Cause Of Sudden Cardiac Death Research Articles

Unsupervised machine learning defines subgroups in ischemic heart disease patients presenting with ventricular tachycardia

Abstract Background Ventricular tachycardia (VT) in ischemic heart disease (IHD) is the leading cause of sudden cardiac death (SCD). Despite the well-defined recommendations, tailoring therapies individually is often a challenge owing to the great heterogeneity in this population. We hypothesized that unsupervised machine learning can uncover hidden patterns to identify patient subgroups with similar characteristics. Aims To use unsupervised machine learning methods on a database of patients with ischemic VT, to discover subgroups with similar characteristics and compare the survival of the identified groups. Methods We collected the data of 566 patients with IHD hospitalized for sustained monomorphic VT, excluding those with acute coronary syndrome. The 17 recorded features included medical history and echocardiography. All-cause mortality was registered with one-year follow-up. We performed dimension reduction using T-distributed Stochastic Neighbor Embedding (TSNE) to produce 3 dimensions of the data. Then, we applied spectral clustering to create three groups within the population. Each group was compared to the rest of the population for each variable. Finally, we compared the survival across the three groups using Kaplan-Meyer analysis, univariate Cox-regression, and Log-rank test. Results We identified three groups with distinct characteristics. Group 1 represented the healthiest population; patients had no previous VT hospitalizations, and none of HD instability, LBBB, SCD, diabetes, VT storm or ICD shocks; additionally, they always had a single VT episode at presentation. They showed better left ventricular ejection fraction (LVEF) (38% vs. 33%, p<0.001) and TAPSE (20 mm vs. 18 mm, p=0.01), less severe mitral and tricuspid regurgitation (MR, TR), smaller left ventricular end-systolic diameter, and longer DT. Conversely, patients in Group 2 (n=349) had more previous VT hospitalizations (30% vs. 18%, p=0,003), more often had diabetes (46% vs. 18%, p<0.001), left bundle branch block (23% vs. 13%, p=0.006), and more often presented with HD instability (47% vs. 28%, p<0.001). Group 3 contained all seriously ill patients with VT storm or incessant VT, more commonly presenting with ICD shocks (34% vs. 21%, p=0.004), SCD (24% vs. 15%, p=0.004), hemodynamic instability (50% vs. 37%, p=0.01). This group had the poorest LVEF (30% vs. 35%, <0.001) and TAPSE (17 mm vs. 19 mm p=0.001), more severe MR and TR, and the shortest DT (140 ms vs. 173 ms p<0.001). Finally, we compared survival across the three groups. Significantly better survival was found in Group 1 (HR: 0.52 CI [0.28 - 0.98]) and Group 2 (HR: 0.61 CI [0.42 - 0.88]), while Group 3 had higher mortality (HR: 2.7 CI [1.83 - 3.97]). Conclusions Using spectral clustering we identified three groups in our cohort of ischemic VT patients. This method delineates the group of ischemic VT patients with the highest risk of mortality who might need more aggressive treatment and closer follow-up.

Sudden Cardiac Death, Post-Mortem Investigation: A Proposing Panel of First Line and Second Line Genetic Tests.

Investigating the causes of Sudden cardiac death (SCD) is always difficult; in fact, genetic cardiac conditions associated with SCD could be "silent" even during autopsy investigation. In these cases, it is important to exclude other aetiology and assist to ask for genetic investigations. Herein, the purpose of this review is to collect the most-implicated genes in SCD and generate a panel with indications for first line and second line investigations. A systematic review of genetic disorders that may cause SCD in the general population was carried out according to the Preferred Reporting Item for Systematic Review (PRISMA) standards. We subsequently listed the genes that may be tested in the case of sudden cardiac death when the autopsy results are negative or with no evidence of acquired cardiac conditions. To make genetic tests more specific and efficient, it is useful and demanded to corroborate autopsy findings with the molecular investigation as evident in the panel proposed. The genes for first line investigations are HCM, MYBPC3, MYH7, TNNT2, TNNI3, while in case of DCM, the most implicated genes are LMNA and TTN, and in second line for these CDM, ACTN2, TPM1, C1QPB could be investigated. In cases of ACM/ARVC, the molecular investigation includes DSP, DSG2, DSC2, RYR2, PKP2. The channelopathies are associated with the following genes: SCN5A, KCNQ1, KCNH2, KCNE1, RYR2. Our work underlines the importance of genetic tests in forensic medicine and clinical pathology; moreover, it could be helpful not only to assist the pathologists to reach a diagnosis, but also to prevent other cases of SCD in the family of the descendant and to standardise the type of analysis performed in similar cases worldwide.

