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 s of intermittent negative upper airway pressure (INAP) applied by a negative pressure device connected to the endotracheal tube. Intermittent negative upper airway pressures were performed before and after PVI. AF-inducibility and atrial effective refractory periods (aERPs) were determined before and during INAP by programmed atrial stimulation. Pulmonary vein isolation 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). Intermittent negative upper airway pressure 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). Intermittent negative upper airway pressure 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.

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.