25 research outputs found
Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review
The prevalence of atrial fibrillation (AF) is bound to increase globally in the following years, affecting the quality of life of millions of people, increasing mortality and morbidity, and beleaguering health care systems. Increasingly effective therapeutic options against AF are the constantly evolving electroanatomic substrate mapping systems of the left atrium (LA) and ablation catheter technologies. Yet, a prerequisite for better long-term success rates is the understanding of AF pathogenesis and maintenance. LA electrical and anatomical remodeling remains in the epicenter of current research for novel diagnostic and treatment modalities. On a molecular level, electrical remodeling lies on impaired calcium handling, enhanced inwardly rectifying potassium currents, and gap junction perturbations. In addition, a wide array of profibrotic stimuli activates fibroblast to an increased extracellular matrix turnover via various intermediaries. Concomitant dysregulation of the autonomic nervous system and the humoral function of increased epicardial adipose tissue (EAT) are established mediators in the pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate and increased inflammasome activity accelerate and perpetuate arrhythmia substrate. Finally, impaired intracellular protein metabolism, excessive oxidative stress, and mitochondrial dysfunction deplete atrial cardiomyocyte ATP and promote arrhythmogenesis. These overlapping cellular and molecular alterations hinder us from distinguishing the cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic modalities target these molecular perturbations and hold promise in combating the AF burden. Namely, atrial selective ion channel inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing, immunomodulators, and indirect cardiac neuromodulation are discussed here
Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review
The prevalence of atrial fibrillation (AF) is bound to increase globally
in the following years, affecting the quality of life of millions of
people, increasing mortality and morbidity, and beleaguering health care
systems. Increasingly effective therapeutic options against AF are the
constantly evolving electroanatomic substrate mapping systems of the
left atrium (LA) and ablation catheter technologies. Yet, a prerequisite
for better long-term success rates is the understanding of AF
pathogenesis and maintenance. LA electrical and anatomical remodeling
remains in the epicenter of current research for novel diagnostic and
treatment modalities. On a molecular level, electrical remodeling lies
on impaired calcium handling, enhanced inwardly rectifying potassium
currents, and gap junction perturbations. In addition, a wide array of
profibrotic stimuli activates fibroblast to an increased extracellular
matrix turnover via various intermediaries. Concomitant dysregulation of
the autonomic nervous system and the humoral function of increased
epicardial adipose tissue (EAT) are established mediators in the
pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate
and increased inflammasome activity accelerate and perpetuate arrhythmia
substrate. Finally, impaired intracellular protein metabolism, excessive
oxidative stress, and mitochondrial dysfunction deplete atrial
cardiomyocyte ATP and promote arrhythmogenesis. These overlapping
cellular and molecular alterations hinder us from distinguishing the
cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic
modalities target these molecular perturbations and hold promise in
combating the AF burden. Namely, atrial selective ion channel
inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing,
immunomodulators, and indirect cardiac neuromodulation are discussed
here
Efficacy, Safety and Feasibility of Superior Vena Cava Isolation in Patients Undergoing Atrial Fibrillation Catheter Ablation: An Up-to-Date Review
Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI