Cases Of Sudden Cardiac Death Research Articles

Family History and Warning Symptoms Precede Sudden Cardiac Death in Arrhythmogenic Right Ventricular Cardiomyopathy (from a Nationwide Study in Sweden)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease explaining about 4% of sudden cardiac death (SCD) cases in the young in Sweden. This study aimed to describe the circumstances preceding SCD in all victims <35 years of age who received an autopsy-confirmed diagnosis of ARVC from January 1, 2000, to December 31, 2010, in Sweden (n=22). Data on demographics, medical and family history, circumstances of death, and anatomopathological findings were collected from several compulsory national health registries, clinical records, family interviews, and autopsy reports. Registry-based data were compared with age-matched, gender-matched, and geographically-matched population controls. During the 6 months preceding SCD, 15 cases (68%) had experienced symptoms of cardiac origin, mainly syncope or presyncope (54%) and chest discomfort (27%). A total of 8 cases (36%) had sought medical care because of cardiac symptoms. The occurrence of hospital visits was significantly increased in cases compared with controls (odds ratio 4.62 [1.35 to 15.8]). A total of 10 cases (45%) had a family history of SCD. The most common activity at the time of death was exercise (41%). A complete cardiac investigation was seldom performed; only 1 case was diagnosed with ARVC before death. In conclusion, in this nationwide study, we observed a high prevalence of symptoms of cardiac origin, healthcare use, and family history of SCD preceding SCD in the young caused by ARVC. Increased awareness of these warning signals in younger patients is critical to improving risk stratification and early disease detection.

Sudden Cardiac Death in Schizophrenia During Hospitalization: An Autopsy-Based Study.

Schizophrenia is a severe mental disorder that is often comorbid with heart dysfunction and even sudden cardiac death (SCD). Clinical studies of SCD in schizophrenia have been largely reported, while there are limited autopsy studies that directly showed whole-scale information of such events. In this study, we present nine autopsy-based SCD cases in schizophrenia patients who died suddenly during hospitalization. Their medical records before and during hospitalization, and postmortem autopsy findings were summarized. These decedents had an average duration of schizophrenia for 6.83 ± 3.75 years with a male/female ratio of 4:5. They were all on intermittent antipsychotics medication before hospitalization and died within 15 days after hospitalization. Seven of the nine cases (77.8%) died of organic heart diseases such as severe coronary artery atherosclerosis (n = 4), myocarditis (n = 1), cardiomyopathy (n = 1), and pulmonary thromboembolism (n = 1). Two cases remained unexplained after systemic autopsy and toxicological examinations. Postmortem autopsy identified hepatic steatosis (n = 6) and respiratory inflammation (n = 3) as the most common associate extra-cardiac lesions. Our data provided autopsy-based data of SCD cases in schizophrenia and highlighted an intensive care of such patients during hospitalization.

Molecular autopsy and clinical family screening in a case of sudden cardiac death reveals ACTN2 mutation related to hypertrophic/dilated cardiomyopathy and a novel LZTR1 variant associated with Noonan syndrome

BackgroundGenetic cardiac diseases are the main trigger of sudden cardiac death (SCD) in young adults. Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiomyopathy and accounts for 0.5 to 1% of SCD cases per year.MethodsHerein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM.ResultsFor the deceased young adult, postmortem whole‐exome sequencing (WES) revealed a missense variant in the ACTN2 gene: c.355G > A; p.(Ala119Thr) confirming the mixed hypertrophic/dilated cardiomyopathy phenotype detected in the autopsy. For the pediatric case, WES allowed us the identification of a novel frameshift variant in the LZTR1 gene: c.1745delT; p.(Val582Glyfs*10) which confirms a clinical suspicion of HCM related to Noonan syndrome.ConclusionThe present study adds further evidence on the pathogenicity of ACTN2: p. Ala119Thr variant in SCD and expands the mutational spectrum of the LZTR1 gene related to Noonan syndrome.

