Search Results (134)

Deleterious variants in SCN5A lead to a wide clinical spectrum that includes pathologies characterized by life-threatening cardiac events (CEs). In the pediatric population, early identification, management, and risk stratification of these pathologies are the main current challenges. This study analyzed a Spanish pediatric cohort (≤18 years) carrying rare SCN5A variants to explore genotype–phenotype correlations. A retrospective descriptive cohort study, including clinical, demographic, and genetic data of probands and their relatives, was conducted. Out of 100 children studied, 69 had definitively deleterious SCN5A variants (26 females, 38%; median age: 3 years, IQR 1–12). The main diagnoses were isolated Brugada syndrome (BrS) (31; 45%); isolated long QT syndrome type 3 (LQT3) (5; 7%); isolated progressive cardiac conduction disease (PCCD) (1; 2%); isolated familial atrial fibrillation (1; 2%); overlapping phenotypes (7; 10%) including: BrS-PCCD (2; 2.8%); BrS-LQT3 (1; 1.4%); premature ventricular contraction-dilated cardiomyopathy (1; 1.4%); BrS-LQT3-PCCD (1; 1.4%); BrS-PCCD-sick sinus syndrome (SSS) (1; 1.4%) and BrS-PCCD-SSS-familial atrial fibrillation (1; 1.4%). Of them, 13 (19%) patients presented with CEs (cardiogenic syncope, ventricular tachycardia/fibrillation, sudden cardiac arrest/death, and appropriate implantable cardio defibrillator shock). These findings underscore the utility of genetic testing for early diagnosis, risk stratification, and personalized management, enhancing preventive strategies for CE prevention in pediatrics. Full article

Inherited arrhythmias and cardiomyopathies are a group of potentially lethal genetic cardiac disorders which are often passed down through generations and pose risks to several family members. While individually rare, these conditions are collectively common and pose significant challenges for clinical management given their variable severity, age of onset, and response to treatments. Earlier genetic analyses revealed crucial insights into the main genetic culprits of these disorders, such as SCN5A for Brugada syndrome, and MYH7 and MYBPC3 for hypertrophic cardiomyopathy, which have revolutionized diagnosis, risk stratification, and medical management. Nonetheless, issues such as variable expressivity and penetrance, low yield of genetic testing, and relative lack of disease-modifying therapies remain significant hurdles for clinical management. The revolution of genome-wide association studies GWASs has transformed our understanding of inherited arrhythmias and cardiomyopathies, shifting the view of these disorders from a monogenic Mendelian inheritance towards a more complex, often polygenic inheritance with nuanced interplay between genetics and environment. Moreover, GWASs have enabled the quantification of polygenic predisposition to disease using polygenic risk scores, which are often complementary to and independent of monogenic risk. In this review, we highlight how GWASs have transformed the field of inherited arrhythmias and cardiomyopathies, with a particular focus on the polygenic risk scores developed and their clinical utility for the four disorders which have been impacted by GWASs—hypertrophic cardiomyopathy, dilated cardiomyopathy, Brugada syndrome, and long QT syndrome. Full article

Pectus excavatum (PE) is the most frequent chest wall deformity, representing 65–95% of all cases, with an estimated prevalence of up to 1 in 300 births. Despite its frequency, it remains underrecognized in sports cardiology. PE results from sternal depression and narrowing of the anterior chest, which may lead to cardiac compression, impaired diastolic filling, and reduced stroke volume during exercise. Consequently, athletes with PE often present with cardiovascular symptoms such as exercise-induced dyspnoea, chest pain, palpitations, presyncope, or reduced physical fitness. Electrocardiographic changes, including right bundle branch block, axis deviation, atrial enlargement, T-wave inversion, QS complexes or Brugada phenocopies, are frequent and may mimic serious cardiovascular conditions, complicating pre-participation screening. Furthermore, PE is associated with potentially high-risk conditions including mitral valve prolapse, ventricular arrhythmias, and connective tissue disorders such as Marfan syndrome, which carry implications for sports eligibility and safety. Assessment of athletes with PE requires multimodal imaging (echocardiography, computed tomography, magnetic resonance), cardiopulmonary exercise testing, and exclusion of concomitant cardiovascular disease. Treatment strategies range from conservative approaches (physiotherapy, vacuum bell therapy) to surgical correction, most commonly with the Nuss procedure, which can improve cardiac function, exercise capacity, and quality of life. Management should involve shared decision making between clinicians, athletes, and families, weighing potential risks against athletic aspirations. Awareness of PE in sports cardiology is crucial, as it not only influences differential diagnosis and screening outcomes but also impacts career decisions and the psychological well-being of athletes. Full article