I'm sick? I don't train!" – Relation between training during upper respiratory infection and myocarditis

IntrocudtionMyocarditis is one of the leading causes of sudden cardiac deaths among athletes. One of the factors increasing the risk of this disease is engaging in sports training during an infection. Many athletes, regardless of their level of advancement, are not aware of the risks associated with training during an infection, and those who are aware often ignore them and continue training. Purpose Assessment of behaviors and awareness among runners in Poland regarding the risk of developing myocarditis as a result of training during respiratory tract infections. Material and method In December 2023, a voluntary and anonymous online survey was conducted among a group of 399 adult runners from Poland. The survey included 13 questions, consisting of 11 single-choice questions and 2 multiple-choice questions. Results The percentage of individuals who do not associate training during an infection with an increased risk of myocarditis amounts to as much as 44.4% (n=177), while a staggering 86.7% (n=346) of respondents declare that they undertake training during respiratory infections. Conslusion After analyzing the survey, it's evident that while the Polish running community recognizes the risks of training during infections, many still exercise despite symptoms. Although most understand that intense training and early return to sports can harm health, awareness of myocarditis risks from exertion during infection is lacking. Despite protocols for post-illness return to sports, there's a need for campaigns to educate the running community on infection-related training risks.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Profile of Cases of Death Due to Coronary Artery Disease: An Autopsy Based Descriptive Study

Background: Most common cause of sudden cardiac death is coronary artery disease, which contributes to 75 to 90%. The present study is undertaken to describe the profile of autopsy cases of coronary artery disease. Methods:Descriptive cross-sectional study was conducted in all cases of sudden and unexpected death brought for autopsy a tertiary level centre in southern Kerala during a period of one year. Gross and microscopical examination of heart and coronary arteries were studied and in cases with coronary artery disease, associated factors like previous history of illness, personal habits, family history of illness, body mass index, abdominal circumference, horizontal earlobe crease were described in detail. Categorical variables were represented as frequency and percentage, continuous variables as mean and standard deviation and association was tested using Chi square test. Conclusions: Statistically significant association (p value = 0.001) was observed between the horizontal earlobe crease and occlusive coronary artery disease. No significant association was obtained between the obesity parameters like body mass index, waist to hip ratio and occlusive coronary artery disease. Majority of the cases with significant occlusion was observed in the left anterior descending artery.The most common site of thrombus was in the proximal third of left anterior descending artery.

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside.

Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

Proarrhythmic drugs, drug levels, and polypharmacy in victims of sudden arrhythmic death syndrome: An autopsy-based study from Denmark

