Fine particulate matter-sudden death association modified by ventricular hypertrophy and inflammation: a case-crossover study.

Background: Sudden death accounts for approximately 10% of deaths among working-age adults and is associated with poor air quality. Objectives: To identify high-risk groups and potential modifiers and mediators of risk, we explored previously established associations between fine particulate matter (PM2.5) and sudden death stratified by potential risk factors. Methods: Sudden death victims in Wake County, NC, from 1 March 2013 to 28 February 2015 were identified by screening Emergency Medical Systems reports and adjudicated (n = 399). Daily PM2.5 concentrations for Wake County from the Air Quality Data Mart were linked to event and control periods. Potential modifiers included greenspace metrics, clinical conditions, left ventricular hypertrophy (LVH), and neutrophil-to-lymphocyte ratio (NLR). Using a case-crossover design, conditional logistic regression estimated the OR (95%CI) for sudden death for a 5 µg/m3 increase in PM2.5 with a 1-day lag, adjusted for temperature and humidity, across risk factor strata. Results: Individuals having LVH or an NLR above 2.5 had PM2.5 associations of greater magnitude than those without [with LVH OR: 1.90 (1.04, 3.50); NLR > 2.5: 1.25 (0.89, 1.76)]. PM2.5 was generally less impactful for individuals living in areas with higher levels of greenspace. Conclusion: LVH and inflammation may be the final step in the causal pathway whereby poor air quality and traditional risk factors trigger arrhythmia or myocardial ischemia and sudden death. The combination of statistical evidence with clinical knowledge can inform medical providers of underlying risks for their patients generally, while our findings here may help guide interventions to mitigate the incidence of sudden death.

Multicenter appraisal of comorbid TANGO2 deficiency disorder in patients with 22q11.2 deletion syndrome.

TANGO2 deficiency disorder (TDD) is a rare, autosomal recessive condition caused by pathogenic variants in TANGO2, a gene residing within the region commonly deleted in 22q11.2 deletion syndrome (22q11.2DS). Although patients with 22q11.2DS are at substantially higher risk for comorbid TDD, it remains underdiagnosed within 22q11.2DS, likely due to overlapping symptomatology and a lack of knowledge about TDD. Initiation of B-vitamin supplementation may provide therapeutic benefit in TDD, highlighting the need for effective screening methods to improve diagnosis rates in this at-risk group. In this retrospective, multicenter study, we evaluated two cohorts of patients with 22q11.2DS (total N = 435) for possible comorbid TDD using two different symptom-based screening methods (free text-mining and manual chart review versus manual chart review alone). The methodology of the cohort 1 screening method successfully identified a known 22q11.2DS patient with TDD. Combined, these two cohorts identified 21 living patients meeting the consensus recommendation for TANGO2 testing for suspected comorbid TDD. Of the nine patients undergoing TANGO2 sequencing with del/dup analysis, none were ultimately diagnosed with TDD. Of the 12 deaths in the suspected comorbid TDD cohort, some of these patients exhibited symptoms (rhabdomyolysis, cardiac arrhythmia, or metabolic crisis) suspicious of comorbid TDD contributing to their death. Collectively, these findings highlight the need for robust prospective screening tools for diagnosing comorbid TDD in patients with 22q11.2DS.

Brugada syndrome: identification of subjects at risk and therapy.

Brugada syndrome mainly affects young subjects with structurally normal heart and can cause x syncope or sudden death due to ventricular arrhythmias, even as the first manifestation, in approximately 5-10% of cases. To date, two questions remain open: how to recognize subjects who will experience arrhythmic events and how to treat them. The guidelines suggest treating subjects with a previous history of cardiac arrest or arrhythmogenic syncope, while they are unconclusive about the management of asymptomatic patients, who represent ∼90% of Brugada patients. We recently demonstrated that in asymptomatic patients, the presence of spontaneous Brugada type 1 electrocardiogram (ECG) pattern and inducibility of ventricular arrhythmias at electrophysiological study allows us to identify a group of patients at greater risk who deserve treatment. Regarding treatment, there are three options: implantable cardioverter defibrillator, drugs, and epicardial transcatheter ablation. Recent studies have shown that the latter is effective and free from serious side effects, thus opening a new scenario in the treatment of Brugada patients at risk. Subjects who present drug-induced-only type 1 Brugada ECG pattern, in whom a spontaneous type 1 pattern has been ruled out with repeated ECGs and 12-lead 24-h Holter monitoring, represent a very low-risk group, provided they adhere to behavioural recommendations and undergo regular follow-up.

