Sudden Death Research Articles

From rare events to systematic data collection: the RESCUED registry for sudden cardiac death in the young in Germany.

Approximately one-third of sudden cardiac deaths in the young (SCDY) occur due to a structural cardiac disease. Forty to fifty percent of SCDY cases remain unexplained after autopsy (including microscopic and forensic-toxicological analyses), suggesting arrhythmia syndromes as a possible cause of death. Due to the possible inheritability of these diseases, blood relatives of the deceased may equally be carriers of the causative genetic variations and therefore may have an increased cardiac risk profile. A better understanding of the forensic, clinical, and genetic data might help identify a subset of the general population that is at increased risk of sudden cardiac death. The German registry RESCUED (REgistry for Sudden Cardiac and UnExpected Death) comprises information about SCDY fatalities and clinical and genetic data of both the deceased and their biological relatives. The datasets collected in the RESCUED registry will allow for the identification of leading causes of SCDY in Germany and offer unique possibilities of scientific analyses with the aim of detecting unrecognized trends, risk factors, and clinical warning signs of SCDY. In a pilot phase of 24months, approximately 180 SCDY cases (< 50years of age) and 500 family members and clinical patients will be included. RESCUED is the first registry in Germany collecting comprehensive data of SCDY cases and clinical data of the biological relatives reviewed by cardiac experts. RESCUED aims to improve individual risk assessment and public health approaches by directing resources towards early diagnosis and evidence-based, personalized therapy and prevention in affected families. Trial registration number (TRN): DRKS00033543.

Evaluation of ventricular repolarization in dermatomyositis and relationship with inflammation and autoimmunity.

Dermatomyositis (DM) is a chronic multi-systemic inflammatory disorder of autoimmune origin, which has been associated with cardiovascular complications, including ventricular arrhythmias and sudden cardiac death. The Tp-e interval and Tp-e/QT ratio have been accepted as new markers for the assessment of myocardial repolarization and ventricular arrhythmogenesis. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with DM, and to assess the relation with inflammation and autoimmunity. This study included 281 DM patients (180 females, 101 males; mean age 52.73 ± 15.80years) and 281 control subjects (180 females, 101 males; mean age 53.38 ± 15.72years). QTc, Tp-e interval and Tp-e/QT ratio were measured from the 12-lead ECG. The plasma level of blood routine test, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) was measured. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QTc, Tp-e interval and Tp-e/QT ratio were significantly increased in DM patients compared to the control group (441.44 ± 26.62ms vs 422.72 ± 11.7ms, 104.16 ± 24.34ms vs 77.23 ± 16.25ms and 0.27 ± 0.06ms vs 0.20 ± 0.04ms, all P value < 0.01). QTc, Tp-e interval and Tp-e/QT were positively correlated with NLR, CRP, and ESR (all P values < 0.01), and were increased in anti-Ro/SSA-52kD positive patients compared to those negative (452.33 ± 24.89ms vs 438.55 ± 26.37ms, 114.05 ± 22.68ms vs 101.53 ± 24.13ms, and 0.29 ± 0.06ms vs 0.27 ± 0.05ms, all P value < 0.01). Our study demonstrated that QTc, Tp-e interval, and Tp-e/QT ratio were increased in DM patients and were associated with inflammatory markers and anti-Ro/SSA-52kD positivity.

Sudden Cardiac Death or Ventricular Arrythmia in Patients Taking Levetiracetam or Oxcarbazepine.

Levetiracetam is a widely used antiseizure medication. Recent concerns have been raised regarding the potential prolongation of the QT interval by levetiracetam and increased risk of sudden cardiac death. This could have profound implications for patient safety and for prescribing practice. This study assessed the potential association of levetiracetam with cardiac outcomes related to QT interval prolongation. We compared outcomes of patients taking levetiracetam with those taking oxcarbazepine as a comparator medication that has not been associated with prolongation of the QT interval. The sample included patients who were newly prescribed levetiracetam or oxcarbazepine from January 31, 2010, to December 31, 2019, using administrative claims data from the OptumLabs Data Warehouse (OLDW). The analysis focused on a combined endpoint of sudden cardiac death or ventricular arrythmia, which are both linked to QT interval prolongation. We used a new user design and selected oxcarbazepine as an active comparator with levetiracetam to minimize bias. We used propensity score weighting to balance the levetiracetam and oxcarbazepine cohorts and then performed weighted Cox regressions to evaluate the association of levetiracetam with the combined endpoint. We identified 104,655 enrollees taking levetiracetam and 39,596 enrollees taking oxcarbazepine. At baseline, enrollees taking levetiracetam were older, more likely to have diagnosed epilepsy, and more likely to have diagnosed comorbidities including hypertension, cerebrovascular disease, and coronary artery disease. In the main analysis, we found no significant difference between levetiracetam and oxcarbazepine in the rate of the combined endpoint for the Cox proportional hazards model (hazard ratio [HR] 0.79, 95% CI 0.42-1.47) or Cox regression with time-varying characteristics (HR 0.78, 95% CI 0.41-1.50). When compared with oxcarbazepine, levetiracetam does not correlate with increased risk of ventricular arrythmia and sudden cardiac death. Our finding does not support the concern for cardiac risk to indicate restriction of levetiracetam use nor the requirement of cardiac monitoring when using it. This study provides Class II evidence that sudden cardiac death and ventricular arrythmia are not more frequent in patients older than 17 years newly prescribed levetiracetam, compared with those prescribed oxcarbazepine.

Video Analyses of Sudden Unexplained Deaths in Toddlers.

Video Analyses of Sudden Unexplained Deaths in Toddlers.

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.

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

BackgroundMultiple 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.MethodsWe 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.ResultsAmong 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.ConclusionsOur 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.

Hypertrophic cardiomyopathy and competitive sports: let 'em play?

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular genetic conditions. Although most patients with HCM typically do well clinically, there is a small but real incidence of sudden cardiac death. A diagnosis of HCM was previously a reason for complete exclusion in sports, particularly competitive sports.However, many of these recommendations are based on expert consensus, and much data has been published in the last decade furthering the scientific knowledge in this area, and allowing athletes who may have been previously excluded the potential to participate in strenuous activities and competitive sports. With recent publications on participation in sports with HCM, as well as an emphasis on shared decision-making, more athletes with HCM are participating in competitive sports, even at a professional level. Even contact sports in the presence of an implantable cardioverter-defibrillator are no longer mutually exclusive in the current era. Previous guidelines were likely overly restrictive for patients with HCM. Although there is a risk of sudden death that cannot be ignored, the potential for shared decision making as well as medical guidance are entering a new era in all aspects of medicine, particularly in sports participation.

Serotonin 2C receptor in a rat model of temporal lobe epilepsy: From brainstem expression to pharmacological blockade in relation to ventilatory function.

Because of its involvement in breathing control and neuronal excitability, dysregulation of the serotonin (5-HT) 2C receptor (5-HT2C) might play a key role in sudden unexpected death in epilepsy. Seizure-induced respiratory arrest is thus prevented by a 5-HT2B/C agonist in different seizure model. However, the specific contribution of 5-HT2C in chronic epilepsy-related respiratory dysfunction remains unknown. In a rat model of temporal lobe epilepsy (EPI rats), in which we previously reported interictal respiratory dysfunctions and a reduction of brainstem 5-HT tone, quantitative reverse transcriptase polymerase chain reaction showed overexpression of TPH2 (5-HT synthesis enzyme), SERT (5-HT reuptake transporter), and 5-HT2C transcript levels in the brainstem of EPI rats, and of RNA-specific adenosine deaminase (ADAR1, ADAR2) involved in the production of 5-HT2C isoforms. Interictal ventilation was assessed with whole-body plethysmography before and 2 h after administration of SB242084 (2 mg/kg), a specific antagonist of 5-HT2C. As expected, SB242084 administration induced a progressive decrease in ventilatory parameters and an alteration of breathing stability in both control and EPI rats. However, the size of the SB242084 effect was lower in EPI rats than in controls. Increased 5-HT2C gene expression in the brainstem of EPI rats could be part of a compensatory mechanism against epilepsy-related low 5-HT tone and expression of 5-HT2C isoforms for which 5-HT affinity might be lower.