Introduction: Atrial fibrillation (AF) is common in patients with Brugada syndrome (BrS). The impact and significance of AF in this patient population needs to be further clarified. Method: We performed a systematic review and meta-analysis of studies comparing the risks of developing major arrhythmic events (MAEs) in patients with BrS with and without AF. Databases including MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to July 2024, using appropriate search and MeSH terms. Data were sought on the comparison of patients with BrS with and without AF. The protocol was specified prior to the searches being performed, and standard meta-analytic techniques were used. Results: Thirteen observational studies were included (a total of 5413 patients). A significant increase in MAEs was observed in patients with both BrS and AF (20.6% vs. 7.8%; OR 2.81, 95% CI 1.82–4.34; p < 0.0001; I² = 46%). Significantly higher rates of syncope (33.3% vs. 23.4%; OR 1.97, 95% CI 1.04–3.76; p = 0.04, I² = 59%) and a significant increase in all-cause mortality (11.3% vs. 3.7%; OR 4.21, 95% CI 1.69–10.45; p = 0.002, I² = 0%) and sodium channel mutations (43.1% vs. 29.9%; OR 1.87, 95% CI 1.07–3.29; p = 0.028, I² = 0%) were observed for patients with BrS and AF. Conclusions: Patients with both BrS and AF seem to have a more severe disease phenotype. More research into the added role of AF in risk stratification of asymptomatic BrS patients is needed, but the prognostic implications of AF may need to be considered when developing future personalised medicine approaches in the BrS population. Full article

Brugada syndrome (BrS) is a cardiac arrhythmic disorder associated with distinctive electrocardiographic (ECG) abnormalities and an increased risk of sudden cardiac death due to ventricular arrhythmias. While the classic BrS ECG pattern is a coved ST-segment elevation in the right precordial leads, a wide spectrum of atypical ECG presentations can mislead the diagnosis. This review discusses rare and under-recognized ECG findings associated with BrS, including its coexistence with right and left bundle branch block, alterations in peripheral leads and in the morphology of the QRS complex, as well as atrioventricular conduction abnormalities. Emphasis is placed on the clinical relevance of these findings, their underlying electrophysiological mechanisms, and their prognostic implications. Recognizing these atypical manifestations is critical to avoid misdiagnosing or failing to recognize the condition in patients with BrS. Full article

Background: Catheter ablation of the arrhythmogenic substrate has emerged as a promising therapeutic strategy for symptomatic Brugada syndrome (BrS). However, high-quality comparative evidence against conventional implantable cardioverter-defibrillator (ICD)-based management remains limited. Objectives: This meta-analysis aimed to evaluate the efficacy of catheter ablation in reducing ventricular fibrillation (VF) recurrence in symptomatic BrS compared to standard therapy. Methods: Medline, Cochrane Library, and Scopus were systematically searched through 1 June 2025. Study selection, data extraction, and quality assessment were independently conducted by three reviewers. Random-effects meta-analyses were used to pool risk estimates. Results: Three studies (two randomized controlled trials, one observational cohort; 130 symptomatic BrS patients) were included. Over a median follow-up of 3.9 years, catheter ablation was associated with a significantly lower risk of VF recurrence compared to standard therapy [risk ratio (RR) = 0.19, 95% confidence interval (CI) = (0.06, 0.60); I² = 36%, p for heterogeneity = 0.21], with no deaths reported in any group. A sensitivity analysis restricted to randomized trials confirmed similar findings in favor of ablation. Conclusions: Catheter ablation was associated with reduced VF recurrence compared to ICD therapy alone, supporting its potential role as first-line treatment in symptomatic BrS or as an alternative for patients who decline ICD implantation. Full article

