Diet and Sudden Death: How to Reduce the Risk.

In addition to the association of dietary patterns, specific foods and nutrients with several diseases, including cardiovascular disease and mortality, there is also strong emerging evidence of an association of dietary patterns with the risk of sudden cardiac death (SCD). In this comprehensive review, data are presented and analyzed about foods and diets that mitigate the risk of ventricular arrhythmias (VAs) and SCD, but also about arrhythmogenic nutritional elements and patterns that seem to enhance or facilitate potentially malignant VAs and SCD. The antiarrhythmic or protective group comprises fish, nuts and other foods enriched in omega-3 polyunsaturated fatty acids, the Mediterranean and other healthy diets, vitamins E, A and D and certain minerals (magnesium, potassium, selenium). The arrhythmogenic-food group includes saturated fat, trans fats, ketogenic and liquid protein diets, the Southern and other unhealthy diets, energy drinks and excessive caffeine intake, as well as heavy alcohol drinking. Relevant antiarrhythmic mechanisms include modification of cell membrane structure by n-3 polyunsaturated fatty acids, their direct effect on calcium channels and cardiomyocytes and their important role in eicosanoid metabolism, enhancing myocyte electric stability, reducing vulnerability to VAs, lowering heart rate, and improving heart rate variability, each of which is a risk factor for SCD. Contrarily, saturated fat causes calcium handling abnormalities and calcium overload in cardiomyocytes, while a high-fat diet causes mitochondrial dysfunction that dysregulates a variety of ion channels promoting VAs and SCD. Free fatty acids have been considered proarrhythmic and implicated in facilitating SCD; thus, diets increasing free fatty acids, e.g., ketogenic diets, should be discouraged and replaced with diets enriched with polyunsaturated fatty acids, which can also reduce free fatty acids. All available relevant data on this important topic are herein reviewed, large studies and meta-analyses and pertinent advisories are tabulated, while protective (antiarrhythmic) and arrhythmogenic specific diet constituents are pictorially illustrated.

Sudden death after oxygen toxicity seizure during hyperbaric oxygen treatment: Case report.

Acute cerebral oxygen toxicity (ACOT) is a known side effect of hyperbaric oxygen treatment (HBOT), which can cause generalised seizures. Fortunately, it has a low incidence and is rarely harmful. Nevertheless, we present a case of a 37 year-old patient with morbid obesity who died unexpectedly after an oxygen toxicity seizure in the hyperbaric chamber. Considering possible causes, physiologic changes in obesity and obesity hypoventilation syndrome may increase the risk of ACOT. Obesity, especially in extreme cases, may hinder emergency procedures, both in- and outside of a hyperbaric chamber. Physicians in the hyperbaric field should be aware of the possibility of a fatal outcome after ACOT through the described mechanisms and take appropriate preventative measures. Basic airway management skills are strongly advised for involved physicians, especially when specialised personnel and equipment are not immediately available.

Chagas cardiomyopathy and heart failure: From epidemiology to treatment.

Chagas disease is among the neglected tropical diseases recognized by the World Health Organization that have received insufficient attention from governments and health agencies. Chagas disease is endemic in 21 Latin America regions. Due to globalization and increased migration, it has crossed borders and reached other regions including North America and Europe. The clinical presentation of the disease is highly variable, from general symptoms to severe cardiac involvement that can culminate in heart failure. Chagas heart disease is multifactorial, and can include dilated cardiomyopathy, thromboembolic phenomena, and arrhythmias that may lead to sudden death. Diagnosis is by methods such as enzyme-linked immunosorbent assay (ELISA) and the degree of cardiac involvement should be investigated with complementary exams including ECG, chest radiography and electrophysiological study. There have been insufficient studies on which to base specific treatment for heart failure due to Chagas disease. Treatment should therefore be derived from guidelines for heart failure that are not specific for this disease. Heart transplantation is a viable option with satisfactory success rates that has improved survival.