BackgroundSudden arrhythmic death syndrome (SADS), characterized by an unknown or inconclusive cause of death at autopsy, together with a negative or non-lethal toxicology screening, is the most common cause of sudden cardiac death (SCD) in victims under the age of 35. The complete causality of SADS remains unclear, with drugs being a potential risk factor. ObjectiveTo describe the toxicological profiles of SADS victims, focusing on proarrhythmic drugs, drug levels, and polypharmacy. MethodsAll deaths in Denmark from 2000–2019 aged 1–35 years and 2007–2019 aged 36–49 years were examined through death certificates, national registries, and autopsy reports with toxicology screenings. We investigated all sudden unexpected death victims with an autopsy performed, and where cause of death was unknown or inconclusive, including negative or non-lethal drug findings (SADS). ResultsWe identified 477 SADS victims; 313 (66%) had a positive toxicology screening (adjudicated non-lethal), with an average of 2.8 drugs/case. More than half of the SADS victims with a positive toxicology screening had QT-prolonging or brugadogenic drugs present. Polypharmacy was present in 66%, psychotropic polypharmacy in 37%, and QT-prolonging polypharmacy in 22%, with the most frequent overall and QT-prolonging drug combination being an antipsychotic and a psychoanaleptic drug. QT-prolonging drugs were more often present at suprapharmacological levels than non-QT-prolonging drugs. ConclusionA majority of the SADS population had a positive toxicology, with a notably large proportion having proarrhythmic drugs and polypharmacy. This highlights the need for future focus on drugs as a risk factor for SADS.

Rationale and design of the French cohort of acute myocarditis diagnosed by cardiac magnetic resonance imaging (MyocarditIRM)

BackgroundAcute myocarditis usually presents as chest pain with rising troponin and normal coronary arteries. Despite frequent favourable evolution at the acute phase, it is associated with heart failure and ventricular rhythm disorders, and is considered the leading cause of sudden cardiac death in young, apparently healthy, adults. There are no specific recommendations for acute myocarditis diagnosis and management, only expert consensus, given the lack of large databases. AimThe main objective is to describe the contemporary presentation of acute myocarditis, its management and in-hospital outcomes. Secondary objectives are to investigate survival and event-free survival for up to 10years of follow-up, the determinants of prognosis, the modalities of treatment and follow-up and the gaps between expert consensus and real-life management. MethodsMyocarditIRM is a prospective multicentre cohort that enrolled 803 consecutive patients with acute myocarditis in 49 participating centres in France between 01 May 2016 and 28 February 2019. The diagnosis of acute myocarditis was acknowledged by cardiac magnetic resonance, using the Lake Louise Criteria. Exclusion criteria were age<18years, lack of health coverage, contraindication to cardiac magnetic resonance and refusal to participate. Detailed information was collected prospectively, starting at admission. Cardiac magnetic resonance imaging (diagnosis and follow-up) is analysed centrally by the certified core laboratory IHU ICAN. Ten years of follow-up for each patient is ensured by linking with the French National Health Database, and includes information on death, hospital admissions, major clinical events and drug consumption. ConclusionThis prospective cohort with long-term follow-up represents the largest database on acute myocarditis worldwide, and will improve knowledge about its presentation, management and outcomes.

АССОЦИАТИВНАЯ РОЛЬ ПОЛИМОРФИЗМА RS121908987 ГЕНА PRKAG2 В РАЗВИТИИ СИНДРОМА WPW

The study of cardiac arrhythmias and conduction is one of the most urgent and important tasks, since these diseases are often the cause of sudden cardiac death. We assumed that the study of the contribution of "predictor genes" of heart rhythm and conduction disorders would expand knowledge about the etiology and pathogenesis of these diseases. Thus, the purpose of our research was to study the contribution of the rs121908987 polymorphism of the PRKAG2 gene to the development of WPW syndrome. Material and methods: 200 patients with VPU syndrome were examined, among them men n=97 [18:32.66;81]; women n=103 [18;47,92;83]. All patients underwent clinical, laboratory, somatometric, instrumental studies, as well as molecular genetic studies DNA isolation was performed by the standard phenol-chloroform method. Genotyping of the PRKAG2 gene was performed by PCR-PDRF analysis (polymerase chain reaction-polymorphism of restriction fragment lengths). Statistical data processing was carried out using the Excel application software package, Statistica for Windows 10.0, IBM SPSS 20.Differences in the frequency distribution of alleles and genotypes of the PRKAG2 gene between the groups were assessed using the χ2 criterion. The relative risk of disease for a specific allele or genotype was calculated as the odds ratio (OR). Results: a statistically significant predominance of the heterozygous GA genotype in patients with VPU syndrome, compared with those in the control group (8 and 2%, respectively; Table 1). There was also a statistically significant predominance of allele A carriers in the group of patients with VPU syndrome by 4%, compared with those in the control group (2%). The risk of developing PRKAG2 genotype GA syndrome, estimated by OSH, was 2.09 times higher (95% CI 1.88–2.32; p &lt;0.001 compared with genotypes GG and AA, and in carriers of the A allele – 2.04 times higher (95% CI 1.90–2.19; p &lt;0.001) compared with allele A (see Table 2). Conclusions: The results of the study confirmed the contribution of polymorphism rs121908987 of the PRKAG2 gene to the development of VPU syndrome.