P167 ECG ABNORMALITIES AND DOUBLE CORONARY FISTULA

Abstract Coronary artery fistula (CAF) is defined as anomalous communication between coronary arteries and cardiac chamber or a major thoracic vessel. CAF are a rare coronary anomaly, mostly congenital, first described by Krause in 1856. In literature the incidence in general population is approximately 0,002%. Detection of CAF during coronary angiography is usually accidental. In 50% of cases CAF originate from right coronary artery, in 30% they originate from LAD, while in the rest of the percentage CAF originate from left circumflex artery. CAF drain into low–pressure chamber (right ventricle or right atrium, superior Vena Cava or pulmonary artery). We can distinguish CAF into little or medium sized, usually with silent clinical course, and large sized CAF, with variable clinical signs, depending on the extent of the shunt and on the hemodynamic overload of the receiving chamber. We describe the case of a 57 y.o woman with hypertension, admitted for femur fracture. ECG showed bifasic T waves in the anterior leads, already described in a previous ECG. Normal systolic function and no valvular defect were found on the echocardiogram. Patient was asymptomatic. Coronary angiography documented normal coronary arteries, with a double coronary fistula: the first from a septal branch of posterior descending and the second one from distal branches of the first diagonal. Even if CAF have often a favorable clinical course with no relevant consequences for the patient, it’s crucial to obtain more information about their functional implication and their anatomic connections. Indeed, rare cases of sudden cardiac death have been described in patients with CAF involved in myocardial ischemia based on the theft syndrome mechanism. Echocardiographic evaluation of the patient to detect associated congenital abnormalities, pressure overload of the receiving chambers and the extent of the shunt on the coronary angiography are crucial for the proper management of CAF. In the case described above we decided to optimize therapy adding beta–blocker (to reduce the overload caused by the two coronary fistula).

Incidence of Sudden Cardiac Death in the European Union

BackgroundAlthough sudden cardiac death (SCD) is recognized as a high-priority public health topic, reliable estimates of the incidence of SCD or, more broadly, out-of-hospital cardiac arrest (OHCA), in the population are scarce, especially in the European Union. ObjectivesThe study objective was to determine the incidence of SCD and OHCA in the European Union. MethodsThe study examined 4 large (ie, >2 million inhabitants) European population-based prospective registries collecting emergency medical services (EMS)–attended (ie, with attempted resuscitation) OHCA and SCD (OHCA without obvious extracardiac causes) for >5 consecutive years from January 2012 to December 2017 in the Paris region (France), the North Holland region (the Netherlands), the Stockholm region (Sweden), and in all of Denmark. ResultsThe average annual incidence of SCD in the 4 registries ranged from 36.8 per 100,000 (95% CI: 23.5-50.1 per 100,000) to 39.7 per 100,000 (95% CI: 32.6-46.8 per 100,000). When extrapolating to each European country and accounting for age and sex, this yields to 249,538 SCD cases per year (95% CI: 155,377-343,719 SCD cases per year). The average annual incidence of OHCA in the 4 registries ranged from 47.8 per 100,000 (95% CI: 21.2-74.4 per 100,000) to 57.9 per 100,000 (95% CI: 19.6-96.3 per 100,000), corresponding to 343,496 OHCA cases per year (95% CI: 216,472-464,922 OHCA cases per year) in the European Union. Incidence rates of SCD and OHCA increased with age and were systematically higher in men compared with women. ConclusionsBy combining data from 4 large, population-based registries with at least 5 years of data collection, this study provided an estimate of the incidence of SCD and OHCA in the European Union.

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.

Cardiac arrest with successful cardiopulmonary resuscitation and survival induce histologic changes that correlate with survival time and lead to misdiagnosis in sudden arrhythmic death syndrome

