Autonomic Nervous System Modulation Research Articles

Long-term recurrence-free survival following second-generation cryoballoon ablation for persistent atrial fibrillation: role of the autonomic nervous system

Abstract Background The cardiac autonomic nervous system (ANS) plays a pivotal role in the regulation of atrial fibrillation (AF). Cryoballon (CB)-guided pulmonary vein isolation (PVI) is an established treatment for AF. Purpose In our present study we evaluated the impact of vagal reactions (VRs), as a surrogate parameter for ANS modulation, on the long-term outcome of CB-ablation in patients with persistent AF (PERS AF). Methods Data from consecutive PERS AF patients undergoing primary CB-guided PVI for symptomatic drug refractory AF between 2013-2023 were analysed. VRs were defined as bradycardia < 40 beats/min, asystole or higher-degree atrioventricular block. Long-term follow-up data were assessed. AF-recurrence was defined as AF lasting > 30 seconds beyond a 3-month blanking period. Results A total of 250 consecutive patients (mean age 63.9±10.0 years, 30% female) were included. VRs were recorded in 61 patients (24%, mean age 64.2±13.0 years, 30% female). The mean follow-up duration amounted to 84±14 months. Within this observation period 101 patients (40%) developed AF-recurrence. Re-ablation procedures were performed in 61 patients (60%). Patients with PVI-associated VRs presented with a significantly higher estimated AF-free survival rate (log-rank p-value < 0.001) (Figure 1) and a significantly longer median AF-free survival time (75 months, interquartile range (IR) 63-92 months) compared to those without (69 months, IR 13-79 months) (p=0.002). Beyond that Kaplan-Meier plot analyses revealed significant gender differences (Figure 1). Multivariate cox regression analyses confirmed VRs (Confidence interval (CI) 0.294-0.838, Hazard Ratio (HR) 0.497, p=0.009) and male gender (CI 0.352-0.781, HR, 524, p=0.001) as independent predictors (IPs) for AF-free-survival. Conclusion CB-ablation procedure associated VRs and male gender seem to be associated with a favorable long-term outcome in PERS AF. Further studies are warranted to verify our observations.Kaplan Meier plot on long-term AF-free s

Heart rate dynamics after pulmonary vein isolation: pulsed-field vs. radiofrequency ablation

Abstract Background The autonomic nervous system (ANS) plays a pivotal role in the onset and maintenance of atrial fibrillation (AF). During thermal ablation, the epicardial ganglionated plexi (GP) can inadvertently be affected, as indicated by a post-ablation increase in heart rate (HR), potentially impacting post-procedural outcomes. Pulsed-field ablation (PFA) offers a safer and potentially more effective alternative, as lesion transmurality is not inversely related to safety as in thermal ablation. However, PFA's tissue selectivity may limit its effectiveness in ablating potential AF triggers like GP. Purpose We aimed to assess the impact of PF and RF energy on GP ablation by examining HR changes following PVI procedures. Methods We examined consecutive paroxysmal AF patients undergoing PVI at a single center, using either a variable-loop circular PFA catheter, as part of the inspIRE trial, or a conventional point-by-point RF catheter (1:2 ratio). ECGs were collected before and after ablation at multiple time points, including 1-hour, 1-day, 1-month, and 3-month intervals, with a 24-hour Holter ECG at 3 months. Patients without obtainable sinus rhythm ECGs at these time points were excluded. We also gathered data on post-ablation antiarrhythmic drug and beta-blocker usage. Data are reported as mean±SD, and analysis employed Student’s t-tests, paired t-tests, chi-squared tests, and multiple linear regression analysis to identify influencing factors. Results A total of 105 patients were included (PF = 35, RF = 70). Baseline demographics were similar (Table A). In the RF group, HR significantly increased at all measured time-points. In contrast, this trend was not observed in the PF group (Figure A and B). Following the procedure, the RF cohort exhibited a significantly higher HR compared to PF (7.3±10.3 vs. 0.8±11 at 1-day, p=0.018), and this difference persisted after 3 months (8.5±10.1 vs. 0.9±9, p<0.001, Figure C). These findings remained consistent when HR was assessed using Holter ECG data (HR at 3 months: mean 72.1±8.8 vs 65.8±9.4, min 55.2 vs 48.9; p=0.002, p=0.001, Figure D). The use of RF energy was the only predictor of HR increase after the ablation procedure (β = 7.687, p < 0.001, Table B). Conclusion Our findings indicates that PFA does not increase resting HR as seen with thermal RF ablation, suggesting limited effect on ANS modulation. The role of adjunctive GP ablation during PVI procedures remains a topic of debate.While PFA shows promising improvement in lesion durability, current evidence does not conclusively establish its advantage over RF. This invites contemplation about whether the addition of GP ablation in RF procedures could be a contributing factor. The absence of HR acceleration may pose issues for patients with sick sinus syndrome or pure vagally mediated AF. Further research is essential to confirm these findings and their clinical implications.Central illustrationTables

