Cardiac Death In Young People Research Articles

Ion Channel Diseases as a Cause of Sudden Cardiac Death in Young People: Aspects of Their Diagnosis, Treatment, and Pathogenesis.

Sudden cardiac death (SCD) is the death of an apparently healthy person within one hour of the onset of symptoms, or within 24 hours of last being seen alive and well-with no evidence of an extra-cardiac cause. In autopsied cases, SCD is defined as the natural unexpected death of unknown or cardiac cause. The reported incidence figures for SCD vary widely. This review is based on clinical registry studies, meta-analyses, randomized controlled trials, systematic reviews, and current guidelines that were retrieved by a selective search in PubMed employing the key words "channelopathy," "Brugada syndrome," "long QT syndrome," "catecholaminergic polymorphic ventricular tachycardia," "short QT syndrome," and "early repolarization." Approximately 18% of cases of SCD in young persons are associated with cardiac channelopathy. The most common ion channel diseases affecting the heart are long QT syndrome and Brugada syndrome. The diagnosis is established by specific ECG abnormalities in the absence of structural heart disease. These can be unmasked by various maneuvers, e.g., the administration of sodium-channel blockers in Brugada syndrome. Imaging studies such as echocardiography, coronary angiography, and computed tomography are used to rule out structural heart disease and coronary artery disease. Long-term ECG and risk stratification scores can be useful aids to therapeutic decision-making. For some of these diseases, it is advisable for the patient to avoid particular triggers of ECG changes and cardiac arrhythmias in his or her everyday life. The near relatives of persons with congenital ion channel diseases should undergo clinical and genetic screening to protect them from SCD. The affected families should be investigated systematically so that appropriate diagnoses and treatments can be established.

Sudden cardiac death due to adrenal insufficiency masquerading as Brugada syndrome. Case report

Sudden cardiac death in young people in 20% of cases is caused by cardiomyopathies and channelopathies. One of the forms of channelopathies is Brugada syndrome, a hereditary disease characterized by ST segment elevation in the right precordial leads (V1-V3) and an increased risk of sudden cardiac death in the absence of structural heart disease. Brugada phenocopies are also known – clinical situations that are manifested by electrocardiogram (ECG) patterns identical to true Brugada syndrome. They are caused by different clinical circumstances and form a group of heterogeneous conditions that are often difficult to distinguish from true congenital Brugada syndrome due to identical ECG patterns. The formation of Brugada phenocopy due to hyperkalemia is presented in the literature in various conditions: with renal failure, after extensive trauma, application of medications. The article presents a case report demonstrating a rare cause of sudden cardiac arrest in a young patient without a history of cardiovascular pathology: the occurrence of the Brugada pattern on the ECG due to severe hyperkalemia in adrenal insufficiency. The stages of the differential diagnostic search are described, which made it possible to verify the final diagnosis and prescribe effective hormone replacement therapy. Performing a provocative test with novocanamide allowed us to confirm that the patient had a phenocopy, and not Brugada syndrome. Differential diagnosis of phenocopies of Brugada syndrome – a series of often life-threatening cardiac and non-cardiac diseases and conditions, manifested by similar ECG changes in the form of a peculiar ST segment elevation in leads V1-V3, is often a difficult task. This case represents a phenocopy of Brugada in the setting of severe hyperkalemia with development of cardiac arrest due to adrenal insufficiency, which resolved with correction of electrolyte abnormalities and treatment of the underlying disease. Typical ECGs are presented: a graph of the Brugada phenomenon, hyperkalemia, a sinusoidal curve during cardiac arrest, recorded over time in a patient, and the pathogenetic mechanisms causing the formation of the Brugada pattern in adrenal insufficiency are explained.

