New approaches for treating atrial fibrillation: Focus on autonomic modulation.
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ABSTRACT:
SUBMITTER: Sohinki D
PROVIDER: S-EPMC7190441 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The cardiac autonomic nerve system (CANS) is a potentially potent modulator of the initiation and perpetuation of atrial fibrillation (AF). In this review, we focus on the relationship between the autonomic nervous system (ANS) and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia from eight aspects. We conclude that Activation and Remodeling of CANS involved in the initiation and maintenance of AF. The network control mechanism, innervation regions, and sympathetic/parasympathetic balance play an important role in AF substrate. And the formation of Complex Fractional Atrial Electrograms also related to CANS activity. In addition, modulating CANS function by potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, and low-level vagal nerve stimulation, may enable AF to be controlled. Although the role of the ANS has long been recognized, a better understanding of the complex interrelationships of the various components of the CANS will lead to improvement of treatments for this common arrhythmia.
| S-EPMC6553352 | biostudies-literature
Project description:BackgroundThe autonomic activity plays a critical role in generating paroxysmal atrial fibrillation (PAF). This study aimed to evaluate the changes in the autonomic nerve activity before and after PAF events in patients with and without ischemic heart disease (IHD).MethodsThe study included 49 patients (71.43 ± 12.24 years old, 26 males) with PAF events lasting more than 30 s during 24-hr ambulatory Holter monitoring. The 20-min intervals before and after PAF events were divided into eight segments of 5 min each. Heart rate variability (HRV) analyses of the time and frequency domains were applied to each time segment.ResultsPatients with IHD had significant increases in the root mean square successive differences (r-MSSD, p = .008) and HF component (p = .04), followed by a significant increase in the LF/HF ratio (p = .02) preceding the onset of PAF. Patients without IHD had only a significant increase in the r-MSSD (p = .045) preceding the onset of PAF. During the termination of PAF events, patients in both the IHD and control groups had a significantly decreased r-MSSD and HF, respectively.ConclusionIschemic heart disease causes a sympathovagal imbalance in the initiation of PAF. Decreased parasympathetic activity regulated the termination of PAF in both the IHD and control groups. The modification of the autonomic nervous system (ANS) activity should be individualized due to the autonomic complexity in AF arrhythmogenesis and termination.
| S-EPMC7507060 | biostudies-literature
Project description:The mechanism(s) for acute changes in electrophysiological properties of the atria during rapid pacing induced atrial fibrillation (AF) is not completely understood. We sought to evaluate the contribution of the intrinsic cardiac autonomic nervous system in acute atrial electrical remodeling and AF induced by 6-hour rapid atrial pacing.Continuous rapid pacing (1200 bpm, 2x threshold [TH]) was performed at the left atrial appendage. Group 1 (n=7) underwent 6-hour pacing immediately followed by ganglionated plexi (GP) ablation; group 2 (n=7) underwent GP ablation immediately followed by 6-hour pacing; and group 3 (n=4) underwent administration of autonomic blockers, atropine (1 mg/kg), and propranolol (0.6 mg/kg) immediately followed by 6-hour pacing. The effective refractory period (ERP) and window of vulnerability (WOV, in milliseconds), ie, the difference between the longest and the shortest coupling interval of the premature stimulus that induced AF, were measured at 2xTH and 10xTH at the left atrium, right atrium, and pulmonary veins every hour before and after GP ablation or autonomic blockade. In group 1, ERP was markedly shortened in the first 2 hours and then stabilized both at 2xTH and 10xTH; however, WOV was progressively widened throughout the 6-hour period. After GP ablation, ERP was significantly longer than before ablation and AF could not be induced (WOV=0) at either 2xTH or 10xTH. In groups 2 and 3, rapid atrial pacing failed to shorten the ERP. AF could not be induced in 6 of 7 dogs in group 2 and all 4 dogs in group 3 during the 6-hour pacing period.The intrinsic cardiac autonomic nervous system plays a crucial role in the acute stages of atrial electrical remodeling induced by rapid atrial pacing.
| S-EPMC2766842 | biostudies-literature
Project description:The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals. This effect was mediated by acetylcholine (ACh) stimulation of nicotinic receptors on splenic macrophages. Hence, the circuit was dubbed the "cholinergic anti-inflammatory pathway". Subsequent work identified the α7 nicotinic ACh receptor (α7nAChR) as the crucial target for attenuation of pro-inflammatory cytokine release from macrophages and dendritic cells. Further investigation made the important discovery that cholinergic T cells within the spleen and not cholinergic nerve cells were the source of ACh that stimulated α7 receptors on splenic macrophages. Given the important role that inflammation plays in numerous disease processes, cholinergic anti-inflammatory mechanisms are under intensive investigation from a basic science perspective and in translational studies of animal models of diseases such as inflammatory bowel disease and rheumatoid arthritis. This basic work has already fostered several clinical trials examining the efficacy of VNS and cholinergic therapeutics in human inflammatory diseases. This review provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response and relevant pharmacology of drugs acting at the α7nAChR.
| S-EPMC5651192 | biostudies-literature
Project description:In this review, the authors describe evolving alternative strategies for the management of AF, focusing on non-invasive and percutaneous autonomic modulation. This modulation can be achieved - among other approaches - via tragus stimulation, renal denervation, cardiac afferent denervation, alcohol injection in the vein of Marshall, baroreceptor activation therapy and endocardial ganglionated plexi ablation. Although promising, these therapies are currently under investigation but could play a role in the treatment of AF in combination with conventional pulmonary vein isolation in the near future.
