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Anatomy of the sympathetic and parasympathetic innervation of the heart. AV: atrioventricular; SA: sinoatrial.
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A 55-year-old hypertensive patient presents atrial fibrillation after vasovagal syncope. Non-invasive cardiac workup is normal. Without antiarrhythmic therapy, the patient has no recurrence for the next 3years, then presents with a stroke. Echocardiography eventually reveals left atrial dilation. This sequence of events illustrates the well-known l...
Context in source publication
Context 1
... extrinsic cardiac nervous system mediates connec- tions between the heart and the cervical, stellate and thoracic ganglia (sympathetic connections) on the one hand, and the medulla oblongata (parasympathetic connections) on the other hand ( Fig. 1). Preganglionic parasympathetic neurons are located primarily in the ventral lateral region of the nucleus ambiguus and, to a lesser extent, in the dorsal motor nucleus and the intermediate zone between these two medullary nuclei. These neurons project axons to postganglionic neurons located in the cardiac ganglionated plexi (GPs). Preganglionic sympathetic neurons located in the spinal cord project axons via the T 1 -T 4 thoracic nerves to neurons located mainly in the cervical and stellate gan- glia. Although sympathetic and parasympathetic activation essentially have opposite effects on cardiac indices, neurons in the intrathoracic ganglia are in constant communication +Model ACVD-1065;No. of Pages 11 Atrial fibrillation: Neurogenic or myogenic ? 3 with one another and with central neurons, forming reflexes that control anatomically overlapping cardiac regions [2]. The intrinsic cardiac nervous system does not act as a simple relay station that processes centrifugal inputs to the heart. This system, consisting of a complex network of neu- rons and GPs nested within epicardial fat pads, is involved in the transduction of local signals (i.e. the system can regulate cardiac function directly, independent of higher autonomic centres). Signals arriving from the central nervous system via the extrinsic cardiac nervous system are also integrated by the intrinsic cardiac nervous system, which processes both centripetal and centrifugal information [3]. In a dog model of AF, Choi et al. demonstrated that although the majority of AF episodes were associated with activation of the extrinsic cardiac nervous system, some episodes were associated with isolated activation of the intrinsic cardiac nervous system ...
Citations
... Increased oxidative stress observed in obese patients activates a series of processes (including atrial inflammation, fibrosis, and electrical remodeling) that are, in turn, involved in the occurrence of AF [153,154]. But, these processes, including oxidative stress, are also a consequence of AF. As a result, ROS inhibition in obese subjects may serve as a new therapeutic strategy for breaking the oxidative stress-AF vicious circle. ...
The adipose tissue has long been thought to represent a passive source of triglycerides and fatty acids. However, extensive data have demonstrated that the adipose tissue is also a major endocrine organ that directly or indirectly affects the physiological functions of almost all cell types. Obesity is recognized as a risk factor for multiple systemic conditions, including metabolic syndrome, type 2 diabetes mellitus, sleep apnea, cardiovascular disorders, and many others. Obesity-related changes in the adipose tissue induce functional and structural changes in cardiac myocytes, promoting a wide range of cardiovascular disorders, including atrial fibrillation (AF). Due to the wealth of epidemiologic data linking AF to obesity, the mechanisms underlying AF occurrence in obese patients are an area of rich ongoing investigation. However, progress has been somewhat slowed by the complex phenotypes of both obesity and AF. The triad inflammation, oxidative stress, and mitochondrial dysfunction are critical for AF pathogenesis in the setting of obesity via multiple structural and functional proarrhythmic changes at the level of the atria. The aim of this paper is to provide a comprehensive view of the close relationship between obesity-induced oxidative stress, inflammation, and mitochondrial dysfunction and the pathogenesis of AF. The clinical implications of these mechanistic insights are also discussed.
... The ICNS pathways comprise a network of neurons and ganglionated-plexi (GPs) present within the epicardial fat pads. They act as a relay station that processes information from the heart and trans-conducts the local signals to regulate cardiac function, independent of the higher ANS [15]. The ICNS is sometimes referred to as the heart's "little brain" [14]. ...
... The extrinsic cardiac nervous system mediates information between the heart and the cervical, stellate, and thoracic ganglia forming sympathetic connections, and the medulla oblongata forming the parasympathetic connections [15]. The ganglia of the parasympathetic division are distributed mainly within the epicardial area and are intrinsic, while the ganglia of the sympathetic division are present in the sympathetic chain or in the paravertebral ganglia [18][19][20]. ...
