Obstructive sleep apnea (OSA) is a highly prevalent disorder in patients with atrial fibrillation (AF). Although there has been an increase in the incidence of AF due to the aging population, it has ...been reported that OSA is still underdiagnosed because many patients remain asymptomatic or unaware of the symptoms associated with OSA, such as daytime sleepiness. Untreated OSA reduces the effectiveness of AF treatment, regardless of pharmacological or non‐pharmacological modes of therapy, such as catheter ablation. Experimental and clinical studies have shown that OSA pathophysiology is multifactorial, comprising of hypoxemia, hypercapnia, autonomic dysfunction, negative intrathoracic pressure changes, and arousals of OSA, and lead to AF. Both the acute and long‐term effects of obstructive apnea episodes are involved in the development of an arrhythmogenic substrate of AF. Undiagnosed OSA causes underutilized opportunities for more effective AF management. Therefore, it is important to screen for OSA in all patients being considered for rhythm control therapy. However, regardless of the growing evidence of the negative prognostic impact of OSA, there is a lack of awareness regarding this connection not only among patients but also among cardiologists and arrhythmia specialists. There is a barrier to performing a systemic screening for OSA in clinical practice. Therefore, it is important to establish a comprehensive OSA care team for the efficient diagnosis and treatment of OSA. This review provides the current understanding of OSA and its relationship to AF and the importance of the diagnosis and management of OSA in AF.
Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important contributor to population morbidity and mortality. An arrhythmia that is particularly common in the elderly, AF ...is growing in prevalence with the aging of the population. Our understanding of the basic mechanisms that govern AF occurrence and persistence has been increasing rapidly. This article reviews the basic pathophysiology of AF over a broad range of levels, touching on the tissue mechanisms that maintain the arrhythmia, the relationship between clinical presentation and basic mechanisms, ion channel and transporter abnormalities that lead to ectopic impulse formation, basic models and tissue determinants of reentry, ion channel determinants of reentry, the nature and roles of electric and structural remodeling, autonomic neural components, anatomic factors, interactions between atrial and ventricular functional consequences of AF, and the basic determinants of atrial thromboembolism. We then review the potential implications of the basic pathophysiology of the arrhythmia for its management. We first discuss consequences for improved rhythm control pharmacotherapy: targeting underlying conditions, new atrium-selective drug targets, new targets for focal ectopic source suppression, and upstream therapy aiming to prevent remodeling. We then review the implications of basic mechanistic considerations for rate control therapy, AF ablation, and the prevention of thromboembolic events. We conclude with some thoughts about the future of translational research related to AF mechanisms.
A 77-year-old man attended our hospital reporting a sudden onset of shortness of breath and a fever. 14 days earlier, the patient had posterior wall isolation, pulmonary vein isolation, and linear ...mitral isthmus ablation for drug-refractory atrial fibrillation. Following the procedure, he was complication-free and had been allowed home; he had been prescribed anticoagulation therapy and a proton pump inhibitor. On examination, the patient was frail but not in a critical state; his blood pressure was 148/68 mm Hg, his pulse was 90 beats per min, and his oxygen saturation was 95% on room air, and his temperature was 38·0°C. Laboratory investigations showed a white blood cell count of 18·8 × 109 per L (typical range 4·5–11·0), C-reactive protein concentration 18·61 mg/dL (typical range <0·3), brain natriuretic peptide 78 pg/mL (typical <18·4), and troponin I 15 pg/mL (typical 26·2 or less).
Cardiac resynchronization therapy (CRT) is well-established for treating symptomatic heart failure with electrical dyssynchrony. The left ventricular (LV) lead position is recommended at LV ...posterolateral to lateral sites in patients with left bundle branch block; however, its preferred region remains unclear in patients being upgraded from right ventricular (RV) apical pacing to CRT. This study aimed to identify the preferred LV lead position for upgrading conventional RV apical pacing to CRT.
We used electrode catheters positioned at the RV apex and LV anterolateral and posterolateral sites via the coronary sinus (CS) branches to measure the ratio of activation time to QRS duration from the RV apex to the LV anterolateral and posterolateral sites during RV apical pacing. Simultaneous biventricular pacing was performed at the RV apex and each LV site, and the differences in QRS duration and LV dP/dt
from those of RV apical pacing were measured.
Thirty-seven patients with anterolateral and posterolateral LV CS branches were included. During RV apical pacing, the average ratio of activation time to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.90 ± 0.06 vs. 0.71 ± 0.11, p < .001). The decreasing ratio of QRS duration and the increasing ratio of LV dP/dt
were higher at the LV anterolateral site than at the posterolateral site (45.7 ± 18.0% vs. 32.0 ± 17.6%, p < .001; 12.7 ± 2.9% vs. 3.7 ± 8.2%, p < .001, respectively) during biventricular pacing compared with RV apical pacing.
The LV anterolateral site is the preferred LV lead position in patients being upgraded from conventional RV apical pacing to CRT.
A highly conductive textile was woven from nano-fibers coated with the PEDOT-PSS polymer. The aim of this study was to assess the usefulness of textile electrodes for ECG recording as a smart ...garment. Electrode textile pads and lead wires were sewn to the lining of sportswear and their tolerability to repeated washings were tested up to 150 times. The electrical conductivity of the textile electrode remained functional for up to 50 machine washes. To assess the level of motion artifacts or noise during the daily monitoring of ECG, a single lead ECG with conventional or textile electrodes was recorded during supine rest, seated rest, upright trunk rotation (i.e., twisting), and stepping movement in 66 healthy adults. A Holter system was used for data storage and analysis. ECG patterns of P, QRS, and T waves were comparable between the conventional and textile electrodes. However, the signal-to-artifact-and/or-noise ratio (SAR) during twisting was larger in the textile electrodes than in the conventional electrodes. No skin irritation was seen in the textile electrodes. The single lead textile electrodes embedded in an inner garment were usable for continuous and/or repeated ECG monitoring in daily life except during vigorous trunk movement.
The goal of this study was to assess mechanisms underlying atrial fibrillation (AF) promotion by exercise training in an animal model.
High-level exercise training promotes AF, but the underlying ...mechanisms are unclear.
AF susceptibility was assessed by programmed stimulation in rats after 8 (Ex8) and 16 (Ex16) weeks of daily 1-h treadmill training, along with 4 and 8 weeks after exercise cessation and time-matched sedentary (Sed) controls. Structural remodeling was evaluated by using serial echocardiography and histopathology, autonomic nervous system with pharmacological tools, acetylcholine-regulated potassium current (IKACh) with patch clamp recording, messenger ribonucleic acid expression with quantitative polymerase chain reaction, and regulators of G protein-signaling (RGS) 4 function in knockout mice.
AF inducibility increased after 16 weeks of training (e.g., AF >30 s in 64% of Ex16 rats vs 15% of Sed rats; p < 0.01) and rapidly returned to baseline levels with detraining. Atropine restored sinus rhythm in 5 of 5 Ex rats with AF sustained >15 min. Atrial dilation and fibrosis developed after 16 weeks of training and failed to fully recover with exercise cessation. Parasympathetic tone was increased in Ex16 rats and normalized within 4 weeks of detraining. Baroreflex heart rate responses to phenylephrine-induced blood pressure elevation and IKACh sensitivity to carbachol were enhanced in Ex16 rats, implicating both central and end-organ mechanisms in vagal enhancement. Ex rats showed unchanged cardiac adrenergic and cholinergic receptor and IKACh-subunit gene expression, but significant messenger ribonucleic acid downregulation of IKACh-inhibiting RGS proteins was present at 16 weeks. RGS4 knockout mice showed significantly enhanced sensitivity to AF induction in the presence of carbachol.
Chronic endurance exercise increased AF susceptibility in rats, with autonomic changes, atrial dilation, and fibrosis identified as potential mechanistic contributors. Vagal promotion is particularly important and occurs via augmented baroreflex responsiveness and increased cardiomyocyte sensitivity to cholinergic stimulation, possibly due to RGS protein downregulation.