Unlocking the enigma: decoding premature ventricular complexes for effective clinical assessment and risk management.

The identification of ventricular premature complexes during a cardiological evaluation necessitates the implementation of diagnostic processes aimed at discerning the clinical context that may predispose individuals to a high risk of sudden cardiac death. Epidemiological studies reveal that ventricular premature beats occur in approximately 75% of healthy (or seemingly healthy) individuals, as long as there is no evidence of underlying structural heart disease, such as benign idiopathic ventricular extrasystole originating from the right and left ventricular outflow tracts. In the real world, however, ventricular ectopic beats with morphologies very similar to seemingly benign occurrences are not uncommon. They are notable in subjects exhibiting rapid and complex repetitive forms during exercise testing and Holter electrocardiogram. Additionally, these subjects may display more or less extensive scarring signs on cardiac magnetic resonance and may have a family history of cardiomyopathy and/or sudden cardiac death. Therefore, the purpose of this review is to critically analyse the process of evaluating premature ventricular complexes, which is crucial for accurate risk stratification. The latter cannot overlook some inevitable elements, including morphology, origin, complexity, and the associated clinical setting (absence or presence of structural heart disease).

500 bee stings in a single fatal encounter.

Incidences of multiple bee stings have been increasing globally; the substantial amount of bee venom injected in such incidents can result in anaphylactic shock, rhabdomyolysis and renal failure, proving fatal in some cases. While anaphylactic reactions are more common and have established treatment protocols, inflammatory response induced by the venom demands a tailored approach. Here we report a case of a 70-year-old male in India who succumbed from approximately 500 bee stings. Based on our literature review, this case stands out as one of the first reported fatalities caused by 500 bee stings in our country. The unidentified species of bees in this case makes management of such bee venom-related toxic reactions more difficult. This report emphasises the importance of prompt and appropriate interventions.

Autopsy of all young sudden death cases is important to increase survival in family members left behind.

Sudden cardiac death (SCD) is an important public health problem worldwide, accounting for an estimated 6-20% of total mortality. A significant proportion of SCD is caused by inherited heart disease, especially among the young. An autopsy is crucial to establish a diagnosis of inherited heart disease, allowing for subsequent identification of family members who require cardiac evaluation. Autopsy of cases of unexplained sudden death in the young is recommended by both the European Society of Cardiology and the American Heart Association. Overall autopsy rates, however, have been declining in many countries across the globe, and there is a lack of skilled trained pathologists able to carry out full autopsies. Recent studies show that not all cases of sudden death in the young are autopsied, likely due to financial, administrative, and organizational limitations as well as awareness among police, legal authorities, and physicians. Consequently, diagnoses of inherited heart disease are likely missed, along with the opportunity for treatment and prevention among surviving relatives. This article reviews the evidence for the role of autopsy in sudden death, how the cardiologist should interpret the autopsy-record, and how this can be integrated and implemented in clinical practice. Finally, we identify areas for future research along with potential for healthcare reform aimed at increasing autopsy awareness and ultimately reducing mortality from SCD.

[Sudden death in adults : Data from 305 consecutive autopsy cases in Algeria]. / Mort subite de l'adulte : données de 305 cas d'autopsies consécutives en Algérie.

BACKGROUND-AIMS: Sudden death in a young adult who showed no prodrome or complaint during his lifetime is a tragedy. The death often remains unexplained by doctors and is often the subject of a judicial investigation following which an autopsy is ordered. Our study joins several studies around the world, where the results have linked sudden death in adults to a cardiac origin. METHODS: Through a series of 305 autopsies carried out in the forensic medicine department of the Frantz Fanon hospital in the city of Bejaia in Algeria over a period of two years, 57 cases corresponded to unexplained sudden deaths, i.e. an incidence of 3 cases per 100,000 inhabitants per year. RESULTS: Sudden death was of cardiac origin in 50.8% of cases (N=28). Two epidemiologic profiles emerge in our study: the first is that of a man aged between 50 and 60 years of age, with several deleterious lifestyle habits (in particular smoking) with a cardiovascular history, previously followed by a cardiologist, who died suddenly out-of-hospital, from ischemic heart disease. The second is that of a young adult under 40 years of age, of average build, with no particular medical history, having not previously consulted a cardiologist, who died suddenly of hypertrophic cardiomyopathy. CONCLUSIONS: In many instances, we observed major anatomical lesion, which had not motivated any prior medical consultation either with a general practitioner or with a cardiologist.