Background and Clinical Significance: Brugada syndrome (BrS) is a rare inherited cardiac channelopathy, often associated with SCN5A loss-of-function mutations. Clinical presentations range from asymptomatic to malignant arrhythmias and sudden cardiac death. Physiological and pharmacological stressors affecting sodium channel function—such as pyrexia, certain medications, and possibly pregnancy—may unmask or exacerbate arrhythmic risk. However, there is limited information regarding pregnancy and obstetric outcomes. Obstetric management remains largely informed by isolated case reports and small case series. A literature review was conducted using OVID Medline and Embase, identifying case reports, case series, and one retrospective cohort study reporting clinical presentation, obstetric management, and outcomes in maternal BrS. A case is presented detailing coordinated multidisciplinary input, antenatal surveillance, and intrapartum and postpartum care to contribute to the growing evidence base guiding obstetric care in this complex setting. Case Presentation: A 30-year-old G2P0 woman with asymptomatic BrS (SCN5A-positive) was referred at 31 + 5 weeks’ gestation for multidisciplinary antenatal care. Regular review and collaborative planning involving cardiology, anaesthetics, maternal–fetal medicine, and obstetrics guided a plan for vaginal delivery with continuous cardiac and fetal monitoring. At 38 + 0 weeks, the woman presented with spontaneous rupture of membranes and underwent induction of labour. A normal vaginal delivery was achieved without arrhythmic events. Epidural block with ropivacaine and local anaesthesia with lignocaine were well tolerated, and 24 h postpartum monitoring revealed no abnormalities. Conclusions: This case adds to the limited but growing literature suggesting that with individualised planning and multidisciplinary care, pregnancies in women with BrS can proceed safely and without complication. Ongoing case reporting is essential to inform future guidelines and optimise maternal and fetal outcomes. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

The electrical ventricular storm (VES) is defined as multiple sustained ventricular arrhythmias arising in a short time, often refractory to standard antiarrhythmic treatment. The three pillars of the physiopathogenesis of the VES are autonomic dysfunction, triggers, and an altered ventricular substrate. Incessant or highly recurrent ventricular arrhythmia impacts the hemodynamic status by worsening heart failure and increasing mortality. A stepwise, team-based, and tailored therapeutic approach is required to stop ventricular arrhythmia and regain the hemodynamic and electric stability of the patient. The authors focused on describing all currently available therapeutic approaches for VES, intending to establish the best VES therapeutic approaches. This process involves considering the patient’s specific condition, responses to previous treatments, and the potential risks and benefits of each approach. The options range from adjusting antiarrhythmic therapy to reprogramming of the ICD, sedation, epidural anaesthesia, stellate ganglia anaesthetic block, and the use of ECMO or left ventricular assist devices and radiofrequency catheter ablation. Particular attention is paid to the detailed management of genetic primary arrhythmia syndromes like long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome and Wolff–Parkinson–White syndrome, early repolarisation syndrome, right ventricular arrhythmogenic dysplasia, and idiopathic ventricular fibrillation. After overcoming the acute events of VES and obtaining hemodynamic stability, the treatment should shift toward an optimal balance of heart failure therapy, controlling the substrate by revascularisation procedures and resolving other pathology-generating ventricular arrhythmias. This article provides a comprehensive overview of ESV’s current management options using the most efficient strategies known to date. Full article

Brugada syndrome is a rare inherited heart disease characterized by ventricular arrhythmias and characteristic ST segment elevation, which increases the risk of sudden death. Studies have shown that the pathogenesis of this disease involves a variety of gene mutations, including abnormal functions of sodium, calcium, and potassium ion channels, resulting in cardiac electrophysiological disorders. These variants affect excitability and conduction of cardiomyocytes, thereby increasing the susceptibility to ventricular arrhythmias and sudden death. However, many genetic variants remain of uncertain significance or are insufficiently characterized, necessitating further investigation. This review summarizes the genetic variants associated with Brugada syndrome and discusses their potential implications for improving diagnosis and therapeutic approaches. Full article

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

Brugada syndrome (BrS) has been traditionally considered a pure electrical disorder without an underlying structural substrate. However, early ECG studies showed the presence of depolarization abnormalities in this condition, while many studies based on advanced imaging have suggested the presence of subtle structural alterations. On the other hand, electrophysiological study (EPS) and electroanatomic mapping (EAM) techniques have provided important data regarding right ventricular functional and structural arrhythmic substrate. More recently, histology and immunology shed light on the possible role of fibrotic and inflammatory substrates in BrS. Notably, a significant overlap between electro anatomical and structural features in BrS and arrhythmogenic cardiomyopathy has been proposed. In this review, we summarized the physio pathological pathways and substrate underlying BrS. A deeper knowledge of the structural abnormalities involved in the pathogenesis of this disease could improve our diagnostic and prognostic approach, while novel findings regarding the role of inflammation and immune activation could potentially lead to new therapeutic strategies for BrS. Full article

