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Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 22 May 2026 | Viewed by 8659

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Dr. Paschalis Karakasis

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Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
Interests: cardiology; statistics; diabetes; heart failure; atrial fibrillation; atherosclerosis; SGLT-2 inhibitors; GLP-1 receptor agonists; myocardial infarction; ablation; arrhythmias
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Special Issue Information

Dear Colleagues,

Cardiac electrophysiology is evolving rapidly, driven by breakthroughs in molecular science, advanced imaging, computational modeling, and innovative therapeutic approaches. This Special Issue seeks broad, multidisciplinary contributions that span the spectrum from basic mechanisms of impulse formation and conduction to clinical applications that refine diagnosis, risk stratification, and treatment of arrhythmias. We welcome original research, reviews, and perspectives exploring topics such as molecular and genetic drivers of arrhythmogenesis, novel biomarkers, advanced mapping and imaging, wearable and remote monitoring, computational and AI-based tools, as well as pharmacological, device-based, and interventional therapies. Submissions addressing atrial and ventricular arrhythmias, inherited channelopathies, conduction system disorders, and arrhythmias in structural heart disease are encouraged, with a particular focus on innovative approaches that bridge mechanistic understanding and precision, patient-centered care.

Dr. Paschalis Karakasis
Guest Editor

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Keywords

cardiac electrophysiology
arrhythmias
inherited channelopathies

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Published Papers (7 papers)

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Research

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11 pages, 1843 KB

Open AccessArticle

Diagonal Earlobe Crease and the Risk of New-Onset Atrial Fibrillation After Cavotricuspid Isthmus Ablation in Patients with Typical Atrial Flutter

by Moo-Nyun Jin, Young Ju Kim and Changho Song

Life 2026, 16(3), 508; https://doi.org/10.3390/life16030508 - 19 Mar 2026

Viewed by 457

Abstract

Background: Atrial fibrillation (AF) frequently develops in patients with atrial flutter (AFL), even after successful cavotricuspid isthmus (CTI) ablation. Identifying simple clinical markers for early detection is crucial. Diagonal earlobe crease (ELC), also known as Frank’s sign, has been proposed as a marker of aging and cardiovascular risk. This study investigates the association between ELC and the risk of new-onset AF following CTI ablation in patients with AFL. Methods: We conducted a retrospective cohort study of 292 patients without a prior history of AF who underwent CTI ablation for typical AFL between 2015 and 2024. The presence of ELC was assessed at baseline CTI ablation. The primary outcome was the occurrence of new-onset AF during follow-up, stratified according to the presence of ELC. The median follow-up duration was 49 months, with a minimum follow-up of 6 months. Results: Among the 292 patients, 72 (24.7%) exhibited ELC. Patients with ELC were older (59 ± 11 years vs. 55 ± 14 years, p = 0.05). During the follow-up period, new-onset AF occurred in 31 patients with ELC (43.1%) and 65 patients without ELC (29.5%) (p = 0.03). Kaplan–Meier analysis demonstrated that the occurrence of AF was significantly higher in the ELC group than in the non-ELC group (log-rank test, p = 0.013). Multivariate analysis revealed that ELC was independently associated with an increased risk of AF (hazard ratio 1.67, 95% confidence interval 1.03–2.72, p = 0.039). Conclusions: The presence of ELC is associated with a higher risk of new-onset AF following CTI ablation in patients with AFL. ELC may serve as a simple, non-invasive clinical marker to identify patients who may benefit from closer rhythm surveillance after AFL ablation. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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12 pages, 471 KB

Open AccessArticle

Impact of CPAP Therapy Adherence on Time to First Recurrence of Paroxysmal Atrial Fibrillation in Patients with Severe Obstructive Sleep Apnea

by Petar Kalaydzhiev, Radostina Ilieva, Natalia Spasova, Slavi Yakov, Dimitar Markov, Neli Georgieva, Elena Kinova and Assen Goudev

