Parasympathetic Denervation Research Articles

Effect of selective renal denervation guided by renal nerve stimulation on atrial remodeling

Abstract Background The renal nerves play a crucial role in regulating blood pressure (BP), and the parasympathetic nervous has been confirmed as one of the components of the renal nerves, with close connections to the central solitary nucleus. Renal nerve stimulation (RNS) can activate not only the sympathetic nerves, leading to an elevation in BP, but also the parasympathetic nerves, resulting in a reduction in BP. Multiple clinical studies have demonstrated that compared to pulmonary vein isolation (PVI), renal denervation (RDN) combined with PVI significantly increased the likelihood of freedom from atrial fibrillation, but its mechanism remains unclear. Purpose Exploring the effects of renal sympathetic denervation and renal parasympathetic denervation on atrial neural remodeling and structural remodeling from a histological perspective of atrial myocardium. Methods 24 adult healthy Kunming dogs were randomly divided into three groups: (1) RNS-guided reduced BP response sites ablation (RRA group, n=8), (2) RNS-guided elevated BP response sites ablation (ERA group, n=8), and (3) RNS only, no ablation (RSC group, n=8). Left atrial samples were obtained after a 4-week follow-up period. Results Compared to the RSC group, the ERA group showed a significant decrease in tyrosine hydroxylase (TH), while the RRA group showed a significant decrease in choline acetyltransferase (CHAT) and muscarinic acetylcholine receptor 2 (CM2) (Fig. 1A-1C). Histological results indicated that compared to the RSC group, the ERA group exhibited orderly arrangement of myocardial cells, with a significant reduction in the degree of mitochondrial swelling and a decrease in average myocardial cell area. In contrast, the RRA group showed disordered arrangement of myocardial cells, with some myofibril dissolution, noticeable swelling of cell nuclei and mitochondria, and an increase in average myocardial cell area (Fig. 1D). Further evaluation of left atrial fibrosis degree revealed that compared to the RSC group, the ERA group showed a significant decrease in Collagen I, with a reduction in interstitial fibrosis degree, while the RRA group showed a significant increase in Collagen I expression, with an increase in myocardial interstitial fibrosis degree (Fig.2). Conclusion Renal sympathetic denervation can reduce atrial sympathetic nerve, improve atrial macrostructure, ultrastructure, and fibrosis levels, which may be one of the reasons why RDN combined with PVI is more effective in maintaining sinus rhythm compared to PVI. Renal parasympathetic denervation can decrease atrial parasympathetic nerve, leading to deterioration of atrial tissue structure and exacerbation of fibrosis. This emphasizes the importance of electrical stimulation guidance during the RDN procedure to avoid "side effects" caused by renal parasympathetic nerves ablation.Figure 1Figure 2

Bilateral tonic pupil during a migraine attack: a case report.

Tonic pupil or Adie's pupil occurs due to parasympathetic denervation, and it is characterized by mydriasis with little or no response to light, with pupillary contraction to accommodation. It is caused by eye pathologies, such as infections, trauma, neoplasms, inflammatory diseases, and systemic diseases with autonomic dysfunction. Few cases have been reported of bilateral tonic pupils associated with migraine attacks. Our aimed to describe the case of a young female patient with a history of chronic migraine without aura, who presented acutely with bilateral pupillary mydriasis during a migraine attack, characterized as tonic pupil, and to discuss the possible causes of mydriasis during a migraine attack.

Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's disease, dementia with Lewy bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations in the CNS of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation. This enables a comprehensive review of cholinergic changes in Lewy body disease, encompassing both central and peripheral regions, various disease stages and diagnostic categories. Across studies, brain regions affected in Lewy body dementia show equal or greater levels of cholinergic impairment compared to the brain regions affected in Lewy body disease without dementia. This observation suggests a continuum of cholinergic alterations between these disorders. Patients without dementia exhibit relative sparing of limbic regions, whereas occipital and superior temporal regions appear to be affected to a similar extent in patients with and without dementia. This implies that posterior cholinergic cell groups in the basal forebrain are affected in the early stages of Lewy body disorders, while more anterior regions are typically affected later in the disease progression. The topographical changes observed in patients affected by comorbid Alzheimer pathology may reflect a combination of changes seen in pure forms of Lewy body disease and those seen in Alzheimer's disease. This suggests that Alzheimer co-pathology is important to understand cholinergic degeneration in Lewy body disease. Thalamic cholinergic innervation is more affected in Lewy body patients with dementia compared to those without dementia, and this may contribute to the distinct clinical presentations observed in these groups. In patients with Alzheimer's disease, the thalamus is variably affected, suggesting a different sequential involvement of cholinergic cell groups in Alzheimer's disease compared to Lewy body disease. Patients with isolated REM sleep behaviour disorder demonstrate cholinergic denervation in abdominal organs that receive parasympathetic innervation from the dorsal motor nucleus of the vagus, similar to patients who experienced this sleep disorder in their prodrome. This implies that REM sleep behaviour disorder is important for understanding peripheral cholinergic changes in both prodromal and manifest phases of Lewy body disease. In conclusion, cholinergic changes in Lewy body disease carry implications for understanding phenotypes and the influence of Alzheimer co-pathology, delineating subtypes and pathological spreading routes, and for developing tailored treatments targeting the cholinergic system.

Cardioneuroablation and the downside of parasympathetic denervation of the heart

Cardioneuroablation and the downside of parasympathetic denervation of the heart

Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies.

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = -0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = -0.52, P = 0.0104) and a measure of non-motor symptoms (rs = -0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia.

Prediction of sinus tachycardia after cardioneuroablation: the utility of atropine test

Abstract Background Acceleration of sinus rhythm (SR) due to parasympathetic denervation of sinus note is a favourable sign during cardioneuroablation (CNA) for the treatment of functional bradyarrhythmias. On the contrary, a faster heart rate may be symptomatic in some patients. Purpose We investigated predictors of sinus tachycardia at the 3-month post-CNA visit. Methods An atropine test (2 mg IV) was performed before the procedure. The endpoint of CNA was complete denervation of the sinus node as assessed by extracardiac vagus nerve stimulation. Sinus tachycardia was defined as a sinus rate ≥100 bpm at the 3-month post-CNA outpatient visit. Factors independently associated with post-CNA SR were investigated by multivariate analysis. Using regression coefficients, a composite continuous-scale index (CCSI) estimating the post-CNA SR was constructed and used for sinus tachycardia prediction. Results The study included 160 patients aged 40 ± 12 years, 56% men, with baseline SR of 63 ± 15 bpm, post-atropine SR of 107 ± 21 bpm, and SR 3-month post-CNA SR of 83 ± 15 bpm. Nineteen patients had sinus tachycardia at a 3-month visit after CNA. Age, gender, baseline SR and post-atropine SR were significantly (and the latter two independently) associated with 3-month post-CNA SR. The CCSI (defined as 36 + 0.32 * baseline SR + 0.25 * post-atropine SR) correlated with 3-month post-CNA SR (Figure) and provided an area under the curve of 0.87 in the analysis of receiver operating characteristic. The CCSI &amp;gt;90 predicted the 3-month post-CNA sinus tachycardia with a sensitivity of 74% and specificity of 86%. Conclusion Sinus tachycardia at 3 months after CNA can be predicted by the baseline and post-atropine sinus rate. This can help to select patients who may benefit from less rigorous sinus nodal denervation to avoid potentially symptomatic sinus tachycardia after the CNA.