Clinical and genetic yield of familial screening after a sudden unexplained death at a young age.

In a population under 45 years of age, the predominant causes of sudden cardiac death (SCD) are inherited cardiac diseases. Determining the underlying cause may help identify relatives at risk and prevent further events but is more difficult if an autopsy has not been performed. We aimed to assess the diagnostic value of clinical and genetic screening in relatives of young non-autopsied sudden unexplained death (SUD) victims. Eighty-seven relatives of 65 young non-autopsied SUD victims from 39 families were evaluated from 2016 to 2019. The relatives underwent extensive noninvasive cardiac workup. Genetic examinations were performed in 39 families. The definite diagnoses were made in 17 of 39 (44%) families. Cardiomyopathies were identified in 10 families (5 hypertrophic, 4 dilated, and 1 arrhythmogenic), followed by long QT syndrome (5 families). In 3 families, probable diagnoses were made, whereas in 20 families no diagnosis was achieved. In total, definite and probable diagnoses were made in 18 and 5 patients, respectively. All affected relatives were offered medical management, one of them died of heart failure and one underwent transplantation during the median follow-up of 3 years. Disease-causing variants were found in 7 of 39 (18%) probands; all in families with a definite diagnosis. Variants of unknown significance were found in 2 probands. Screening of relatives of SUD victims is warranted and may save lives, even if it is not guided by autopsy results. Genetic testing in families without the disease phenotype has little effectiveness.

Exploring biomarkers for identifying acute myocardial infarction based on lipidomics

ABSTRACT Acute myocardial infarction(AMI) is one of the most common causes of sudden cardiac death, but the accurate AMI identification biomarkers are still lacking. Recently, lipidomics shed new light on the exploration of AMI biomarkers. In this study, lipid molecules were examined in rat myocardial tissue based on Liquid chromatography-tandem mass spectrometry (LC-MS/MS) lipidomics to screen for metabolic markers for the identification of AMI. Results showed that 70 lipid molecules with different expressions identified by distinguishing between the sham group and the AMI 5 min group, 275 differentially expressed lipid molecules identified by distinguishing between the sham group and the AMI 4 hour group. And 257 differentially expressed lipid molecules identified by distinguishing between the AMI 5 min group and the AMI 4 hour group. Comprehensive analysis shows that PC (18:0_18:1)+HCOO and PC (16:0_18:2)+HCOO exhibited more significant changes. Two lipid molecules were applied to build AMI-identification models, the accuracy rate reached 77.8% and R2 = 0.539.

Catheter Ablation for Channelopathies: When Is Less More?