Case report of sudden death in a twin infant given melatonin supplementation: A challenging interpretation of postmortem toxicology.

Melatonin (MEL) is a neurohormone in humans produced in a number of locations. Starting with the amino acid tryptophan, MEL is produced through a number of enzymatic steps that includes serotonin as an intermediate compound. The primary production of MEL is in the pineal gland located in the brain. It is directly associated with the the suprachiasmatic nucleus (SCN) located in the hypothalamus. In young and adult humans, the blood levels of MEL are typically in the picogram levels and produced in a cyclic schedule highly regulated by light detected in the retina by intrinsically photosensitive retinal ganglion cells (ipRGCs), resulting in production primarily during periods of darkness. During periods of light, MEL levels are typically very low or undetectable. Basal levels of MEL in infants have been observed to be either undetectable or also in the picogram levels, although some medical treatment has involved administration of exogenous MEL resulting in peak levels in the nanogram range. MEL is considered to be well tolerated and there have been limited reports of toxicity. In this case, an infant was found unresponsive and cause of death was ruled as Undetermined. Melatonin was detected in the peripheral blood at a concentration of 1,400ng/mL.

Association of Rivaroxaban With Thromboembolic Events in Patients With Heart Failure, Coronary Disease, and Sinus Rhythm: A Post Hoc Analysis of the COMMANDER HF Trial.

Importance: Whether anticoagulation benefits patients with heart failure (HF) in sinus rhythm is uncertain. The COMMANDER HF randomized clinical trial evaluated the effects of adding low-dose rivaroxaban to antiplatelet therapy in patients with recent worsening of chronic HF with reduced ejection fraction, coronary artery disease (CAD), and sinus rhythm. Although the primary end point of all-cause mortality, myocardial infarction, or stroke did not differ between rivaroxaban and placebo, there were numerical advantages favoring rivaroxaban for myocardial infarction and stroke. Objective: To examine whether low-dose rivaroxaban was associated with reduced thromboembolic events in patients enrolled in the COMMANDER HF trial. Design, Setting, and Participants: Post hoc analysis of the COMMANDER HF multicenter, randomized, double-blind, placebo-controlled trial in patients with CAD and worsening HF. The trial randomized 5022 patients postdischarge from a hospital or outpatient clinic after treatment for worsening HF between September 2013 and October 2017. Patients were required to be receiving standard care for HF and CAD and were excluded for a medical condition requiring anticoagulation or a bleeding history. Patients were randomized in a 1:1 ratio. Analysis was conducted from June 2018 and January 2019. Intervention: Patients were randomly assigned to receive 2.5 mg of rivaroxaban given orally twice daily or placebo in addition to their standard therapy. Main Outcomes and Measures: For this post hoc analysis, a thromboembolic composite was defined as either (1) myocardial infarction, ischemic stroke, sudden/unwitnessed death, symptomatic pulmonary embolism, or symptomatic deep venous thrombosis or (2) all of the previous components except sudden/unwitnessed deaths because not all of these are caused by thromboembolic events. Results: Of 5022 patients, 3872 (77.1%) were men, and the overall mean (SD) age was 66.4 (10.2) years. Over a median (interquartile range) follow-up of 19.6 (11.7-30.8) months, fewer patients assigned to rivaroxaban compared with placebo had a thromboembolic event including sudden/unwitnessed deaths: 328 (13.1%) vs 390 (15.5%) (hazard ratio, 0.83; 95% CI, 0.72-0.96; P = .01). When sudden/unwitnessed deaths were excluded, the results analyzing thromboembolic events were similar: 153 (6.1%) vs 190 patients (7.6%) with an event (hazard ratio, 0.80; 95% CI, 0.64-0.98; P = .04). Conclusions and Relevance: In this study, thromboembolic events occurred frequently in patients with HF, CAD, and sinus rhythm. Rivaroxaban may reduce the risk of thromboembolic events in this population, but these events are not the major cause of morbidity and mortality in patients with recent worsening of HF for which rivaroxaban had no effect. While consistent with other studies, these results require confirmation in prospective randomized clinical trials. Trial Registration: ClinicalTrials.gov identifier: NCT01877915.