Cardioneuroablation for vasovagal syncope. Results from an EHRA Survey

Abstract Background Cardioneuroablation (CNA) is a recently introduced catheter-based therapy for vasovagal syncope (VVS), involving the modulation of the cardiac autonomic nervous system. Over the past decade, the body of evidence supporting CNA has consistently grown, sparking increased interest, and leading to broader adoption of this novel therapy for VVS treatment. However, several knowledge gaps persist, particularly concerning clinical indications, methodology, and long-term outcomes. Purpose The aim of this survey is to provide a comprehensive overview of the daily utilization of CNA in Europe. Methods and Results Among 204 participants, half reported that they are already performing CNA in their centres. The survey indicated CNA as an emerging therapy, with most centres initiating this treatment within the last two years. A significant majority of those who responded (71%) adopted a systematic approach by targeting ganglionated plexuses (GPs) in both the right atrium (RA) and left atrium (LA) as their first-line approach. The second most common approach (16%) involved performing ablation LA GPs only in the cases where there is no response following RA ablation. Figure 1 shows the GPs usually targeted for ablation. The most frequent procedural endpoint was the increase in the heart rate. Ninety percent of respondents relied on an anatomical approach for GP localization, while 59% also guided the procedure using electrogram analysis. Less frequently used approaches included pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Only 11% of physicians discharged patients who underwent CNA without anticoagulation or antiplatelet therapy. In most cases (58%), respondents discharged their patients with anticoagulation, while 28% on single antiplatelet therapy. Overall, CNA is considered an effective procedure (80% of responders rating its effectiveness at or above 70%) and a safe procedure (with an estimated 1% rate of procedure-related complications, with symptomatic sinus tachycardia being the most frequently reported). Conclusions This survey confirmed high expectations for the future of this therapy, as most responders anticipate that CNA will be indicated as a first-line therapy for patients with recurrent cardioinhibitory VVS. Future efforts are necessary to standardize the procedural flow and peri-procedural patient management.

Cardioneuroablation for vasovagal syncope: insights on patients' selection, centre settings, procedural workflow and endpoints-results from an European Heart Rhythm Association survey.

Cardioneuroablation (CNA) is a catheter-based intervention for recurrent vasovagal syncope (VVS) that consists in the modulation of the parasympathetic cardiac autonomic nervous system. This survey aims to provide a comprehensive overview of current CNA utilization in Europe. A total of 202 participants from 40 different countries replied to the survey. Half of the respondents have performed a CNA during the last 12 months, reflecting that it is considered a treatment option of a subset of patients. Seventy-one per cent of respondents adopt an approach targeting ganglionated plexuses (GPs) systematically in both the right atrium (RA) and left atrium (LA). The second most common strategy (16%) involves LA GP ablation only after no response following RA ablation. The procedural endpoint is frequently an increase in heart rate. Ganglionated plexus localization predominantly relies on an anatomical approach (90%) and electrogram analysis (59%). Less utilized methods include pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Post-CNA, anticoagulation or antiplatelet therapy is prescribed, with only 11% of the respondents discharging patients without such medication. Cardioneuroablation is perceived as effective (80% of respondents) and safe (71% estimated <1% rate of procedure-related complications). Half view CNA emerging as a first-line therapy in the near future. This survey offers a snapshot of the current implementation of CNA in Europe. The results show high expectations for the future of CNA, but important heterogeneity exists regarding indications, procedural workflow, and endpoints of CNA. Ongoing efforts are essential to standardize procedural protocols and peri-procedural patient management.