Life 2026, 16(3), 389; https://doi.org/10.3390/life16030389 - 28 Feb 2026

Viewed by 716

Abstract

Background: Obstructive sleep apnea (OSA) is a major modifiable risk factor for atrial fibrillation (AF), promoting arrhythmogenesis through intermittent hypoxia, autonomic activation, and atrial remodeling. Although continuous positive airway pressure (CPAP) effectively treats OSA, real-world evidence linking objectively measured CPAP exposure to clinically relevant AF recurrence remains limited. Aims: We aimed to evaluate the association between CPAP adherence and risk of recurrent paroxysmal AF, and to compare time to first recurrence between patients with mean nightly CPAP use ≥4 h/night versus <4 h/night. Materials and Methods: In this prospective observational cohort (2017–2024), consecutive hospitalized and outpatient adults with severe obstructive sleep apnea (OSA; apnea–hypopnea index > 30 events/h) and documented paroxysmal atrial fibrillation (AF) were enrolled. Persistent and long-standing persistent AF were excluded to ensure a homogeneous population with respect to atrial substrate. OSA was assessed using home sleep apnea testing (ResMed ApneaLink), and all patients initiated continuous positive airway pressure (CPAP) therapy (ResMed AirSense 10). Objective adherence data were obtained via the ResMed AirView telemonitoring platform. Exclusion criteria included permanent AF, prior pulmonary vein isolation, central sleep apnea, left ventricular ejection fraction < 50%, end-stage chronic kidney disease (eGFR < 15 mL/min/1.73 m² or dialysis), or inability to initiate or maintain CPAP therapy. Patients were followed for 12 months. The primary endpoint was time to first documented recurrence of paroxysmal AF (≥30 s on 12-lead electrocardiography or 24-h Holter monitoring). Progression to permanent AF, defined after unsuccessful rhythm control attempts and subsequent transition to a rate control strategy, was assessed as a secondary endpoint. Time-to-event analyses used Kaplan–Meier estimates with log-rank testing, and Cox proportional hazards regression adjusted for age, body mass index, apnea–hypopnea index, heart failure, left atrial volume index, and antiarrhythmic drug therapy. Results: The final analysis included 91 patients (mean age 62.15 ± 8.29 years; 68.13% men). Mean nightly CPAP use was ≥4 h/night in 49 patients and <4 h/night in 42 patients. During follow-up, paroxysmal AF recurrence occurred in 12/49 (24.5%) patients in the ≥4 h/night group and 16/42 (38.1%) in the <4 h/night group. Mean arrhythmia-free survival at 12 months was numerically higher in the ≥4 h/night group (11.25 vs. 10.51 months), without a statistically significant difference in Kaplan–Meier curves (log-rank p = 0.11). In multivariable Cox regression, binary adherence (≥4 h/night) was not independently associated with recurrence (HR 0.52, p = 0.13), whereas mean nightly CPAP use analyzed as a continuous variable remained independently associated with delayed recurrence (per 1-h increase: HR 0.66, 95% CI 0.48–0.91, p = 0.01). Progression to permanent AF occurred in 4/49 (10.0%) versus 9/42 (17.6%) patients, respectively (p = 0.29). Conclusions: In this real-world cohort of patients with severe OSA and paroxysmal AF, higher objectively measured CPAP exposure was independently associated with delayed AF recurrence when analyzed as a continuous variable, suggesting a graded association between objectively measured CPAP exposure and AF recurrence. Larger studies with extended follow-up and continuous rhythm monitoring are warranted to confirm long-term rhythm benefits and effects on AF progression. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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12 pages, 645 KB

Open AccessArticle

Transthoracic Echocardiography as a Tool for Early Detection of Atrial Fibrillation in Patients Receiving Ibrutinib

by Vittoria Gammaldi, Martina Pucci, Francesca La Rocca, Pasquale Megaro, Daniele Paoletta, Mariateresa Pontoriero, Luca Maria Capece, Roberto Luise, Marina Iacono and Roberta Esposito

Life 2026, 16(2), 324; https://doi.org/10.3390/life16020324 - 13 Feb 2026

Viewed by 498

Abstract

Background: Bruton’s tyrosine kinase inhibitors, particularly ibrutinib, have improved outcomes in patients with chronic lymphocytic leukemia but are associated with an increased risk of atrial fibrillation. The early identification of patients with increased susceptibility to atrial fibrillation remains a major challenge in cardio-oncology. Methods: This prospective pilot study included 45 patients with chronic lymphocytic leukemia treated with ibrutinib. All patients underwent comprehensive transthoracic echocardiography at baseline and after 6 months. Left atrial structure and function were assessed, with particular emphasis on speckle-tracking-derived left atrial strain parameters, including peak atrial longitudinal strain and peak atrial contraction strain. Results: At follow-up, a modest but significant increase in indexed left atrial volume was observed, while left atrial functional parameters remained stable. Patients who developed atrial fibrillation showed significantly lower baseline Peak Atrial Contraction Strain values compared with those who remained in sinus rhythm, whereas no significant differences in Peak Atrial Longitudinal Strain were detected. Conclusions: Ibrutinib-related atrial fibrillation appears to be driven primarily by pre-existing atrial vulnerability rather than early drug-induced atrial dysfunction. The baseline impairment of left atrial contractile function may represent a candidate echocardiographic marker of atrial functional vulnerability and may inform cardiovascular surveillance and monitoring strategies in patients treated with ibrutinib. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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13 pages, 345 KB

