This letter challenges the prevailing assumption that residual shunt following patent foramen ovale (PFO) closure is a primary driver of recurrent stroke risk. While residual shunt has been associated with higher rates of neurologic events in observational studies, the author argues that this relationship is not supported by randomized data and may be confounded by diagnostic ambiguity, particularly the inclusion of transient ischemic attack alongside stroke outcomes. The complex pathophysiology of PFO-related stroke, requiring thrombus formation, transient right-to-left shunting, and specific anatomic factors, is often substantially mitigated by the closure procedure itself. Emerging evidence suggests that device-related factors, including incomplete endothelialization and altered atrial hemodynamics, may independently contribute to thromboembolic risk after closure, irrespective of residual shunting. The letter proposes that residual shunt may be an inadequate surrogate endpoint and that clinical focus should instead remain on true stroke recurrence. It further cautions against routine re-intervention to eliminate residual shunt, advocating instead for consideration of prolonged antithrombotic therapy and alternative closure strategies, such as suture-based approaches, which may avoid device-related complications. Overall, this perspective calls for a reassessment of current paradigms in post-PFO closure management and outcome evaluation.
Background:Sudden cardiac arrest (SCA) in young adults (18-40 years) is rare but devastating, often occurring without prior symptoms. It often occurs in the absence of preceding symptoms or known structural heart disease. A comprehensive and systematic evaluation of its multifactorial aetiology, diagnostic challenges and preventive strategies is fundamental to reducing morbidity and mortality in this population. Objective:This systematic review aims to comprehensively evaluate the epidemiology, underlying aetiologies, associated risk factors, diagnostic approaches and preventive strategies for SCA in adults aged 18-40 years. Methods:PubMed, Scopus, Embase, Web of Science and Google Scholar were searched from January 2015 to June 2025. Eligible studies examined aetiologic mechanisms, screening strategies, clinical outcomes or public health interventions targeting the prevention, detection or management of SCA in individuals aged 18-40 years. Study quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist, the Risk of Bias in Nonrandomized Studies of Exposures (ROBINS-E), A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and the Newcastle-Ottawa Scale (NOS). Results:Of 3,000 records identified through the literature search, 55 studies met the inclusion criteria. The reported incidence of SCA among young adults ranged from 1 to 2 per 100,000 person-years in Western countries, with higher incidence rates observed in Asian populations. Structural cardiomyopathies were the predominant aetiologies, most notably hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. These were followed by inherited channelopathies, including long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, as well as acquired conditions such as myocarditis and substance-related cardiac toxicity involving cocaine, amphetamines and anabolic steroids. Additional risk factors included systemic comorbidities, particularly sarcoidosis, chronic kidney disease and autonomic dysfunction. Diagnostic evaluation most frequently incorporated electrocardiography, transthoracic echocardiography, cardiac magnetic resonance imaging and genetic testing. Survival following out-of-hospital cardiac arrest was significantly improved in settings with prompt bystander cardiopulmonary resuscitation, widespread availability of automated external defibrillators and the implementation of community-based education initiatives. Conclusion:Targeted screening strategies, improved access to advanced diagnostic modalities and population-level community interventions are essential for reducing the burden of SCA among young adult individuals. Further prospective research is warranted to enhance risk stratification and optimize prevention strategies in this high-impact population.
Ventricular fibrillation (VF) is a malignant tachyarrhythmia underlying cardiac arrest, yet the mechanisms maintaining VF remain incompletely understood. Ethical constraints and technical limitations have largely precluded systematic investigation of sustained VF in humans, resulting in a body of evidence derived predominantly from animal models and ex vivo human preparations, often yielding apparently conflicting mechanistic interpretations. This article summarizes the experimental studies and conceptual frameworks that underpin the contemporary understanding of VF maintenance. We discuss evidence derived from frequency-and phase-based mapping approaches in short-and long-duration VF studies across species, highlighting how methodological constraints, animal models, spatial scale and VF duration critically influence mechanistic interpretation. Despite the heterogeneity across studies, overall, the data indicate that VF is not inherently chaotic but exhibits transient spatiotemporal organization that evolves dynamically over time. The underlying drivers sustaining VF throughout its progression are not uniform: multiple at times co-existing mechanisms, including reentrant activity, self-perpetuating wavelets and rapid focal activation, have been implicated. The predominance and temporal evolution of these mechanisms are shaped by progressive global ischaemia with metabolic deterioration, pre-existing structural remodelling and the involvement as well as architecture of the Purkinje network. Collectively, these observations support the concept of duration-dependent and likely also substrate-specific electrophysiological phenotypes of VF, while also exposing a paucity of studies that have explicitly and systematically evaluated the effect of pre-existing structural and electrical substrate characteristics to examine their reciprocal interaction with VF dynamics. We conclude by outlining future directions, emphasizing the need for true 3D transmural mapping technologies and multimodal integration of structural and functional substrate features to enable mechanistic phenotyping and inform more personalized and effective strategies for VF management and prevention.