Clinical epidemiology of cardiovascular disease in advanced chronic kidney disease prior to dialysis to a tertiary care centre in Bangladesh

Background: Patients with advanced CKD stages exhibit a markedly elevated risk of cardiovascular disease. Patients with chronic kidney disease (CKD) exhibit an elevated cardiovascular risk manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death .The main objective of this study was to observe the clinical epidemiology of cardiovascular disease in advanced stages of CKD prior to dialysis to a tertiary care centre in Bangladesh. Methods: This was a cross-sectional observational study on 150 cases of diagnosed advanced stages (4&amp;5) of CKD patients in the indoor Department of Medicine of Sir Salimullah Medical College Mitford Hospital, Dhaka, Bangladesh from July 2022to January2023 for 6 months. Data was analyzed SPSS 25. Results: Out of the total group, 62.0% are male, 38.0% are female, and the average (mean) age of the entire group was 55.2 ±10.3. Patients are compared in terms of their relative percentages and the associated cardiovascular disease (CVD) risk, with the hypothesis that lower hemoglobin levels (&lt;9 mg/dL), common in advanced CKD, may be associated with higher CVD risk. A statistically significant P-value (0.036) indicates a significant association between lower hemoglobin levels and increased risk of CVD. Hypertension is the most common risk factor in both stages showing (80%) in stage 4 and 86.6% in Stage -5 of CKD respectively that increasing prevalence as stages of CKD increases . Other factors like diabetes 50.6%) and 53.3% , dyslipidemia 61.3% and 66.7% , and family history of cardiovascular disease (CVD) 40% and 46.6% also in prevalence from Stage 4 to Stage 5. However, the differences in the prevalence of these risk factors between the two stages are not statistically significant, as indicated by the P-values. The prevalence of Congestive Heart Failure rises from 44% in Stage 4 to 52% in Stage 5, and a similar trend is observed in Coronary Artery Disease from 40% in Stage 4 to 48% in Stage 5 and for other diseases, albeit with lesser increments. The provided pvalues, which assess statistical significance, indicate that the differences in disease prevalence between the two stages are not statistically significant, suggesting that the progression from Stage 4 to Stage 5. Conclusion: This study stated that increased prevalence and progression of cardiovascular risks in advanced CKD stages. Bangladesh J Medicine 2024; 35: 96-100

New York Heart Association functional class and implantable cardioverter-defibrillator in non-ischaemic heart failure with reduced ejection fraction: Extended follow-up of the DANISH trial.

Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure, a left ventricular ejection fraction of ≤35%, and New York Heart Association (NYHA) class II-III. However, the evidence regarding the benefit of primary prevention ICD is less consistent in patients with NYHA class III. We investigated the long-term effects of primary prevention ICD implantation according to NYHA class in an extended follow-up study of the DANISH trial. The DANISH trial randomized 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Outcomes were analysed according to NYHA class at baseline (NYHA class II and III/IV). The primary outcome was all-cause mortality. Of the 1116 patients randomized in the DANISH trial, 597 (53.5%) were in NYHA class II at baseline, 505 (45.3%) in NYHA class III, and 14 (1.3%) in NYHA class IV. During a median follow-up of 9.5 years, NYHA class III/IV, compared with NYHA class II, were associated with a greater long-term rate of all-cause mortality (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.20-1.93) and cardiovascular death (HR 1.95 [1.47-2.60]). ICD implantation, compared with usual care, did not reduce the long-term rate of all-cause mortality (all participants: HR 0.89 [95% CI 0.74-1.08]; NYHA class II: HR 0.85 [0.64-1.13]; NYHA class III/IV: HR 0.89 [0.69-1.14]; pinteraction = 0.78) or cardiovascular death (all participants: HR 0.87 [95% CI 0.70-1.09]; NYHA class II: HR 0.78 [0.54-1.12]; NYHA class III/IV: HR 0.89 [0.67-1.19]; pinteraction = 0.58), irrespective of NYHA class. Similarly, NYHA class did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (all participants: HR 0.60 [95% CI 0.40-0.92]; NYHA class II: HR 0.73 [0.40-1.36]; NYHA class III/IV: HR 0.52 [0.29-0.94]; pinteraction = 0.39). In patients with non-ischaemic HFrEF, ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce sudden cardiovascular death, regardless of baseline NYHA class. ClinicalTrials.gov NCT00542945.