Ventricular fibrillation (VF) is a common cause of sudden cardiac death in patients with channelopathies, particularly in the young population. Although pharmacological treatment, cardiac sympathectomy, and implantable cardioverter defibrillators (ICD) have been the mainstay in the management of VF in patients with channelopathies, they are associated with significant adverse effects and complications, leading to poor quality of life. Given these drawbacks, catheter ablation has been proposed as a therapeutic option for patients with channelopathies. Advances in imaging techniques and modern mapping technologies have enabled increased precision in identifying arrhythmia triggers and substrate modification. This has aided our understanding of the underlying pathophysiology of ventricular arrhythmias in channelopathies, highlighting the roles of the Purkinje network and the epicardial right ventricular outflow tract in arrhythmogenesis. This review explores the role of catheter ablation in managing the most common channelopathies (Brugada syndrome, congenital long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). While the initial results for ablation in Brugada syndrome are promising, the long-term efficacy and durability of ablation in different channelopathies require further investigation. Given the genetic and phenotypic heterogeneity of channelopathies, future studies are needed to show whether catheter ablation in patients with channelopathies is associated with a reduction in VF, and psychological distress stemming from recurrent ICD shocks, particularly relative to other available therapeutic options (e.g., quinidine in high-risk Brugada patients).

Possible Mechanisms for Adverse Cardiac Events Caused by Exercise-Induced Hypertension in Long-Distance Middle-Aged Runners: A Review.

Sudden cardiac death (SCD) is rare among athletes. However, hypertrophic cardiomyopathy is the leading cause of SCD among those <35 years of age. Meanwhile, coronary artery disease (CAD) is the primary SCD cause among those ≥35 years of age. CAD-induced plaque ruptures are believed to be a significant cause of cardiovascular diseases in middle-aged individuals who participate in extreme long-distance running activities such as marathons. A total of 1970 articles related to EIH were identified using search terms. Out of these, 1946 studies were excluded for reasons such as arterial hypertension, exercise-induced pulmonary hypertension, the absence of exercise stress testing (EST), and a lack of relevance to EIH. The study analyzed 24 studies related to both long-distance runners with exercise-induced hypertension (EIH) and the general public. Among these, 11 studies were quasi-experimentally designed studies used in randomized controlled trials (RCTs) on long-distance runners with EIH. Additionally, 12 studies utilized cohort designs, and one study with a quasi-experimental design was conducted among the general population. Recent studies suggest that an imbalance between oxygen demand and supply due to ventricular hypertrophy may be the actual cause of cardiovascular disease, regardless of CAD. Exercising excessively over an extended period can reduce endothelial function and increase arterial stiffness, which in turn increases afterload and leads to an excessive increase in blood pressure during exercise. Exercise-induced hypertension (EIH), which increases the morbidity rate of resting hypertension and is a risk factor for cardio-cerebro-vascular diseases, is more prevalent in middle-aged long-distance runners than in runners from other age groups, and it increases the prevalence of critical arrhythmias, such as atrial fibrillation or ventricular arrhythmias. EIH is associated with angiotensin II activity, and angiotensin II receptor blockers show promising effects in middle-aged runners. Further, guidelines for preventing excessive participation in races and restricting exercise intensity and frequency would be useful. This review identifies EIH as a potential risk factor for cardiovascular diseases and describes how EIH induces SCD.

ECG Signal Classification for Detection of Hyperkalemia

Potassium Imbalance is a serious problem that is the leading cause of sudden cardiac deaths in chronic kidney patients (CKD). Currently blood test is the gold standard for detection of potassium imbalances. Electrocardiogram (ECG) signals provide a non- invasive way to view the cardiac activity of the heart. It can also be used to detect potassium imbalance in Chronic Kidney patients. However the unique characteristics and complexity of ECG signals make it a very challenging process. This paper presents a machine learning classifier for detection of hyperkalaemia in patients using features extracted from ECG. Feature extraction plays a very crucial role in the machine learning process as it helps to capture the essential information for the learning task which can be used for applications such as classification and detection. Ten statistical features were extracted from ECG signals of patients having potassium within normal range and those with elevated levels of potassium. Classification performance of four different classifiers namely Naïve Bayes Classifier, Support Vector Machine(SVM), K Nearest Neighbors(kNN) and Artificial Neural Networks(ANN) was compared using statistical features. kNN and ANN performed best with classification accuracy of 97.9%.The results we found are in-line with other state-of-art hyperkalaemia classification approaches

