Diagnosis Of Sudden Cardiac Death Research Articles

Prognostic algorithm for early diagnosis of subcritical conditions as predictors of sudden cardiac death

Aim. To develop a method for early diagnosis of subcritical homeostasis disorders leading to sudden cardiac death (SCD). The basis is to improve the efficiency of predictive algorithms.Material and methods. This pilot, controlled, open-label, randomized, prospective clinical trial included 220 patients at risk of SCD and 150 patients without risk of SCD. Main and control groups was formed according to the global cardiovascular risk score. Based on the informative features proposed by specialized experts using multivariate statistics methods (discriminant analysis), two condition classes were formed. The conducted exploratory analysis confirmed the significance of diagnostic criteria in relation to SCD manifestation (manifestation of cardiac arrest — MCA), which is an integral assessment of a fatal complication. The development of decision rules was carried out on the basis of soft computing technology.Results. Taking into account the priority of clinical research, namely, the identification of subcritical stages of MCA, a classifier is proposed according to basic severity of patients — the severity of critical condition risk (SCCR). The discriminant function and intersection areas between MCA subclasses in the conditions of early SCD diagnosis determine the transition to soft computing technology. Membership functions for severe MCA are formed, followed by their iteration according to E. Shortliffe. The final decision rule, using a fuzzy classifier, differentiates the MCA into stages with different SCCR. In parallel with standard protocols for the management of severe somatic patients (chronic obstructive pulmonary disease, chronic kidney disease, hepatocellular failure), based on the proposed algorithm with an integral assessment of critical conditions, using the MCA decision rule in the main group in 30,5% of cases, subcritical stage was revealed, followed by targeted treatment and preventive support. In the first group, a subcritical condition was detected in 67 patients (30,5%); a critical condition without SCD — in 3 patients (1,4%). In all noted cases, early prevention of SCD was successfully carried out (these patients were transferred to a class with a lower SCD degree). Using conventional prognostic scores in this group, 46 patients (20,9%) were identified with a subcritical condition and 1 (0,4%) with a critical condition. In the control group, subcritical condition was determined in 35 patients (23,3%), of which 17 patients (11,3%) had a moderate risk of SCD. Using conventional prognostic scores, 23 patients (15,3%) with subcritical condition were identified.Conclusion. In the conditions of intensive care unit, general medicine departments, hemodialysis department, cardiac surgery, and organ transplantation department, an algorithm for early diagnosis and risk stratification of SCD with an integral assessment (MCA) should be used. The fuzzy classifier MCA according to SCCR makes it possible to carry out timely correction of treatment measures in addition to standard protocols.

Forensic significance of intracardiac expressions of Nrf2 in acute myocardial ischemia

When exposed to oxidative and electrophilic stress, a protective antioxidant response is initiated by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the extent of its importance in the forensic diagnosis of acute ischemic heart diseases (AIHD), such as myocardial infarction (MI), remains uncertain. On the other hand, immunohistochemical analyses of fibronectin (FN) and the terminal complement complex (C5b-9) prove valuable in identifying myocardial ischemia that precedes necrosis during the postmortem diagnosis of sudden cardiac death (SCD). In this study, we investigated the immunohistochemical levels of Nrf2, FN, and C5b-9 in human cardiac samples to explore their forensic relevance for the identification of acute cardiac ischemia. Heart samples were obtained from 25 AIHD cases and 39 non-AIHD cases as controls. Nrf2 was localized in the nuclei of cardiomyocytes, while FN and C5b-9 were detected in the myocardial cytoplasm. The number of intranuclear Nrf2 positive signals in cardiomyocytes increased in AIHD cases compared to control cases. Additionally, the grading of positive portions of cardiac FN and C5b-9 in the myocardium was also significantly enhanced in AIHD, compared to controls. Collectively, these results indicate that the immunohistochemical investigation of Nrf2 combined with FN, and/or C5b-9 holds the potential for identifying early-stage myocardial ischemic lesions in cases of SCD.

