Innovations in atrial fibrillation ablation

Kim, Jitae A; Khan, Khurrum; Kherallah, Riyad; Khan, Shamis; Kamat, Ishan; Ulhaq, Owais; Marashly, Qussay; Chelu, Mihail G.

doi:10.1007/s10840-022-01215-y

Cited by 4 publications

(4 citation statements)

References 137 publications

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“…The management of atrial fibrillation (AF) is complex and many patients experience recurrence of symptoms after an invasive treatment with catheter ablation [ 1 ]. Although general outcomes of AF ablation have improved over the years, due to innovations of ablation techniques, recurrence of arrhythmias is still experienced by at least one in five patients [ 2 , 3 ]. The prevalence of AF in Europe is currently estimated at 8 million and is expected to rise to 10 million in a decade [ 4 ].…”

Section: Background and Rationalementioning

confidence: 99%

Improving outcomes of AF ablation by integrated personalized lifestyle interventions: rationale and design of the prevention to improve outcomes of PVI (POP) trial

et al. 2023

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Progression of atrial fibrillation (AF) and outcomes of ablation therapy are strongly affected by modifiable risk factors. Although previous studies show beneficial effects of modifying single risk factors, there is lack of evidence from randomized controlled trials on the effects of integrated AF lifestyle programmes. The POP trial is designed to evaluate the clinical outcomes of a dedicated nurse-led AF lifestyle outpatient clinic in patients with symptomatic AF. This study is a prospective, 1:1 randomized, single centre, investigator-initiated clinical trial in 150 patients with paroxysmal or persistent AF referred for a first pulmonary vein isolation (PVI). Prior to the ablation, patients in the intervention group receive a personalized risk factor treatment programme in a specialized, protocolized, nurse-led outpatient clinic. Patient education and durable lifestyle management is promoted with an e-health platform. Patients in the control group receive standard care by cardiologists before ablation. The primary endpoint is the number of hospitalizations for re-ablation and cardioversion, with a follow-up of 12 months after ablation. Secondary endpoints include mortality, number of acute ischemic events, stroke or hospitalizations for heart failure, quality of life, number of ablations cancelled because of symptom reduction, and ablation success rate at 12 months. Determinants of patient and staff experience are explored and a cost-effectiveness analysis is included. The POP trial will help ascertain the efficacy and cost-effectiveness of an integrated technology-supported lifestyle therapy in patients with symptomatic AF. The trial is funded by the Netherlands Organisation for Health Research and Development [10070012010001]. Home sleep apnoea testing devices were provided by Itamar Medical, Ltd.ClinicalTrials.gov Identifier NCT05148338. Graphical abstract AF atrial fibrillation, OSA obstructive sleep apnoea, PFA pulsed field ablation, PVI pulmonary vein isolation.

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Section: Background and Rationalementioning

confidence: 99%

Improving outcomes of AF ablation by integrated personalized lifestyle interventions: rationale and design of the prevention to improve outcomes of PVI (POP) trial

et al. 2023

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“…Different ablation technologies could be exposed, such as radiofrequency, cryoballoon ablation, laser balloon, etc. [ 150 ]. It is beyond the scope of this article to describe each of them which are reviewed elsewhere [ 151 ].…”

Section: Rhythm Control In Atrial Fibrillation: Toward a Translationa...mentioning

confidence: 99%

Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients

Parra-Lucares,

Villa,

Romero-Hernández

et al. 2023

IJMS

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Atrial fibrillation (AF) is a prevalent cardiac condition predominantly affecting older adults, characterized by irregular heartbeat rhythm. The condition often leads to significant disability and increased mortality rates. Traditionally, two therapeutic strategies have been employed for its treatment: heart rate control and rhythm control. Recent clinical studies have emphasized the critical role of early restoration of sinus rhythm in improving patient outcomes. The persistence of the irregular rhythm allows for the progression and structural remodeling of the atria, eventually leading to irreversible stages, as observed clinically when AF becomes permanent. Cardioversion to sinus rhythm alters this progression pattern through mechanisms that are still being studied. In this review, we provide an in-depth analysis of the pathophysiological mechanisms responsible for maintaining AF and how they are modified during sinus rhythm restoration using existing therapeutic strategies at different stages of clinical investigation. Moreover, we explore potential future therapeutic approaches, including the promising prospect of gene therapy.

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“…This problematic clinical trial record, together with high costs, and the inherent deadly risks associated with targeting heart rhythm disorders, has slowed the development of anti-arrhythmic drugs. While there are new and growing methods of treating arrhythmias, such as catheter ablation [7, 8] neuroscientific therapies [9], or even optogenetic methods [10], there remains considerable academic and clinical interest in new mechanistic targets to address the growing unmet clinical need for safe and effective pharmacologic treatment of disorders of cardiac electrical rhythm [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of the Mode-of-Action of Inhibitory and Agonist Peptides Targeting the Voltage-Gated Sodium Channel SCN1B/β1 Subunit

Williams,

Alvarez-Laviada,

Hoagland

et al. 2023

Preprint

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Treatment of cardiac arrhythmias by targeting ion channels is challenging, with safe and effective therapies remaining an unmet clinical need. Modeling and experimental studies have shown that a voltage-gated sodium channel (VGSC)-rich nanodomain at edge of the gap junction (GJ) called the perinexus could provide new mechanistic insights into normal and abnormal conduction of action potentials in the heart. We have reported that a 19 amino acid SCN1B (β1/β1B) mimetic peptide derived from the immunoglobulin domain of the VGSC subunit called βadp1 acutely disrupts β1-mediated adhesive interactions at cardiac perinexii, prompting arrhythmogenic changes during time courses of up to an hour. In the present study, we sought to gain further insight on βadp1 mode-of-action, as well as identifying new SCN1B (β1/β1B) mimetic peptides, with potential for inhibiting and/or promoting β1-mediated adhesion. This included studies of the effect of βadp1 and related peptides on SCN1B (β1/β1B) Regulated Intramembrane Proteolysis (RIP) - a signaling pathway that has been shown to effect gene transcription, including that of VGSC subunits. Using patch clamp to assay cell-cell contact-associated VGSC activity in cardiomyocytes, and electric cell substrate impedance sensing (ECIS) to assess intercellular adhesion in cells heterologously expressing β1, we find that inhibitory effects of βadp1 can persist for up to 5 hours. However, this acute inhibition is not sustained, with βadp1 effects on β1-mediated adhesion lost after 24 hours. We also determined that a short peptide (LQLEED) near the carboxyl-terminal portion of βadp1 inhibited adhesion in β1-expressing cells in a manner similar to βadp1. Paradoxically, dimeric peptides incorporating a repeat of the LQLEED sequence promoted intercellular adhesion at all time points studied over a 2-day time course. Inhibitory and agonistic peptides were found to effect β1 RIP, with βadp1increasing RIP continuously over 48 hours, whilst dimeric agonists acutely increased RIP at 6 hours post-treatment, but not thereafter. In the presence of DAPT, an inhibitor of RIP, the effects of βadp1 on ECIS-measured intercellular adhesion were lost, suggesting a relationship between RIP and inhibitory effects of the peptide. In sum, we identify novel SCN1B (β1/β1B) mimetic peptides with potential to inhibit and promote intercellular β1-mediated adhesion, possibly including by effects on β1 RIP, suggesting paths to development of anti-arrhythmic drugs targeting the perinexus.

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Innovations in atrial fibrillation ablation

Cited by 4 publications

References 137 publications

Improving outcomes of AF ablation by integrated personalized lifestyle interventions: rationale and design of the prevention to improve outcomes of PVI (POP) trial

Improving outcomes of AF ablation by integrated personalized lifestyle interventions: rationale and design of the prevention to improve outcomes of PVI (POP) trial

Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients

Development and Characterization of the Mode-of-Action of Inhibitory and Agonist Peptides Targeting the Voltage-Gated Sodium Channel SCN1B/β1 Subunit

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