Resting membrane potential is less negative in trabeculae from right atrial appendages of women, but action potential duration does not shorten with age
Graphical abstract
Introduction
Atrial fibrillation (AF) is the most common rhythm disorder and associated with high comorbidity and increased mortality risk [1]. Research in recent years yielded detailed information about epidemiology and comorbidities affecting AF [2]. The incidence of AF increases with age, and women are at lower risk of developing the disease [1,3,4]. Many classical cardiovascular risk factors and comorbidities, e.g. heart failure, myocardial infarction, sleep disordered breathing, are known to affect AF [4]. However, their impact on atrial electrophysiology remains unclear. A more detailed understanding of the underlying pathophysiological mechanisms would be a further step towards improving personalized medicine [2]. Therefore, we set out to investigate retrospectively the impact of clinical variables on action potentials (AP) recorded in right atrial tissue obtained during open heart surgery from patients in sinus rhythm (SR) and in persistent atrial fibrillation (AF).
Section snippets
Human tissue samples
The study followed the declaration of Helsinki and all patients gave written informed consent. All investigations were approved by the Medical Faculty Ethics Committee of the Technical University Dresden; approval number EK 114082202. Each patient gave written, informed consent. Clinical parameters were collected from the medical records of patients and analyzed after anonymisation. Part of data were previously used for a preliminary analysis on sex effects on AP [5]. Some data were used for
Results
We analyzed data from 521 patients undergoing open heart surgery. 320 patients with SR and 201 patients with longstanding persistent AF were included in this retrospective analysis.
Principal findings
In our large data set we investigated the impact of clinical variables on human atrial AP by multivariable analyses. We found only moderate effects of age on APD90, which we assume cannot explain the steep increase in AF prevalence with age. However, there were clear sex-related differences that could be relevant for the lower incidence of AF in women.
Clinical context: age
The higher likelihood of AF observed in the elderly suggests distinct electrophysiological changes that facilitate the occurrence of AF. Effects
Conclusions
In humans, the increase in AF with age cannot be explained by a shortening in APD. The lower incidence of AF in women associates with less negative RMP and reduced sodium channel function. One may speculate whether pharmacological inhibition of currents regulating RMP could be helpful to prevent reoccurrence of AF.
The following are the supplementary data related to this article.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. RBS has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union's Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK) (81Z1710103); German
Data availability statement
The data underlying this article will be shared on reasonable request to the corresponding author.
Declaration of Competing Interest
SP has received lecture fees and advisory board fees from Medtronic and Philips Healthcare outside this work. RBS has received lecture fees and advisory board fees from BMS/Pfizer outside this work.
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These authors contributed equally.