Catheter-based pulmonary vein isolation fails to prevent transient atrial arrhythmogenic changes related to acute obstructive respiratory events in a porcine model.

AIMS: Pulmonary vein isolation (PVI) is the corner stone of modern rhythm control strategies in patients with atrial fibrillation (AF). Sleep-disordered breathing (SDB) is prevalent in more than 50% of patients undergoing AF ablation and studies have indicated a greater recurrence rate after PVI in patients with SDB. Herein, we study the effect of catheter-based PVI on AF in a pig model for SDB. METHODS AND RESULTS: In 11 sedated spontaneously breathing pigs, obstructive apnoeas were simulated by 75 seconds of intermittent negative upper airway pressure (INAP) applied by a negative pressure device connected to the endotracheal tube. INAPs were performed before and after PVI. AF-inducibility and atrial effective refractory periods (aERP) were determined before and during INAP by programmed atrial stimulation. PVI prolonged the aERP by 48 ± 27 ms in the right atrium (RA) (p < 0.0001) and by 40 ± 34 ms in the left atrium (LA) (p = 0.0004). Following PVI, AF-inducibility dropped from 28 ± 26% to 0% (p = 0.0009). INAP was associated with a transient aERP-shortening (ΔaERP) in both atria, which was not prevented by PVI (INAP indued ΔaERP after PVI in the RA: -57 ± 34 ms, p = 0.0002; in the LA: -42 ± 24 ms, p < 0.0001). INAP was associated with a transient increase in AF-inducibility (from 28 ± 26% to 69 ± 21%; p = 0.0008), which was not attenuated by PVI (INAP-associated AF-inducibility after PVI: 58 ± 33% (p = 0.5)). CONCLUSION: Transient atrial arrhythmogenic changes related to acute obstructive respiratory events are not prevented by electrical isolation of the pulmonary veins, which partially explains the increased AF recurrence in patients with SDB after PVI procedures.

Inhibition of the acetylcholine-regulated potassium current prevents transient apnea-related atrial arrhythmogenic changes in a porcine model.

BACKGROUND: More than 50% of patients with atrial fibrillation (AF) suffer from sleep disordered breathing (SDB). Obstructive respiratory events contribute to a transient, vagally mediated atrial arrhythmogenic substrate, which is resistant to most available antiarrhythmic drugs. OBJECTIVE: The purpose of this study was to investigate the effect of pharmacologic inhibition of the G-protein-gated acetylcholine-regulated potassium current (IK,ACh) with and without acute autonomic nervous system activation by nicotine in a pig model for obstructive respiratory events. METHODS: In 21 pigs, SDB was simulated by applying an intermittent negative upper airway pressure (INAP). AF inducibility and atrial effective refractory periods (aERPs) were determined before and during INAP by an S1S2 atrial pacing-protocol. Pigs were randomized into 3 groups-group 1: vehicle (n = 4); group 2: XAF-1407 (IK,ACh inhibitor) (n = 7); and group 3: nicotine followed by XAF-1407 (n = 10). RESULTS: In group 1, INAP shortened aERP (ΔaERP -42.6 ms; P = .004) and transiently increased AF inducibility from 0% to 31%. In group 2, XAF-1407 prolonged aERP by 25.2 ms (P = .005) during normal breathing and prevented INAP-induced aERP shortening (ΔaERP -3.6 ms; P = .3) and AF inducibility. In group 3, INAP transiently shortened aERP during nicotine perfusion (ΔaERP -33.6 ms; P = .004) and increased AF inducibility up to 61%, which both were prevented by XAF-1407. CONCLUSION: Simulated obstructive respiratory events transiently shorten aERP and increase AF inducibility, which can be prevented by the IK,ACh-inhibitor XAF-1407. XAF-1407 also prevents these arrhythmogenic changes induced by obstructive respiratory events during nicotine perfusion. Whether IK,ACh channels represent a target for SDB-related AF in humans warrants further study.

The role of cellular senescence in profibrillatory atrial remodelling associated with cardiac pathology.