The Association Between Heart Rate Variability and Sleep Quality - a Narrative Review

Introduction Heart rate variability (HRV) serves as a non-invasive marker to assess autonomic nervous system (ANS) modulation on cardiac rhythm. Its link with sleep quality, particularly in the context of insomnia, posits HRV as a potential indicator of autonomic state variations during sleep disturbances. The prevalence of insomnia, affecting up to 20% of the general population, emphasizes the need to understand its extensive impact. Material and Methods For this review - 41 relevant titles from 1985 to 2024 were selected Analysis of the Literature: Recent studies highlight a bidirectional relationship between insomnia and ANS function, with increased sympathetic activity indicated by physiological and subjective measures in individuals with insomnia. The role of medications like beta-blockers in disrupting ANS and leading to sleep deprivation further connects measurable and perceived aspects of sleep quality, impacting health negatively. Moreover, HRV's application has expanded beyond professional athletics to daily activity and sleep quality monitoring by the general population, emphasizing its potential in evaluating stress and training intensity. Conclusion: The complex interplay between HRV, insomnia, and health outcomes necessitates further research. However, integrating HRV measurements into clinical and everyday monitoring may offer a promising avenue for improving sleep disorder management and enhancing quality of life.

Use of a wearable device to compare subjective and objective fatigue in lung cancer patients and cancer-free controls

PurposeThe study evaluates the use of heart rate variability (HRV), a measure of autonomic nervous system (ANS) modulation via wearable smart bands, to objectively assess cancer-related fatigue (CRF) levels. It aims to enhance understanding of fatigue by distinguishing between LF/HF ratios and LF/HF disorder ratios through HRV and photoplethysmography (PPG), identifying them as potential biomarkers. MethodsSeventy-one lung cancer patients and 75 non-cancer controls wore smart bands for one week. Fatigue was assessed using Brief Fatigue Inventory, alongside sleep quality and daily interference. HRV parameters were analyzed to compare groups. ResultsCancer patients showed higher fatigue and interference levels than controls (64.8% vs. 54.7%). Those with mild fatigue had elevated LF/HF disorder ratios during sleep (40% vs. 20%, P = 0.01), similar to those with moderate to severe fatigue (50% vs. 20%, P = 0.01), indicating more significant autonomic dysregulation. Notably, mild fatigue patients had higher mean LF/HF ratios than controls (1.9 ± 1.34 vs. 1.2 ± 0.6, P = 0.01), underscoring the potential of disorder ratios in signaling fatigue severity. ConclusionsUtilizing wearable smart bands for HRV-based analysis is feasible for objectively assess CRF levels in cancer patients, especially during sleep. By distinguishing between LF/HF ratios and LF/HF disorder ratios, our findings suggest that wearable technology and detailed HRV analysis offer promising avenues for real-time fatigue monitoring. This approach has the potential to significantly improve cancer care by providing new methods for managing and intervening in CRF, particularly with a focus on autonomic dysregulation as a crucial factor.

Hypnotic Modulation of Autonomic Nervous System (ANS) Activity.

Hypnosis, a time-honored therapeutic approach, has gained widespread recognition for its effectiveness in addressing a range of psychological and somatic disorders. While its primary effects are mediated by central top-down mechanisms, hypnosis also exerts peripheral influence by modulating the autonomic nervous system (ANS). Psychophysiological measures, such as heart rate (HR) and its variability (HRV), electrodermal activity (EDA), respiratory rate (RR), and the analgesia nociceptive index (ANI), serve as reliable indicators of ANS activity. Studies have consistently demonstrated hypnosis' ability to significantly impact ANS functions, lowering sympathetic activity and enhancing parasympathetic tone. This effect is particularly pronounced during relaxation procedures and is influenced by mediating factors like hypnotizability and task conditions. Despite methodological limitations, this review highlights the potential of enhanced ANS modulation through hypnosis, including its connections to the central nervous system (CNS), to optimize therapeutic outcomes in patients with psychosomatic disorders associated with ANS dysfunction.