ЭЛЕКТРОКАРДИОГРАФИЧЕСКИЕ СИНДРОМЫ

Introduction. Sudden cardiac death (SCD) is a global health concern, often associated with specific clinical and electrocardiographic syndromes. While electrocardiography (ECG) is a crucial diagnostic tool in cardiology, it does not always provide a direct diagnosis or prediction of SCD. However, there are indirect criteria and syndromes that aid in diagnosing complex clinical cases in cardiology. Aim. This study aims to review various electrocardiographic syndromes known to predict sudden cardiac death, drawing from both domestic and foreign literature. Results. Wellens syndrome (WS) is an ECG pattern indicating a high risk of anterior wall myocardial infarction caused by anterior interventricular artery occlusion or critical stenosis. The de Winter pattern is an ECG sign associated with proximal LAD occlusion and the absence of ST segment elevation. Aslanger pattern is linked to coronary artery occlusion in patients with multivessel coronary artery disease, reflecting a combination of inferior MI and diffuse ischemia. Chaterrier's phenomenon (cardiac memory phenomenon) manifests as abnormal T wave inversion during normal sinus rhythm after myocardial electrical stimulation cessation.The Sgarbossa criteria aid in diagnosing acute myocardial infarction in patients with previous left bundle branch block. ECG signs of arrhythmogenic dysplasia of the right ventricle include negative T-waves in leads V1-V3 and an "epsilon" wave in lead V1, reflecting delayed depolarization of the right ventricle. Conclusion. Early recognition of these ECG patterns can aid in secondary prevention of AMI, fatal rhythm disturbances, and SCD, while also preventing overdiagnosis of myocardial ischemia in patients with implanted devices.

Application of Targeted Coronary Angiography in the Diagnosis of Sudden Cardiac Death.

To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.

Exploring the Potential of Proteome Analysis as a Promising Tool for Evaluation of Sudden Cardiac Death (SCD) in Forensic Settings: A Literature Review.

Sudden cardiac death (SCD) represents a global emergency, with a high number of cases affecting all age groups every year. The prevention of these fatal events requires an accurate knowledge of etiology and pathogenesis, which can vary. Autopsy is an indispensable tool in cases of SCD for diagnostic purposes, as well as for judicial and preventive purposes for family members. Despite the completion of all routine post-mortem investigations, it is often complicated for the forensic pathologist to define the triggering cause of these events. The study of the proteome is proving to be extremely promising in the field of human cardiovascular disease. This paper aims to offer a literature review on the study of the proteome in post-mortem cadaveric biological samples obtained from SCD cases. The aim of this work is to outline the state of the art of the scientific advances that protein analysis can offer in the diagnosis of SCD and the limits that various studies have traced up to now. In conclusion, the work defines the future perspectives of this field in SCD, suggesting strategies to overcome the reported limits and improve the diagnostics of these events.

Postmortem biochemical analysis of soluble ST2 in the pericardial fluid of patients with sudden cardiac death caused by ischemic heart disease: a pilot study.

Soluble growth stimulation expressed gene 2 protein (sST2) is a myocardial protein induced by biomechanical stress. sST2 is widely present in the serum of patients with heart failure and is recommended as an important indicator to predict adverse outcomes in these patients. However, no postmortem biochemical analysis of sST2 in forensic practice has been reported. The present pilot study aimed to investigate the expression of sST2 in the pericardial fluid of patients with sudden cardiac death (SCD) caused by ischemic heart disease (IHD). In addition, to explore the relationship of sST2 with CK-MB, cTnT, and NT-proBNP, which have been proven to be auxiliary biomarkers for the diagnosis of SCD, we analyzed CK-MB, cTnT, NT-proBNP, and sST2 levels in twenty-one pericardial fluid samples from the Center of Forensic Investigation, China Medical University, with a Roche cobas e 411 electrochemiluminescence automatic immunoassay system and ST2/IL-33R Valukine™ enzyme-linked immunosorbent assay kit. The levels of sST2 in the pericardial fluid of patients with SCD caused by IHD were significantly increased (P < 0.01) and positively correlated with CK-MB and NT-proBNP (P < 0.0001). Receiver operating characteristic curve analysis indicated that the combined measurement of sST2 and NT-proBNP has a higher diagnostic value for SCD caused by IHD than the measurement of either indicator alone. This study preliminarily demonstrated that sST2 in the pericardial fluid was significantly increased in patients with SCD caused by IHD and might be used as a novel auxiliary biomarker for postmortem diagnosis of SCD in forensic practice.