Open AccessArticle

Arrhythmias as Part of Long COVID Syndrome in Hospitalized Patients That Survived a Severe COVID-19 Infection and the Potential Protective Role of Metformin in These Patients

by Haydee Ninette Morales-Vazquez, David Cardona-Müller, Fernando Grover-Paez, Carlos Gerardo Ramos-Becerra, Ernesto Germán Cardona-Muñoz, Maria Guadalupe Ramos-Zavala, Jaime Carmona-Huerta, Jorge Eduardo Hernandez-del-Rio, Tomas Miranda-Aquino, Christian Gonzalez-Padilla and Christopher Josue Lopez-Gradilla

Life 2026, 16(2), 319; https://doi.org/10.3390/life16020319 - 12 Feb 2026

Viewed by 1105

Abstract

Background: Cardiac arrhythmias are a frequent complication of acute SARS-CoV-2 infection. However, their long-term prevalence and clinical determinants among patients with post-COVID-19 syndrome, especially those previously hospitalized, remain poorly defined. Objectives: To assess the prevalence and types of arrhythmias in long COVID patients following hospitalization and to identify associated clinical risk factors. Methods: In this cross-sectional study, 53 patients previously hospitalized with confirmed COVID-19 were evaluated ≥3 months post-infection. All participants underwent a standardized clinical assessment, 12-lead electrocardiography, and 24 h Holter monitoring. Logistic and Cox regression analyses were performed to identify predictors of arrhythmia. Results: Arrhythmias were identified in 41.5% (n = 22) of patients. Atrial fibrillation (32%) was the most frequent arrhythmia, followed by sinus bradycardia (27%) and sinus tachycardia (18%). Age (OR 1.06, 95% CI 1.01–1.10, p = 0.01) and length of hospital stay (OR 1.1, 95% CI 1.01–1.2, p = 0.04) were independently associated with arrhythmia. Biguanide (metformin) therapy was inversely associated with the occurrence of arrhythmia (Exp(B) = 0.017, p = 0.008). Dyspnea (82.4%) and palpitations (41.5%) were the most commonly reported symptoms. Conclusions: Arrhythmias are common in patients with long COVID following severe disease. Advanced age and prolonged hospitalization are significant risk factors, while biguanide use may offer a protective effect. These findings underscore the need for targeted cardiac surveillance in this population. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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Review

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27 pages, 1197 KB

Open AccessReview

Inflammation, Endothelial Dysfunction, and Platelet Dysregulation in Atrial Fibrillation with Chronic Kidney Disease: Toward a Biology-Informed Anticoagulation Strategy

by Maria-Daniela Tanasescu, Andrei-Mihnea Rosu, Alexandru Minca, Maria-Mihaela Grigorie, Delia Timofte and Dorin Ionescu

Life 2026, 16(4), 547; https://doi.org/10.3390/life16040547 - 26 Mar 2026

Viewed by 583

Abstract

Atrial fibrillation (AF) frequently coexists with chronic kidney disease (CKD), and their combination confers a disproportionate risk of both thromboembolic and bleeding events. Conventional anticoagulation strategies rely primarily on creatinine clearance-based dosing, which reflects pharmacokinetic safety but does not fully capture the biological processes underlying thrombohemorrhagic instability. This narrative review synthesizes recent mechanistic and translational evidence regarding the bidirectional cardio–renal axis in AF and CKD, focusing on systemic inflammation, endothelial dysfunction, platelet dysregulation, and altered coagulation. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science (2018–2026) was performed, complemented by manual review of key references and guidelines. The evidence indicates that inflammatory cytokine activation, oxidative stress, glycocalyx degradation, von Willebrand factor dysregulation, uremic platelet dysfunction, and enhanced thrombin generation converge to create a disrupted vascular interface in which stroke and bleeding arise from shared pathophysiological mechanisms. Renal trajectory and selected circulating biomarkers further highlight the dynamic and heterogeneous nature of risk in advanced CKD. These findings support reframing anticoagulation decision-making in AF with CKD from a static filtration-based model toward a biology-informed approach that integrates renal dynamics, endothelial and platelet phenotype, and clinical context to better align thromboembolic protection with hemorrhagic safety. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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23 pages, 923 KB

