Preventing Postoperative Atrial Fibrillation
2019; Lippincott Williams & Wilkins; Volume: 12; Issue: 10 Linguagem: Inglês
10.1161/circep.119.007865
ISSN1941-3149
Autores Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculation: Arrhythmia and ElectrophysiologyVol. 12, No. 10Preventing Postoperative Atrial Fibrillation Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBPreventing Postoperative Atrial FibrillationA Stimulating New Approach Jordana Kron, MD and Alex Y. Tan, MD Jordana KronJordana Kron Jordana Kron, MD, Virginia Commonwealth University Medical Center, PO Box 980053, Richmond, VA 23298. Email E-mail Address: [email protected] Pauley Heart Center, Virginia Commonwealth University (J.K.). and Alex Y. TanAlex Y. Tan Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA (A.Y.T.). Originally published10 Oct 2019https://doi.org/10.1161/CIRCEP.119.007865Circulation: Arrhythmia and Electrophysiology. 2019;12:e007865This article is a commentary on the followingElectrical Stimulation of the Greater Auricular Nerve to Reduce Postoperative Atrial FibrillationSee Article by Andreas et alPostoperative atrial fibrillation (POAF) occurs in up to 50% of patients undergoing open-heart surgery and is associated with worse outcomes, including stroke, mortality, increased length of hospital stay, and increased health care costs.1 AF typically occurs within one week after cardiac surgery and 70% of patients who have AF after coronary artery bypass surgery have episodes within the first 3 days.2 POAF is no longer considered a transient one-off event, as it highlights an increased long term vulnerability to the development of AF.3 Therefore, the consequences of POAF are more substantial and sustained than may first appear.The mechanism(s) of POAF (Figure) is a combination of postoperative pro-fibrillatory milieu consisting of pericarditis, atrial injury, heightened sympathetic tone, ischemia-reperfusion, hemodynamic and metabolic derangements, superimposed on preexisting electrophysiological and structural atrial abnormalities.4,5 An imbalance, specifically, overactivity in both sympathetic and parasympathetic activities of the cardiac autonomic nervous system (CANS), plays a crucial role in promoting AF, including postoperative AF.6–8Download figureDownload PowerPointFigure. Mechanisms and effects of postoperative atrial fibrillation (AF).Current guidelines recommend medical therapy for AF after cardiac and thoracic surgery, but do not include any nonpharmacological interventions for treatment or prevention of AF.1 To treat postoperative AF, beta blockers are recommended as first-line therapy, followed by nondihydropyridine calcium channel blockers if adequate rate control is not achieved with beta blockers. For prevention of postoperative AF in high-risk patients undergoing cardiac surgery, preoperative amiodarone can be used to reduce the incidence of AF (Class IIA recommendation). There is also data to support using sotalol or colchicine to reduce the risk of postoperative AF (Class IIB recommendation). However, pharmacological preventative measures and treatments can be limited by medication side effects, including hypotension and bradycardia.In the current issue, Andreas et al9 present pilot data on the use of noninvasive low level transcutaneous electrical stimulation (LLTS) of the greater auricular nerve to reduce the risk of postoperative AF.9 Their hypothesis is that LLTS modulates activity of an imbalanced CANS triggered by the postoperative insult, leading to protection against POAF. In this single-center, randomized, double-blind study, 40 patients were randomized to LLTS treatment (n=20) or sham group (n=20). After cardiac surgery, patients in the treatment group received stimulation applied via electrodes in the triangular fossa of the ear for 40-minute increments followed by a 20-minute break for up to 2 weeks. All patients had continuous ECG monitoring as well as inflammatory markers including C-reactive protein and interleukin-6 measured immediately postsurgery and day 2 and 7 postsurgery. The key finding was that patients receiving LLTS had a significantly lower incidence of POAF (4 of 20) compared with the control group (11 of 20, P=0.022). However, the timing and duration of POAF and level of inflammatory markers did not differ between the treatment and control groups. The patients in each group with POAF experienced increased length of hospital stays compared with those without POAF, however, due to small numbers, this did not translate to reduced duration of hospital stays between the groups. Nevertheless, these findings demonstrate the feasibility of LLTS as a preventative therapy for POAF and support the design of a future larger multicenter trial for this prevalent and troublesome problem.An important question that arises from this thought-provoking study is what among the multiple mechanisms of POAF is modulated by LLTS? Low level vagus nerve stimulation (LLVNS) has been shown to suppress POAF and attenuate the inflammatory response post-cardiac surgery.10 In a prospective, randomized, sham-controlled study of 54 patients, 26 patients received LLVNS via a bipolar wire sutured to the vagus nerve preganglionic fibers near the lateral aspect of the superior vena cava for 72 hours. POAF occurred in 12% of the treatment group compared with 36% of the control group (P=0.027). At 72 hours post-surgery, inflammatory markers including tumor necrosis factor-α and interleukin-6 were significantly lower in the patients with LLVNS. The findings of this study highlight the pivotal role that inflammation and the CANS play in POAF. In a canine model, myeloperoxidase activity and neutrophil infiltration were higher in right atrial myocardium post-surgery compared with the control group.11 Furthermore, atrial inflammation after cardiac surgery was associated with a