Cardiopulmonary nerve stimulation as a novel therapy for cardiac autonomic nervous system modulation.

Cardiopulmonary nerve stimulation as a novel therapy for cardiac autonomic nervous system modulation.

A Narrative Review on the Viability of Osteopathic Manipulative Medicine in Treating Irritable Bowel Syndrome With Constipation (IBS-C).

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits, with global prevalence.The etiology of the disease is likely multifactorial; however, autonomic nervous system (ANS) dysfunction and immune-mediated inflammation may contribute the most to the hallmark symptoms of abdominal pain and altered motility of the gut. Current pharmacological therapies operate to modulate intestinal transit, alter the composition of the gut flora and control pain. Non-pharmacological approaches include dietary changes, increased physical activity, or fecal microbiota transplants. None of these therapies can modulate ANS dysfunction or impact the underlying inflammation that is likely perpetuating the symptoms of IBS. Osteopathic Manipulative Medicine (OMM) is a clinical approach focused on physical manipulation of the body's soft tissues to correct somatic dysfunctions. OMM can directly target the pathophysiology of IBS through many approaches such as ANS modulation and lymphatic techniques to modify the inflammatory mechanisms within the body. Particular OMM techniques of use are lymphatic manipulation, myofascial release, sympathetic ganglia treatment, sacral rocking, counterstrain, and viscerosomatic treatment. The aim of this study is to identify OMM treatments that can be used to potentially reduce the inflammation and ANS dysfunction associated with IBS symptoms, thereby providing a new non-pharmacological targeted approach for treating the disease.

Abstract 15076: Long-Term Recurrence Free Survival in Second Generation Cryoballoon Ablation for Persistent Atrial Fibrillation: It’s All About the Autonomic Nervous System

Introduction: Cryoballon (CB)-guided pulmonary vein isolation (PVI) is an accepted treatment option for atrial fibrillation (AF). The cardiac autonomic nervous system (ANS) plays a crucial role in the regulation of AF. Hypothesis: ANS modulation has an impact on patients’ AF free survival following CB-ablation. The aim of this observational clinical trial was to analyze the impact of vagal reactions (VRs), as a surrogate parameter for ANS modulation, on the long-term outcome of CB-ablation in patients with persistent AF (PERS AF). Methods: Data from consecutive PERS AF patients treated with a CB-guided PVI for symptomatic drug refractory AF between 2013-2023 were analyzed. VRs were defined as bradycardia &lt; 40 beats/min, asystole or higher-degree atrioventricular block. All patients were continuously followed up in our outpatient clinic. AF-recurrence was defined as AF lasting &gt; 30 seconds beyond a 3-month blanking period. Results: A total of 250 consecutive patients (mean age 63.9 ± 10.0 years, 70% male) were included. VRs were recorded in 61 patients (24%). The mean follow-up duration amounted to 84±14 months. Within this observation period 101 patients (40%) developed AF recurrence a mean of 1.75 ± 0.80 times. Re-ablation procedures were performed in 61 patients (60%) a mean of 1.28 ± 0.55 times. Reconnected PVs were documented in 41 cases (67%). An additional substrate modification was performed in 34 procedures (42%). Patients with procedure associated VRs presented with a significantly higher estimated AF-free survival rate compared to those without (log-rank p-value=0.016) (Figure1). Multivariate analyses revealed the days to first AF recurrence following primary CB-ablation as an independent predictor for AF-free survival (CI 0.841-0.928, HR, 0.883, p&lt;0.01). Conclusions: CB-ablation procedure associated VRs seem to be associated with a favorable long-term outcome in PERS AF. Thus, our findings may influence future CB-ablation strategies.