Functional characterization of ABCC9 variants identified in sudden unexpected natural death.

BACKGROUND: Genetic variation in ion channel genes ('channelopathies') are often associated with inherited arrhythmias and sudden death. Genetic testing ('molecular autopsies') of channelopathy genes can be used to assist in determining the likely causes of sudden unexpected death. However, different in silico approaches can yield conflicting pathogenicity predictions and assessing their impact on ion channel function can assist in this regard. METHODS AND RESULTS: We performed genetic testing of cases of sudden expected death in the New York City metropolitan area and found four rare or novel variants in ABCC9, which codes for the regulatory SUR2 subunit of KATP channels. All were missense variants, causing amino acid changes in the protein. Three of the variants (A355S, M941V, and K1379Q) were in cases of infants less than six-months old and one (H1305Y) was in an adult. The predicted pathogenicities of the variants were conflicting. We have introduced these variants into a human SUR2A cDNA, which we coexpressed with the Kir6.2 pore-forming subunit in HEK-293 cells and subjected to patch clamp and biochemical assays. Each of the four variants led to gain-of-function phenotypes. The A355S and M941V variants increased in the overall patch current. The sensitivity of the KATP channels to inhibitory 'cytosolic' ATP was repressed for the M941V, H1305Y and K1379Q variants. None of the variants had any effect on the unitary KATP channel current or the surface expression of KATP channels, as determined with biotinylation assays, suggesting that all of the variants led to an enhanced open state. CONCLUSIONS: All four variants caused a gain-of-function phenotype. Given the expression of SUR2-containing KATP channels in the heart and specialized cardiac conduction, vascular smooth muscle and respiratory neurons, it is conceivable that electrical silencing of these cells may contribute to the vulnerability element, which is a component of the triple risk model of sudden explained death in infants. The gain-of-function phenotype of these ABCC9 variants should be considered when assessing their potential pathogenicity.

Taquicardia ventricular polimórfica catecolaminérgica com necessidade de implante de cardiodesfibrilador implantável (CDI): Um relato de caso / Ventricular Catecolaminergic Polymorphic Tachycardia (VCPT) with ICD implantation requirement: A case report

Relato de caso de uma paciente do sexo feminino, com 16 anos de idade à ocasião de sua admissão no Instituto de Cardiologia. A mesma foi encaminhada por serviço de saúde externo devido a síncopes durante atividade física e foi submetida à investigação, com diagnóstico final de taquicardia ventricular catecolaminérgica. Após a definição diagnóstica, foi realizado tratamento medicamentoso com betabloqueador, sendo necessário o implante de marcapasso definitivo por conta da incompetência cronotrópica secundária ao tratamento farmacológico instituído. Posteriormente, por persistência das arritmias ventriculares mesmo com o uso de terapia otimizada, optou-se por realizar um implante de CDI

Case report of a 16-year-old female patient at the time of her admission to the Institute of Cardiology. She was referred by an external healthcare service due to syncope during physical activity and was submitted to the investigation with a final diagnosis of catecholaminergic ventricular tachycardia. Once the diagnosis was established, the patient was administered a beta-blocker and definitive pacemaker implant was required due to chronotropic incompetence secondary to drug therapy. Subsequently, due to the persistence of ventricular arrhythmias despite the use of optimized therapy, we decided to implant an ICD

Knock on the right door. How we are treating the patient with acute myocardial infarction / Bata na porta certa. Como estamos tratando o paciente com infarto agudo do miocárdio