The interplay between neurology and cardiology has gained significant attention in recent years, particularly regarding the shared pathophysiological mechanisms and clinical comorbidities observed in epilepsy and arrhythmias. Neuro-cardiac electrophysiology mapping involves the comprehensive assessment of both neural and cardiac electrical activity, aiming to unravel the intricate connections and potential cross-talk between the brain and the heart. The emergence of artificial intelligence (AI) has revolutionized the field by enabling the analysis of large-scale data sets, complex signal processing, and predictive modeling. AI algorithms have been applied to neuroimaging, electroencephalography (EEG), electrocardiography (ECG), and other diagnostic modalities to identify subtle patterns, classify disease subtypes, predict outcomes, and guide personalized treatment strategies. In this review, we highlight the potential clinical implications of neuro-cardiac mapping and AI in the management of epilepsy and arrhythmias. We address the challenges and limitations associated with these approaches, including data quality, interpretability, and ethical considerations. Further research and collaboration between neurologists, cardiologists, and AI experts are needed to fully unlock the potential of this interdisciplinary field.
... Atrial fibrillation (AF) is a prevalent clinical arrhythmia that can result in severe complications, including heart failure and stroke, and has a high incidence of disability and mortality. The cardiac autonomic nervous system (ANS) is crucial in maintaining the electrical activity and mechanical contraction of the heart (1)(2)(3)(4)(5). Remodeling of the cardiac autonomic nerves is a significant structural basis for promoting the development and maintenance of AF. ...
... Besides, cardiac ANS can be divided into extrinsic and intrinsic nerves. Extrinsic nerves connect the fibers between the heart and the nervous system, while intrinsic nerves are located within the pericardium (1)(2)(3). ...
... In addition, the cardiac ANS displays a cross-linked structure of interconnected ganglionated plexi. These autonomic structures provide fine regional regulation of various cardiac functions (e.g., cardiac automaticity and conductivity) and act as integrating centers that process both centripetal and centrifugal information, coordinate the sympathetic and parasympathetic inputs received from the rest of the cardiac ANS, and modulate the complex interactions between the extrinsic and the intrinsic systems (Hou et al., 2007;Scridon et al., 2018). They are mainly located at the surface of the right (e.g., on the right atrium, at the junction between the inferior vena cava and the right atrium) and the left (at the pulmonary veins ostia) atria, whereas ventricular ganglionated plexi are mainly located at the origins of the aorta and the main branches of the coronary system (Armour et al., 1997). ...
The heart is one of the most richly innervated organs and the impact of the complex cardiac autonomic network on atrial electrophysiology and arrhythmogenesis, including on atrial ectopy, is widely recognized. The aim of this review is to discuss the main mechanisms involved in atrial ectopic activity. An overview of the anatomic and physiological aspects of the cardiac autonomic nervous system is provided as well as a discussion of the main pathophysiological pathways linking autonomic imbalance and atrial ectopic activity. The most relevant data on cardiac neuromodulation strategies are emphasized. Unanswered questions and hotspots for future research are also identified.
... The exact short-and long-term effects of the oral anticoagulants on platelet function is another open area for research. This is particularly important given the expanding use of direct oral anticoagulants, especially in patients exposed to such agents for decades, such as those with atrial fibrillation [74,77]. If long-term direct thrombin and/or activated factor X inhibition induce a clinically-relevant increase in platelet reactivity, this effect may translate into an increased risk of thrombosis in certain high-risk populations [78][79][80], particularly following abrupt drug discontinuation [81,82], or could potentially interfere with patients' responses to concomitant antiplatelet therapy [83,84]. ...
Hemostasis is a physiological process critical for survival. Meanwhile, thrombosis is amongst the leading causes of death worldwide, making antithrombotic therapy one of the most crucial aspects of modern medicine. Although antithrombotic therapy has progressed tremendously over the years, it remains far from ideal, and this is mainly due to the incomplete understanding of the exceptionally complex structural and functional properties of platelets. However, advances in biochemistry, molecular biology, and the advent of ‘omics’ continue to provide crucial information for our understanding of the complex structure and function of platelets, their interactions with the coagulation system, and their role in hemostasis and thrombosis. In this review, we provide a comprehensive view of the complex role that platelets play in hemostasis and thrombosis, and we discuss the major clinical implications of these fundamental blood components, with a focus on hemostatic platelet-related disorders and existing and emerging antithrombotic therapies. We also emphasize a number of questions that remain to be answered, and we identify hotspots for future research.