Prevalence and clinical significance of late gadolinium enhancement in children and adolescents with hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death among the paediatric population. The aim of this study is to investigate the prevalence and clinical significance of late gadolinium enhancement, as assessed by cardiac MRI, in paediatric hypertrophic cardiomyopathy. A systematic literature search was conducted in PubMed, SCOPUS, and Ovid SP to identify relevant studies. Pooled estimates with a 95% confidence interval were calculated using the random-effects generic inverse variance model. Statistical analysis was performed using Review Manager v5.4 and R programming. Seventeen studies were included in this meta-analysis, encompassing a total of 778 patients. Late gadolinium enhancement was highly prevalent in paediatric hypertrophic cardiomyopathy, with a pooled prevalence of 51% (95% confidence interval, 40-62%). The estimated extent of focal fibrosis expressed as a percentage of left ventricular mass was 4.70% (95% confidence interval, 2.11-7.30%). The presence of late gadolinium enhancement was associated with an increased risk of adverse cardiac events (pooled odds ratio 3.49, 95% confidence interval 1.10-11.09). The left ventricular mass index of late gadolinium enhancement-positive group was higher than the negative group, with a standardised mean difference of 0.91 (95% confidence interval, 0.42-1.41). This meta-analysis demonstrates that prevalence of late gadolinium enhancement in paediatric hypertrophic cardiomyopathy is similar to that in the adult population. The presence and extent of late gadolinium enhancement are independent predictors of adverse cardiac events, underscoring their prognostic significance among the paediatric population.

Base genética de las arritmias primarias hereditarias más frecuentes: síndrome de QT largo, el síndrome de brugada y taquicardia ventricular polimórfica catecolaminérgica

Inherited primary arrhythmias correspond to a group of genetic disorders, including long QT syndrome (LQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT), among others. They are usually caused by pathogenic variants in genes related to ion channels, predisposing to arrhythmias and cardiac events. Inherited primary arrhythmias affect approximately 1 in 3,000 people and are an important cause of sudden cardiac death, mainly in young adults. Diagnosis is based on clinical history, particular electrocardiographic patterns, and detection of mutations. Given that mutation carriers are usually diagnosed after presenting a cardiac event and that the consequences of not identifying or treating them promptly can be fatal, genetic studies are very relevant to guide management, define prognosis, and detect asymptomatic individuals in the family, after performing cascade genetic studies, which allows early intervention in this risk group. This article reviews the genetic causes of LQTS, BrS, and CPVT, highlighting the relevance of genetic studies in patients with these arrhythmias.

Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.

Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a major cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases and pathological immune responses. However, little is known regarding how infection can acutely induce an arrhythmogenic substrate before significant immune responses. Adenovirus is a leading cause of myocarditis, but due to species specificity, models of infection are lacking, and it is not understood how adenoviral infection may underlie sudden cardiac arrest. Mouse adenovirus type-3 was previously reported as cardiotropic, yet it has not been utilized to understand the mechanisms of cardiac infection and pathology. We have developed mouse adenovirus type-3 infection as a model to investigate acute cardiac infection and molecular alterations to the infected heart before an appreciable immune response or gross cardiomyopathy. Optical mapping of infected hearts exposes decreases in conduction velocity concomitant with increased Cx43Ser368 phosphorylation, a residue known to regulate gap junction function. Hearts from animals harboring a phospho-null mutation at Cx43Ser368 are protected against mouse adenovirus type-3-induced conduction velocity slowing. Additional to gap junction alterations, patch clamping of mouse adenovirus type-3-infected adult mouse ventricular cardiomyocytes reveals prolonged action potential duration as a result of decreased IK1 and IKs current density. Turning to human systems, we find human adenovirus type-5 increases phosphorylation of Cx43Ser368 and disrupts synchrony in human induced pluripotent stem cell-derived cardiomyocytes, indicating common mechanisms with our mouse whole heart and adult cardiomyocyte data. Together, these findings demonstrate that adenoviral infection creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients.

