Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular hypertrophy without abnormal loading conditions. Despite significant advances in management, HCM remains a major cause of sudden cardiac death, particularly in young individuals. Prevention relies on accurate arrhythmic risk stratification and the selective implantation of implantable cardioverter-defibrillators (ICDs). This article reviews current indications for primary prevention ICD implantation in sarcomeric HCM based on the European Society of Cardiology (ESC) guidelines and compares them with the more integrative approach proposed by the American College of Cardiology/American Heart Association (ACC/AHA).

Inherited cardiovascular diseases (ICVDs) are a broad category of hereditary disorders resulting from pathogenic mutations that alter cardiac anatomy, electrical conduction, and metabolic pathways. The main types include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), cardiac channelopathies, and familial hypercholesterolemia (FH) and are associated with heart failure, malignant arrhythmias, and sudden cardiac death, particularly in young people. Current treatments, such as pharmacological therapies, implantable cardioverter-defibrillators, and heart transplantation, have significantly improved outcomes; however, these treatments are mainly targeted toward symptom control and the prevention of complications without correcting the underlying genetic defects. Recent advancements in genome editing have transformed precision cardiovascular care, with clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies emerging as potential methods for targeting and modifying disease-causing variants. Emerging platforms, such as base editing, prime editing, and epigenome editing, have widened the therapeutic potential of genome engineering by enhancing editing precision and reducing some of the constraints of the traditional CRISPR-Cas9 strategy. In the setting of inherited cardiovascular disorders, promising early results have been obtained in preclinical studies using human induced pluripotent stem cell and animal models, including correction of MYBPC3 and MYH7 mutations in HCM; targeting of TTN-, RBM20-, and LMNA-associated mechanisms in DCM; restoration of ion channel function in inherited arrhythmia syndromes; and modulation of lipid-related genes such as PCSK9, LDLR, and ANGPTL3 in FH. However, major challenges remain, including off-target effects, effective delivery to cardiac tissues, immunological responses, interpretation of genetic variants, and ethical concerns. This review provides a translational, integrated view of the evolution of CRISPR-based genome editing technologies, their application to ICVDs, current preclinical and clinical advances, and the challenges that need to be addressed to achieve safe and effective translation into cardiovascular therapeutics.

Streptococcus suis is a pathogenic bacterium primarily found in pigs, where it causes sudden death and meningitis, but it is also capable of causing septic shock and meningitis in humans, being the most important cause of adult bacterial meningitis in Southeast Asia. As the host's innate immune system serves as the first line of defense against microbial invaders, it is crucial to understand the intricate relationship between the bacterium and this system. Despite an increasing number of studies performed in the last 20 years, the pathogenesis of S. suis infection is not fully understood, and there is still an absence of effective vaccines on the market. Recent population-genomic studies have further highlighted that pathogenic S. suis is not a single uniform entity but comprises multiple lineages with distinct genome content and disease associations, raising the possibility that innate immune evasion mechanisms may not be equivalent across lineage. In the current article, we conducted a comprehensive review of the literature, focusing on the innate response developed mainly by phagocytes against this Gram-positive bacterium. Our aim was to summarize the last findings and to identify the main gaps in knowledge to guide future research efforts toward areas that require further investigation.

Rupture of ventricular aneurysm is an unusual pathology in children. This case describes a preterm infant who had been in the hospital since birth due to necrotizing enterocolitis, which was complicated by narrowing of the ascending colon that required surgery. Throughout the entire period, the infant exhibited signs of infection, first caused by Staphylococcus haemolyticus and subsequently by Staphylococcus epidermidis. Several echocardiographic examinations did not reveal any significant changes; however, the final echocardiography revealed a structure connected to the left ventricular cavity. The infant experienced sudden cardiac arrest due to significant pericardial effusion. Despite continued resuscitation efforts, including emergency pericardiocentesis, the asystole recurred, further advanced life support measures were unsuccessful, and death was pronounced. Autopsy revealed a small outpouching on the anterior wall of the left ventricle, associated with thinning of the myocardium and a linear rupture with uneven edges. Histological examination showed that the aneurysm wall was composed of myocardium and connective tissue, exhibiting signs of inflammation, necrosis, and hemorrhage.

Aortic aneurysms are abnormal dilations of the aortic wall and represent a significant cause of morbidity and mortality worldwide. In many cases, especially when the thoracic aorta is involved, the first and only symptom is sudden death. While aortic aneurysms are traditionally associated with factors such as advanced age, hypertension, and atherosclerosis, growing evidence points to a critical role for autoimmune diseases in their pathogenesis. The hallmarks of autoimmune disorders, such as chronic systemic inflammation, immune dysregulation, and vascular tissue remodeling, can create a pro-aneurysmal environment within the vasculature. This review explores the complex interplay between autoimmune diseases and aortic aneurysm formation, focusing on pathogenic mechanisms, specific disease associations, and implications for diagnosis and management. A better understanding of these relationships is vital for advancing therapeutic strategies aimed at mitigating vascular complications in affected patients.