BackgroundSudden arrhythmic death syndrome (SADS), defined as sudden cardiac death (SCD) with a morphologically normal heart, is an important cause of sudden death. Hypoperfusion due to cardiac arrest followed by successful cardiopulmonary resuscitation (CPR) may induce histologic changes that mimic pathologic conditions. Detailed characterisation of such features and whether they could confound SADS diagnosis are not described. MethodsRetrospective observational study analysing all consecutive cases of sudden death prospectively referred to a UK national cardiac pathology centre between 2017 and 2021. Cases showing hypoperfusion features were identified after review of clinical information and examination by expert cardiac pathologists. ResultsOut of 2,568 SCD cases, 126 (4.9%) were identified with hypoperfusion changes. Macroscopically, the commonest finding was left ventricular focal or diffuse subendocardial haemorrhage (13.5%). Microscopically, haemorrhage and contraction band necrosis (n = 50, 37.7%), subendocardial acute infarction (n = 44, 34.1%), interstitial mixed inflammatory cell infiltrates (n = 31, 24.9%), healing granulation tissue (n = 9, 7.1%) and subendocardial fibrosis (n = 1, 0.7%) were observed. These changes correlated to duration of survival following resuscitation. In a subcohort of 41 cases, autopsy pathologists misinterpreted such changes as ischaemic myocardial infarction (n = 7; 17%), myocarditis (n = 5; 12.1%), or other pathologies (n = 2; 4.8%) in 14 SADS cases. ConclusionWe provide a comprehensive characterisation of hypoperfusion-related changes in the heart following successful CPR with survival, which are time related. These features can lead to diagnostic confusion among pathologists but knowledge of history of resuscitation with survival should help with general and expert pathology assessment and improve SADS diagnostic yield, prompting genetic screening of decedents’ relatives.

Next-Generation Sequencing in Genetic Testing of Kazakhstani Sudden Cardiac Death Cases

<h3>Purpose</h3> The use of next-generation sequencing (NGS) enables a rapid analysis of many genes associated with sudden cardiac death (SCD). It is particularly useful in cases where traditional autopsy is negative or only shows non-diagnostic features, i.e., in sudden unexplained deaths (SUDs), which are often due to an underlying inherited arrhythmogenic cardiac disease. SCD most commonly occurs in patients with coronary heart disease, whereas inherited cardiomyopathies and primary electrical disorders prevail in younger SCD victims (up to 30% of all SCD in the young). The aim of the study was to elucidate the mutational spectrum in Kazakhstani SCD victims revealed by NGS of 96 genes associated with cardiac diseases and compare the diagnostic yield of postmortem genetic testing in (1) cases with structural findings of uncertain significance at autopsy to (2) cases with autopsy findings diagnostic of cardiomyopathy. <h3>Methods</h3> We screened 37 suspected SCD cases (<45 years) using the customized HaloPlex Target Enrichment System (Agilent) and NGS for 96 genes associated with inherited cardiac syndromes and cardiomyopathies. 27 cases had non-diagnostic structural cardiac abnormalities and 10 cases, diagnosed with a cardiomyopathy post-mortem. ACMG/AMP guidelines were applied for variant interpretation of clinical significance. <h3>Results</h3> 31 rare variants were identified in 17 (63%) of the deceased individuals with non-diagnostic structural cardiac abnormalities. Among them pathogenic variants in KCNQ1, KCNJ2, SCN5A, RYR2 genes were identified. The corresponding frequency in deceased individuals with cardiomyopathies was 35%. The most abundant mutations observed in MYBPC3, LAMA2, MYH6 and GAA. <h3>Conclusion</h3> Genetic screening revealed variants with likely functional effects at high rates, in 63% and 35% of the SCD cases with non-diagnostic and diagnostic cardiac abnormalities, respectively. Targeted NGS screening can support the forensic investigation and help the cardiologist's decision to offer counselling and clinical evaluation to relatives of young SCD victims. NGS has nonetheless brought new challenges to molecular autopsy, especially regarding the clinical interpretation of the large number of variants of unknown significance detected in each individual. Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan (AP09563474).

Burden of sudden cardiac death in persons aged 1-40 years in the Czech Republic.

The aim of the study was to ascertain the incidence, circumstances and causes of sudden cardiac death in persons aged 1-40 years in the Czech Republic. De-identified autopsy reports of all individuals who died suddenly between the ages of 1-40 years during the period 2014-2019 inclusive in a selected area of the Czech Republic were analysed retrospectively. Persons with substantial cardiovascular pathology defined by histopathological criteria and those with a negative autopsy were included in the study. The latter were designated as sudden arrhythmic death syndrome. In total, 245 sudden cardiac death cases were identified resulting in an incidence rate of 2.4/100,000 person-years. Among the deceased, we found an enormous gender gap with men representing 81% of cases. More than 80% of deaths occurred during everyday activities or sleep, whereas only 7% were sports-related. The most common cause of death was coronary artery disease detected in 38%, which was followed by cardiomyopathies in 15%, sudden arrhythmic death syndrome in 12%, left ventricular hypertrophy in 10%, and congenital heart defects in 7%. Coronary artery disease is the predominant cause of sudden cardiac death in the young population of the Czech Republic. Hence, effective preventive measures targeted at the reduction of risk factors associated with early coronary artery disease should be reinforced. The second most prevalent cause in our population are potentially heritable heart conditions such as cardiomyopathies and sudden arrhythmic death syndrome. This fact has already prompted the introduction of molecular autopsy and cardiogenetic care for relatives in the Czech Republic.