| S-EPMC8728882 | biostudies-literature
Project description:Dronedarone is an amiodarone derivative that was approved in the US in July 2009 to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF), who are in sinus rhythm (SR), or who will be cardioverted.This article reviews the pharmacology, adverse effects, and clinical evidence available to date on the use of dronedarone in the management of AF and its potential role in the emergency department setting.In the EURIDIS and ADONIS studies evaluating the efficacy of dronedarone in maintaining SR, dronedarone significantly reduced the risk of recurrence of AF compared to placebo, by 22% and 27%, respectively. The ERATO study examined the ability of dronedarone to control ventricular rate in permanent AF. The DIONYSOS study demonstrated that recurrences of AF were more frequent with dronedarone. However, discontinuation of therapy due to intolerance was more frequent with amiodarone. Furthermore, the ATHENA study demonstrated that dronedarone reduced mortality and cardiovascular hospitalization by 24% (P < 0.05) in patients in SR but with other associated risks and a history of AF. However, the ANDROMEDA study, evaluating the use of dronedarone in patients with recent decompensated heart failure, and the PALLAS study, evaluating the use of dronedarone in patients with chronic AF, were both terminated prematurely due to a trend toward an increased risk of cardiovascular events.Dronedarone has been demonstrated to be effective in reducing the incidence of AF recurrence. It appears to be less effective but better tolerated than amiodarone. Dronedarone appears to have a low proarrhythmic risk and is the first anti-arrhythmic that has been demonstrated to reduce cardiovascular mortality and cardiovascular hospitalization in clinically stable patients with other risk factors for recurrent AF. Therefore, dronedarone can be recommended as an anti-arrhythmic of choice in clinically stable patients for maintaining SR. If dronedarone is to be used in a patient with chronic stable heart failure, the patient must be monitored closely for any worsening of heart failure symptoms. The drug must be discontinued should the heart failure symptoms worsen.
| S-EPMC4753968 | biostudies-other
Project description:BackgroundAtrial fibrillation (AF) is associated with loss of cognition and dementia. Cardiac autonomic dysfunction has been linked to cognitive decline. We aimed to investigate if reduced cardiac autonomic function (CAF) is associated with cognitive impairment in AF patients.MethodsPatients with paroxysmal, persistent and permanent AF were enrolled from a multicenter cohort study if they had AF ("AF group") or sinus rhythm ("SR group") on a baseline 5 min ECG recording. Parameters quantifying CAF (heart rate variability triangular index (HRVI), mean heart rate (MHR), RMSSD, SDNN, total power and power in the VLF, LF, HF ranges) were calculated. We used the Montreal Cognitive Assessment (MoCA) to assess global cognitive function.Results1685 AF patients with a mean age of 73 ± 8 years, 29% females, were included. MoCA score was 24.5 ± 3.2 in the AF group (N = 710 patients) and 25.4 ± 3.2 in the SR group (N = 975 patients). After adjusting for multiple confounders, lower HRVI was associated with lower MoCA scores, both in the SR group [β = 0.049; 95% confidence interval (CI) 0.016-0.081; p = 0.003] and in the AF group (β = 0.068; 95% CI 0.020-0.116; p = 0.006). In the AF group, higher MHR was associated with a poorer performance in the MoCA (β = - 0.008; 95% CI - 0.014 to - 0.002; p = 0.014). We found no convincing evidence of association for other CAF parameters with cognition.ConclusionOur data suggest that impaired CAF is associated with worse cognitive performance in patients with AF. Among standard HRV parameters, HRVI might be the most promising ECG index.Trial registrationClinicalTrials.gov Identifier: NCT02105844.
| S-EPMC8766386 | biostudies-literature
Project description:CONTEXT:Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. OBJECTIVE:To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME MEASURES:Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ?65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. RESULTS:Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009). CONCLUSIONS:In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.
| S-EPMC3073054 | biostudies-literature
Project description:START-Register--Survey on anTicoagulated pAtients RegisTer--is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1 ± 1.1, CHADSVASc score was 3.1 ± 1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) <30 ml/min]. Moderate renal failure (CrCl 30-59 ml/min) was found in 1265 patients (39.5%). The analysis of the START-Register data shows that two-third of patients who started chronic anticoagulant treatment had NVAF, one-third of them was > 80 years with high prevalence of renal failure.
| S-EPMC4441383 | biostudies-other
Project description:Autonomic nervous system activation can induce significant and heterogeneous changes of atrial electrophysiology and induce atrial tachyarrhythmias, including atrial tachycardia and atrial fibrillation (AF). The importance of the autonomic nervous system in atrial arrhythmogenesis is also supported by circadian variation in the incidence of symptomatic AF in humans. Methods that reduce autonomic innervation or outflow have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. In this review, we focus on the relationship between the autonomic nervous system and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia. We conclude that autonomic nerve activity plays an important role in the initiation and maintenance of AF, and modulating autonomic nerve function may contribute to AF control. Potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, cervical vagal nerve stimulation, baroreflex stimulation, cutaneous stimulation, novel drug approaches, and biological therapies. Although the role of the autonomic nervous system has long been recognized, new science and new technologies promise exciting prospects for the future.
| S-EPMC4043633 | biostudies-literature