AIMS: Cellular senescence is a stress-related or aging response believed to contribute to many cardiac conditions; however, its role in atrial fibrillation (AF) is unknown. Age is the single most important determinant of the risk of AF. The present study was designed to (i) evaluate AF susceptibility and senescence marker expression in rat models of aging and myocardial infarction (MI), (ii) study the effect of reducing senescent-cell burden with senolytic therapy on the atrial substrate in MI rats, and (iii) assess senescence markers in human atrial tissue as a function of age and the presence of AF. METHODS AND RESULTS: AF susceptibility was studied with programmed electrical stimulation. Gene and protein expression was evaluated by immunoblot or immunofluorescence (protein) and digital polymerase chain reaction (PCR) or reverse transcriptase quantitative PCR (messenger RNA). A previously validated senolytic combination, dasatinib and quercetin, (D+Q; or corresponding vehicle) was administered from the time of sham or MI surgery through 28 days later. Experiments were performed blinded to treatment assignment. Burst pacing-induced AF was seen in 100% of aged (18-month old) rats, 87.5% of young MI rats, and 10% of young control (3-month old) rats (P ≤ 0.001 vs. each). Conduction velocity was slower in aged [both left atrium (LA) and right atrium (RA)] and young MI (LA) rats vs. young control rats (P ≤ 0.001 vs. each). Atrial fibrosis was greater in aged (LA and RA) and young MI (LA) vs. young control rats (P < 0.05 for each). Senolytic therapy reduced AF inducibility in MI rats (from 8/9 rats, 89% in MI vehicle, to 0/9 rats, 0% in MI D + Q, P < 0.001) and attenuated LA fibrosis. Double staining suggested that D + Q acts by clearing senescent myofibroblasts and endothelial cells. In human atria, senescence markers were upregulated in older (≥70 years) and long-standing AF patients vs. individuals ≤60 and sinus rhythm controls, respectively. CONCLUSION: Our results point to a potentially significant role of cellular senescence in AF pathophysiology. Modulating cell senescence might provide a basis for novel therapeutic approaches to AF.

An inflammation resolution-promoting intervention prevents atrial fibrillation caused by left ventricular dysfunction.

AIMS: Recent studies suggest that bioactive mediators called resolvins promote an active resolution of inflammation. Inflammatory signalling is involved in the development of the substrate for atrial fibrillation (AF). The aim of this study is to evaluate the effects of resolvin-D1 on atrial arrhythmogenic remodelling resulting from left ventricular (LV) dysfunction induced by myocardial infarction (MI) in rats. METHODS AND RESULTS: MI was produced by left anterior descending coronary artery ligation. Intervention groups received daily intraperitoneal resolvin-D1, beginning before MI surgery (early-RvD1) or Day 7 post-MI (late-RvD1) and continued until Day 21 post-MI. AF vulnerability was evaluated by performing an electrophysiological study. Atrial conduction was analysed by using optical mapping. Fibrosis was quantified by Masson's trichrome staining and gene expression by quantitative polymerase chain reaction and RNA sequencing. Investigators were blinded to group identity. Early-RvD1 significantly reduced MI size (17 ± 6%, vs. 39 ± 6% in vehicle-MI) and preserved LV ejection fraction; these were unaffected by late-RvD1. Transoesophageal pacing induced atrial tachyarrhythmia in 2/18 (11%) sham-operated rats, vs. 18/18 (100%) MI-only rats, in 5/18 (28%, P < 0.001 vs. MI) early-RvD1 MI rats, and in 7/12 (58%, P < 0.01) late-RvD1 MI rats. Atrial conduction velocity significantly decreased post-MI, an effect suppressed by RvD1 treatment. Both early-RvD1 and late-RvD1 limited MI-induced atrial fibrosis and prevented MI-induced increases in the atrial expression of inflammation-related and fibrosis-related biomarkers and pathways. CONCLUSIONS: RvD1 suppressed MI-related atrial arrhythmogenic remodelling. Early-RvD1 had MI sparing and atrial remodelling suppressant effects, whereas late-RvD1 attenuated atrial remodelling and AF promotion without ventricular protection, revealing atrial-protective actions unrelated to ventricular function changes. These results point to inflammation resolution-promoting compounds as novel cardio-protective interventions with a particular interest in attenuating AF substrate development.