Functional Epicardial Conduction Disturbances Due to a SCN5A Variant Associated With Brugada Syndrome

BackgroundBrugada syndrome is a significant cause of sudden cardiac death (SCD), but the underlying mechanisms remain hypothetical. ObjectivesThis study aimed to elucidate this knowledge gap through detailed ex vivo human heart studies. MethodsA heart was obtained from a 15-year-old adolescent boy with normal electrocardiogram who experienced SCD. Postmortem genotyping was performed, and clinical examinations were done on first-degree relatives. The right ventricle was optically mapped, followed by high-field magnetic resonance imaging and histology. Connexin-43 and NaV1.5 were localized by immunofluorescence, and RNA and protein expression levels were studied. HEK-293 cell surface biotinylation assays were performed to examine NaV1.5 trafficking. ResultsA Brugada-related SCD diagnosis was established for the donor because of a SCN5A Brugada-related variant (p.D356N) inherited from his mother, together with a concomitant NKX2.5 variant of unknown significance. Optical mapping demonstrated a localized epicardial region of impaired conduction near the outflow tract, in the absence of repolarization alterations and microstructural defects, leading to conduction blocks and figure-of-8 patterns. NaV1.5 and connexin-43 localizations were normal in this region, consistent with the finding that the p.D356N variant does not affect the trafficking, nor the expression of NaV1.5. Trends of decreased NaV1.5, connexin-43, and desmoglein-2 protein levels were noted; however, the RT-qPCR results suggested that the NKX2-5 variant was unlikely to be involved. ConclusionsThis study demonstrates for the first time that SCD associated with a Brugada-SCN5A variant can be caused by localized functionally, not structurally, impaired conduction.

Deep learning-based measurement of echocardiographic data and its application in the diagnosis of sudden cardiac death

ABSTRACT This study aimed to evaluate the potential of deep learning applied to the measurement of echocardiographic data in patients with sudden cardiac death (SCD). 320 SCD patients who met the inclusion and exclusion criteria underwent clinical evaluation, including age, sex, BMI, hypertension, diabetes, cardiac function classification, and echocardiography. The diagnostic value of deep learning model was observed by dividing the patients into two groups: training group (n=160) and verification group (n=160), as well as two groups of healthy volunteers (n=200 for each group) during the same period. Logistic regression analysis showed that MLVWT, LVEDD, LVEF, LVOT-PG, LAD, E/e' were all risk factors for SCD. Subsequently, a deep learning-based model was trained using the collected images of the training group. The optimal model was selected based on the identification accuracy of the validation group and showed an accuracy of 91.8%, sensitivity of 80.00%, and specificity of 91.90% in the training group. The AUC value of the ROC curve of the model was 0.877 for the training group and 0.995 for the validation groups. This approach demonstrates high diagnostic value and accuracy in predicting SCD, which is clinically important for the early detection and diagnosis of SCD.

Whole-exome sequencing and electrophysiological study reveal a novel loss-of-function mutation of KCNA10 in epinephrine provoked long QT syndrome with familial history of sudden cardiac death