... In the present study, systolic blood pressure < 110 mmHg and LVEF < 43% on admission, age > 51 years, and presence of CKD independently predicted the occurrence of STEMI-related arrhythmic complications. Meanwhile, in line with the recent data reported by Crenshaw et al. [26], other classic cardiovascular risk factors known to promote proarrhythmic atrial electrical and/or structural remodeling, such as hypertension, heart failure, diabetes mellitus, or chronic respiratory disease [27][28][29], many of which are included in the CHA2DS2-VASc score, had no significant impact on the occurrence of post-STEMI arrhythmias. Consequently, the CHA2DS2-VASc score had no predictive value for post-STEMI arrhythmias. ...
... Meanwhile, both chronic and acute atrial changes seem to contribute to the occurrence of STEMI-related atrial arrhythmias. It is now widely accepted that the pathophysiology of AF relies on a combination of ectopic triggers that initiate the arrhythmia and an arrhythmogenic substrate that ensures the formation of reentry circuits and, hence, the persistence of the arrhythmia [27]. In STEMI, factors such as acute ischemia, myocardial inflammation, sympathetic overactivation, metabolic and electrolyte imbalance, and hemodynamic impairment have been related to a significant increase in atrial ectopic activity, whereas the burden of chronic cardiovascular risk factors, such as those included in the CHA2DS2-VASc score, are known to promote atrial proarrhythmic electrical and structural remodeling [27,28,30]. ...
... It is now widely accepted that the pathophysiology of AF relies on a combination of ectopic triggers that initiate the arrhythmia and an arrhythmogenic substrate that ensures the formation of reentry circuits and, hence, the persistence of the arrhythmia [27]. In STEMI, factors such as acute ischemia, myocardial inflammation, sympathetic overactivation, metabolic and electrolyte imbalance, and hemodynamic impairment have been related to a significant increase in atrial ectopic activity, whereas the burden of chronic cardiovascular risk factors, such as those included in the CHA2DS2-VASc score, are known to promote atrial proarrhythmic electrical and structural remodeling [27,28,30]. The combination of chronic and acute risk factors and its ability to provide the optimal environment for AF to occur could, thus, explain the ability of both the CHA2DS2-VASc and GRACE scores to independently predict STEMI-related new-onset AF. ...
Arrhythmic and hemodynamic complications related to ST-segment elevation myocardial infarction (STEMI) represent a major clinical challenge. Several scores have been developed to predict mortality in STEMI. However, those scores almost exclusively include factors related to the acute phase of STEMI, and no score has been evaluated to date for its ability to specifically predict arrhythmic and hemodynamic complications. We, thus, aimed to assess the ability of chronic risk factors burden, as expressed by the CHA2DS2-VASc score, to predict STEMI-related arrhythmic and hemodynamic complications. Data were collected from 839 consecutive STEMI patients treated by primary percutaneous coronary interventions (pPCI). CHA2DS2-VASc and GRACE scores were calculated for all patients, and their ability to predict STEMI-related arrhythmic (i.e., new-onset atrial fibrillation (AF), ventricular tachycardia/fibrillation) and hemodynamic (i.e., cardiogenic shock, asystole) complications was assessed in univariate and multiple regression analysis. Arrhythmic and hemodynamic complications occurred in 14.8% and 10.2% of patients, respectively. Although the GRACE score outweighed the CHA2DS2-VASc score in the ability to predict STEMI-related hemodynamic complications (p < 0.0001), both scores had a similar predictive value for STEMI-related new-onset AF (p = 0.20), and both remained independent predictors of new-onset AF and of hemodynamic complications in the multiple regression analyses. A CHA2DS2-VASc score > 2 points independently predicted new-onset AF (p < 0.01) and hemodynamic complications (p = 0.04). Alongside the GRACE score, the CHA2DS2-VASc score independently predicted new-onset AF and hemodynamic complications in STEMI patients treated by pPCI. These data suggest that a combination of acute and chronic risk factors could provide additional benefit in identifying patients at risk of STEMI-related complications, who could benefit from closer follow-up and more intensive prophylactic and therapeutic strategies.
... Chronic administration of both highdose and usual-dose BPA was used, making this study much more clinically-relevant than the vast majority of previous studies in this fi eld. The multidisciplinary approach used in this study provided a comprehensive view on the impact of BPA exposure on atrial arrhythmogenicity and atrial arrhythmogenicity-related electrical remodeling, modulated by changes in various ion currents, structural remodeling, via fi brosis, and autonomic remodeling, expressed as an alteration in sympathetic and/or vagal tone [36][37][38] . ...
Objectives
We aimed to evaluate the effects of chronic exposure to bisphenol A (BPA) on atrial fibrillation (AF) occurrence in rats.