Muscarinic acetylcholine receptors M2 are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Background: Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone. Aim: To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M2) and the G protein-gated inwardly rectifying K+ (GIRK4) channel that mediates the cardiac IK,ACh current. Method: Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assigned to the control group, while 17 horses with a high burden of second-degree AV block (median: 408 block per 20 h, IQR: 1,436 per 20 h) were assigned to the AV block group. Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing (n = 16). Furthermore, the expression levels of the M2 receptor and the GIRK4 subunit of the IKACh channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis (n = 9 + 9). Results: The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s; p < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86 ms; p = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered (p = 0.80). The AV block group had significantly higher expression of the M2 receptor (p = 0.02), but not the GIRK4 (p = 0.25) in the AV node compared to the control group. Both M2 and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles. Conclusion: Here, we demonstrate the involvement of the m2R-IK,ACh pathway in underlying second-degree AV block in horses. The high expression level of the M2 receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.

Chronic kidney disease promotes atrial fibrillation via inflammasome pathway activation.

Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanistic link between CKD and AF remains elusive. IL-1ß, a main effector of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, is a key modulator of conditions associated with inflammation, such as AF and CKD. Circulating IL-1ß levels were elevated in patients with CKD who had AF (versus patients with CKD in sinus rhythm). Moreover, NLRP3 activity was enhanced in atria of patients with CKD. To elucidate the role of NLRP3/IL-1ß signaling in the pathogenesis of CKD-induced AF, Nlrp3-/- and WT mice were subjected to a 2-stage subtotal nephrectomy protocol to induce CKD. Four weeks after surgery, IL-1ß levels in serum and atrial tissue were increased in WT CKD (WT-CKD) mice versus sham-operated WT (WT-sham) mice. The increased susceptibility to pacing-induced AF and the longer AF duration in WT-CKD mice were associated with an abbreviated atrial effective refractory period, enlarged atria, and atrial fibrosis. Genetic inhibition of NLRP3 in Nlrp3-/- mice or neutralizing anti-IL-1ß antibodies effectively reduced IL-1ß levels, normalized left atrial dimensions, and reduced fibrosis and the incidence of AF. These data suggest that CKD creates a substrate for AF development by activating the NLRP3 inflammasome in atria, which is associated with structural and electrical remodeling. Neutralizing IL-1ß antibodies may be beneficial in preventing CKD-induced AF.

Recent Advances in Antiarrhythmic Drug Therapy.

Cardiac arrhythmias remain a common cause of death and disability. Antiarrhythmic drugs (AADs) and antiarrhythmic agents remain a cornerstone of current cardiac arrhythmia management, despite moderate efficacy and the potential for significant adverse proarrhythmic effects. Due to conceptual, regulatory and financial considerations, the number of novel antiarrhythmic targets and agents in the development pipeline has decreased substantially during the last few decades. However, several promising candidates remain and there are exciting developments in repurposing and reformulating already existing drugs for indications related to cardiac arrhythmias. This review discusses the key conceptual considerations for the development of new antiarrhythmic agents, summarizes new compounds and formulations currently in clinical development for rhythm control of atrial fibrillation, and highlights the potential for drug repurposing. Finally, future directions in AAD development are discussed. Together with an ever-increasing understanding of the molecular mechanisms underlying cardiac arrhythmias, these components support a cautiously optimistic outlook towards improved pharmacological treatment opportunities for patients suffering from cardiac arrhythmias.

Long-Term Training Increases Atrial Fibrillation Sustainability in Standardbred Racehorses.

Atrial fibrillation (AF) is more prevalent in athletes, and currently, the mechanisms are not fully understood. Atrial fibrillation inducibility and stability was investigated in trained and untrained Standardbred racehorses. The horses underwent echocardiography for evaluation of atrial size. High-density mapping during AF was performed, and the presence of structural remodeling, as well as the expression of inflammatory and pro-inflammatory markers in the atria, was studied. Atrial fibrillation sustained significantly longer after tachypacing in the trained horses, whereas no difference in AF inducibility was found. The untrained horses displayed a significant difference in the AF complexity when comparing right and left atria, whereas such difference was not observed in the trained animals. No evidence of increased structural remodeling or inflammation could be identified. Left atrial dimensions were not significantly increased. The increased AF sustainability in trained horses was not related to fibrosis or inflammation as seen in other animal exercise models.

Enhanced Ca2+-Dependent SK-Channel Gating and Membrane Trafficking in Human Atrial Fibrillation.