Transthyretin-derived amyloid (ATTR) and sarcoidosis: Does ATTR deposition cause a granulomatous inflammatory response in older adults with sarcoidosis?

This study aimed to assess the frequency and association between transthyretin-derived (ATTR) amyloidosis and sarcoidosis in a large autopsy cohort including many cases of sudden cardiac death (SCD). We identified 73 sporadic ATTR amyloidosis cases and 11 sarcoidosis cases, among which we found two cases with concomitant ATTR amyloidosis and sarcoidosis (2.4% of all cases; 2.7% within the sporadic ATTR group). The first case involved a 92-year-old man who experienced SCD. In this patient's heart, we observed ATTR deposition and noncaseating epithelioid granulomas consistent with sarcoidosis. Focally, ATTR deposits and granulomas co-localized, with histiocyte phagocytosis of transthyretin-immunoreactive fragments. However, in most lesions, they were distributed independently. The second case was that of an 86-year-old woman who also experienced SCD. In this patient, we detected ATTR deposition in the heart and lung, while noncaseating epithelioid granulomas were only observed in the lung, liver, kidney, and thyroid. Furthermore, no co-localization of the two lesions was observed. Based on these findings, we concluded that the coexistence of ATTR amyloidosis and sarcoidosis was likely coincidental. Nevertheless, despite the rarity of the combination of these two diseases, it should be recognized as a potential cause of SCD, especially among elderly people.

Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.

Ventricular arrhythmias are the leading cause of sudden cardiac death in patients after myocardial infarction (MI). Connexin43 (Cx43) is the most important gap junction channel-forming protein in cardiomyocytes. Dysfunction of Cx43 contributes to impaired myocardial conduction and the development of ventricular arrhythmias. Following an MI, Cx43 undergoes structural remodeling, including expression abnormalities, and redistribution. These alterations detrimentally affect intercellular communication and electrical conduction within the myocardium, thereby increasing the susceptibility to post-infarction ventricular arrhythmias. Emerging evidence suggests that post-translational modifications play essential roles in Cx43 regulation after MI. Therefore, Cx43-targeted management has the potential to be a promising protective strategy for the prevention and treatment of post infarction ventricular arrhythmias. In this article, we primarily reviewed the regulatory mechanisms of Cx43 mediated post-translational modifications on post-infarction ventricular arrhythmias. Furthermore, Cx43-targeted therapy have also been discussed, providing insights into an innovative treatment strategy for ventricular arrhythmias after MI.

Development of the NOCSAE Standard to Reduce the Risk of Commotio Cordis.

Commotio cordis, sudden cardiac death (SCD) caused by relatively innocent impact to the chest, is one of the leading causes of SCD in sports. Commercial chest protectors have not been demonstrated to mitigate the risk of these SCDs. To develop a standard to assess chest protectors, 4 phases occurred. A physiological commotio cordis model was utilized to assess variables that predicted for SCD. Next, a surrogate model was developed based on data from the physiological model, and the attenuation in risk was assessed. In the third phase, this model was calibrated and validated. Finally, National Operating Committee on Standards for Athletic Equipment adopted the standard and had an open review process with revision of the standard over 3 years. Of all variables, impact force was the most robust at predicting SCD. Chest wall protectors which could reduce the force of impact to under thresholds were predicted to reduce the risk of SCD. The correlation between the experimental model and the mechanical surrogate ranged from 0.783 with a lacrosse ball at 30 mph to 0.898 with a baseball at 50 mph. The standard was licensed to National Operating Committee on Standards for Athletic Equipment which initially adopted the standard in January 2018, and finalized in July 2021. An effective mechanical surrogate based on physiological data from a well-established model of commotio cordis predicts the reduction in SCD with chest protectors. A greater reduction in force provides a great degree of protection from commotio cordis. This new National Operating Committee on Standards for Athletic Equipment standard for chest protectors should result in a significant reduction in the risk of commotio cordis on the playing field.