Excess psychological stress is one of the precipitating factors for paroxysmal atrial fibrillation (AF), although the involved mechanisms are still uncertain. To test a hypothesis that one of the ...stress-induced hormones, glucocorticoid, is involved in the pathogenesis of stress-induced AF, we investigated whether the glucocorticoid could alter the temporal profile of cardiac ion channels gene expression, thereby leading to atrial arrhythmogenesis.Dexamethasone (DEX, 1.0 mg/kg) was injected subcutaneously in Sprague-Dawley rats. At predetermined times after DEX injection (0, 1, 3, 6, 12, and 24 hours), the mRNA levels of cardiac ion channel genes (erg, KvLQT1, Kv4.3, Kv4.2, Kv2.1, Kv1.5, Kv1.4, Kv1.2, SUR2A, Kir6.2, Kir3.4, Kir3.1 Kir2.2, Kir2.1, SCN5A, and α1C) were determined using RNase protection assay. DEX induced immediate and transient increase in the mRNA level of Kv1.5 and Kir2.2 with peaks at 6 (5.0 fold) and 3 hours (3.3 fold) after DEX injection, respectively. Patch-clamp studies revealed a significantly increased current density of the corresponding current, IKur and IK1 at 6 hours after DEX injection. Simultaneously, electrophysiological study in isolated perfused hearts showed significantly increased number of repetitive atrial responses induced by single atrial extrastimulus (3.2 ± 2.4 to 26.7 ± 16.4, P = 0.004) with shorting of the refractory period (36.4 ± 4.6 to 27.4 ± 5.5 ms, P = 0.049) after DEX injection.Glucocorticoid immediately modified Kv1.5 and Kir2.2 gene expression at pretranslational levels, thus leading to effective refractory period shortening that could be arrhythmogenic. These results implied that transient glucocorticoid-induced biochemical modification of cardiac ion channels might be one of the mechanisms underlying the stress-induced paroxysmal AF.
Abstract Background Obstructive sleep apnea (OSA) importantly contributes to the occurrence of atrial fibrillation (AF) in humans, but the mechanisms are poorly understood. Experimental research has ...provided insights into AF promotion by acute OSA episodes. However, patients with OSA usually have frequent nocturnal episodes for some time before manifesting AF. Objectives The goal of this study was to test the hypothesis that repetitive OSA causes cardiac remodeling that predisposes to AF. Methods We mimicked OSA by using a mechanical ventilator and closing the airway at end-expiration with a 3-way stopcock (OSA rats). Matched control groups included rats with the ventilator stopped but airway left open (open airway rats) and continuously ventilated rats (sham rats). OSA rats were exposed to 20 consecutive 2-min cycles of 40 s of apnea/80 s of ventilation per day, 5 days per week for 4 weeks. Results OSA significantly increased the duration of AF from (median interquartile range) 2.6 s 1.9 s to 8.9 s (shams) and 16 s 1.8 s to 93 s (open airway) to 49s 34 s to 444 s. AF inducibility increased to 56% (9 of 16) of OSA rats; this is up from 15% (2 of 13) and 13% (2 of 15) in open airway and sham rats, respectively (p < 0.05). OSA rats exhibited substantial atrial conduction slowing on optical mapping, along with connexin-43 down-regulation on both quantitative immunofluorescence (expression reduced by 58% vs sham rats) and Western blot (reduced by 38%), as well as increased atrial fibrous tissue content (by 71%). OSA also caused left ventricular hypertrophy, dilation, and diastolic dysfunction and enhanced AF inducibility during superimposed acute OSA episodes to 82.4% of rats. Conclusions Chronically repeated OSA episodes cause AF-promoting cardiac remodeling, with conduction abnormalities related to connexin dysregulation and fibrosis playing a prominent role. This novel animal model provides mechanistic insights into an important clinical problem and may be useful for further exploration of underlying mechanisms and therapeutic approaches.
PDF