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.

Predicting and Recognizing Drug-Induced Type I Brugada Pattern Using ECG-Based Deep Learning.

Brugada syndrome (BrS) has been associated with sudden cardiac death in otherwise healthy subjects, and drug-induced BrS accounts for 55% to 70% of all patients with BrS. This study aims to develop a deep convolutional neural network and evaluate its performance in recognizing and predicting BrS diagnosis. Consecutive patients who underwent ajmaline testing for BrS following a standardized protocol were included. ECG tracings from baseline and during ajmaline were transformed using wavelet analysis and a deep convolutional neural network was separately trained to (1) recognize and (2) predict BrS type I pattern. The resultant networks are referred to as BrS-Net. A total of 1188 patients were included, of which 361 (30.3%) patients developed BrS type I pattern during ajmaline infusion. When trained and evaluated on ECG tracings during ajmaline, BrS-Net recognized a BrS type I pattern with an AUC-ROC of 0.945 (0.921-0.969) and an AUC-PR of 0.892 (0.815-0.939). When trained and evaluated on ECG tracings at baseline, BrS-Net predicted a BrS type I pattern during ajmaline with an AUC-ROC of 0.805 (0.845-0.736) and an AUC-PR of 0.605 (0.460-0.664). BrS-Net, a deep convolutional neural network, can identify BrS type I pattern with high performance. BrS-Net can predict from baseline ECG the development of a BrS type I pattern after ajmaline with good performance in an unselected population.

Research on J wave detection based on transfer learning and VGG16

The J wave in the electrocardiogram indicates that the patient may suffer from malignant arrhythmia, ventricular tachycardia and other diseases, and the probability of sudden death is greatly increased. Due to the low incidence of J wave syndrome, J wave data in public databases are scarce, which hinders the research progress of J wave detection. Therefore, this study aims to automatically identify J wave signals, construct relevant datasets, and combine transfer learning with the pre-trained VGG16 model to detect J wave signals. Given the limited availability of J wave data, we utilized a local transformation method to simulate the generation of J wave signals. Subsequently, the simulated J wave signals underwent a continuous wavelet transform, converting them into grayscale images suitable for input into the pre-trained network. Finally, we fine-tuned the VGG16 network structure, which was initially trained on ImageNet, and modified the network for binary classification output for J wave data training. According to experimental results, this method achieves a 99.34 % accuracy rate, 99.35 % sensitivity, and 99.32 % specificity for the identification of J wave data. The aforementioned results outperform existing J wave research methodologies, effectively facilitating the identification of J wave signals.

Utilizing median and maximum QTc values improves prediction of breakthrough cardiac events in pediatric long QT syndrome.

Although prior studies indicate that a QTc > 500 ms on a single baseline 12-lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS. We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD). During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups. The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.

Mechanical and electrical uncoupling: the role of cardiac magnetic resonance imaging in arrhythmogenic cardiomyopathy proof of concept