Assessing the cardiac autonomic response to bicycle exercise in Olympic athletes with different loads of endurance training: new insights from statistical indicators based on multilevel exploratory factor analysis.

Aim: The mechanisms governing the organism's response to exercise are complex and difficult to study. Spectral analysis of heart rate variability (HRV) could represent a convenient methodology for studying humans' autonomic nervous system (ANS). However, difficulties in interpreting the multitude of correlated HRV-derived indices, mainly when computed over different time segments, may represent a barrier to its usage. This preliminary investigation addressed to elite athletes proposes a novel method describing the cardiac autonomic response to exercise based on multilevel exploratory factor analysis (MEFA), which reduces the multitude of HRV-derived indices to fewer uncorrelated ANS indicators capable of accounting for their interrelationships and overcoming the above difficulties. Methods: The study involved 30 Italian Olympic athletes, divided into 15 cyclists (prevalent high-intensity endurance training) and 15 shooters (prevalent technical training with low-intensity endurance component). All athletes underwent a complete test of a dynamic protocol, constituted by a rest-stand test followed by a stepwise bicycle stress test subdivided into a single bout of progressive endurance (from aerobic to anaerobic) exercise and recovery. Then, by spectral analysis, values of 12 ANS proxies were computed at each time segment (9 epochs in all) of the complete test. Results: We obtained two global ANS indicators (amplitude and frequency), expressing the athletes' overall autonomic response to the complete test, and three dynamic ANS indicators (amplitude, signal self-similarity, and oscillatory), describing the principal dynamics over time of the variability of RR interval (RRV). Globally, cyclists have significantly higher amplitude levels (median ± MAD: cyclists 69.9 ± 20.5; shooters 37.2 ± 19.4) and lower frequency levels (median ± MAD: cyclists 37.4 ± 14.8; shooters 78.2 ± 10.2) than shooters, i.e., a parasympathetic predominance compared to shooters. Regarding the RRV dynamics, the signal self-similarity and oscillatory indicators have the strongest sensitivity in detecting the rest-stand change; the amplitude indicator is highly effective in detecting the athletes' autonomic changes in the exercise fraction; the amplitude and oscillatory indicators present significant differences between cyclists and shooters in specific test epochs. Conclusion: This MEFA application permits a more straightforward representation of the complexity characterizing ANS modulation during exercise, simplifying the interpretation of the HRV-derived indices and facilitating the possible real-life use of this non-invasive methodology.

Quantitative assessment of transient autonomic modulation after single-shot pulmonary vein isolation with pulsed-field ablation.

Pulmonary vein isolation (PVI) with thermal energy is characterized by concomitant ablation of the surrounding ganglionated plexi (GP). Pulsed-field ablation (PFA) selectively targets the myocardium and seems associated with only negligible effects on the autonomic nervous system (ANS). However, little is known about the dynamic effects of PFA on the GP immediately after PVI. This study sought to investigate the degree and acute vagal modulation induced by the FarapulseTM PFA system during PVI compared with single-shot thermal ablation. A total of 76 patients underwent first-time PVI with either FarapulseTM PFA (PFA group, n = 40) or cryoballoon ablation (thermal ablation group, n = 36) for paroxysmal atrial fibrillation (AF). The effect on the ANS in the two groups was assessed before and after PVI with extracardiac vagal stimulation (ECVS). To capture any transient effects of PFA on the ANS, in a subgroup of PFA patients ECVS was repeated at three predefined timepoints: (1) before PVI (T0); (2) immediately after PVI (T1); and (3) 10 min after the last energy application (T2). Despite similar baseline values, the vagal response induced by ECVS after PVI almost disappeared in the thermal ablation group but persisted in the PFA group (thermal group: 840 [706-1090] ms, p < .001 compared to baseline; PFA group: 11 466 [8720-12 293] ms, p = .70 compared to baseline). Intraprocedural vagal reactions (defined as RR increase >50%, transitory asystole, or atrioventricular block) occurred more frequently with PFA than thermal ablation (70% vs. 28%, p = .001). Moreover, heart rate 24 h post-PVI increased more with thermal ablation than with PFA (16.5 ± 9.0 vs. 2.6 ± 6.1 beats/min, p < .001). In the subgroup of PFA patients undergoing repeated ANS modulation assessment (n = 11), ECVS demonstrated that PFA determined a significant acute suppression of the vagal response immediately after PVI (p < .001 compared to baseline), which recovered almost completely within 10 min. PVI with the FarapulseTM PFA system is associated with only transitory and short-lasting vagal effects on the ANS which recover almost completely within a few minutes after ablation. The impact of this phenomenon on AF outcome needs to be further investigated.