Congenital long QT syndrome (LQTS), the first identified cardiac ion channelopathy, is characterized by delayed ventricular repolarization and a prolonged heart rate-corrected QT interval (QTc), conferring an increased risk of malignant ventricular arrhythmias and sudden cardiac death. Current standard-of-care management for LQTS, including beta-blockers, sodium channel blockers, left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillators (ICDs), reduces adverse events and improves survival but primarily mitigates downstream electrophysiological consequences rather than correcting the underlying genetic defects. Rapid advances in molecular biology have driven the development of mechanism-directed strategies such as gene editing, RNA interference (RNAi), and experimental antibody-based interventions, which aim to restore channel function or modulate channel regulation at the source. This review synthesizes current knowledge on LQTS classification and pathogenesis and evaluates both guideline-directed therapies and emerging molecular interventions. We emphasize subtype-specific approaches, highlight the rationale and preclinical progress for gene- and RNA-based therapies, and outline practical considerations for translation, including delivery, durability, and safety. Therefore, this review provides a comprehensive, mechanism-based framework to inform future precision medicine approaches for LQTS.

Excited Delirium Syndrome remains one of the most controversial topics in contemporary forensic pathology. Although the term has been increasingly challenged because of the lack of universally accepted diagnostic criteria and formal recognition within major nosological systems, episodes of severe psychomotor agitation associated with sudden death continue to represent a significant clinical and medico-legal concern. We report two cases of sudden death occurring during physical restraint in individuals presenting with severe agitation. The first case involved a 60-year-old man with a history of depression who threatened suicide by defenestration and was restrained by family members in a prone position with his limbs bound. The second case concerned a 40-year-old man with psychiatric comorbidities and a history of alcohol abuse who exhibited aggressive behaviour in a public setting and was restrained by police officers and healthcare personnel during transport to the hospital. These cases highlight the diagnostic challenges associated with deaths occurring during episodes of extreme agitation and restraint. In the absence of pathognomonic post-mortem findings, diagnosis requires a thorough multidisciplinary evaluation and careful exclusion of alternative causes of death. A narrative review is also provided to outline the current state of knowledge on the issue. Furthermore, the ongoing debate surrounding the terminology should not obscure the existence of a clinically recognisable syndrome characterised by acute agitation, altered mental status, and autonomic dysregulation. Collaboration among forensic pathologists, clinicians, toxicologists, psychiatrists, and law-enforcement personnel is essential to improve diagnostic accuracy, patient management, and medico-legal assessment in these complex cases.

Epsilon toxin (Etx) is a major exotoxin secreted by Clostridium perfringens that causes Enterotoxaemia (ET) in small ruminants leading to 'sudden death' and is known to induce protective antibodies. This study describes an indirect-ELISA based on recombinant quadruple-point Etx-mutant protein (~ 36 kDa), a well-defined and non-toxic antigen to detect epsilon specific antibodies in sheep and goat sera samples. The assay was evaluated for diagnostic sensitivity and specificity, along with cross-reactivity, as well as compared with a commercial ELISA kit. Furthermore, rEtx-iELISA was used to assess antibody titers in randomly collected sheep (n = 584) and goat (n = 555) serum samples from different regions of Odisha, an ET endemic state in India. The rEtx mutant protein (125 ng/well) based indirect ELISA platform demonstrated the area under the curve (AUC) of 0.997, diagnostic sensitivity (DSn) of 98.7%, and diagnostic specificity (DSp) of 96.2% using a pre-established test serum panel with 95% CI of 93.2-99.2% (p < 0.0001) against an optimal cut-off criterion of 10.42 PP. A comparison of the assay with a commercial kit yielded a kappa value of 0.912. A higher (> 95%) degree of sero-positivity with an average protective flock immunity of > 56% (≥0.15 IU/mL) was noted in sheep and goat populations of Odisha state. The study indicated the potential diagnostic utility of recombinant Etx-mutant antigen based indirect-ELISA for sero-monitoring of ET-specific antibodies in small ruminants.

Sudden cardiac arrest (SCA) is a life-threatening emergency that requires immediate intervention from lay responders. To address this critical need, the national Sudden Cardiac Arrest Foundation (SCAF) was established in 2005 to raise awareness, promote community engagement, and support survivors. The history of cardiopulmonary resuscitation, defibrillation, and public response programs illustrates decades of progress in resuscitation science and has helped lay the groundwork for the creation of SCAF. In addition to serving as a trusted information hub, SCAF leads several key initiatives. The Cardiac Arrest Survivor Alliance™ provides an online community for those affected by cardiac arrest, offering connection, support, and resources. The Call-Push-Shock campaign promotes three lifesaving steps to address out-of-hospital cardiac arrest: call 911, perform CPR, and use an automated external defibrillator (AED). While SCA remains a major cause of death, significant progress has been made in public education and response. Technological innovations such as dispatcher-assisted CPR, the widespread placement of AEDs, and improved EMS and cardiac arrest registries, have all strengthened the chain of survival. Public understanding has also improved, with the media increasingly distinguishing SCA from heart attacks, thanks in part to SCAF's tireless advocacy. As SCAF marks its 20th anniversary, the organization celebrates two decades of progress and looks ahead with optimism. Its mission remains steadfast: to raise awareness, empower bystanders to act, support survivors, and advance innovations that reduce preventable deaths from sudden cardiac arrest.