Background: To reduce mortality of acute myocardial infarction, medical care must be provided within the first hours of the event. Objective: To identify the "front door" to medical care of acute coronary patients and the time elapsed between patients'admission and performance of myocardial reperfusion in the public health system of the city of Joinville, Brazil. Methods: The study was a retrospective analysis of the medical records of 112 consecutive patients diagnosed with acute myocardial infarction by coronary angiography. We identified the place of the first medical contact and calculated the time between admission to this place and admission to the referral hospital, as well as the time until coronary angiography, with or without percutaneous transluminal angioplasty. A descriptive analysis of data was made using mean and standard deviation, and a p < 0.05 was set as statistically significant. Results: Only 16 (14.3%) patients were admitted through the cardiology referral unit. Door-to-angiography time was shorter than 90 minutes in 50 (44.2%) patients and longer than 270 minutes in 39 (34.5%) patients. No statistically significant difference was observed in door-to-angiography time between patients transported directly to the referral hospital and those transferred from other health units (p < 0.240). Considering the time between pain onset and angiography, only 3 (2.9%) patients may have benefited from myocardial reperfusion performed within less than 240 minutes. Conclusion: Management of patients with acute myocardial infarction is not in conformity with current guidelines for the treatment of this condition. The structure of the healthcare system should be urgently modified so that users in need of emergency services receive adequate care in accordance with local conditions

Deficient post-ictal cardiorespiratory compensatory mechanisms mediated by the periaqueductal gray may lead to death in a mouse model of SUDEP.

Post-ictal cardiorespiratory failure is implicated as a major cause of sudden unexpected death in epilepsy (SUDEP) in patients. The DBA/1 mouse model of SUDEP is abnormally susceptible to fatal seizure-induced cardiorespiratory failure (S-CRF) induced by convulsant drug, hyperthermia, electroshock, and acoustic stimulation. Clinical and pre-clinical studies have implicated periaqueductal gray (PAG) abnormalities in SUDEP. Recent functional neuroimaging studies observed that S-CRF resulted in selective changes in PAG neuronal activity in DBA/1 mice. The PAG plays a critical compensatory role for respiratory distress caused by numerous physiological challenges in non-epileptic individuals. These observations suggest that abnormalities in PAG-mediated cardiorespiratory modulation may contribute to S-CRF in DBA/1 mice. To evaluate this, electrical stimulation (20 Hz, 20-100 µA, 10 s) was presented in the PAG of anesthetized DBA/1 and C57BL/6 (non-epileptic) control mice, and post-stimulus changes in respiration [inter-breath interval (IBI)] and heart rate variability (HRV) were examined. The post-stimulus period was considered analogous to the post-ictal period when S-CRF occurred in previous DBA/1 mouse studies. PAG stimulation caused significant intensity-related decreases in IBI in both mouse strains. However, this effect was significantly reduced in DBA/1 vis-a-vis C57BL/6 mice. These changes began immediately following cessation of stimulation and remained significant for 10 s. This time period is critical for initiating resuscitation to successfully prevent seizure-induced death in previous DBA/1 mouse experiments. Significant post-stimulus increases in HRV were also seen at ≥60 µA in the PAG in C57BL/6 mice, which were absent in DBA/1 mice. These data along with previous neuroimaging findings suggest that compensatory cardiorespiratory modulation mediated by PAG is deficient, which may be important to the susceptibility of DBA/1 mice to S-CRF. These observations suggest that correcting this deficit pharmacologically or by electrical stimulation may help to prevent S-CRF. These findings further support the potential importance of PAG abnormalities to human SUDEP.

Sudden unexpected death in epilepsy in patients treated with brain-responsive neurostimulation.

OBJECTIVE: To study the incidence and clinical features of sudden unexpected death in epilepsy (SUDEP) in patients treated with direct brain-responsive stimulation with the RNS System. METHODS: All deaths in patients treated in clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA) approval (N = 451) through May 5, 2016, were adjudicated for SUDEP. RESULTS: There were 14 deaths among 707 patients (2208 postimplantation years), including 2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036 patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant years. Stored electrocorticograms around the time of death were available for 4 patients with probable/definite SUDEP and revealed the following: frequent epileptiform activity ending abruptly (n = 2), no epileptiform activity or seizures (n = 1), and an electrographic and witnessed seizure with cessation of postictal electrocorticography (ECoG) activity associated with apnea and pulselessness (n = 1). SIGNIFICANCE: The SUDEP rate of 2.0/1000 patient stimulation years among patients treated with the RNS System is favorable relative to treatment-resistant epilepsy patients randomized to the placebo arm of add-on drug studies or with seizures after resective surgery. Our findings support that treatments that reduce seizures reduce SUDEP risk and that not all SUDEPs follow seizures.