Methods
Twenty-two healthy female Wistar rats were randomized into three groups: Control (no BPA; n=7), BPA (exposed to usual BPA doses; 50 μg/kg/day, 9 weeks; n=7), and hBPA (exposed to high BPA doses; 25 mg/kg/day, 9 weeks; n=8). 24-h ECG monitoring was performed using radiotelemetry ECG devices prior to and after transesophageal atrial pacing. Spontaneous and pacing-induced atrial arrhythmias, autonomic tone, and in vivo an in vitro atrial arrhythmogenicity-related parameters were evaluated.
Results
All studied parameters were similar between Control and BPA (all p>0.05). However, compared to Control, hBPA presented more atrial premature beats both at baseline (p=0.04) and after pacing (p=0.03), more AF episodes (p<0.001) and of longer duration (p=0.02) following transesophageal stimulation, and significantly higher vagal tone (all p<0.05).
Conclusions
Chronic exposure to high, but not usual BPA doses induced significant atrial proarrhythmic effects in healthy rats, and this may be at least partially due to BPA-induced vagal hyperactivation. Exposure to high BPA doses, such as that occurring in plastics industry workers, could favor AF occurrence even in the absence of underlying cardiovascular disease.
... Extending this finding, others found rhythm control after ablation therapy to also be determined by atrial remodeling and circulating biomarkers like transforming growth factor beta-1 [19], indicating that beyond non-modifiable genetic determination, a certain modulation of rhythm control and response is existing. Moreover, as one of the most innervated organs, the electrophysiological activity of the human heart is significantly modulated by extrinsic and intrinsic nerve fibers [20]. The sympathetic and parasympathetic nervous system can influence ion channels, ion currents and atrial electrophysiology and thereby facilitate electrical triggers and reentry mechanisms [20]. ...
... Moreover, as one of the most innervated organs, the electrophysiological activity of the human heart is significantly modulated by extrinsic and intrinsic nerve fibers [20]. The sympathetic and parasympathetic nervous system can influence ion channels, ion currents and atrial electrophysiology and thereby facilitate electrical triggers and reentry mechanisms [20]. By stimulating beta-adrenergic receptors, the activity of hyperpolarization-activated inward current (If) can be intensified, whereas stimulation of atrial alpha-adrenergic receptors can reduce inwardly rectifying Kir current (IK1) activity [20]. ...
... The sympathetic and parasympathetic nervous system can influence ion channels, ion currents and atrial electrophysiology and thereby facilitate electrical triggers and reentry mechanisms [20]. By stimulating beta-adrenergic receptors, the activity of hyperpolarization-activated inward current (If) can be intensified, whereas stimulation of atrial alpha-adrenergic receptors can reduce inwardly rectifying Kir current (IK1) activity [20]. By stimulation of alpha1-and beta1-adrenoceptors, increasing activity in the rat pulmonary vein could be demonstrated [21,22]. ...
Background and Objectives: Atrial fibrillation (AF) is the most common arrythmia of the human heart. Patients mostly present highly symptomatic with dyspnea and tachycardia and have a disproportionate risk of developing heart failure or stroke events. We aimed to evaluate the determinants of early conversion into sinus rhythm during initial stay at the emergency department of a large tertiary care center. Materials and Methods: A total of 1384 subjects with recent-onset AF were recruited between October 2014 and April 2017. Patients with longstanding AF were excluded, resulting in a total of 935 patients for the present analysis. Results: In multivariate adjusted logistic regression analyses, previous catheter ablation therapy was a strong predictor of conversion in sinus rhythm during the stay in the emergency department, with an odds ratio (OR) of 3.87 (95% CI 2.40, 6.54; p < 0.001). In contrast, existing antiarrhythmic medication showed no association with facilitated conversion [OR 0.89 (95%CI 0.65, 1.20); p = 0.44]. Likewise, conventional cardiovascular risk factors (hypertension, dyslipidemia, diabetes) were also not associated with conversion during hospital stay. Conclusion: This is the first report on the relevance of previous ablation therapy for early restoration of sinus rhythm in recent-onset AF. Although catheter ablation is associated with relevant risk of late recurrence of atrial fibrillation, it seems to have a large benefit for patients with recent-onset AF.
... In atherosclerosis, concepts have moved from a purely lipid-related, to a more complex, lipid-inflammatory pathophysiology [45]. In atrial fibrillation, concepts have moved from a purely electrical disease to a more tangled combination of electrical, structural, autonomic, and molecular underlying changes [46][47][48]. In AMI, for years, biomarkers have been focused on the concept of myocardial necrosis. ...