Catecholaminergic polymorphic ventricular tachycardia (CPVT): an insidious disease that can often lead to sudden cardiac death in young people

The first symptoms of catecholaminergic polymorphic ventricular tachycardia (CPVT) usually occur in childhood and adolescence. 60% of patients experience syncope before the age of 40. Sudden cardiac death (SCD) is the first symptom of the disease in 30-50% of patients with CPVT. Early diagnosis is therefore crucial for the patient's prognosis. The diagnosis of CPVT is confirmed by a normal resting ECG, exclusion of structural heart disease, detection of bidirectional or polymorphic ventricular tachycardia (VT) in the stress ECG and/or detection of a pathogenic mutant in a gene associated with CPVT. Up to 60% of CPVT patients carry changes in the RYR2 gene. This gene encodes the cardiac ryanodine receptor, the most important Ca2+-releasing channel of the sarcoplasmic reticulum, which plays a central role in the contraction and relaxation of the heart muscle. If the function of the ryanodine receptor is impaired, too much calcium enters the cells, which triggers life-threatening arrhythmias. The overactive ryanodine receptor is therefore the main target for gene therapy methods. Even though the development of gene therapy is progressing, there is still no causal therapy available and it is all the more important to make a diagnosis as early as possible, which enables appropriate behavior and adequate symptomatic therapy. The decisive factor here is the evaluation of the genetic analysis in the context of the clinical findings. Based on this, recommendations can be made for preventive measures and the avoidance of specific triggers that could lead to life-threatening arrhythmias.

Sudden Cardiac Death in the Young: State-of-the-Art Review in Molecular Autopsy.

Sudden cardiac death (SCD) is defined as unexpected death due to a cardiac cause that occurs rapidly. Despite the identification of prevention strategies, SCD remains a serious public health problem worldwide, accounting for 15-20% of all deaths, and is therefore a challenge for modern medicine, especially when it affects young people. Sudden cardiac death in young people affects the population aged ≤ 35 years, including athletes and non-athletes, and it is due to various hereditary and non-hereditary causes. After an autopsy, if the cause remains unknown, it is called sudden unexplained death, often attributable to genetic causes. In these cases, molecular autopsy-post-mortem genetic testing-is essential to facilitate diagnostic and therapeutic pathways and/or the monitoring of family members of the cases. This review aims to elaborate on cardiac disorders marked by genetic mutations, necessitating the post-mortem genetic investigation of the deceased for an accurate diagnosis in order to facilitate informed genetic counseling and to implement preventive strategies for family members of the cases.

Preventing Atrial Fibrillation in Hypertrophic Cardiomyopathy using Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs)

Hypertrophic cardiomyopathy (HCM), a genetic cardiovascular disease, is the leading cause of cardiac death in young people, often due to atrial fibrillation (AF). AF is generally treated using antiarrhythmics and anticoagulants, which have adverse side effects after long-term use, and are therefore unsuitable for young HCM patients. AF is characterized by a rapid and irregular atrial heartbeat, marked by a short action potential duration and atrial effective refractory period in atrial cardiomyocytes. Prior studies have indicated that the renin-angiotensin system is involved in lowering both, so it has been hypothesized that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which inhibit the renin-angiotensin system, could prevent AF. Therefore, in this study, we propose a research protocol to examine the viability of ACE inhibitors and ARBs as prophylactic measures against the development of AF in HCM patients. To test this, we suggest extracting atrial cardiomyocytes from HCM patients by performing enzyme dissociation on myocardial tissue. The isolated cardiomyocytes will then be treated in vitro with an ACE inhibitor, an ARB, a combination of both, or a control saline solution, and the patch-clamp technique will be used to determine the frequency and duration of their action potentials. We expect action potential duration and atrial effective refractory period to be longer in treated cells, while neither medication will provide a greater advantage, and, as prior research suggests, the combination will not yield significant benefits. The study will continue by testing the effects of ACE inhibitors and ARBs on the function of atrial myocardial organoids created from differentiated stem cells with an HCM mutation. The results of this study could present a new preventative measure against AF for HCM patients which would be safe for long-term use.

Cardiomyopathy

Cardiomyopathy is a heart muscle disorder that cannot be attributed to ischemic heart disease or abnormal loading conditions such as hypertension and valvular heart disease. It can lead to the development of arrhythmia and heart failure, and is also the leading cause of sudden cardiac death in young people. Early detection is vital for delaying or preventing complications. This review discusses the four major subtypes, i.e. hypertrophic, dilated, restricted, and arrhythmogenic cardiomyopathy, which are likely to be encountered in primary care.

Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Perspective from Fibroblasts.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and the leading cause of sudden cardiac death in young people. Mutations in genes that encode structural proteins of the cardiac sarcomere are the more frequent genetic cause of HCM. The disease is characterized by cardiomyocyte hypertrophy and myocardial fibrosis, which is defined as the excessive deposition of extracellular matrix proteins, mainly collagen I and III, in the myocardium. The development of fibrotic tissue in the heart adversely affects cardiac function. In this review, we discuss the latest evidence on how cardiac fibrosis is promoted, the role of cardiac fibroblasts, their interaction with cardiomyocytes, and their activation via the TGF-β pathway, the primary intracellular signalling pathway regulating extracellular matrix turnover. Finally, we summarize new findings on profibrotic genes as well as genetic and non-genetic factors involved in the pathophysiology of HCM.

Risk factors of sudden cardiac death in Egyptian patients younger than 40 years

BackgroundSudden cardiac death in young people is a major problem. The causes are well known; however, they may not be discovered before the episode of sudden death. A challenge for the future is identifying patients at risk before an episode of sudden cardiac death. Development of preventive and educational programs is required to identify sudden cardiac death/sudden cardiac arrest (SCD/SCA) risk factors, causes and characteristics. We aimed to study the characteristics of SCD/SCA in a cohort of young Egyptian population. Our retrospective cohort study included 246 patients of SCD/SCA who were collected from 5000 records of arrhythmia patients from January 2010 till January 2020. The records of the specialized arrhythmia clinic were reviewed to collect the families of SCD/SCA. All patients and/or their first-degree relatives were subjected to thorough history taking and clinical evaluation and investigations. Comparisons were done regarding age group and presence of positive family history of SCD.ResultsMales constituted 56.9% of the study population. Mean age was 26.6 ± 12.73 years. Positive family history was present in 202 (82.1%) cases. Sixty-one percent of the cases had history of syncopal attacks. SCD/SCA during non-exertion or sleep occurred in 50.4% of cases. Hypertrophic cardiomyopathy was the most common cause of SCD/SCA (20.3%), followed by dilated cardiomyopathy (19.1%), long QT Syndrome (11.4%), complete heart block (8.5%), and Brugada syndrome (6.8%). In the older age group of 18–40 years, hypertrophic cardiomyopathy was responsible for SCD in 44 patients (25.3%) versus 6 patients (8.3%) in younger age group (p-value: 0.003). DCM was also dominant in older age group (42 patients; 24.1%) versus 5 patients (6.9%) in younger age group. Hypertrophic cardiomyopathy was more prevalent in positive family history group (46 patients; 22.8%) versus 4 patients (9.1%) in negative family history group (p-value: 0.041).ConclusionFamily history of SCD was the most common risk factor of SCD. The most common cause of SCD in young Egyptian patients below 40 years was hypertrophic cardiomyopathy, followed by dilated cardiomyopathy. Both diseases were more common in the age group between 18 and 40 years. Hypertrophic cardiomyopathy was more common in patients with positive family history of SCD/SCA.

PO-05-192 LOCAL HETEROGENEITY OF LATE GADOLINIUM ENHANCEMENT PREDICTS VENTRICULAR ARRHYTHMIA IN HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people. Despite recent advances in risk stratification using cardiac magnetic resonance (CMR) imaging, risk prediction remains suboptimal. Improved risk stratification is therefore warranted. Whether local heterogeneity of Late Gadolinium Enhancement (LGE) signal is associated with ventricular arrhythmia remains unknown. To determine whether local heterogeneity of LGE signal on CMR predicts ventricular arrhythmia and appropriate shocks after implantable cardioverter defibrillator (ICD) implantation in patients with HCM. Local heterogeneity was quantified by LGE-CMR signal dispersion score and compared with cardiovascular outcomes in 179 HCM patients who underwent ICD implantation. The primary outcome was appropriate ICD shocks. During a median follow-up time of 7.3 years the event rate was 0.015 per person year. History of ventricular arrhythmia (HR 9.413, p<0.001) and sudden cardiac death (HR 13.82, p<0.001) were associated with receiving an appropriate ICD shock in both univariable and multivariable analyses. History of syncope, family history of sudden cardiac death, non-sustained ventricular tachycardia, left ventricular wall thickness and presence of LGE were not associated with the primary outcome. When compared to patients without ICD shock, patients who received ICD shocks had higher burden of LGE gray zone (16.8±7.5% vs 25.8±3.5% p<0.001) and scar (10.5±6.7% vs 18.7±4.3% p<0.001) on CMR. Importantly, patients with ICD shocks had a higher dispersion score (1.20 vs 0.97, respectively), signifying higher degree of LGE signal heterogeneity (p=0.047). Dispersion score, a marker of local LGE signal heterogeneity of scar and gray zone was associated with a higher burden of ICD shocks in HCM patients who received ICDs. Mechanistically, local LGE signal heterogeneity could represent complex scar. These results may contribute to improved risk stratification for ventricular arrhythmia in HCM patients.