Combined metabolomics and machine learning algorithms to explore metabolic biomarkers for diagnosis of acute myocardial ischemia.

Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model's value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis.

Clinical characteristics of patients with various genetic types of long QT syndrome

The aim of the study is to evaluate clinical characteristics, including adverse events and outcomes, in patients with various genetic types of long QT syndrome (LQTS).Material and methods. We examined 24 patients with a clinical diagnosis of LQTS, observed in the for 5 years. The clinical and instrumental study included registration of electrocardiography (ECG), Holter monitoring, collection of a genealogical history with an ECG assessment of all family members and identification of cases of sudden cardiac death (SCD) in the family or the presence of a family form of the disease, echocardiography and cardiac magnetic resonance imaging to exclude structural changes in the myocardium. The search for mutations in the coding sequences of genes associated with the development of channelopathy and other hereditary heart rhythm disorders was carried out by next generation sequencing (NGS).Results. Mutations in 4 genes associated with LQTS (KCNQ1, KCNH2, CACNA1C, ANK2) were detected in 18 out of 24 (75.0%) patients. Mutations in the KCNQ1, KCNH2 and CACNA1C genes were detected in 14 (58.0%) patients. In 4 out of 24 (17%) patients, two or more variants of clinical significance (VUS) were detected in the genes associated with LQTS and hereditary arrhythmias, 6 patients had no genetic changes. The most severe form of the disease with pronounced clinical manifestations and episodes of clinical death with subsequent resuscitation measures, as well as a significant increase in the QTc interval exceeding 500 ms, was observed in patients with LQT2 and multiple mutations. Implantation of a cardioverter-defibrillator (CD) was required in 14 (58.3%) patients, including 11 (78.56%) - for secondary prevention of SCD and 3 (21.4%) - for primary prevention.Conclusion. A comparative analysis between different genetic types of LQTS (LQT1; LQT2; patients with multiple VUS) showed that in patients with LQT1 syndrome, despite the early manifestation of the disease and the presence of syncopal conditions, life-threatening arrhythmias, SCD and the frequency of CD implantation were significantly less often recorded than in other LQTS. The most severe form of the disease with pronounced clinical manifestations, episodes of clinical death with subsequent resuscitation and CD implantation was observed both in the group of probands with LQT2 and in patients with several nucleotide variants (VUS), one of which was in the CACNA1C or ANK2 genes.

Sudden cardiac death in young people and in adults: primary and contributing causes. The experience of the multidisciplinary network in Emilia-Romagna

The multidisciplinary network of Emilia-Romagna for the study of juvenile sudden cardiac death (SCD) was started in Bologna in June 2018 in order to: (1) define the spectrum of etiologies and mechanisms of SCD in young people; (ii) standardize diagnostic terminology and categories; (iii) identify potentially hereditary genetic heart diseases and define the contribution of post-mortem genetic analysis (so-called molecular autopsy) to the overall diagnostic process; (iv) identify preclinical forms of the pathologies in the first-degree relatives of the deceased subject using both phenotypic and genotypic evaluation and, where possible, undertake therapeutic/prophylactic measures (primary prevention). In the first 2 years of activity (01/06/2018-27/08/2020) 50 cases of SCD came to the attention of the Cardiovascular Pathology Unit of the S. Orsola-Malpighi Polyclinic in Bologna, from Centres of Forensic Medicine and Pathological Anatomy in most of the region. Sixty-two percent of cases were sent by forensic pathologists, 36% by clinical pathologists and 2% by the family of the deceased. Medico-legal cases were prompted by autopsies requested by the Judicial Authority in 70% of cases; 55.5% of patients referred by pathologists came from the Cardiovascular Tissue Bank, as part of the regional program for the quality and safety control of organs and tissues from multiorgan-multitissue donors. The average age of the subjects was 35 ± 13.6 years (70% male, range: 1-55 years; median: 38 years). The spectrum of the final diagnoses includes: structurally normal hearts 14%, cardiomyopathies 40%, coronary heart disease 23%, Brugada syndrome 6%, aortic dissection 4%, substance abuse 6%, valvular heart disease 2%, mixed causes 2%. The network is necessarily centered on post-mortem pathological activities, but it does not end with these. If in 60% of cases the pathological autopsy examination was decisive in identifying the cause of death, in the other cases a detailed final diagnosis was reached only with more complex pathways involving molecular genetics, clinical genetics, and toxicology.