Relationship Between Genotype Status and Clinical Outcome in Hypertrophic Cardiomyopathy.

BACKGROUND: The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved. METHODS AND RESULTS: We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease-causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G-). Patients were followed up for a median of 7.8 years (interquartile range, 3.5-13.4 years); HCM end points were examined by cumulative event incidence. Over follow-up, 135 (9%) patients died, 33 from a variety of HCM-related causes. After adjusting for age, all-cause and HCM-related mortality did not differ between G- versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46-1.31]; P=0.37; HR, 0.93 [95% CI, 0.38-2.30]; P=0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G- versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63-2.26]; P=0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88-2.21]; P=0.16). In multivariable analysis, age was the only independent predictor of all-cause and HCM-related mortality, heart failure progression, and sudden death events. CONCLUSIONS: In this large consecutive cohort of patients with HCM, genotype (G+ or G-) was not a predictor of clinical course, including all-cause and HCM-related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.

Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists' perspectives.

BACKGROUND: Multiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists' current practices and experiences in delivering the diagnosis of MSA. METHODS: We conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique. RESULTS: Among the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA. CONCLUSIONS: Our findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient's personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term "sudden death" in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement.

Sudden cardiac death during scuba diving: a case report of a patient with unknown hypertrophic cardiomyopathy.

Background: Scuba diving is a recreational activity usually considered at low impact on cardiovascular system. However, when diving, increased ambient pressure exerts several effects on the cardiovascular and pulmonary systems, mainly due to redistribution of peripheral blood into the central circulation. This phenomenon, also known as blood shift, may produce a significant overload on a non-healthy heart. Case summary: We present the case of a female patient who experienced sudden cardiac death during scuba diving: post-mortem cardiac magnetic resonance and autopsy revealed that the patient was affected by previously unknown hypertrophic cardiomyopathy. Discussion: Diving exposes the body to significant physiological changes that may overstress a diseased heart. This case suggests the need for some cardiovascular exams, such as an echocardiogram or, at least, an electrocardiogram, for screening cardiovascular abnormalities in subjects who wish to practice scuba diving.

An innovative 12-lead resting electrocardiogram dataset in professional football.

This paper aims to provide a comprehensive and innovative 12-lead electrocardiogram (ECG) dataset tailored to understand the unique needs of professional football players. Other ECG datasets are available but collected from common people, normally with diseases confirmed, while it is well known that ECG characteristics change in athletes and elite players as a result of their intense long-term physical training. This initiative is part of a broader research project employing machine learning (ML) to analyse ECG data in this athlete population and explore them according to the International criteria for ECG interpretation in athletes. The dataset is generated through the establishment of a prospective observational cohort consisting of 54 male football players from La Liga, representing a UEFA Pro-level team. Named the Pro-Football 12-lead Resting Electrocardiogram Database (PF12RED), it comprises 163 10-s ECG recordings, offering a detailed examination of the at-rest heart activity of professional football athletes. Data collection spans five phases over multiple seasons, including the 2018-2019 postseason, the 2019-20 preseason, the 2020-21 preseason, and the 2021-22 preseason. Athletes undergo medical evaluations that include a 10-s resting 12-lead ECG performed with General Electric's USB-CAM 14 module (https://co.services.gehealthcare.com/gehcstorefront/p/900995-002), with data saved using General Electric's CardioSoft V6.73 12SL V21 ECG Software. (https://www.gehealthcare.es/products/cardiosoft-v7) The data collection adheres to ethical principles, with clearance granted by the Autonomous Community of Andalusia Ethics Committee (Spain) under protocol number 1573-N-19 in December 2019. Participants provide informed consent, and data sharing is permitted following anonymization. The study aligns with the Declaration of Helsinki and adheres to the recommendations of the International Committee of Medical Journal Editors (ICMJE). The generated dataset serves as a valuable resource for research in sports cardiology and cardiac health. Its potential for reuse encompasses:1.International Comparison: Enabling cross-regional comparisons of cardiac characteristics among elite football players, enriching international studies.2.ML Model Development: Facilitating the development and refinement of machine learning models for arrhythmia detection, serving as a benchmark dataset.3.Validation of Diagnostic Methods: Allowing the validation of automatic diagnostic methods, contributing to enhanced accuracy in detecting cardiac conditions.4.Research in Sports Cardiology: Supporting future investigations into specific cardiac adaptations in elite athletes and their relation to cardiovascular health.5.Reference for Athlete Protection Policies: Influencing athlete protection policies by providing data on cardiac health and suggesting guidelines for medical assessments.6.Health Professionals Training: Serving as a training resource for health professionals interested in interpreting ECGs in sports contexts.7.Tool and Application Development: Facilitating the development of tools and applications related to the visualization, simulation and analysis of ECG signals in athletes.