Open AccessReview

From Beat to Risk: How Heart Rate Variability Predicts Arrhythmias in Type 2 Diabetes

by Amelian Madalin Bobu, Ștefania-Teodora Duca, Andrei Ionut Cucu, Diana Alina Avieriței, Cosmina-Georgiana Ponor, Maria-Ruxandra Cepoi, Sandu Cucută, Bianca-Ana Dmour, Claudia Florida Costea, Gina Botnariu and Irina-Iuliana Costache-Enache

Life 2026, 16(3), 520; https://doi.org/10.3390/life16030520 - 21 Mar 2026

Viewed by 904

Abstract

Type 2 diabetes mellitus is associated with major cardiovascular complications, including cardiac autonomic neuropathy, which contributes to sympathetic–parasympathetic imbalance and increases susceptibility to arrhythmias and sudden cardiac death. Heart rate variability, assessed through R–R intervals on electrocardiography and 24 h Holter monitoring, represents a sensitive, non-invasive marker of autonomic dysfunction and arrhythmogenic risk. In patients with type 2 diabetes mellitus, chronic hyperglycaemia, oxidative stress, and metabolic inflammation lead to early impairment of the autonomic nervous system, manifested by consistent reductions in SDNN, RMSSD, pNN50, total power, and the high-frequency component, indicating diminished parasympathetic tone and sympathetic predominance. Nonlinear HRV indices demonstrate a loss of complexity and fractal organisation, providing additional prognostic value beyond conventional time- and frequency-domain analyses. Reduced HRV correlates with the severity of cardiac autonomic neuropathy, duration of diabetes, and poor glycaemic control, identifying patients with increased arrhythmogenic vulnerability. HRV analysis enables prediction of arrhythmic risk, facilitating the identification of high-risk individuals and guiding personalised interventions. The integration of HRV assessment into routine clinical practice may improve the early detection of subclinical autonomic neuropathy and optimise cardiovascular risk stratification and management in patients with type 2 diabetes mellitus. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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29 pages, 845 KB

Open AccessReview

Arrhythmia-Induced Cardiomyopathy in Atrial Fibrillation: Pathogenesis, Diagnosis, and Treatment

by Paschalis Karakasis, Panagiotis Theofilis, Panayotis K. Vlachakis, Anastasios Apostolos, Nikolaos Ktenopoulos, Konstantinos Grigoriou, Dimitrios Patoulias, Antonios P. Antoniadis and Nikolaos Fragakis

Life 2025, 15(11), 1675; https://doi.org/10.3390/life15111675 - 28 Oct 2025

Cited by 1 | Viewed by 3532

Abstract

Arrhythmia-induced cardiomyopathy (AIC) represents a potentially reversible form of LV dysfunction in which sustained atrial fibrillation (AF) and irregular, often rapid, ventricular activation drive maladaptive electrical, structural, and metabolic remodeling. Beyond simple rate effects, AIC reflects perturbed calcium handling, oxidative stress, and fibro-inflammatory signaling that propagate atrial–ventricular crosstalk and energetic failure. Clinically, attribution remains challenging because AF may be the cause, consequence, or marker of underlying myocardial disease; however, substantial improvement in LVEF after durable rhythm control is strongly supportive of an AIC component. A disciplined diagnostic pathway—integrating rhythm burden quantification, echocardiographic deformation indices, cardiac magnetic resonance, and natriuretic peptide trajectories—can refine pre-test probability and guide treatment intensity. Early rhythm control has emerged as a disease-modifying strategy in AF with HF, with catheter ablation often central to burden reduction and reverse remodeling; in parallel, rapid initiation of guideline-directed HF therapy and targeted cardiometabolic interventions may favor substrate regression and facilitate durable sinus rhythm. Uncertainties persist regarding standardized AIC case definition, arrhythmia burden thresholds that secure sustained recovery, optimal sequencing of rhythm- and substrate-directed therapies, and criteria for de-escalation of HF treatment after recovery. This review synthesizes contemporary mechanistic, diagnostic, and therapeutic evidence on AIC in AF and delineates priorities for future trials. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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