BACKGROUND: Small-conductance Ca2+-activated K+ (SK)-channel inhibitors have antiarrhythmic effects in animal models of atrial fibrillation (AF), presenting a potential novel antiarrhythmic option. However, the regulation of SK-channels in human atrial cardiomyocytes and its modification in patients with AF are poorly understood and were the object of this study. METHODS: Apamin-sensitive SK-channel current (ISK) and action potentials were recorded in human right-atrial cardiomyocytes from sinus rhythm control (Ctl) patients or patients with (long-standing persistent) chronic AF (cAF). RESULTS: ISK was significantly higher, and apamin caused larger action potential prolongation in cAF- versus Ctl-cardiomyocytes. Sensitivity analyses in an in silico human atrial cardiomyocyte model identified IK1 and ISK as major regulators of repolarization. Increased ISK in cAF was not associated with increases in mRNA/protein levels of SK-channel subunits in either right- or left-atrial tissue homogenates or right-atrial cardiomyocytes, but the abundance of SK2 at the sarcolemma was larger in cAF versus Ctl in both tissue-slices and cardiomyocytes. Latrunculin-A and primaquine (anterograde and retrograde protein-trafficking inhibitors) eliminated the differences in SK2 membrane levels and ISK between Ctl- and cAF-cardiomyocytes. In addition, the phosphatase-inhibitor okadaic acid reduced ISK amplitude and abolished the difference between Ctl- and cAF-cardiomyocytes, indicating that reduced calmodulin-Thr80 phosphorylation due to increased protein phosphatase-2A levels in the SK-channel complex likely contribute to the greater ISK in cAF-cardiomyocytes. Finally, rapid electrical activation (5 Hz, 10 minutes) of Ctl-cardiomyocytes promoted SK2 membrane-localization, increased ISK and reduced action potential duration, effects greatly attenuated by apamin. Latrunculin-A or primaquine prevented the 5-Hz-induced ISK-upregulation. CONCLUSIONS: ISK is upregulated in patients with cAF due to enhanced channel function, mediated by phosphatase-2A-dependent calmodulin-Thr80 dephosphorylation and tachycardia-dependent enhanced trafficking and targeting of SK-channel subunits to the sarcolemma. The observed AF-associated increases in ISK, which promote reentry-stabilizing action potential duration shortening, suggest an important role for SK-channels in AF auto-promotion and provide a rationale for pursuing the antiarrhythmic effects of SK-channel inhibition in humans.

3D-electroanatomical mapping of the left atrium and catheter-based pulmonary vein isolation in pigs: A practical guide.

Aim: To propose a standardized workflow for 3D-electroanatomical mapping guided pulmonary vein isolation in pigs. Materials and methods: Danish female landrace pigs were anaesthetized. Ultrasound-guided puncture of both femoral veins was performed and arterial access for blood pressure measurement established. Fluoroscopy- and intracardiac ultrasound-guided passage of the patent foramen ovale or transseptal puncture was performed. Then, 3D-electroanatomical mapping of the left atrium was conducted using a high-density mapping catheter. After mapping all pulmonary veins, an irrigated radiofrequency ablation catheter was used to perform ostial ablation to achieve electrical pulmonary vein isolation. Entrance- and exit-block were confirmed and re-assessed after a 20-min waiting period. Lastly, animals were sacrificed to perform left atrial anatomical gross examination. Results: We present data from 11 consecutive pigs undergoing pulmonary vein isolation. Passage of the fossa ovalis or transseptal puncture was uneventful and successful in all animals. Within the inferior pulmonary trunk 2-4 individual veins as well as 1-2 additional left and right pulmonary veins could be cannulated. Electrical isolation by point-by-point ablation of all targeted veins was successful. However, pitfalls including phrenic nerve capture during ablation, ventricular arrhythmias during antral isolation close to the mitral valve annulus and difficulties in accessing right pulmonary veins were encountered. Conclusion: Fluoroscopy- and intracardiac ultrasound-guided transseptal puncture, high-density electroanatomical mapping of all pulmonary veins and complete electrical pulmonary vein isolation can be achieved reproducibly and safely in pigs when using current technologies and a step-by-step approach.

Adiposity-associated atrial fibrillation: molecular determinants, mechanisms, and clinical significance.