Kidney function and the risk of sudden cardiac death in the general population.

ABSTRACTBackgroundChronic kidney disease increases sudden cardiac death (SCD) risk, but the association between kidney function and SCD in a general population is largely unknown. Therefore, we investigated the association between kidney function and SCD in a general middle-aged and elderly population.MethodsWe included individuals aged ≥45 years from a prospective population-based cohort study. The association between kidney function assessments [estimated glomerular filtration rate based on serum creatinine (eGFRcreat), cystatin C (eGFRcys) or both (eGFRcreat-cys)] and SCD was investigated using Cox proportional-hazards and joint models. Absolute 10-year risks were computed using competing risk analyses. Mediation analyses were performed using a four-way decomposition method.ResultsWe included 9687 participants (median follow-up 8.9 years; mean age 65.3 years; 56.7% women; 243 SCD cases). Lower eGFRcys and eGFRcreat-cys were associated with increased SCD risk [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12–1.34 and HR 1.17, 95% CI 1.06–1.29, per 10 mL/min/1.73 m2 eGFR decrease]. A significant trend (P = 0.001) across eGFRcys categories was found, with an HR of 2.11 (95% CI 1.19–3.74) for eGFRcys <60 compared with eGFRcys >90 mL/min/1.73 m2. Comparing eGFRcys of 90 to 60 mL/min/1.73 m2, absolute 10-year risk increased from 1.0% to 2.5%. Identified subgroups at increased risk included older participants and participants with atrial fibrillation. The associations were not mediated by coronary heart disease, hypertension or diabetes.ConclusionsReduced kidney function is associated with increased SCD risk in the general population, especially with eGFRcys. eGFRcys could be added to prediction models and screening programmes for SCD prevention.

A 45-year-old man with sudden cardiac death, cutaneous abnormalities and a rare desmoplakin mutation: a case report and literature review

BackgroundArrhythmogenic cardiomyopathy (AC) is a rare, heritable myocardial disorder that is a leading cause of ventricular arrhythmia and sudden cardiac death (SCD) in young people. Desmoplakin (DSP) mutations account for 3–20% of AC cases. However, the number of patients with DSP mutations is extremely small in all published reports and genotype–phenotype correlations are scant and mostly non-gene-specific.Case presentationA 45-year-old man was admitted after an out-of-hospital cardiac arrest, with documented ventricular fibrillation. He had no previous history of heart disease or family history of SCD or cardiomyopathy. The cardiac magnetic resonance showed a mildly dilated left ventricle with an ejection fraction of 30% and a non-dilated right ventricle with mildly depressed systolic function, and extensive subepicardial late gadolinium enhancement. Genetic screening identified a heterozygote nonsense mutation in DSP (NM_004415.2: c.478 C > T; p.Arg160Ter). Cascade genetic screening of the relatives revealed a high prevalence of the genotype and cutaneous phenotype, but a very low penetrance of the cardiac phenotype.ConclusionsWe report a case of SCD and an autosomal dominant mutation in DSP that causes arrhythmogenic dilated cardiomyopathy/AC. Like the recessive mutation in DSP known to cause Carvajal syndrome, Arg160Ter may be associated with cutaneous abnormalities.