... Myocardial inflammation is a critical process occurring in the setting of AMI that has been related to a variety of deleterious consequences, including electrical instability and increased risk of cardiac arrhythmias, autonomic dysfunction, and fibrosis development [48,[62][63][64]. A wide variety of pro-inflammatory cytokines have been shown to increase in the setting of AMI and to predict prognosis in this population. ...
Despite important advancements in acute myocardial infarction (AMI) management, it continues to represent a leading cause of mortality worldwide. Fast and reliable AMI diagnosis can significantly reduce mortality in this high-risk population. Diagnosis of AMI has relied on biomarker evaluation for more than 50 years. The upturn of high-sensitivity cardiac troponin testing provided extremely sensitive means to detect cardiac myocyte necrosis, but this increased sensitivity came at the cost of a decrease in diagnostic specificity. In addition, although cardiac troponins increase relatively early after the onset of AMI, they still leave a time gap between the onset of myocardial ischemia and our ability to detect it, thus precluding very early management of AMI. Newer biomarkers detected in processes such as inflammation, neurohormonal activation, or myocardial stress occur much earlier than myocyte necrosis and the diagnostic rise of cardiac troponins, allowing us to expand biomarker research in these areas. Increased understanding of the complex AMI pathophysiology has spurred the search of new biomarkers that could overcome these shortcomings, whereas multi-omic and multi-biomarker approaches promise to be game changers in AMI biomarker assessment. In this review, we discuss the evolution, current application, and emerging blood biomarkers for the diagnosis of AMI; we address their advantages and promises to improve patient care, as well as their challenges, limitations, and technical and diagnostic pitfalls. Questions that remain to be answered and hotspots for future research are also emphasized.
... April 2021 | Volume 12 | Article 596956 8 suggests that the beneficial effects of ivabradine could extend to other settings associated with increased sympathetic activity, in which the ivabradine-induced increase in vagal modulation could reduce myocardial oxygen demand and ischemia, diminish sympathetic stimulation and adrenoreceptor-mediated cytotoxicity, apoptosis, and hypertrophy, and reduce the likelihood of ventricular tachyarrhythmias and sudden death (Böhm et al., 2015). On the other hand, vagal hyperactivity has been shown to promote ectopic activity, reentry, and atrial fibrillation via multiple mechanisms (Scridon et al., 2018). Given the highly proarrhythmic effects of vagal activation at the atrial level, the increase in vagal modulation induced by ivabradine demonstrated in the present study could provide an explanation for the increased risk of atrial fibrillation associated with ivabradine use in clinical trials (Martin et al., 2014;Cammarano et al., 2016). ...
Background: The complex interactions that exist between the pacemaker current, I f, and the parasympathetic nervous system could significantly influence the course of patients undergoing chronic therapy with the I f blocker ivabradine. We thus aimed to assess the effects of chronic ivabradine therapy on autonomic modulation and on the cardiovascular response to in situ and in vitro parasympathetic stimulation. The right atrial expression of HCN genes, encoding proteins for I f, was also evaluated.
Methods: Sympathetic and parasympathetic heart rate variability parameters and right atrial HCN(1-4) RNA levels were analyzed in 6 Control and 10 ivabradine-treated male Wistar rats (IVA; 3 weeks, 10 mg/kg/day). The heart rate (HR) and systolic blood pressure (SBP) responses to in situ electrical stimulation of the vagus nerve (2–20 Hz) were assessed in 6 additional Control and 10 IVA rats. The spontaneous sinus node discharge rate (SNDR) response to in vitro cholinergic receptors stimulation using carbamylcholine (10⁻⁹–10⁻⁶ mol/L) was also assessed in these later rats.
Results: Ivabradine significantly increased vagal modulation and shifted the sympatho-vagal balance toward vagal dominance. In Control, in situ vagus nerve stimulation induced progressive decrease in both the SBP (p = 0.0001) and the HR (p< 0.0001). Meanwhile, in IVA, vagal stimulation had no effect on the HR (p = 0.16) and induced a significantly lower drop in SBP (p< 0.05). IVA also displayed a significantly lower SNDR drop in response to carbamylcholine (p< 0.01) and significantly higher right atrial HCN4 expression (p = 0.02).
Conclusion: Chronic ivabradine administration enhanced vagal modulation in healthy rats. In addition, ivabradine reduced the HR response to direct muscarinic receptors stimulation, canceled the cardioinhibitory response and blunted the hemodynamic response to in situ vagal stimulation. These data bring new insights into the mechanisms of ivabradine-related atrial proarrhythmia and suggest that long-term I f blockade may protect against excessive bradycardia induced by acute vagal activation.