The role of SMAD signaling in hypertrophic obstructive cardiomyopathy: an immunohistopathological study in pediatric and adult patients

Hypertrophic obstructive cardiomyopathy (HOCM) can bring a high risk of sudden cardiac death in young people. It is particularly urgent to understand the development and mechanism of HOCM to prevent unsafe incidents. Here, the comparison between pediatric and adult patients with HOCM has been performed to uncover the signaling mechanism regulating pathological process through histopathological analysis and immunohistochemical analysis. We found SMAD proteins played an important role during myocardial fibrosis for HOCM patients. In patients with HOCM, Masson and HE staining showed that myocardial cells were diffusely hypertrophied with obvious disorganized myocardial fiber alignment, and myocardial tissue was more damaged and collagen fibers increased significantly, which come early in childhood. Increased expressions of SMAD2 and SMAD3 contributed to myocardial fibrosis in patients with HOCM, which happened early in childhood and continued through adulthood. In addition, decreased expression of SMAD7 was closely related to collagen deposition, which negatively expedited fibrotic responses in patients with HOCM. Our study indicated that the abnormal regulation of SMAD signaling pathway can lead to severe myocardial fibrosis in childhood and its fibrogenic effects persist into adulthood, which is a crucial factor in causing sudden cardiac death and heart failure in HOCM patients.

Review of Genetic Changes and Factors Causing Cardiac Arrhythmias

Introduction: Cardiovascular diseases are currently the leading cause of death in the world. Arrhythmias are one of the most common cardiovascular diseases. In arrhythmia, the heartbeat becomes slow, fast, or irregular, which affects the efficiency of the heart, and in this case, the heart may not have enough ability to pump blood. Cardiac arrhythmias are the leading causes of sudden cardiac death in young people, affecting even patients with anatomically normal hearts. Arrhythmia syndromes are ion channel diseases that lead to abnormal electrical properties of the heart. This article examined the genetic causes affecting all types of cardiac arrhythmias. A detailed search was performed on Google Scholar and PubMed to identify research articles related to arrhythmia genetics. All duplicate articles based on the title and articles published before the year 2000 were removed during the screening. Finally, after several rounds of content review of the articles, 50 research articles were selected for this study.&#x0D; Conclusion: It has been found that mutations cause arrhythmias in nuclear genes encoding membrane channels in heart muscle cells. However, the causes of some cases of arrhythmia are unclear and the possibility of multifactorial of these cardiac disorders is raised. The importance of this type of review article, while revealing the relationship between gene loci and types of arrhythmogenic syndromes, is to provide a molecular basis that can provide researchers with new diagnostic methods in addition to echocardiogram.

Juvenile sudden cardiac death due to congenital coronary ostial valve-like ridges: A case report and literature review.

Coronary artery anomalies are a heterogeneous group of congenital disorders affecting the coronary pattern with a characteristic (origin, number, number of hosts, course, etc.). They are rarely found in the population. We report the case of a 21-year-old male who died from sudden cardiac death caused by an isolated coronary ostial obstruction, secondary to a rare anomaly, the presence of a valve-like ridge consisting of a small fold in the Valsalva aortic sinus. The study provides a brief literature review on the pathophysiology, diagnosis, and clinical and medico-legal issues in coronary artery anomaly cases that may be helpful in forensic practice when dealing with sudden cardiac death in young people and highlights key points for further research and public health measures.