Obesity is an important contributing factor to the pathophysiology of atrial fibrillation (AF) and its complications by causing systemic changes, such as altered haemodynamic, increased sympathetic tone, and low-grade chronic inflammatory state. In addition, adipose tissue is a metabolically active organ that comprises various types of fat deposits with discrete composition and localization that show distinct functions. Fatty tissue differentially affects the evolution of AF, with highly secretory active visceral fat surrounding the heart generally having a more potent influence than the rather inert subcutaneous fat. A variety of proinflammatory, profibrotic, and vasoconstrictive mediators are secreted by adipose tissue, particularly originating from cardiac fat, that promote atrial remodelling and increase the susceptibility to AF. In this review, we address the role of obesity-related factors and in particular specific adipose tissue depots in driving AF risk. We discuss the distinct effects of key secreted adipokines from different adipose tissue depots and their participation in cardiac remodelling. The possible mechanistic basis and molecular determinants of adiposity-related AF are discussed, and finally, we highlight important gaps in current knowledge, areas requiring future investigation, and implications for clinical management.

Cartilaginous Intrusion of the Atrioventricular Node in a Quarter Horse with a High Burden of Second-Degree AV Block and Collapse: A Case Report.

Second-degree atrioventricular (AV) block is the most common cardiac arrhythmia in horses, affecting 40-90% depending on breed. Usually, the AV blocks occur while the horses are resting and disappear upon exercise and are, therefore, considered to be uneventful for horses. However, if the AV blocks occur frequently, this may result in syncope and collapse. Identifying the cause of second-degree AV block is difficult and often subscribed to high vagal tone. In this report, we present an eight-year-old Quarter horse with a high burden of second-degree AV blocks and multiple collapses. The clinical examination, including neurological examination, blood analysis, 24-h ECG recording and cardiac echocardiography, did not reveal any signs of general or cardiovascular disease besides a high burden of second-degree AV blocks (~300 blocks per hour) and a hyperechoic area in the AV nodal region. An implantable loop recorder (ILR) was inserted to monitor the cardiac rhythm. The ILR detected several consecutive second-degree AV blocks and pauses above 5 s. However, unfortunately, no recordings were available during the collapses. Eventually, the horse was euthanized and the heart inspected. The aortic root was severely cartilaginous and appeared to penetrate the AV node, especially in the His bundle region, possibly explaining the hampered AV conduction. Nevertheless, it is still uncertain if the AV nodal disruption caused the collapses and more knowledge on AV nodal diseases in horses is warranted.

TGF-ß1-induced endothelial-mesenchymal transition: a potential contributor to fibrotic remodeling in atrial fibrillation?

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide, with an unmet therapeutic need. Fibrotic remodeling, in which collagen-producing atrial fibroblasts play a crucial role, substantially contributes to arrhythmia promotion and progression. In this issue of the JCI, Lai, Tsai, and co-authors reveal that TGF-ß1 promoted endothelial-mesenchymal transition during AF and put forward the notion that, in the adult heart, atrial fibroblasts can originate from different cellular sources. These important findings extend our understanding of the origin, biology, and function of fibroblasts and offer possibilities for therapeutic targeting of fibrosis in AF.

Emerging Antiarrhythmic Drugs for Atrial Fibrillation.

Atrial fibrillation (AF), the most common cardiac arrhythmia worldwide, is driven by complex mechanisms that differ between subgroups of patients. This complexity is apparent from the different forms in which AF presents itself (post-operative, paroxysmal and persistent), each with heterogeneous patterns and variable progression. Our current understanding of the mechanisms responsible for initiation, maintenance and progression of the different forms of AF has increased significantly in recent years. Nevertheless, antiarrhythmic drugs for the management of AF have not been developed based on the underlying arrhythmia mechanisms and none of the currently used drugs were specifically developed to target AF. With the increased knowledge on the mechanisms underlying different forms of AF, new opportunities for developing more effective and safer AF therapies are emerging. In this review, we provide an overview of potential novel antiarrhythmic approaches based on the underlying mechanisms of AF, focusing both on the development of novel antiarrhythmic agents and on the possibility of repurposing already marketed drugs. In addition, we discuss the opportunity of targeting some of the key players involved in the underlying AF mechanisms, such as ryanodine receptor type-2 (RyR2) channels and atrial-selective K+-currents (IK2P and ISK) for antiarrhythmic therapy. In addition, we highlight the opportunities for targeting components of inflammatory signaling (e.g., the NLRP3-inflammasome) and upstream mechanisms targeting fibroblast function to prevent structural remodeling and progression of AF. Finally, we critically appraise emerging antiarrhythmic drug principles and future directions for antiarrhythmic drug development, as well as their potential for improving AF management.