Autonomic nervous system modulation during self-induced non-ordinary states of consciousness

Self-induced cognitive trance (SICT) is a voluntary non-ordinary state of consciousness characterized by a lucid yet narrowed awareness of the external surroundings. It involves a hyper-focused immersive experience of flow, expanded inner imagery, modified somatosensory processing, and an altered perception of self and time. SICT is gaining attention due to its potential clinical applications. Similar states of non-ordinary state of consciousness, such as meditation, hypnosis, and psychedelic experiences, have been reported to induce changes in the autonomic nervous system. However, the functioning of the autonomic nervous system during SICT remains poorly understood. In this study, we aimed to investigate the impact of SICT on the cardiac and respiratory signals of 25 participants proficient in SICT. To accomplish this, we measured various metrics of heart rate variability (HRV) and respiration rate variability (RRV) in three conditions: resting state, SICT, and a mental imagery task. Subsequently, we employed a machine learning framework utilizing a linear discriminant analysis classifier and a cross-validation scheme to identify the features that exhibited the best discrimination between these three conditions. The results revealed that during SICT, participants experienced an increased heart rate and a decreased level of high-frequency (HF) HRV compared to the control conditions. Additionally, specific increases in respiratory amplitude, phase ratio, and RRV were observed during SICT in comparison to the other conditions. These findings suggest that SICT is associated with a reduction in parasympathetic activity, indicative of a hyperarousal state of the autonomic nervous system during SICT.

An Open-Label Study of Cranial Electrotherapy Stimulation on Behavioral Regulation in a Mixed Neurodevelopmental Clinical Cohort.

Individuals with neurodevelopmental disorders often report disturbances in the autonomic nervous system (ANS)-related behavioral regulation, such as sensory sensitivity, anxiety, and emotion dysregulation. Cranial electrotherapy stimulation (CES) is a method of non-invasive neuromodulation presumed to modify behavioral regulation abilities via ANS modulation. Here we examined the feasibility and preliminary effects of a 4-week CES intervention on behavioral regulation in a mixed neurodevelopmental cohort of children, adolescents, and young adults. In this single-arm open-label study, 263 individuals aged 4-24 who were receiving clinical care were recruited. Participants received at-home CES treatment using an Alpha-Stim® AID CES device for 20 minutes per day, 5-7 days per week, for four weeks. Before and after the intervention, a parent-report assessment of sensory sensitivities, emotion dysregulation, and anxiety was administered. Adherence, side effects, and tolerance of the CES device were also evaluated at follow-up. Results showed a 75% completion rate, an average tolerance score of 68.2 (out of 100), and an average perceived satisfaction score of 58.8 (out of 100). Additionally, a comparison between pre- and post-CES treatment effects showed a significant reduction in sensory sensitivity, anxiety, and emotion dysregulation in participants following CES treatment. Results provide justification for future randomized control trials using CES in children and adolescents with behavioral dysregulation. CES may be a useful therapeutic tool for alleviating behavioral dysregulation symptoms in children and adolescents with neurodevelopmental differences.

The Impact of Heart Rate Variability Monitoring on Preventing Severe Cardiovascular Events.