Abstract Funding Acknowledgements None. Introduction Arrhythmogenic Cardiomyopathy (ACM) has a high risk of sudden cardiac death, especially under 60 years old (1:5,000 prevalence). ACM involves the replacement of normal heart tissue with fibro-adipose tissue in specific areas of the right ventricle (RV). Cardiac Magnetic Resonance Imaging (CMR) is vital for ACM stratification and prognosis, focusing on RV volume and ejection fraction. Simulations suggest that ACM's abnormal deformation patterns are primarily due to mechanical changes like reduced contractility and increased stiffness, rather than electrical issues. Ventriculo-arterial coupling (VAC) is a valuable metric for assessing RV efficiency, with the TAPSE/sPAP index reflecting the RV's length-force relationship. CMR assists in ACM stratification and prognosis, with VAC potentially serving as a key predictor of outcomes based on mechanical and structural abnormalities identified through CMR. Purpose Examine and establish a relationship between mechanical uncoupling, ventricular arrhythmias, and findings from CMR in patients with ACM. Methods We examined 25 ACM patients (median age 34, 72% men) using the 2019 Modified Task Force and Padua criteria. We investigated two key factors in ACM: Right ventricular-arterial coupling (TAPSE/SPAP ratio) and clinically relevant ventricular tachycardia (requiring cardioversion). We compared clinical, ECG, and imaging data (transthoracic echocardiogram and CMR as the gold standard). We used Spearman rank tests for correlations, Fisher exact tests for nominal characteristics, and Mann-Whitney-U tests for group comparisons. In predefined regression models involving left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) function with VAC, we used flexible nonparametric regressions. A p-value &amp;lt;0.05 was considered statistically significant. The analysis was conducted using SPSSv22 and SAS-University-Edition. Results A positive association of VAC with LVEF (ρ=0.472, p=0.023), RVEF (ρ=0.522, p=0.038) and RV indexed stroke volume (ρ=0.79, p&amp;lt;0.001) was found. Low-rank regression splines showed a mainly positive association of LVEF (df=3 F=20.75 p&amp;lt;0.001), RVEF (df=4 F=24.34 p&amp;lt;0.001) and the RV indexed stroke volume, a positive linear association (df=1 F=31.67 p&amp;lt;0.001). In comparison with patients without crVT, those with crVT had a positive correlation with RV shortening, reduced RVEF (39.6 vs. 32.2%. p=0.025), higher LV mass (38.99 vs. 45.55, p=0.045), and LV end-diastolic volume (LVEDV) (56.99 vs. 68.15 ml/m2, p=0.045) by echocardiogram and CMR respectively; notwithstanding positive associations for VAC were seen with LVEDV (p=0.039), LV mass (p=0.039); and negative with RVEF by CMR (p=0.023), and RV shortening by echo (p=0.026). Conclusions We found that right VAC by echo correlates with RV and LV EF by CMR and RV stroke volume in patients with ACM. RVEF, LV mass, and end-diastolic volume correlate with clinically relevant arrhythmias.

Cardiac Sympathetic Denervation as a Treatment for Ventricular Arrhythmias Refractory to Conventional Treatment: A Case Series

Background: Ventricular arrhythmias are a leading cause of sudden death. The objective of this study was to characterise the results of patients with ventricular arrhythmias refractory to standard medical management, undergoing Video-assisted thoracoscopic cardiac sympathetic denervation (VAT-CSD) during 2012–2022 in Cali, Colombia. Methods: This was an observational retrospective study, using the Institutional General Thoracic Surgery Database for patient identification and retrospectively reviewing the clinical charts for data description and analysis. Results: Clinical records of 19 patients who underwent VAT-CSD for ventricular arrhythmia were analysed. The patients were predominantly male (73.7%) with an mean age of 62 years. Ischaemic heart disease was the main underlying condition (52.6%); all individuals had a diagnosis of heart failure, with comorbidities such as hypertension (63.1%), acute MI (57.8%) and diabetes (26.3%) also present. The procedure was performed bilaterally in 89.4% of cases and was successful with minimal perioperative complications. Postoperative follow-up showed improvement in symptoms, including a significant reduction in the number of ICD shocks and emergency department visits. Conclusion: VAT-CSD is a viable, safe and palliative therapeutic option for patients with ventricular arrhythmias who have not responded to conventional treatments, achieving a significant decrease in symptoms with low mortality and perioperative complications.

Molecular Autopsy With Banked Cord Blood Reveals Brugada Syndrome in Past Sudden Death Case.