Case Report: A Sudden Thyroid-Related Death of a 15-Year-Old Girl.

A 15-year-old young girl was found dead at home. There were no indications of any intervention or the application of force. On the previous day, she was admitted to hospital because of palpitations, fatigue, a headache, and a swollen neck. During a physical examination, a swollen thyroid gland and tachycardia were found. In the family history, her mother had thyroid disease. According to the laboratory values, she had elevated thyroid hormone levels. After administration of beta-blockers, the patient was discharged and died at home during the night. The parents denounced the hospital for medical malpractice; therefore, a Forensic Autopsy was performed. Based on the available clinical data, the autopsy, histological and toxicological results, the cause of death was stated as multiorgan failure due to disseminated intravascular coagulation (DIC) caused by the autoimmune Graves disease. The forensic assessment of the case does not reveal medical malpractice. Post-mortem diagnoses of thyroid disorders in cases of sudden death can be challenging. However, as the reported case illustrates, the diagnosis could be established after a detailed evaluation of antemortem clinical data, autopsy results, histology, and a toxicological examination.

Aborted sudden cardiac death in a young patient with epilepsy and the Gorlin Goltz syndrome.

Epilepsy is one of the most common chronical neurological conditions affecting over 50 million people worldwide. In addition to the stigma and discrimination, individuals with epilepsy suffer from a nearly three-fold increased risk of premature death compared to the general population. Although these premature deaths occur due to multiple causes, sudden unexpected death in epilepsy (SUDEP) still challenges neurologists and clinicians dealing with individuals with epilepsy. Recently, an increased interest in cardiac outcomes related to acute seizures and chronic epilepsy resulted in the groundbreaking development of the "epileptic heart" concept, and sudden cardiac death in individuals with epilepsy, which is 4.5 times as frequent as SUDEP according to some observational data, has gained more attention. As we gather information and learn about possible comorbidities and consequences of seizures and/or chronic epilepsy, we present a clinical case of a young patient with an unusual association of epilepsy, the Gorlin Goltz syndrome, and a cardiac fibroma with Wolf-Parkinson-White (WPW), who had multiple aborted cardiac arrests. Diagnostic challenges and multiple possible causes of sudden cardiac death in this single patient report are discussed.

Challenging situation of coronary artery anomaly associated with ischemia and/or risk of sudden death.

Coronary artery anomaly is known as one of the causes of angina pectoris and sudden death and is an important clinical entity that cannot be overlooked. The incidence of coronary artery anomalies is as low as 1%-2% of the general population, even when the various types are combined. Coronary anomalies are practically challenging when the left and right coronary ostium are not found around their normal positions during coronary angiography with a catheter. If there is atherosclerotic stenosis of the coronary artery with an anomaly and percutaneous coronary intervention (PCI) is required, the suitability of the guiding catheter at the entrance and the adequate back up force of the guiding catheter are issues. The level of PCI risk itself should also be considered on a case-by-case basis. In this case, emission computed tomography in the R-1 subtype single coronary artery proved that ischemia occurred in an area where the coronary artery was not visible to the naked eye. Meticulous follow-up would be crucial, because sudden death may occur in single coronary arteries. To prevent atherosclerosis with full efforts is also important, as the authors indicated admirably.

Sudden pediatric death unveiling pulmonary arteriovenous malformations.

Pulmonary arteriovenous malformations (PAVMs) are abnormal vascular connections between pulmonary arteries and veins, often associated with hereditary hemorrhagic telangiectasia (HHT). Most PAVMs are asymptomatic, but life-threatening complications like pulmonary hemorrhage, brain abscesses, and paradoxical emboli can emerge, so prompt diagnosis and treatment are crucial. We report a case of sudden pediatric death in a two-year-old female with no past medical history. Initial vomiting and fast deterioration resulted in a sudden cardiac arrest. The postmortem examination found histological evidence of consistent, extensive lung damage. The absence of the characteristic symptoms made for some challenges when it came to diagnosis, showing precisely that in early life, you could well have many difficulties in catching PAVMs. This case highlights the need to take PAVMs into account as a potential cause of sudden death, particularly when there are no conspicuous symptoms. Awareness among forensic pathologists and consideration of genetic analysis for HHT in such cases is crucial for accurate diagnosis and management.