The increase in the incidence of cardiovascular diseases worldwide raises concerns about the urgent need to increase definite measures for the self-determination of different parameters, especially those defining cardiac function. Heart rate variability (HRV) is a non-invasive method used to evaluate autonomic nervous system modulation on the cardiac sinus node, thus describing the oscillations between consecutive electrocardiogram R-R intervals. These fluctuations are undetectable except when using specialized devices, with ECG Holter monitoring considered the gold standard. HRV is considered an independent biomarker for measuring cardiovascular risk and for screening the occurrence of both acute and chronic heart diseases. Also, it can be an important predictive factor of frailty or neurocognitive disorders, like anxiety and depression. An increased HRV is correlated with rest, exercise, and good recovery, while a decreased HRV is an effect of stress or illness. Until now, ECG Holter monitoring has been considered the gold standard for determining HRV, but the recent decade has led to an accelerated development of technology using numerous devices that were created specifically for the pre-hospital self-monitoring of health statuses. The new generation of devices is based on the use of photoplethysmography, which involves the determination of blood changes at the level of blood vessels. These devices provide additional information about heart rate (HR), blood pressure (BP), peripheral oxygen saturation (SpO2), step counting, physical activity, and sleep monitoring. The most common devices that have this technique are smartwatches (used on a large scale) and chest strap monitors. Therefore, the use of technology and the self-monitoring of heart rate and heart rate variability can be an important first step in screening cardiovascular pathology and reducing the pressure on medical services in a hospital. The use of telemedicine can be an alternative, especially among elderly patients who are associated with walking disorders, frailty, or neurocognitive disorders.

Cardioneuroablation Using Epicardial Pulsed Field Ablation for the Treatment of Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people worldwide. The cardiac autonomic nervous system (ANS) is widely recognized as playing a key role in both the initiation and propagation of AF. This paper reviews the background and development of a unique cardioneuroablation technique for the modulation of the cardiac ANS as a potential treatment for AF. The treatment uses pulsed electric field energy to selectively electroporate ANS structures on the epicardial surface of the heart. Insights from in vitro studies and electric field models are presented as well as data from both pre-clinical and early clinical studies.

Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer's disease.

The heart is a functional syncytium controlled by a delicate and sophisticated balance ensured by the tight coordination of its several cell subpopulations. Accordingly, cardiomyocytes together with the surrounding microenvironment participate in the heart tissue homeostasis. In the right atrium, the sinoatrial nodal cells regulate the cardiac impulse propagation through cardiomyocytes, thus ensuring the maintenance of the electric network in the heart tissue. Notably, the central nervous system (CNS) modulates the cardiac rhythm through the two limbs of the autonomic nervous system (ANS): the parasympathetic and sympathetic compartments. The autonomic nervous system exerts non-voluntary effects on different peripheral organs. The main neuromodulator of the Sympathetic Nervous System (SNS) is norepinephrine, while the principal neurotransmitter of the Parasympathetic Nervous System (PNS) is acetylcholine. Through these two main neurohormones, the ANS can gradually regulate cardiac, vascular, visceral, and glandular functions by turning on one of its two branches (adrenergic and/or cholinergic), which exert opposite effects on targeted organs. Besides these neuromodulators, the cardiac nervous system is ruled by specific neuropeptides (neurotrophic factors) that help to preserve innervation homeostasis through the myocardial layers (from epicardium to endocardium). Interestingly, the dysregulation of this neuro-signaling pathway may expose the cardiac tissue to severe disorders of different etiology and nature. Specifically, a maladaptive remodeling of the cardiac nervous system may culminate in a progressive loss of neurotrophins, thus leading to severe myocardial denervation, as observed in different cardiometabolic and neurodegenerative diseases (myocardial infarction, heart failure, Alzheimer's disease). This review analyzes the current knowledge on the pathophysiological processes involved in cardiac nervous system impairment from the perspectives of both cardiac disorders and a widely diffused and devastating neurodegenerative disorder, Alzheimer's disease, proposing a relationship between neurodegeneration, loss of neurotrophic factors, and cardiac nervous system impairment. This overview is conducive to a more comprehensive understanding of the process of cardiac neuro-signaling dysfunction, while bringing to light potential therapeutic scenarios to correct or delay the adverse cardiovascular remodeling, thus improving the cardiac prognosis and quality of life in patients with heart or neurodegenerative disorders.

