergoing genetic testing may require additional support. The challenges of CPVT management should extend beyond the clinical and genetic aspects of care to incorporate greater psychosocial support, and further reinforces the need for a multidisciplinary approach to care.

The Use of Intravenous Sotalol in Cardiac Arrhythmias.

Sotalol is a non-selective beta-adrenergic blocking agent without intrinsic sympathomimetic activity. It has the additional unique property of producing pronounced prolongation of the cardiac action potential duration. Sotalol therapy has been indicated for the management of supraventricular arrhythmias, refractory life threatening ventricular arrhythmias and atrial fibrillation/flutter. Until recently, sotalol was only available in the oral form, however, it was approved for intravenous administration by the US Food & Drug Administration (FDA). The current recommendations are for sotalol 75-150mg to be administered intravenously over 5hours. This rate of administration does not reflect the majority of the research that has been performed with regards to intravenous sotalol. Also, the safety of intravenous bolus dosing of 100mg over 1 and 5minutes has previously been demonstrated. The antiarrhythmic action of sotalol depends on its ability to prolong refractoriness in the nodal and extra nodal tissue. Hence, by giving a lower dose over a long duration, patients may not necessarily benefit from its anti-arrhythmic potential. The purpose of this article is to review the research that has been conducted with regards to dosage and safety of intravenous sotalol, its electrophysiological effects and finally the spectrum of arrhythmias in which it has been used to date.

Long-term outcomes of dilated cardiomyopathy diagnosed during childhood: results from a national population-based study of childhood cardiomyopathy.

BACKGROUND: Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy. METHODS AND RESULTS: The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings. The primary study end point included time to the combined outcome of death or cardiac transplantation. There were 175 patients 0 to <10 years of age at the time of diagnosis. Survival free from death or transplantation was 74% (95% confidence interval, 67-80) 1 year after diagnosis, 62% (95% confidence interval, 55-69) at 10 years, and 56% (95% confidence interval, 46-65) at 20 years. In multivariable analysis, age at diagnosis <4 weeks or >5 years, familial cardiomyopathy, and lower baseline left ventricular fractional shortening Z score were associated with increased risk of death or transplantation, as was lower left ventricular fractional shortening Z score during follow-up. At 15 years after diagnosis, echocardiographic normalization had occurred in 69% of surviving study subjects. Normalization was related to higher baseline left ventricular fractional shortening Z score, higher left ventricular fractional shortening Z score during follow-up, and greater improvement in left ventricular fractional shortening Z score. Children with lymphocytic myocarditis had better survival and a higher rate of echocardiographic normalization. At the latest follow-up, 100 of 104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer receiving pharmacotherapy. CONCLUSIONS: Death or transplantation occurred in 26% of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and ~1% per year thereafter. Risk factors for death or transplantation include age at diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction. The majority of surviving subjects are well and free of cardiac medication.

A prepatellar Morel-Lavallée lesion in a pedestrian vs automobile collision.

A small truck collided with a 67-year-old female pedestrian. She sustained blunt, closed trauma to her right knee, and developed a prepatellar Morel-Lavallée lesion (MLL). A MLL is a closed soft tissue degloving injury, resulting from high-energy shearing forces, which separate the skin and subcutaneous tissue from the underlying fascia. The resultant space collects fluid and is prone to infection, tissue necrosis, and symptoms of ongoing mass effects. The diagnosis is elusive because of its rarity and often subtle initial symptoms. Prompt diagnosis is critical, given the potentially severe complications when missed, and less invasive and more successful treatment when found early. Most reported cases are proximal to the pelvis, whereas the few reported peri­knee MLLs involve young athletes or postsurgical complications. To our knowledge, this is the third reported case of a non­sport-related MLL of the knee, all of which involved high-inertia force to the knee. Therefore, MLL of the knee should be considered in patients with knee trauma, particularly in the setting of pedestrians struck by motor vehicles.

The epidemiology of arrhythmia in infants: a population-based study.