Leg massage by mother resulting in fatal pulmonary thromboembolism.

We report the sudden death of a 23-year-old male with hairline ankle fracture after massage of the leg by his mother. Autopsy confirmed the cause of death as pulmonary thromboembolism due to deep vein thrombosis of the leg veins which was dislodged and travelled to his lungs consequent to the leg massage. The treating doctors did not warn the patient of the risk of developing pulmonary thromboembolism.

Accidental selenium toxicosis in lambs.

Acute selenium toxicosis occurred in 3-week-old lambs after accidental over-supplementation by intramuscular injection and caused dyspnea, cyanosis, and sudden death. Pathological lesions included myocardial necrosis, skeletal muscle necrosis, pulmonary edema, hydrothorax, and hydropericardium.

Toxicose accidentelle au sélénium chez des agneaux. Une toxicose aiguë au sélénium s'est produite chez des agneaux âgés de 3 semaines après une supplémentation excédentaire accidentelle par injection intramusculaire et elle a causé des signes de dyspnée, de cyanose et de mort soudaine. Les lésions pathologiques incluaient une nécrose du myocarde, une nécrose du muscle squelettique, un œdème pulmonaire, de l'hydrothorax et de l'hydropéricarde.(Traduit par Isabelle Vallières).

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP.

Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death.

Pediatric cardiomyopathy is a rare but severe disease with high morbidity and mortality. The causes are poorly understood and can only be established in one-third of cases. Recent advances in genetic technologies, specifically next-generation sequencing, now allow for the detection of genetic causes of cardiomyopathy in a systematic and unbiased manner. This is particularly important given the large clinical variability among pediatric cardiomyopathy patients and the large number of genes (>100) implicated in the disorder. We report on the performance of whole-exome sequencing in members of a consanguineous family with a history of pediatric hypertrophic cardiomyopathy and sudden cardiac death, which led to the identification of a homozygous stop variant in the SLC22A5 gene, implicated in primary carnitine deficiency, as the likely genetic cause. Targeted carnitine tandem mass spectrometry analysis in the patient revealed complete absence of plasma-free carnitine and only trace levels of total carnitine, further supporting the causality of the SLC22A5 variant. l-carnitine supplementation in the proband led to a rapid and marked clinical improvement. This case illustrates the use of exome sequencing as a systematic and unbiased diagnostic tool in pediatric cardiomyopathy, providing an efficient route to the identification of the underlying cause, which lead to appropriate treatment and prevention of premature death.

Descending necrotizing mediastinitis after a trigger point injection

Descending necrotizing mediastinitis (DNM) is a rare form of mediastinal infection. Most cases are associated with esophageal rupture. DNM after a trigger point injection in the upper trapezius has not been described previously. We present a case of DNM after a trigger point injection in the upper trapezius. A 70-year-old man visited the emergency department with chest discomfort and fever after a trigger point injection in the left upper trapezius. Chest computed tomography showed evidence of DNM, and antibiotic therapy was immediately administered intravenously. Because of the risk of sudden death, poor prognosis due to underlying disease, and his age, he declined surgical treatment and died of septic shock. Although trigger point injections are generally considered safe, caution should be used in patients with an underlying disease or in the elderly. Early diagnosis, broad-spectrum antibiotics, and aggressive surgical management are essential to improve the prognosis.

Piperidylmethyloxychalcone improves immune-mediated acute liver failure via inhibiting TAK1 activity

Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.