proportional increase in the inhomogeneity of atrial conduction and AF duration. Anti-inflammatory therapy decreased atrial conduction inhomogeneity after atriotomy.11 In clinical trials, anti-inflammatory medications, including corticosteroids, statins, and colchicine, have been shown to lower the incidence of POAF after cardiac surgery12 However, in the current study, C-reactive protein and interleukin-6 were not significantly lower in patients receiving LLTS. While it may be that a larger trial will show an impact of LLTS of the greater auricular nerve on inflammatory markers, it is possible that this treatment lowers POAF predominantly through its effect on the cardiac autonomic system rather than through modulation of post-surgical inflammation. Alternatively, LLTS modulates the CANS and therefore protects POAF despite post-surgical inflammation. Shen et al13 demonstrated that LLVNS suppresses sympathetic nerve activity and paroxysmal atrial tachyarrhythmias in a canine model.13 Our group recently demonstrated that postoperative cardiac inflammation lowers atrial effective refractory period and causes sympathetic surge to promote AF, whereas modulation of the CANS by targeting cardiac ganglionated plexi has vagolytic, sympatholytic and anti-arrhythmic effects, lengthening atrial refractory period and insulating against postoperative sympathetic storm.8 Finally, modulation of the CANS may suppress activity of the cardiac ganglionated plexi which in turn suppresses pulmonary vein triggers for AF.14 Therefore, LLTS may potentially dampen POAF triggers to protect against the pro-inflammatory, pro-fibrillatory substrate of the postoperative state. Questions remain about the autonomic pathway and effect of LLTS versus that of LLVNS. These questions highlight the necessity of further work in the lead up to clinical translation of this therapy.Greater auricular nerve stimulation has the advantage of being noninvasive, in contrast to LLVNS which is delivered via a pair of epicardial temporary pacing wires that may increase operative time and risk and must be removed at the end of the therapy. Importantly, vagal nerve stimulation appears to be very safe. In the LLVNS study, no patients had complications related to the epicardial wire placement for vagus nerve stimulation.10 Some patients had minor discomfort from greater auricular nerve stimulation not requiring intervention, and one patient in the stimulation group had a seizure.9Other novel autonomic modulation strategies have been studied to reduce POAF. In the first-in-human study, botulinum toxin injections into epicardial fat pads significantly reduced the rate of any atrial tachyarrhythmia at 12, 24, and 36 months in patients with history of paroxysmal AF who underwent coronary artery bypass grafting.15 Sixty patients were randomized to botulinum toxin injections (n=30) or placebo (n=30) into 4 posterior epicardial fat pads. At 36 months, 23.3% of patients in the treatment group had any atrial tachyarrhythmia compared with 50.0% in the control group (P=0.02). Botulinum inhibits acetylcholine release and reduces atrial cholinergic neurotransmission that plays a role in triggering AF.14 The prolonged anti-arrhythmic effect may result from reverse atrial remodeling due to early reduction in AF burden.14Recently, our group demonstrated that epicardial injection of timed-release nanoformulated CaCl2 in a canine POAF model exerts an anticholinergic modulation of atrial tissue, increasing atrial effective refractory period.8 The cardiac ganglionic plexi injections induced neuroapoptosis and suppressed POAF without any observed adverse effects or effects on ventricular function.AF after cardiac surgery exacts a high toll in terms of worse patient outcomes and increased health care costs. A noninvasive, highly effective, low-risk preventative therapy to decrease the incidence of POAF would be a great step forward in the field. However, many knowledge gaps remain. Comparative clinical trials are needed to determine the most effective and best-tolerated site for post-op vagal nerve stimulation. The optimal delivery strategy is not known, including the schedule and duration of stimulation. The effect of LLTS on long-term AF rates has not been studied, and the device is not yet approved for prevention of POAF. Finally, the autonomic and anti-arrhythmic mechanisms of noninvasive vagus nerve stimulation remain unclear. Both basic science studies and larger, multicenter clinical trials are needed in parallel to help address some of these issues, particularly the magnitude of therapeutic effect and whether the postoperative inflammatory milieu is diminished by greater auricular nerve stimulation. The authors are commended on a provocative pilot study that offers hope to reduce the risk of POAF while also providing further insight into the mechanisms driving this burdensome arrhythmia.DisclosuresDr Kron is supported by the Virginia Commonwealth University Wright Center for Clinical and Translational Research. Dr Tan is supported by American Heart Association Scientist Development Grant (AHA SDG16SDG3128001) and Virginia Commonwealth Research Commercialization Fund MF16-041-LS).FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Jordana Kron, MD, Virginia Commonwealth University Medical Center, PO Box 980053, Richmond, VA 23298. Email jordana.[email protected]orgReferences1. 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Circulation: Arrhythmia and Electrophysiology. 2019;12 October 2019Vol 12, Issue 10 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.119.007865PMID: 31597475 Originally publishedOctober 10, 2019 Keywordsvagus nerve stimulationpost-operativeEditorialsatrial fibrillationcoronary artery bypassPDF download Advertisement SubjectsAtrial FibrillationCardiovascular Surgery
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