Cardiac involvement in athletes infected by SARS COV-2 disease

ObjectivesThe aim of the present study was to conduct a review of the current literature evaluating the available evidence to date in terms of epidemiology, pathophysiology and clinical presentation of COVID-19 in relation to cardiovascular involvement, with a special focus on the myocarditis model, in the population of athletes (professional and recreational) who are preparing to return to competitions, with the ultimate aim of guaranteeing maximum safety for resuming sports activities.NewsThe COVID-19 pandemic has resulted in the inevitable cancellation of most sports activities, practiced at both a professional and amateur level, in order to minimize the risk of spreading the infection. Since the number of athletes who tested positive was rather high, the potential cardiac involvement in this peculiar population of subjects contracting the disease in a mild (asymptomatic, slightly symptomatic) or moderate form, has recently raised concerns following the observation of cases of recorded myocardial damage, myocarditis, arrhythmias and a first reported case of Sudden Cardiac Death (SCD) in a 27-year-old professional basketball player. Several studies even seem to confirm the possibility of permanent impairment of the cardiorespiratory system following the infection. Medical history, biomarkers, electrocardiographical and cardiac imaging features appear to be crucial in distinguishing cardiovascular alterations related to COVID-19 infection from typical adaptations to exercise related to athletes' heart.Prospects and ProjectsClarifications and prospective data based on long-term follow-ups on larger populations of athletes are still needed to exclude the development of myocardial damage capable of negatively affecting prognosis and increasing cardiovascular risk in athletes recovered from COVID-19 in asymptomatic (simple positivity to SARS-COV-2) or in a mild form.ConclusionFrom a clinical point of view extreme caution is necessary when planning the return to sport (Return To Play–RTP) of athletes recovered from a mild or asymptomatic form of COVID-19: a careful preliminary medical-sports evaluation should be carried out in order to assess the potential development of myocardial damage that would increase their cardiovascular risk.

Sudden Cardiac Death and Ex-Situ Post-Mortem Cardiac Magnetic Resonance Imaging: A Morphological Study Based on Diagnostic Correlation Methodology.

During the last years, post-mortem imaging has gradually been assumed within research in the field of forensic pathology. This role appears to be clearly and simply applied in the trauma field with the use of conventional radiography or Post Mortem Computed Tomography (PMCT). Recently, particular attention was paid to cardiovascular imaging using Post Mortem Magnetic Resonance Imaging (PMMRI). The present experimental study aims to: (i) confirm the efficacy of a Post Mortem Cardiac Resonance Imaging (PMCRI) study protocol for the study of human hearts collected during the autopsy; (ii) apply the defined protocol on subjects who died of “SCD (sudden cardiac death)”, to identify alterations that could guide subsequent sampling. Two hearts of healthy subjects (A: male 22 years; B: female 26 years), who died from causes other than SCD were collected and compared to hearts that belonged to SCD individuals (C: male, 47 years old; D: female, 44 years old; E: male; 72 years old). The exams were performed on a 1.5 T scanner (Philips Intera Achieva, Best, the Netherlands) on hearts collected during autopsy and after a 30-day formalin fixation. Two readers analyzed the obtained images blindly and after randomization. From the comparison between the data from imaging and the macroscopic and histological investigations carried out, the present study proved the effectiveness of a PMMRI protocol to study ex-situ hearts. Moreover, it suggested the following semeiology in post-mortem SCD cases: the hyperintense area with indistinct margins in the Short Tau Inversion Recovery (STIR) sequence was linked to edema or area of pathological fibers, whereas the hypointense area in the T2-FFE sequences was linked to fibrosis. PMMRI can provide a valuable benefit to post-mortem investigations, helping to distinctly improve the success rate of histological sampling and investigations, which remains the gold standard in the diagnosis of sudden death.

Post-mortem genetic investigation in sudden cardiac death victims: complete exon sequencing of forty genes using next-generation sequencing.

Sudden cardiac death (SCD) in young people is predominantly caused by genetic causes as cardiomyopathies. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disease and is responsible for the major proportion of SCD in the young. The purpose of this study was to identify the genetic variants present in young SCD victims with HCM characteristics. From the Portuguese records of autopsies performed at the National Institute of Legal Medicine and Forensic Sciences, North Delegation, 16 young (16-50 years) SCD victims whose death was suspected to be a manifestation of HCM were selected. Using next-generation sequencing, the coding regions of 40 genes associated with HCM, candidates, or strongly related to HCM-phenocopies were investigated. The victims included in this study were all males, with a mean age of 33.4 ± 11.7 years, left ventricle mean thickness of 21.5 ± 6.28 mm, and the majority of deaths occurred during sleep (36%). A pathogenic or likely pathogenic variant was identified in six out of 16 (37.5%) victims, in the most common HCM genes (MYBPC3 and MYH7). Our results indicate that molecular autopsy of SCD victims contributes to a more precise identification of a cause of death, and this can be used in the prevention of SCD cases through family screening of first relatives who may carry the same pathogenic variant.