Researchers in cardiology - Why and how to get on Twitter?

Social media (SoMe) for professional use has gained importance for scientific impact. In cardiology, Twitter is among the preferred SoMe platforms for scientific dissemination. We are in the middle of a paradigm shift within scientific dissemination as more scientific content is presented on Twitter, and it is crucial to embrace it. Therefore, this paper includes a description and discussion of the existing literature reporting the impact of Twitter on research dissemination, as well as a guide on how to get started. In addition, we describe a case of the Danish Cardiovascular Academy Summer Meeting 2021 as an example of a scientific event that was promoted on Twitter before, during and after the event and present a survey showing that participants were inspired to increase the use of SoMe professionally. Finally, the paper addresses limitations of Twitter and SoMe for scientific use and discuss a need for an increased evidence base.

Pharmacological inhibition of acetylcholine-regulated potassium current (I K,ACh) prevents atrial arrhythmogenic changes in a rat model of repetitive obstructive respiratory events.

BACKGROUND: In obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase atrial fibrillation (AF) susceptibility by cholinergic activation. OBJECTIVE: To investigate short-term atrial electrophysiological consequences of obstructive respiratory events, simulated by intermittent negative upper airway pressure (INAP), and the role of atrial acetylcholine-regulated potassium current (I K,ACh) activated by the M2 receptor. METHODS: In sedated (2% isoflurane), spontaneously breathing rats, INAP was applied noninvasively by a negative pressure device for 1 minute, followed by a resting period of 4 minutes. INAP was applied repeatedly throughout 70 minutes, followed by a 2-hour recovery period. Atrial effective refractory period (AERP) and AF inducibility were determined throughout the protocol. To study INAP-induced I K,ACh activation, protein levels of protein kinase C (PKCƐ) were determined in membrane and cytosolic fractions of left atrial (LA) tissue by Western blotting. Moreover, an I K,ACh inhibitor (XAF-1407: 1 mg/kg) and a muscarinic receptor inhibitor (atropine: 1 µg/kg) were investigated. RESULTS: In vehicle-treated rats, repetitive INAP shortened AERP (37 ± 3 ms vs baseline 44 ± 3 ms; P = .001) and increased LA membrane PKCƐ content relative to cytosolic levels. Upon INAP recovery, ratio of PKCƐ membrane to cytosol content normalized and INAP-induced AERP shortening reversed. Both XAF-1407 and atropine increased baseline AERP (control vs XAF-1407: 61 ± 4 ms; P > .001 and control vs atropine: 58 ± 3 ms; P = .011) and abolished INAP-associated AERP shortening. CONCLUSION: Short-term simulated OSA is associated with a progressive, but transient, AERP shortening and a PKCƐ translocation to LA membrane. Pharmacological I K,ACh and muscarinic receptor inhibition prevented transient INAP-induced AERP shortening, suggesting an involvement of I K,ACh in the transient arrhythmogenic AF substrate in OSA.

Sleep apnea and atrial fibrillation: challenges in clinical and translational research.

INTRODUCTION: Sleep-disordered breathing (SDB) is present in 21-74% of all patients with atrial fibrillation (AF). Treatment of SDB by positive airway pressure may help to prevent recurrence of AF after electrical cardioversion and help to improve AF ablation success rates in non-randomized studies. AREAS COVERED: In this review, the current understanding of the atrial arrhythmogenic pathophysiology of SDB is summarized, and diagnostic and therapeutic challenges in AF patients are discussed. Current international recommendations are presented, and a comprehensive literature search is undertaken. EXPERT OPINION: AF patients with SDB rarely report SDB-related symptoms such as daytime sleepiness. Therefore, systematic home sleep testing evaluation should be considered for all patients eligible for rhythm control strategy. A close interdisciplinary collaboration between the electrophysiologist/cardiologist, nurses and sleep-specialists are required for the management of SDB in AF patients. An arrhythmia-orientated assessment of SDB may better quantify SDB-related AF risk in an individual patient and may help to better guide targeted and personalized SDB treatment in AF patients as a component of rhythm and symptom control strategies. Finally, randomized controlled trials are needed to confirm the relationship between SDB and AF, and the benefits of routine testing and treatment of SDB in AF patients.