Rare and Common Genetic Variation Underlying the Risk of Hypertrophic Cardiomyopathy in a National Biobank

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death in young people. Although rare genetic variants are well-established contributors to HCM risk, common genetic variants have recently been implicated in disease pathogenesis. To assess the contributions of rare and common genetic variation to risk of HCM in the general population. This cohort study of the UK Biobank (data from 2006-2010) and the Mass General Brigham Biobank (2010-2019) assessed the relative and joint contributions of rare genetic variants and a common variant (polygenic) score to risk of HCM. Both rare and common variant predictors were then evaluated in the context of relevant clinical risk factors. Data analysis was conducted from May 2021 to February 2022. Pathogenic rare variants, common-variant (polygenic) score, and clinical risk factors. Risk of HCM. The primary study population comprised 184 511 individuals from the UK Biobank. Mean (SD) age was 56 (8) years, 83 690 (45%) of participants were men, and 204 (0.1%) participants had HCM. Of 51 genes included in clinical genetic testing panels for HCM, pathogenic or likely pathogenic variants in 14 core genes (designated by the American College of Medical Genetics and Genomics [ACMG]) were associated with 55-fold higher odds (95% CI, 35-83) of HCM, while those in the remaining 37 non-ACMG genes were not significantly associated with HCM (OR, 1.8; 95% CI, 0.6-4.0). ClinVar pathogenic or likely pathogenic mutations in MYBPC3 (OR, 72; 95% CI, 39-124) and MYH7 (OR, 61; 95% CI, 26-121) were strongly associated with HCM, as were loss-of-function variants in ALPK3 (OR, 13; 95% CI, 4.4-28). A polygenic score was strongly associated with HCM (OR per SD increase in score, 1.6; 95% CI, 1.4-1.8), with concordant results in the Mass General Brigham Biobank. Genetic factors enhanced clinical risk prediction for HCM: addition of rare variant carrier status and the polygenic score to clinical risk factors (obesity, hypertension, atrial fibrillation, and coronary artery disease) improved the area under the receiver operator characteristic curve from 0.71 (95% CI, 0.65-0.77) to 0.82 (95% CI, 0.77-0.87). Both rare and common genetic variants contribute substantially to HCM susceptibility in the general population and improve HCM risk prediction beyond that achieved with clinical factors.

Hypertrophic Obstructive Cardiomyopathy: Comparison of Outcomes After Myectomy or Alcohol Ablation.

Introduction and ObjectivesThe risk of ventricular arrhythmia and heart failure in patients with hypertrophic obstructive cardiomyopathy (HOCM) is much higher than that in the general population. More and more pieces of evidence showed that HOCM is the leading cause of sudden cardiac death in young people. We reported our experience in a study, comparing surgical myectomy, alcohol septal ablation (ASA), and medical therapy.MethodsThe original cohort included 965 consecutive patients with HOCM. The patients were divided into three groups according to treatment strategies: myectomy group (n = 502), ASA group (n = 138), and medical treatment group (n = 325). The median follow-up duration was 42.99 ± 18.32 months, and the primary endpoints were all-cause mortality and heart transplantation.ResultsBoth in short- and long-term observations, surgical myectomy reduced the left ventricular outflow tract (LVOT) gradients more effectively (7 days, 16.15 ± 12.07 mmHg vs. 42.33 ± 27.76 mmHg, p < 0.05; 1 year, 14.65 ± 13.18 mmHg vs. 41.17 ± 30.76 mmHg, p < 0.05). Among the three groups, the patients in the medical treatment group were at a higher risk of mortality and cardiac transplantation (vs. the myectomy group, p < 0.001 by log-rank test; vs. the alcohol septal ablation group, p = 0.017 by log-rank test), and the myectomy group shows a lower risk of reaching the primary endpoint than the two other groups. In the multivariate Cox regression analysis, previous atrial fibrillation (AF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and surgical myectomy predicted an HOCM prognosis. However, the impact of surgical myectomy on HOCM prognosis seems to be limited to the <56 years group.ConclusionsThe patients with medical treatments seemed to suffer from the highest risk of achieving an all-cause mortality and the endpoint of heart transplantation. In the long-term survival and clinical outcome, myectomy seemed better than alcohol septal ablation, especially the younger patients. Due to the less-controllable degree, periprocedural complication frequency after alcohol septal ablation was higher, compared with myectomy. Furthermore, gradients after myectomy are lower at late follow-up. To sum up, when selecting treatment strategies, the patients should be individually evaluated by a multidisciplinary team of cardiologists and surgeons.

Exercise Test for Patients with Long QT Syndrome.