Congenital long QT syndrome (LQTS) is one type of inherited fatal cardiac arrhythmia that may lead to sudden cardiac death (SCD). Mutations in more than 16 genes have been reported to be associated with LQTS, whereas the genetic causes of about 20% of cases remain unknown. In the present study, we investigated a four-generation pedigree with familial history of syncope and SCD. The proband was a 33-year-old young woman who experienced 3 episodes of syncope when walking at night. The electrocardiogram revealed a markedly epinephrine-provoked prolonged QT interval (QT = 468 ms, QTc = 651 ms) but no obvious arrhythmia in the resting state. Three family members have died of suspected SCD. Whole-exome sequencing and bioinformatic analysis based on pedigree revealed that a novel missense mutation KCNA10 (c.1397G＞A/Arg466Gln) was the potential genetic lesion. Sanger sequencing was performed to confirm the whole-exome sequencing results. This mutation resulted in the KV1.8 channel amino acid residue 466 changing from arginine to glutamine, and the electrophysiological experiments verified it as a loss-of-function mutation of KV1.8, which reduced the K+ currents of KV1.8 and might result in the prolonged QT interval. These findings suggested that KCNA10 (c.1397G＞A) mutation was possibly pathogenic in this enrolled LQTS family, and may provide a new potential genetic target for diagnosis and counseling of stress-related LQTS families as well as the postmortem diagnosis of SCD.

Brugada Syndrome in Women: What Do We Know After 30 Years?

Brugada syndrome (BrS) was initially described in 1992 by Josep and Pedro Brugada as an arrhythmogenic disease characterized by ST segment elevation in the right precordial leads and increased risk of sudden cardiac death (SCD). Alterations in the SCN5A gene are responsible for approximately 30% of cases of BrS, following an autosomal dominant pattern of inheritance. However, despite its autosomal transmission, sex-related differences are widely accepted. BrS is more prevalent in males than in females (8–10 times), with males having a 5.5-fold higher risk of SCD. There are also differences in clinical presentation, with females being more frequently asymptomatic and older than males at the time of diagnosis. Some factors have been identified that could explain these differences, among which testosterone seems to play an important role. However, only 30% of the available publications on the syndrome include sex-related information. Therefore, current findings on BrS are based on studies conducted mainly in male population, despite the wide acceptance of gender differences. The inclusion of complete clinical and demographic information in future publications would allow a better understanding of the phenotypic variability of BrS in different age and sex groups helping to improve the diagnosis, management and risk management of SCD.

Novel Indel Variation of NPC1 Gene Associates With Risk of Sudden Cardiac Death

Background and Aims: Sudden cardiac death (SCD) was defined as an unexpected death from cardiac causes during a very short duration. It has been reported that Niemann-Pick type C1 (NPC1) gene mutations might be related to cardiovascular diseases. The purpose of the study is to investigate whether common genetic variants of NPC1 is involved in SCD susceptibility. Methods: Based on a candidate-gene-based approach and systematic screening strategy, this study analyzed an 8-bp insertion/deletion polymorphism (rs150703258) within downstream of NPC1 for the association with SCD risk in Chinese populations using 158 SCD cases and 524 controls. The association of rs150703258 and SCD susceptibility was analyzed using logistic regression. Genotype-phenotype correlation analysis was performed using public database including 1000G, expression quantitative trait loci (eQTL), and further validated by human heart tissues using PCR. Dual-luciferase assay was used to explore the potential regulatory role of rs150703258. Gene expression profiling interactive analysis and transcription factors prediction were performed. Results: Logistic regression analysis exhibited that the deletion allele of rs150703258 significantly increased the risk of SCD [odds ratio (OR) = 1.329; 95% confidence interval (95%CI):1.03–1.72; p = 0.0289]. Genotype-phenotype correlation analysis showed that the risk allele was significantly associated with higher expression of NPC1 at mRNA and protein expressions level in human heart tissues. eQTL analysis showed NPC1 and C18orf8 (an adjacent gene to NPC1) are both related to rs150703258 and have higher expression level in the samples with deletion allele. Dual-luciferase activity assays indicate a significant regulatory role for rs150703258. Gene expression profiling interactive analysis revealed that NPC1 and C18orf8 seemed to be co-regulated in human blood, arteries and heart tissues. In silico analysis showed that the rs150703258 deletion variant may create transcription factor binding sites. In addition, a rare 12-bp allele (4-bp longer than the insertion allele) of rs150703258 was discovered in the current cohort. Conclusion: In summary, our study revealed that rs150703258 might contribute to SCD susceptibility by regulating NPC1 and C18orf8 expression. This indel may be a potential marker for risk stratification and molecular diagnosis of SCD. Validations in different ethnic groups with larger sample size and mechanism explorations are warranted to confirm our findings.