Ultrasound-mediated piezoelectric nanoparticle modulation of intrinsic cardiac autonomic nervous system for rate control in atrial fibrillation.

Rate control is a cornerstone of atrial fibrillation treatment. Barium titanate nanoparticles (BTNPs) are piezoelectric nanomaterials that can generate local electromagnetic fields under ultrasound activation, stimulating nearby neuronal tissue. This study aimed to modulate the inferior right ganglionated plexus (IRGP) of the heart and reduce the ventricular rate during rapid atrial pacing (RAP)-induced atrial fibrillation using ultrasound-mediated BTNPs. Adult male beagles were randomly divided into a phosphate-buffered saline (PBS) group (n = 6) and a BTNP group (n = 6). PBS or nanoparticles were injected into the IRGP of both groups before RAP. The biological safety of the material was evaluated according to electrophysiology recordings, thermal effects and level of inflammation. Compared to the PBS group, the BaTiO3 piezoelectric nanoparticle group had reduced ventricular rates in the sinus rhythm and atrial fibrillation models after stimulating the IRGP by applying ultrasound. In addition, transient stimulation by BTNPs did not lead to sustained neuronal excitation in the IRGP. The activation of the BTNPs did not induce inflammation or thermal damage effects in the IRGP. Ultrasound-mediated BTNP neuromodulation can significantly reduce the ventricular rate by stimulating the IRGP. Thus, ultrasound-mediated BTNP neuromodulation is a potential therapy for atrial fibrillation rate control.

Acquirement of the autonomic nervous system modulation evaluated by heart rate variability in medaka (Oryzias latipes).

Small teleosts have recently been established as models of human diseases. However, measuring heart rate by electrocardiography is highly invasive for small fish and not widely used. The physiological nature and function of vertebrate autonomic nervous system (ANS) modulation of the heart has traditionally been investigated in larvae, transparent but with an immature ANS, or in anesthetized adults, whose ANS activity may possibly be disturbed under anesthesia. Here, we defined the frequency characteristics of heart rate variability (HRV) modulated by the ANS from observations of heart movement in high-speed movie images and changes in ANS regulation under environmental stimulation in unanesthetized adult medaka (Oryzias latipes). The HRV was significantly reduced by atropine (1 mM) in the 0.25-0.65 Hz and by propranolol (100 μM) at 0.65-1.25 Hz range, suggesting that HRV in adult medaka is modulated by both the parasympathetic and sympathetic nervous systems within these frequency ranges. Such modulations of HRV by the ANS in adult medaka were remarkably suppressed under anesthesia and continuous exposure to light suppressed HRV only in the 0.25-0.65 Hz range, indicating parasympathetic withdrawal. Furthermore, pre-hatching embryos did not show HRV and the power of HRV developed as fish grew. These results strongly suggest that ANS modulation of the heart in adult medaka is frequency-dependent phenomenon, and that the impact of long-term environmental stimuli on ANS activities, in addition to development of ANS activities, can be precisely evaluated in medaka using the presented method.

Neuromodulation as a Potential Disease-Modifying Therapy for Osteoarthritis.

The following review discusses the therapeutic potential of targeting the autonomic nervous system (ANS) for osteoarthritis (OA) treatment and encourages the field to consider the candidacy of bioelectronic medicine as a novel OA treatment strategy. The study of OA pathogenesis has focused on changes occurring at the joint level. As such, treatments for OA have been aimed at the local joint environment, intending to resolve local inflammation and decrease pain. However, OA pathogenesis has shown to be more than joint wear and tear. Specifically, OA-related peripheral and central sensitization can prompt neuroplastic changes in the nervous system beyond the articular joint. These neuroplastic changes may alter physiologic systems, like the neuroimmune axis. In this way, OA and related comorbidities may share roots in the form of altered neuroimmune communication and autonomic dysfunction. ANS modulation may be able to modify OA pathogenesis or reduce the impact of OA comorbidities. Moreover, blocking chronic nociceptive drive from the joint may help to prevent maladaptive nervous system plasticity in OA.