Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction DOI Open Access
Pegah Bahrami Taqanaki,

Kelly A. Aromolaran,

Ademuyiwa S. Aromolaran

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13423 - 13423

Published: Dec. 14, 2024

Heart failure with preserved ejection fraction (HFpEF) is increasing at an alarming rate worldwide, limited effective therapeutic interventions in patients. Sudden cardiac death (SCD) and ventricular arrhythmias present substantial risks for the prognosis of these Obesity a risk factor HFpEF life-threatening arrhythmias. its associated metabolic dysregulation, leading to syndrome, are epidemic that poses significant public health problem. More than one-third world population overweight or obese, enhanced incidence mortality due cardiovascular disease (CVD). predisposes patients atrial fibrillation supraventricular arrhythmias—conditions caused by dysfunction electrical activity heart. To date, current options cardiomyopathy obesity limited, suggesting there considerable room development novel mechanisms action will help normalize sinus rhythms obese Emerging candidates modulation ion channels Ca-handling proteins. However, underlying molecular impact on proteins remain incompletely understood. marked accumulation adipose tissue, which variety adverse adaptations, including dyslipidemia (or abnormal systemic levels free fatty acids), increased secretion proinflammatory cytokines, fibrosis, hyperglycemia, insulin resistance, cause remodeling and, thus, predispose Furthermore, tissue also subcutaneous visceral fat, distinct signaling mechanisms. Thus, may be functional differences effects regional distribution fat deposits channel/Ca-handling protein expression. Evaluating alterations their expression lead progress knowledge responsible obesity-related These advances likely reveal new targets pharmacological modulation. Understanding how related have medical economic impact. Nevertheless, gaps regarding treatment, requiring further investigations identify potential targets. The objective this study review predisposition This highlights interleukin-6 (IL-6) as target, bridging integrator 1 (cBIN1) promising gene therapy agent, leukotriene B4 (LTB4) underappreciated pathway future management.

Language: Английский

Brugada syndrome update DOI Creative Commons
Xu Tingting, Shaokun Wang, Jiawen Wang

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

Brugada syndrome (BrS), a genetic disorder affecting cardiac ion channels, predominantly manifests due to mutations that impair the function of Nav1.5 sodium channel's α-subunit. This condition, identified by Josep and Pedro Brugada, is often marked symptoms such as syncope episodes polymorphic ventricular tachycardia (PVT) or fibrillation (VF). These arrhythmias, if not managed promptly, can escalate sudden death (SCD), notably in patients whose structure appears normal. Given this, prompt recognition stratification individuals at elevated risk are critical. review elaborates on current insights into BrS, focusing recent diagnostic techniques, assessment strategies, therapeutic advancements. It also critically examines ongoing controversies field.

Language: Английский

Citations

0
Autoimmune cardiac channelopathies and heart rhythm disorders: a contemporary review. DOI Creative Commons
Pietro Enea Lazzerini, Mohamed Boutjdir

Heart Rhythm, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Cardiac arrhythmias still represent a major health problem worldwide, at least in part because the fundamental pathogenic mechanisms are not fully understood thus impacting efficacy of therapeutic measures. In fact, while cardiac most cases due to structural heart diseases, underlying cause remains elusive significant number patients despite intensive investigations even including post-mortem examination and molecular autopsy. A large body data progressively accumulated over last decade provides strong evidence that autoimmune may be involved such unexplained or poorly explained arrhythmias. Several pro-arrhythmic anti-cardiac ion-channel autoantibodies have been discovered, all able directly interfere with electrophysiological properties heart, but leading different arrhythmic phenotypes, long-QT-syndrome, short-QT-syndrome, atrioventricular block. These autoantibodies, which develop independent history could help explain percentage events unknown origin, thereby opening new frontiers for diagnosis treatment rhythm disorders. Based on this evidence, novel term "autoimmune channelopathies" was coined 2017. Since then, interest field cardio-immunology has shown tumultuous growth, so much arrhythmogenic anti-ion channel reported significantly increased, also association previously described as atrial fibrillation, Brugada syndrome, ventricular fibrillation/cardiac arrest. Thus, an updated reassessment topic, highlighting perspectives unmet needs, become necessary represents main objective present review.

Language: Английский

Citations

0
Anti-Ro/SSA antibodies in adult arrhythmias: pathogenesis, clinical implications, and therapeutic strategies DOI Creative Commons
Ruiyuan Cao, Huakun Lv, Baopeng Tang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 5, 2025

Anti-Ro/SSA antibodies, prevalent autoantibodies in connective tissue diseases, have well-established roles fetal arrhythmias but their significance adult remains underrecognized. Recent evidence highlights that anti-Ro/SSA antibodies may induce by disrupting cardiac ion channel function, particularly through interactions with calcium and potassium channels, leading to electrophysiological disturbances including QT prolongation, atrioventricular block, increased susceptibility sudden death. Additionally, these can initiate inflammatory cascades, further contributing myocardial fibrosis conduction abnormalities. Despite the growing clinical relevance, detection of unexplained is not routinely performed, limiting early recognition intervention. Therapeutic strategies, currently based primarily on immunomodulatory therapies, show promise yet lack definitive from randomized controlled trials. This review systematically summarizes recent advances regarding pathogenic mechanisms, implications, therapeutic strategies for antibody-associated arrhythmias, aiming enhance awareness, diagnostic precision, management this increasingly recognized entity.