Brugada syndrome (BrS) is a cardiac disease associated with characteristic ECG abnormalities and a heightened risk of sudden cardiac death, especially in young individuals with structurally normal hearts. The primary aim of this study was to highlight, for the first time, the potential of using droplet digital PCR (ddPCR), a highly sensitive method, to detect C-type natriuretic peptide (CNP) and its receptors, NPR-B and NPR-C, expression in BrS. Whole-blood samples from 12 subjects with type 1 BrS and 12 controls were analyzed. CNP expression was detectable and lower in BrS patients than in the controls, although not significantly. NPR-B and NPR-C expression was significantly reduced in the same patients (p ≤ 0.05). Strong correlations were observed between CNP and NPR-B (p = 0.01) and NPR-C (p < 0.0001), as well as between NPR-B and NPR-C (p = 0.0002). Body weight correlated with CNP (p = 0.02), NPR-B (p = 0.03), and NPR-C (p = 0.02); meanwhile, NPR-B expression was related to height (p = 0.05). This study is the first to analyze CNP expression and its specific receptors using ddPCR technology, showing for the first time their presence and activation in individuals with BrS. Although further research is needed to clarify CNP-related mechanisms, these findings offer a valuable starting point for exploring its role in BrS. Full article

Cardiovascular diseases increase among pregnant women and complicate 1–4% of pregnancies worldwide. The incidence of maternal deaths due to cardiovascular causes has increased dramatically, rising from 3% three decades ago to 15% in recent years. The aim of this study is to provide a comprehensive overview of the current status of knowledge in sudden maternal death (SMD) described in the literature and to present two cases of autopsy findings in sudden cardiac death in pregnant women. Among the most common causes of sudden maternal deaths are peripartum cardiomyopathies, aortic dissection, acute myocardial infarction, arrhythmias, ischemic heart disease, and coronary artery dissection, and among the less common causes, we list coronary artery dissection, congenital heart diseases, valvulopathies, hypertension, fibroelastosis, and borderline myocarditis. The Centers for Disease Control and Prevention (CDC) reported that over 80% of pregnancy-related deaths were preventable. To reduce the number of maternal deaths caused by cardiovascular diseases, the implementation of specialized multidisciplinary teams has been proposed. Molecular biology techniques are proving their effectiveness in forensic medicine. PCR or DNA sequencing can be utilized in “molecular autopsy”, which holds particular value in cases of sudden death where the forensic autopsy is negative but there is a suspicion that death was caused by arrhythmia. Susceptibility genes can be analyzed, such as KCNQ1, KCNH2, KCNE1, and KCNE2, which are involved in long QT syndrome, the RYR2 gene implicated in catecholaminergic polymorphic ventricular tachycardia type 1, or the SCN5A gene associated with Brugada syndrome. Early identification of risk factors involved in sudden maternal death prenatally and during pregnancy is essential. At the same time, genetic determinations and molecular biology techniques are absolutely necessary to prevent the occurrence of sudden deaths among close relatives. Full article

Background and Clinical Significance: Dental demineralization is a multifactorial process influenced by biofilm activity, diet, and systemic conditions. While gastroesophageal reflux disease (GERD) is known for its role in enamel erosion, its contribution to cariogenic processes remains underexplored. Additionally, Brugada syndrome, a genetic arrhythmia disorder, may indirectly affect oral health due to medical complexities and reduced motivation for dental care. This case highlights the management of extensive mineral loss in a patient with GERD and Brugada syndrome, emphasizing the importance of personalized remineralization strategies and interdisciplinary collaboration. Case Presentation: A 27-year-old male with Brugada syndrome, treated with a subcutaneous implantable cardioverter defibrillator (S-ICD), presented with widespread enamel demineralization, multiple active carious lesions, and gingival inflammation. Clinical evaluation revealed a high DMFT index (15), significant plaque accumulation, and an oral pH of 5.8, indicating an elevated risk of mineral loss. Poor hygiene habits, frequent sugar intake, and GERD-related acid exposure contributed to his condition. The therapeutic approach included patient education, fluoride-functionalized hydroxyapatite toothpaste and mousse, dietary modifications, and restorative procedures. After 120 days, improvements included enhanced enamel integrity, a reduction in plaque index (from 50% to 25%), and the resolution of gingival inflammation (BOP: 38% to 12%). Conclusions: This case underscores the importance of an integrated approach to managing dental demineralization in patients with systemic conditions. The combination of remineralization therapy, behavioral modifications, and structured follow-up yielded significant clinical benefits. Further research is needed to develop standardized protocols for individuals at high risk due to systemic factors affecting oral health. Full article