Congenital long QT syndrome (LQTS) causes life-threatening cardiac arrhythmias and is the leading cause of sudden cardiac death in young people. Measurements of QT prolongation during exercise or postural change have been recommended to assist in the diagnosis of LQTS, particularly in those with hidden phenotypes. However, most evidence has come from single-center studies without external validation in an independent cohort. Inter-study heterogeneity leads to significant difficulties in interpreting and applying consistent diagnostic criteria for LQTS. A comprehensive systematic review is critically needed to summarize the evidence and validate the diagnostic performance of QT intervals during exercise or postural change across a variety of studies. In this study, we review cross-sectional and cohort studies evaluating the efficacy and feasibility of exercise tests or postural changes in diagnosing LQTS, and propose possible problems resulting from exercise tests.

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.

Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy.

Hereditary hypertrophic cardiomyopathy (HCM), due to mutations in sarcomere proteins, occurs in more than 1/500 individuals and is the leading cause of sudden cardiac death in young people. The clinical course exhibits appreciable variability. However, typically, heart morphology and function are normal at birth, with pathological remodeling developing over years to decades, leading to a phenotype characterized by asymmetric ventricular hypertrophy, scattered fibrosis and myofibrillar/cellular disarray with ultimate mechanical heart failure and/or severe arrhythmias. The identity of the primary mutation-induced changes in sarcomere function and how they trigger debilitating remodeling are poorly understood. Support for the importance of mutation-induced hypercontractility, e.g., increased calcium sensitivity and/or increased power output, has been strengthened in recent years. However, other ideas that mutation-induced hypocontractility or non-uniformities with contractile instabilities, instead, constitute primary triggers cannot yet be discarded. Here, we review evidence for and criticism against the mentioned hypotheses. In this process, we find support for previous ideas that inefficient energy usage and a blunted Frank–Starling mechanism have central roles in pathogenesis, although presumably representing effects secondary to the primary mutation-induced changes. While first trying to reconcile apparently diverging evidence for the different hypotheses in one unified model, we also identify key remaining questions and suggest how experimental systems that are built around isolated primarily expressed proteins could be useful.

A Deep Learning-Enabled Electrocardiogram Model for theIdentification of a Rare Inherited Arrhythmia: BrugadaSyndrome.

Brugada syndrome is a major cause of sudden cardiac death in young people and has distinctive electrocardiographic (ECG) features. We aimed to develop a deep learning-enabled ECG model for automatic screening for Brugada syndrome to identify these patients at an early point in time, thus allowing for life-saving therapy. A total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for 1:1 allocation) were extracted from the hospital-based ECG database for a 2-stage analysis with a deep learning model. After trained network for identifying right bundle branch block pattern, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared with that of board-certified practicing cardiologists. The model was further validated in an independent ECG data set collected from hospitals in Taiwan and Japan. The diagnoses by the deep learning model (area under the receiver operating characteristic curve [AUC] 0.96, sensitivity 88.4%, specificity 89.1%) were highly consistent with the standard diagnoses (kappa coefficient 0.78). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (kappa coefficient 0.63). In the independent ECG cohort, the deep learning model still reached a satisfactory diagnostic performance (AUC 0.89, sensitivity 86.0%, specificity 90.0%). We present the first deep learning-enabled ECG model for diagnosing Brugada syndrome, which appears to be a robust screening tool with a diagnostic potential rivalling trained physicians.

Differentiating right ventricular remodelling from cardiac pathology in athletes

AbstractArrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death in young people and athletes. Prominent right ventricular remodelling can occur in highly trained endurance athletes, raising concern about underlying right ventricular pathology, such as ARVC. Distinguishing between physiological adaptation and cardiac pathology in athletes can be challenging, particularly in elite endurance athletes. This article describes a systematic approach used in sports cardiology to review the physiological adaptation of the right ventricle to exercise and the overlap with ARVC, focusing on the diagnostic investigations used to distinguish between athlete's heart and ARVC.

A clinical case of arrhythmogenic right ventricular dysplasia

Arhythmogenic right ventricular dysplasia (ADP) refers to hereditary myocardial diseases, in which there are structural and functional disorders in the right ventricular myocardium, causing rhythm and conduction disorders, including fatal ventricular arrhythmias. ADP is considered one of the most common causes of sudden cardiac death in young people and people who are engaged in sports. However, in practice, there are cases of this disease in people of an older age category. Diagnosis of ADP is still difficult due to the possible long-term asymptomatic course of the disease. The article describes a clinical case of ADP in a 48-year-old man.