AIM: Cardiac arrhythmias are an important cause of morbidity in infants. Although the spectrum of types of arrhythmia has been reported, there has been no previous population-based study of the incidence of arrhythmias in infancy. Our aim was to define the population incidence of arrhythmia in infants. METHODS: We based this study on the Northern Region of England with a resident population of 3.1 million and an annual live birth rate of 33,000. We identified all clinically significant arrhythmias in infants in 1991-2010 from the regional cardiac database. All diagnoses were based on analysis of the electrocardiogram. Infants with only the substrate for arrhythmia (such as QT prolongation or ventricular pre-excitation) were excluded. RESULTS: In 20 years, there were 662,698 live births. We identified 162 cases of newly diagnosed arrhythmia of which 22 had associated structural cardiovascular malformations. The incidence of arrhythmia was 24.4 per 100,000 live births. The most common arrhythmia was atrioventricular re-entry tachycardia with an incidence of 16.3 per 100,000. Complete atrioventricular block and atrial flutter both occurred at 2.1 cases per 100,000 live births, and other arrhythmias were rare. CONCLUSIONS: This study is the first to report a population incidence of arrhythmia in infants.

Outcomes of interventional electrophysiology in children under 2 years of age.

BACKGROUND: Despite the increasing utilisation of interventional electrophysiology in adults and older children with arrhythmias, there are few data reflecting the safety and efficacy of this procedure in the age group under 2 years. AIM: We describe our experience in assessing the efficacy and safety with this group of children. METHODS: We undertook a retrospective review of all infants under 2 years of age who underwent an interventional electrophysiology procedure between 1995 and 2009 to determine indications, procedural details, short- and long-term success, and complication rate. RESULTS: A total of 23 interventional electrophysiology procedures were performed in 17 patients initially under 2 years of age. Of these, three patients had congenital heart disease. The most common indication was arrhythmia resistant to pharmacological agents (59%), with the remaining cases being arrhythmia complicated by cardiovascular instability (41%). There was initial success in 15 patients after the first procedure, with early recurrence in four. Following six repeat procedures, there was long-term success in 15 patients (88%), with three repeat procedures being performed after 2 years of age. There was one non-procedural death related to persisting arrhythmia. There were three minor complications. In one patient, cryotherapy was used successfully. CONCLUSIONS: The interventional electrophysiology procedure is a viable therapeutic option in infants under 2 years with arrhythmia resistant to other conventional medical management.

Primary cardiac arrest following sport or exertion in children presenting to an emergency department: chest compressions and early defibrillation can save lives, but is intravenous epinephrine always appropriate?

OBJECTIVES: The objective of this study was to describe the characteristics and outcome of pediatric patients presenting to an emergency department (ED) following out-of-hospital primary cardiac arrest (OHPCA), to determine if long-term survival is influenced by specific resuscitation interventions. METHODS: This was a prospective observational study of cases of OHPCA during sport or exertion in young patients presenting to an ED over a 5-year period. Cases were identified from a resuscitation database, which documented patient demographics, nature of event, emergency treatment, response times, and clinical progress. These data were analyzed to determine outcomes. RESULTS: Nine children were identified who presented following OHPCA during the study period. The mean age was 10.7 (±4.2) years. All were subsequently diagnosed with an underlying primary cardiac disorder. Six patients (66.6%) survived to make a full recovery. All patients who survived had received early chest compressions (within 5 minutes) and early defibrillation (within 10 minutes). The initial cardiac arrest rhythm in all survivors had been an electrically cardiovertable rhythm. Five (83%) of the 6 survivors did not receive epinephrine during resuscitation. CONCLUSIONS: The importance of early chest compressions and defibrillation in collapsed young athletes is highlighted in this report. These interventions can result in full long-term neurological recovery. Use of epinephrine in these patients may be dangerous. We suggest that special consideration should be given to this subgroup of patients in the development of future resuscitation guidelines.

Update on the use and outcomes of implantable cardioverter defibrillators in pediatric patients.