Molecular autopsy has recently been gaining attention as a means of postmortem diagnosis; however, it is usually performed using the victim's blood sample at the time of death. Here, we report the first case of a deceased infant with Brugada syndrome whose diagnosis was made with banked cord blood. A seemingly healthy 1-year-old male infant collapsed while having a fever; this collapse was witnessed by his mother. Despite cardiopulmonary resuscitation, he died of ventricular fibrillation. No abnormalities of cardiac structure were identified on autopsy. Genomic samples were not stored at the time because of a lack of suspicion for familial arrhythmia. Five years later, his sister showed Brugada electrocardiogram pattern while febrile from Kawasaki disease. Their father showed a spontaneous type 1 Brugada electrocardiogram pattern. A heterozygous SCN5A p.R893C variant was found by genetic testing in the proband's father and sister. Furthermore, the proband's genetic testing was performed using his banked cord blood, which identified the same variant. Family history of Brugada syndrome with an SCN5A-R893C variant and clinical evidence led to a postmortem diagnosis of Brugada syndrome in the proband. Identification of this variant in this case later contributed to verifying SCN5A-R893C as a pathogenic variant through data accumulation. Banked cord blood may prove useful for conducting molecular autopsies in previously undiagnosed cases of sudden death in which genomic samples were not stored.

Detection of macropodid alphaherpesvirus 2 infection and lesions in sudden death of a captive Virginia opossum and a water opossum

Macropodid alphaherpesvirus 2 (MaAHV2) is best described in macropods and has been implicated in outbreaks among captive marsupial populations in Australia. Natural disease caused by herpesviruses has not been reported previously in opossum species, to our knowledge. One Virginia opossum ( Didelphis virginiana) and 1 water opossum ( Chironectes minimus) were submitted for postmortem examination from a zoo that housed 6 opossums, all of which died within several weeks. Red kangaroos ( Macropus rufus) and red-necked wallabies ( Macropus rufogriseus) were also present at the facility. Liver samples from both opossums were submitted for transmission electron microscopy and whole-genome sequencing. Microscopically, both opossums had multifocal necrosis in the liver and lung, with intranuclear inclusion bodies within hepatocytes and pneumocytes. Another significant finding in the Virginia opossum was sepsis, with isolation of Streptococcus didelphis from various organs. Ultrastructural analysis of formalin-fixed liver tissue identified herpesviral replication complexes in both opossums; negative-stain electron microscopy of unfixed liver tissue repeatedly yielded a negative result. The herpesvirus had &gt;99% nucleotide identity with MaAHV2. These 2 cases indicate that both opossum species are susceptible to MaAHV2 infection, and the outbreak has implications for mixed-species facilities that house macropods.

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 to 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.

Global Proteomic Analysis Reveals Alterations in Differentially Expressed Proteins between Cardiopathic Lamin A/C Mutations.

Lamin A/C (LMNA) is an important component of nuclear lamina. Mutations cause arrhythmia, heart failure, and sudden cardiac death. While LMNA-associated cardiomyopathy typically has an aggressive course that responds poorly to conventional heart failure therapies, there is variability in severity and age of penetrance between and even within specific mutations, which is poorly understood at the cellular level. Further, this heterogeneity has not previously been captured to mimic the heterozygous state, nor have the hundreds of clinical LMNA mutations been represented. Herein, we have overexpressed cardiopathic LMNA variants in HEK cells and utilized state-of-the-art quantitative proteomics to compare the global proteomic profiles of (1) aggregating Q353 K alone, (2) Q353 K coexpressed with WT, (3) aggregating N195 K coexpressed with WT, and (4) nonaggregating E317 K coexpressed with WT to help capture some of the heterogeneity between mutations. We analyzed each data set to obtain the differentially expressed proteins (DEPs) and applied gene ontology (GO) and KEGG pathway analyses. We found a range of 162 to 324 DEPs from over 6000 total protein IDs with differences in GO terms, KEGG pathways, and DEPs important in cardiac function, further highlighting the complexity of cardiac laminopathies. Pathways disrupted by LMNA mutations were validated with redox, autophagy, and apoptosis functional assays in both HEK 293 cells and in induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) for LMNA N195 K. These proteomic profiles expand our repertoire for mutation-specific downstream cellular effects that may become useful as druggable targets for personalized medicine approach for cardiac laminopathies.