CLINICAL CASES OF LIFE-THREATENING ARRHYTHMIAS: LONG AND SHORT QT SYNDROMES.

The aim: To present clinical cases of sudden cardiac death in patients with prolonged and shortened QT interval. Materials and methods: The study includes description of two different clinical cases with prolonged and shortened QT interval after sudden cardiac death. Verification of the diagnosis was performed using the criteria recommended by the European Society of Cardiology (ESC) and European Heart Rhythm Association (EHRA). Clinical case: Two clinical cases of syncopе with life-threatening arrhythmias, confirmed by electrocardiographic and clinical diagnostic criteria, indicating a change in the dispersion of the QT interval, are presented. The first case represents a patient with intermittent syncope. The patient had previously had attacks of sudden palpitations with fainting. The patient came after another episode of syncope. Further follow-up revealed clinical and electrocardiographic signs of ventricular tachycardia paroxysm. Than the prolongation of the QT interval is set. In this clinical case, verification of QT prolongation syndrome was established in the elderly. Another clinical case is associated with QT syndrome, which remains difficult to diagnose. Such cases have been described relatively recently. The clinical picture of the syndrome of short QT interval in the presented clinical case was characterized by the appearance of syncopal states. The patient showed changes in the adjusted QT interval <320 ms. The causes of syncope in a patient with a short QT interval were paroxysms of atrial fibrillation (AF) or ventricular arrhythmias. At the same time the anatomical structure of a myocardium remains normal and unchanged. The hereditary nature of the disease in the patient has been proven. Conclusions: Timely diagnosis of prolongation (LQTS) or shortening (SQTS) of the QT interval after ECG and Holter monitoring allows you to identify a group of patients with an increased risk of developing ventricular arrhythmias, syncope and sudden cardiac death. Implantation of a cardioverter-defibrillator is an effective and safe method of preventing sudden cardiac death in patients with long and short QT syndromes.

Muerte súbita cardíaca asociada a enfermedades mitocondriales

Mitochondrial diseases (MD) constitute a heterogeneous group of genetic disorders that result from the dysfunction of the final common pathway of energy metabolism. The responsible mutation can be found in genes encoded in nuclear DNA or in mitochondrial DNA, causing differences in the clinical presentation and inheritance pattern. Most of these diseases have a multisystemic impact, mainly affecting tissues with a high oxidative energy requirement (heart muscle, skeletal muscle, and brain, for instance). Although death in DM is usually related to the clinical severity of the disease, sudden cardiac death (SCD) is possible also in patients with mild manifestations or even in asymptomatic individuals. This review aims to identify reported cases of SCD in MD (either diagnosed in life or at post mortem studies) and comprehensively analyze the macroscopic and microscopic pathological features described. There are only few documented cases (27), but the lack of notable cardiac phenotypic features in some cases, their low specificity, the scarce clinical personal and family information when the autopsy is performed and the little awareness of these diseases among doctors raise the suspicion that MD are infradiagnosed and many cases remain overlooked. Definitely, a correct diagnosis requires a high level of suspicion and a multidisciplinary approach with pathological and cardiological specialized tests both in the deceased proband and in the at-risk relatives to confirm or discard DM in order to tailor the follow-up, treatment and genetic counselling.

EP News: Clinical

Miles et al (J Am Coll Cardiol 2021;78:1511, PMID 34620408) evaluated the presence and distribution of ventricular myocardial fibrosis in a cohort of decedents experiencing sudden cardiac death caused by Brugada syndrome (BrS). The investigators evaluated 28 whole hearts from consecutive sudden cardiac death cases attributed to BrS and 29 hearts from a comparator group comprising noncardiac deaths (control subjects). Of 28 BrS decedents (75% men; median age of death 25 years), death occurred in sleep or at rest in 24 of 28 (86%).