Deep Learning-Based Cardiac Imaging Data Measurement and Its Application in Diagnosis of Sudden Cardiac Death

In the field of forensic medicine, diagnosis of sudden cardiac death is limited by subjective factors and manual measurement methods, so some parameters may have estimation deviation or measurement deviation. As postmortem CT imaging plays a more and more important role in the appraisal of cause of death and cardiopathology research, the application of deep learning such as artificial intelligence technology to analyze vast amounts of cardiac imaging data has provided a possibility for forensic identification and scientific research workers to conduct precise diagnosis and quantitative analysis of cardiac diseases. This article summarizes the main researches on deep learning in the field of cardiac imaging in recent years, and proposes a feasible development direction for the application of deep learning in the virtual anatomy of sudden cardiac death at present.

The coronary artery calcification severity on postmortem CT could be a clue for the diagnosis of sudden cardiac death

About two-thirds of sudden deaths are sudden cardiac deaths (SCD), and ischemic heart disease (IHD) accounts for 60% of these. Although an autopsy needs to be performed to prove SCD, the forensic autopsy rate is very low in Japan. To diagnose the cause of death, postmortem computed tomography (PMCT) is often performed. Because coronary artery calcification (CAC) is a risk factor in cardiac diseases such as IHD and its severity can be evaluated with CT, we examined its ability to diagnose SCD. We collected 104 autopsy cases with CT scans. On the basis of the autopsy report, we separated the cases into two groups: SCD suspected as the cause of death and SCD not suspected. We calculated each CAC severity with the Agatston score from the CT images. Cases with Agatston scores of more than 400 were labeled as severe. The relationship between SCD and CAC severity was confirmed with Fisher's exact test (p < 0.05). The sensitivity and specificity of CAC severity for SCD were 20.3% and 97.5%, respectively, and the positive likelihood ratio was 8.1. Severe CAC can increase the probability of SCD. In cases in which only PMCT can be performed, this finding can be helpful for diagnosing SCD.

Exercise-Associated Sudden Death in Finnish Standardbred and Coldblooded Trotters - A Case Series With Pedigree Analysis

Exercise-associated sudden deaths (EASDs) are deaths occurring unexpectedly during or immediately after exercise. Sudden cardiac death (SCD) is one cause of EASD. Cardiac arrhythmias caused by genetic variants have been linked to SCD in humans. We hypothesize that genetic variants may be associated with SCD in animals, including horses. Genetic variants are transmitted to offspring and their frequency might increase within a family. Therefore, the frequency of such variants might increase with the inbreeding factor. Higher inbreeding could have a negative impact on racing performance. Pedigree data and career earnings from racehorses diagnosed with SCD between 2002 and 2017 were compared using non-parametric tests with 1) control horses that died due to catastrophic musculoskeletal injuries and 2) horses that raced during the same period without reported problems. Diagnosis of SCD was based on necropsy reports, including macroscopic and microscopic examinations. Death was registered in the study period for 61 horses. Eleven of these horses were excluded due to missing autopsy reports. In 25 cases, the diagnosis remained unknown and death was possibly caused by cardiac arrhythmia, in two cases cardiac disease was identified, in seven cases a rupture of a major vessel had occurred. In addition, 16 horses died or were euthanized due to severe musculoskeletal injuries. No significant differences in inbreeding coefficients or in career earnings were found between the groups or between horses with EASD compared with other horses racing during the same period. The study provides no evidence for increased inbreeding factor in Finnish racehorses with SCD.

A Functional Indel Polymorphism Within MIR155HG Is Associated With Sudden Cardiac Death Risk in a Chinese Population.