Language: Английский

Citations

0
Cardiac arrhythmias: the growing role of autoantibodies in diagnosis and treatment DOI Creative Commons
Funsho E. Fakuade, Jana Grune, Niels Voigt

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(40), P. 4349 - 4351

Published: Sept. 25, 2024

Graphical AbstractRole of autoantibodies against atrial and ventricular ion channels in cardiac arrhythmias their therapeutic potential. Autoantibodies targeting various can have inhibitory (−) stimulatory (+) effects on depolarizing (purple: INa,peak ICa,L) repolarizing (green: IK) currents, contributing to pathogenesis arrhythmias, including fibrillation (AF). Additionally, may offer opportunities develop specific personalized antiarrhythmic approaches. For a detailed explanation, please refer the text. INa,peak, peak sodium current; ICa,L, L-type-calcium IK, potassium QTc, corrected QT-interval; Tdp, Torsades de pointes tachycardia.Open new tabDownload slide

Language: Английский

Citations

2
Cardiac Cross-Reactivity of NaV Autoantibodies in Metastatic Breast Cancer: A Possible Trigger for Sudden Cardiac Death DOI Creative Commons
Carlo Pappone, Adriana Tarantino, Dario Melgari

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Abstract Background and Aims Patients with metastatic breast cancer have an increased risk of sudden cardiac death (SCD) that cannot be fully explained by cardiotoxic treatments. Recent evidence shows autoantibodies targeting the NaV1.5 sodium channel in Brugada syndrome (BrS) can trigger arrhythmias elevate SCD risk. Similarly, against neonatal isoform been found patients. Given high homology between these isoforms, we investigated whether cross-react isoform, potentially contributing to this population. Methods Plasma from twenty patients was analyzed for anti-NaV1.5 using HEK293A cells expressing protein, followed Western blotting. The effects on current density were assessed cellular models wild-type mice, electrocardiographic monitoring after plasma infusion. Results Fifteen samples tested positive autoantibodies, significantly reducing vitro. Mice injected developed severe a syndrome-like ECG pattern. In contrast, either without or IgG depletion showed no such effects, underscoring role reduction confirming pathogenicity autoantibodies. Conclusions This study demonstrates leading fatal arrhythmias. These findings highlight novel mechanism rate population suggest therapies involving blockers should used caution avoid exacerbating Reliable diagnostic tests targeted are urgently needed mitigate affected

Language: Английский

Citations

1
Innovative approaches to the management of recurrent atrial fibrillation, aortic dilation, and Brugada syndrome DOI
Filippo Crea

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(40), P. 4245 - 4248

Published: Oct. 21, 2024

Language: Английский

Citations

0
Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction DOI Open Access
Pegah Bahrami Taqanaki,

Kelly A. Aromolaran,

Ademuyiwa S. Aromolaran

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13423 - 13423

Published: Dec. 14, 2024

Heart failure with preserved ejection fraction (HFpEF) is increasing at an alarming rate worldwide, limited effective therapeutic interventions in patients. Sudden cardiac death (SCD) and ventricular arrhythmias present substantial risks for the prognosis of these Obesity a risk factor HFpEF life-threatening arrhythmias. its associated metabolic dysregulation, leading to syndrome, are epidemic that poses significant public health problem. More than one-third world population overweight or obese, enhanced incidence mortality due cardiovascular disease (CVD). predisposes patients atrial fibrillation supraventricular arrhythmias—conditions caused by dysfunction electrical activity heart. To date, current options cardiomyopathy obesity limited, suggesting there considerable room development novel mechanisms action will help normalize sinus rhythms obese Emerging candidates modulation ion channels Ca-handling proteins. However, underlying molecular impact on proteins remain incompletely understood. marked accumulation adipose tissue, which variety adverse adaptations, including dyslipidemia (or abnormal systemic levels free fatty acids), increased secretion proinflammatory cytokines, fibrosis, hyperglycemia, insulin resistance, cause remodeling and, thus, predispose Furthermore, tissue also subcutaneous visceral fat, distinct signaling mechanisms. Thus, may be functional differences effects regional distribution fat deposits channel/Ca-handling protein expression. Evaluating alterations their expression lead progress knowledge responsible obesity-related These advances likely reveal new targets pharmacological modulation. Understanding how related have medical economic impact. Nevertheless, gaps regarding treatment, requiring further investigations identify potential targets. The objective this study review predisposition This highlights interleukin-6 (IL-6) as target, bridging integrator 1 (cBIN1) promising gene therapy agent, leukotriene B4 (LTB4) underappreciated pathway future management.

Language: Английский

Citations

0