Abstract 14709: Association Between Esophageal and Cardiac Autonomic Dysfunction in Chagas Disease

Introduction: Chronic Chagas disease (ChD) may manifest as the indeterminate form, or with chronic cardiopathy (CCM), digestive or mixed forms. CCM is characterized by complex arrhythmias and sudden death, linked to autonomic dysfunction. Pathological involvement of the enteric nervous system triggers the development of the digestive form, and esophageal dysmotility may be another surrogate for dysautonomia. We aimed to assess the association between esophageal autonomic denervation and cardiac autonomic dysfunction in individuals in the indeterminate (ICF) and CCM forms of ChD. Methods: Consented patients with serological diagnosis of ChD and ICF ( n = 30) and CCM ( n = 33) forms were enrolled. All patients underwent esophageal scintigraphy, and esophageal transit time (ETT) and percentage of esophageal emptying (%EE) were recorded. They also underwent 24h Holter monitoring, and heart rate variability (HRV) indices and burden of ventricular extrasystoles (VES) were revised by a cardiologist. The correlation between ETT, %EE and HRV indices ((SDNN (standard deviation of adjacent RR intervals), low and high-frequency power (LFP, HFP(ms)), in addition to the number of VES in 24h was assessed with the SPSS 23 software. Results: 63 patients were enrolled, 54% women, with mean age of 58 years. Left ventricular ejection fraction was lower in the CCM group (44,0 ± 10,8 vs. 64,9 ± 6,6, p&lt;0.001). Autonomic dysfunction showed a distinct pattern between ICF and CCM, with lower SDNN and LF/HF values in the CCM group (100,0 ± 49,9 vs. 124,6 ± 43,2, p=0.042 and 1,4 (0,9 - 2,2) vs. 4,5 (1,5 - 9,5), p&lt;0.001, respectively). The CCM group also had higher 24h VES values (890,0 (120,0 - 2743,0) vs. 47,0 (1,7 - 395,7), p=0.002). There was significant inverse correlation between ETT and SDNN (ß=-0,449, p=0.001), LFP (ms) (ß=-0.288, p=0.025), HFP (ms) (ß=-0.368, p=0.004) and LH/FH (ß=-0.334, p=0.008) in the total sample. There was also a statistically significant and direct correlation between ETT and VES (ß=0.578, p&lt;0.05) in the total sample. Conclusions: ChD individuals with greater esophageal dysmotility showed a decrease in the oscillatory components of HRV and greater arrhythmic density, possibly as a result of more severe sympathetic and parasympathetic cardiac denervation.

Incidental parasympathetic cardiac denervation during atrial fibrillation ablation using high power short duration: a marker of long-term success.

There are multiple factors in both technique and substrate that lead to recurrence of atrial fibrillation after ablation. We sought to examine whether the degree of heart rate increase (HRI) caused by concurrent high-power-short-duration (HPSD) incidental parasympathetic denervation during AF ablation predicts long term success. Between December 2018 and December 2021, prospectively enrolled 214 patients who presented in sinus rhythm at AF ablation. Used 50 W of power and contact force (CF) of 5-15g and 10-20g at a flow rate of 40mL/min on the anterior and posterior left atrial walls, respectively. Males were 143 (66.8%) and paroxysmal was 124 (57.9%) patients. Mean age 61.1 ± 12.3years and follow-up time was 32.8 ± 13.2months. Arrhythmia occurred after 90days in 39 (18.2%) patients, 19 (48.7%) from the paroxysmal and 20 (51.3%) from the persistent AF patients. Recurrence group showed a lower HRI from a mean of 57 ± 7.7 to 64.4 ± 10.4bpm (12.3%) while in success group HRI was from 53.8 ± 9.7 to 66.8 ± 11.6bpm [(24.2%) p = 0.04]. We divided HRI in 3 percentiles of ≤ 8%, > 8 ≤ 37% and > 37%. A predictor of recurrence was identified in those in the first (< 8%, p = 0.006) and a predictor of success in the later (> 37%, p = 0.01) HRI percentile. Atrial fibrillation ablation with HPSD incidental cardiac parasympathetic denervation identified that patients with lower heart rate increase are prone to recurrence while those with higher heart rate increase had higher maintenance of sinus rhythm at a long-term follow-up.