The role for ambulatory electrocardiogram monitoring in the diagnosis and prognostication of Brugada syndrome: a sub-study of the Rare Arrhythmia Syndrome Evaluation (RASE) Brugada study.

AIMS: Brugada syndrome (BrS) diagnosis and risk stratification rely on the presence of a spontaneous type 1 (spT1) electrocardiogram (ECG) pattern; however, its spontaneous fluctuations may lead to misdiagnosis and risk underestimation. This study aims to assess the role for repeat high precordial lead (HPL) resting and ambulatory ECG monitoring in identifying a spT1, and evaluate its prognostic role. METHODS AND RESULTS: HPL resting and ambulatory monitoring ECGs of BrS subjects were reviewed retrospectively, and the presence of a spT1 associated with ventricular dysrhythmias and sudden cardiac death (SCD). Three-hundred and fifty-eight subjects (77 with spT1 pattern at presentation, Group 1, and 281 without, Group 2) were included. In total, 1651 resting HPL resting and 621 ambulatory monitoring ECGs were available for review, or adequately described. Over a median follow-up of 72 months (interquartile range - IQR - 75), 42/77 (55%) subjects in Group 1 showed a spT1 in at least one ECG. In Group 2, 36/281 subjects (13%) had a newly detected spT1 (1.9 per 100 person-year) and 23 on an HPL ambulatory recording (8%). Seven previously asymptomatic subjects, five of whom had a spT1 (four at presentation and one at follow-up), experienced arrhythmic events; survival analysis indicated that a spT1, either at presentation or during lifetime, was associated with events. Univariate models showed that a spT1 was consistently associated with increased risk [spT1 at presentation: hazard ratio (HR) 6.3, 95% confidence interval (CI) 1.4-28, P = 0.016; spT1 at follow-up: HR 3.1, 95% CI 1.3-7.2, P = 0.008]. CONCLUSION: Repeated ECG evaluation and HPL ambulatory monitoring are vital in identifying transient spT1 Brugada pattern and its associated risk.

Sudden Infant Death Associated with Rhinovirus Infection.

A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant's environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS.

Analysis of ventricular arrhythmias and sudden death from prospective, randomized clinical trials of acalabrutinib.

This analysis investigated the incidence of sudden deaths (SDs) and non-fatal and fatal ventricular arrhythmias (VAs) in five acalabrutinib clinical trials. In total, 1299 patients received acalabrutinib (exposure, 4568.4 patient-years). Sixteen (1.2%) patients experienced SD or VA (event rate, 0.350/100 patient-years). Non-fatal VAs occurred in 11 (0.8%) patients, nine (0.7%) of whom had premature ventricular contractions only. SD and fatal VAs occurred in five (0.4%) patients (event rate, 0.109/100 patient-years; median time to event: 46.2 months). SDs and VAs with acalabrutinib occurred at low rates, and there are insufficient data to point to an increased risk of SD or VA with acalabrutinib.

Sudden death due to spontaneous rupture of the right atrium in the setting of chronic lung disease: A case report and review.

Sudden death from haemopericardium as a result of a right atrial rupture is uncommon, most particularly when this occurs spontaneously without any prior trauma or evidence of atrial wall pathology. The deceased was a 32-year-old man. At lunchtime his symptoms of unease, giddiness and unconsciousness began and within 45 minutes he arrived at the hospital. His vitals could not be recorded in the emergency department, and after CPR, he was pronounced dead. At autopsy, an isolated right atrial rupture, without any disease of the heart wall, was discovered. The right atrium has the weakest wall and is frequently the site of spontaneous rupture brought on by increased intraluminal pressure. Both liquid blood and clotted blood were found in the pericardial cavity. Low atrial pressure encourages clot formation because it causes considerably slower blood entry into the pericardium at the time of atrial rupture compared with entry at the time of ventricular rupture. Evidence of chronic lung disease was found which explains the raised intraluminal pressure of the heart chambers. Even with no history of trauma or myocardial infarction, the Beck triad - an engorged neck vein, a muffled heart sound, and low blood pressure - should alert the emergency room staff to the possibility of cardiac tamponade because, in a very unlikely scenario, spontaneous cardial wall rupture might occur.