OPINION STATEMENT: The vast majority of implantable cardioverter defibrillators (ICDs) continue to be implanted in the adult population. Accordingly, manufacturers develop devices and leads primarily for the adult population. Whilst the number of ICDs implanted in children is small in comparison, the potential benefits are large to this group. It is a common frustration among pediatric cardiologists whom implant devices that impressive technological developments continue to be developed for the adult population; as the population of children with ICDs is small, robust clinical studies often lag behind. By necessity, pediatric cardiologists and cardiothoracic surgeons have developed innovative techniques utilizing adult components in unusual configurations for children with complex congenital heart disease. As in the adult population, inappropriate shocks are one of the most limiting and concerning complications in the use of ICDs. Unfortunately, as will be discussed below, children are at increased risk of inappropriate shocks when compared with adults. The true impact of inappropriate shocks is increasingly being realized, and much of the focus in management of children with ICDs surrounds the prevention of inappropriate shocks.

Phenobarbital for the management of severe acute alcohol withdrawal (the PHENOMANAL trial): a pilot randomized controlled trial.

BACKGROUND: Benzodiazepines are considered first-line treatment for patients experiencing severe acute alcohol withdrawal syndrome (sAAWS). Although several medications have been evaluated as potential adjuvant treatments for sAAWS, barbiturates show particular promise. OBJECTIVE: In the PHENOMANAL trial, we will assess the feasibility of conducting an allocation-concealed, quadruple-blinded, randomized controlled trial (RCT) comparing symptom-triggered benzodiazepine therapy with either a single dose of adjuvant intravenous (IV) phenobarbital (7.5 mg/kg of ideal body weight) or a single dose of matching IV placebo for patients with sAAWS. METHODS: We will recruit adult patients from the Emergency Department, Intensive Care Unit, or hospital wards with a Clinical Institute of Withdrawal - Adult revised (CIWA-Ar) score of 16 or more after receipt of at least 60 mg of diazepam or equivalent within 16 h of diagnosis of sAAWS, and an anticipated need for hospitalization. We will randomize participants (n=39) in a 2:1 manner to treatment and placebo groups, respectively. The primary objective of the PHENOMANAL pilot trial will be to demonstrate our ability to recruit the desired population over the trial period. As secondary objectives, we will evaluate clinician compliance with the treatment protocols, assess crossover rates from the placebo arm to the treatment arm, and obtain preliminary estimates of treatment effect. All trial participants will be followed for 7 days or until hospital discharge. RELEVANCE: The PHENOMANAL trial is novel in investigating a new treatment for a common and understudied condition, repurposing an existing medication for a novel indication, and addressing an important evidence gap. Through conduct of the multidisciplinary pilot trial, we aim to advance methodology in acute care research through the use of a hybrid consent model and inform the design of a large-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov Registration NCT03586089 ; first registered July 13, 2018.

Life-threatening cardiac arrhythmia and sudden death during electronic gaming: An international case series and systematic review.

BACKGROUND: Electronic gaming has recently been reported as a precipitant of life-threatening cardiac arrhythmia in susceptible individuals. OBJECTIVE: The purpose of this study was to describe the population at risk, the nature of cardiac events, and the type of game linked to cardiac arrhythmia associated with electronic gaming. METHODS: A multisite international case series of suspected or proven cardiac arrhythmia during electronic gaming in children and a systematic review of the literature were performed. RESULTS: Twenty-two patients (18 in the case series and 4 via systematic review; aged 7-16 years; 19 males [86%]) were identified as having experienced suspected or proven ventricular arrhythmia during electronic gaming; 6 (27%) had experienced cardiac arrest, and 4 (18%) died suddenly. A proarrhythmic cardiac diagnosis was known in 7 (31%) patients before their gaming event and was established afterward in 12 (54%). Ten patients (45%) had catecholaminergic polymorphic ventricular tachycardia, 4 (18%) had long QT syndrome, 2 (9%) were post-congenital cardiac surgery, 2 (9%) had "idiopathic" ventricular fibrillation, and 1 (after Kawasaki disease) had coronary ischemia. In 3 patients (14%), including 2 who died, the diagnosis remains unknown. In 13 (59%) patients for whom the electronic game details were known, 8 (62%) were war games. CONCLUSION: Electronic gaming can precipitate lethal cardiac arrhythmias in susceptible children. The incidence appears to be low, but syncope in this setting should be investigated thoroughly. In children with proarrhythmic cardiac conditions, electronic war games in particular are a potent arrhythmic trigger.