Sudden cardiac death (SCD) is a devastating complication of multiple disease processes and has gradually became a major public health issue. miR-155 is one of the best characterized miRNAs and plays a critical role in several physiological and pathological process, including cardiovascular diseases. In this study, we systematically screened the whole region of miR-155 host gene (MIR155HG) and identified a 4-bp insertion/deletion variant (rs72014506) residing in the intron region of MIR155HG as the candidate polymorphism. The association of rs72014506 with SCD susceptibility was evaluated using 166 SCD cases and 830 healthy controls in a Chinese population. Logistic regression analysis suggested that the homozygote del/del genotype significantly decreased the risk of SCD [odds ratio (OR) = 0.29; 95% confidence interval (CI) = 0.12–0.74; Ptrend = 0.0004]. Further genotype–expression association study using human myocardium tissue samples suggested that the deletion allele was intimately linked to lower the expression of both MIR155HG and mature miR155. Luciferase activity assay also revealed that the deletion allele of rs72014506 inhibited gene transcriptional activity. Finally, we performed electrophoretic mobility shift assay and verified the preferential binding affinity of the deletion allele with POU2F1 (POU domain class 2 transcription factor 1). Collectively, we have successfully identified a SCD risk conferring polymorphism in the MIR155HG gene and a likely biological mechanism for the decreased risk of SCD associated with the deletion allele. This novel variant may thus serve as a potential genetic marker for SCD diagnosis and prevention in natural populations, if validated by further studies with a larger sample size.

Regulatory variation within 3’UTR of STAT5A correlates with sudden cardiac death in Chinese populations

Definitive diagnosis to sudden cardiac death (SCD) is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death. It is therefore important to uncover the inherited risk component to SCD. Signal transducer and activators of transcription 5 A (STAT5A) is a member of the STAT family and a transcription factor that is activated by many cell ligands and associated with various cardiovascular processes. In this study, we performed a systematic variant screening on the STAT5A to filter potential functional genetic variations. Based on the screening results, an insertion/deletion polymorphism (rs3833144) in 3’UTR of STAT5A was selected as the candidate variant. A total of 159 SCD cases and 668 SCD matched healthy controls was enrolled to perform a case-control study and evaluate the association between rs3833144 and SCD susceptibility in Chinese populations. Logistic regression analysis showed that the deletion allele of rs3833144 had significantly increased the SCD risk (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.18–2.01; P = 0.000955). Further genotype-expression eQTL analysis showed that samples with deletion allele appeared to lower expression of STAT5A, and in silico prediction suggested the local 3 D structure changes of STAT5A mRNA caused by the variant. On the other hand, the bioinformatic analysis presented that promoters of RARA and PTGES3L-AARSD1 could interact with rs3833144, and eQTL analysis showed the higher expression of both genes in samples with deletion allele. Dual-luciferase activity assays also suggested the significant regulatory role of rs3833144 in gene transcription. Our current data thus suggested a possible involvement of rs3833144 to SCD predisposition in Chinese populations and rs3833144 with potential function roles may become a candidate marker for SCD diagnosis and prevention.

CircSLC8A1 and circNFIX can be used as auxiliary diagnostic markers for sudden cardiac death caused by acute ischemic heart disease

Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide. Circular RNAs (circRNAs) are abundant in the heart and play important roles in cardiovascular diseases, but the role of circRNAs as biomarkers in the forensic diagnosis of SCD caused by acute IHD remains poorly characterized. To investigate the potential of two heart-enriched circRNAs, circNFIX and circSLC8A1, we explored the expression of these two circRNAs in different kinds of commonly used IHD models, and further verified their expressions in forensic autopsy cases. The results from both the IHD rat and H9c2 cell models revealed that circSlc8a1 level was upregulated, while the circNfix level was elevated in the early stage of ischemia and subsequently downregulated. The time-dependent expression patterns of the two circRNAs suggested their potential as SCD biomarkers. In autopsy cases, the results showed that the expression of these two circRNAs in the myocardium with acute IHD-related SCDs corresponded to the observations in the ischemic models. Further analysis related to myocardial ischemia indicated that circSLC8A1 showed high sensitivity and specificity for myocardial infarction and was positively correlated with creatine kinase MB in pericardial fluid. Downregulated circNFIX level could indicate the ischemic myocardial damage, and it was negatively correlated with the coronary artery stenosis grade. The combination of circSLC8A1 and circNFIX had better performance to discriminate IHD-related SCDs. The results suggested that circSLC8A1 and circNFIX may be used as auxiliary diagnostic markers for SCD caused by acute IHD in forensic medicine.

Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.

Diagnostic value of high-sensitivity troponin T in postmortem diagnosis of sudden cardiac death

IntroductionIschemic heart disease is the most common cause of sudden cardiac death. By autopsy, there may be no histologic evidence of acute myocardial damage few hours after death. The use of cardiac troponins in the postmortem diagnosis of sudden cardiac death is well known in the forensic setting. However, high-sensitivity cardiac troponin T (Hs-TnT) assay in cadaver fluids was tested in few studies. The aim of this study is to assess the diagnostic value of postmortem dosage of Hs-TnT in the diagnosis of sudden cardiac death. Material and methodsOur study is prospective, dealing with cadavers autopsied at the Department of Forensic Medicine of the University Hospital Habib Bourguiba of Sfax-Tunisia from December 2016 to April 2018. Were excluded from the study resuscitated cases, severely traumatized victims and cadavers that were examined more than 36 h after death. Levels of Hs-TnT were measured in pericardial fluid, cardiac blood and peripheral blood. ResultsA total of 80 cases were identified with an average age of 44.5 ± 19 years. Hs-TnT levels in pericardial fluid and heart blood were correlated significantly between cardiac and non-cardiac groups with a p-value respectively at 0.14 and 0.04. Receiver-operator characteristic curves analysis showed that the pericardial fluid had the best sensibility (75%) and specificity (64%) with a cut-off level at 17.72 ng/ml and an area under the curve at 0.747. We found also a significant correlation between postmortem interval and Hs-TnT levels in pericardial fluid, cardiac and peripheral blood. ConclusionOur data indicate that determination of cardiac troponin T by a highly sensitive assay in pericardial fluid may be a powerful aid in the postmortem diagnosis of sudden cardiac death.

Temporal changes in Egr-1 and c-fos expression in rat models of myocardial ischemia.

The pathological diagnosis of sudden cardiac death caused by myocardial ischemia is a difficult problem. Relevant evidence shows that the expression of Egr-1 and c-fos undergo changes in the early stage of myocardial ischemia, but the detailed temporal variation of them is not clear. Therefore, the aim of this study was to observe the temporal changes in mRNA and protein expression of Egr-1 and c-fos in ischemic myocardium in rats. Sixty-six Sprague-Dawley rats were divided into the control group, the early myocardial ischemia (EMI) group, the sham operated group and the allergy group. The EMI rats were further divided into eight subgroups according to the different time points (30 min and 1, 2, 4, 8, 12, 24, and 48 h) after modeling. The mRNA and protein of Egr-1 and c-fos of each group were detected by real-time quantitative polymerase chain reaction and immunohistochemistry, respectively. In the EMI group, Egr-1 mRNA in ischemic myocardium rose 30 min after ischemia and peaked at 2 h; the plateau was maintained up to 8 h after ischemia, and then returned to the baseline level at 12 h. The c-fos mRNA in ischemic myocardium demonstrated a consistent changing curve with that of Egr-1. The mRNA of Egr-1 and c-fos showed no significant changes in the control group, the sham operated group and the allergy group. Immunohistochemistry showed that Egr-1 protein in the myocardial ischemic area was slightly positive 30 min after ischemia, and then strongly positive at 4 and 8 h, decreased at 12 h, and was negative at 24 h. The changing trends of c-fos protein were almost the same as that of Egr-1. Immunohistochemistry of Egr-1 and c-fos protein were all negative in the control group, the sham operated group and the allergy group. The mRNA and protein expression of Egr-1 and c-fos presented rapid and temporal changes after myocardial ischemia, and this may be helpful in distinguishing sudden death induced by myocardial ischemia from that of allergy.