Effect of Radiofrequency Current Application during Catheter Ablation on Heart Rate Variability in Patients with Supraventricular Tachycardia

Abstract Background The autonomic nervous system has a significant regulatory effect on heart function; in addition to heart rate, cardiac conduction properties, hemodynamics, the cellular properties of cardiac myocytes, and cardiac arrhythmogenesis are also affected by the autonomic nervous system. Objectives In this study, we aimed to assess the Relationship between RF current application during Catheter ablation and it's effect on Heart Rate variability in patients undergoing RF catheter ablation for supraventricular Tachycardia. Patients and Methods This study is a cohort study, randomized clinical study, recruiting 20 patients from Ain Shams University hospitals, Cairo, Egypt. All patients were symptomatic with drug refractory documented supraventricular tachycardias. who underwent RF ablation March 2020 till February 2021 and were followed up for 1 month after the procedure. Results Compared with preablation data, HRV were shorter in all the RFA at the follow-up assessment. The 24-h Holter monitoring showed that mean and maximal HR were increased, whereas the HRV parameters, including time domain indices (SDNN, rMSSD) and frequency domain index, which reflect the attenuation of parasympathetic tone, were decreased in the RFA during the postablation period. In this study, there was significant increasing in mean heart rate regarding basal and the subsequent follow up after 1 week and 1 month. Post ablation high sinus rate (PA-HSR) was defined as an increase in resting sinus rate &amp;gt; or = 20 bpm or a resting sinus rate &amp;gt; or = 92 bpm without physiological or hemodynamic causes. In this study PAHSR was found in 10 patients (50%) by month-1 follow up. There is relation between the target site of RF ablation and the difference of HRV parameters. Conclusion Cardiac autonomic dysfunction assessed by changes in time domain and frequency domain heart rate variability parameters persisted for 1 month after radiofrequency ablation. Parasympathetic denervation may be one mechanism of Post ablation high sinus rate.

PO-04-064 QUANTIFICATION OF AUTONOMIC MODULATION DURING SINGLE-SHOT PULMONARY VEIN ISOLATION WITH PULSED FIELD ABLATION

Additional ganglionated plexi (GPs) ablation beyond pulmonary vein isolation (PVI) has been associated with better outcomes after radiofrequency ablation. Because of the anatomical relationship between the major atrial GPs and the pulmonary veins, single-shot PVI with cryoballoon catheter ablation (CBA) has been demonstrated to concomitantly affect the GPs, as documented by intraprocedural vagal reactions and increased heart rates (HR) after ablation. The novel multispline pulsed field ablation catheter (PFA) is emerging as a safe and effective non-thermal single-shot alternative for PVI, with ablation selectivity for the cardiac tissue. To quantify the degree of parasympathetic denervation during single-shot PVI with PFA compared with CBA. We prospectively included consecutive patients undergoing autonomic modulation assessment with extracardiac vagal stimulation (ECVS) during single-shot PVI for paroxysmal AF with PFA and CBA. Patients with previous ablations were excluded. The response to ECVS was determined as the sinus pause following stimulation, measuring the maximum PP interval (sinus node response). Baseline and post-ablation responses to ECVS were collected and analysed. The degree of autonomic modulation in the two groups was assessed by evaluating the difference between pre- and post-ablation responses to ECVS. A total of 30 patients (PFA group, n=15 vs CBA group, n=15) were included in the analysis. Baseline patients’ characteristics were similar between the two groups (Table 1). Pre-ablation responses to ECVS were similar between the PFA and CBA groups (10757.3 ± 3155.2 ms vs. 11155.9 ± 2472.3 ms, p=0.70). Vagal reactions during PVI occurred more frequently with PFA than CBA (86.7% vs 20%, p=0.001), more commonly during left superior PVI. After PVI, the sinus pause following ECVS was significantly longer after PFA compared with CBA (9897.9 ± 2702.0 ms vs. 874.6 ± 213.6 ms; p<0.001, Figure 1). Despite similar baseline values, 24h post-ablation HR increased significantly more with CBA than PFA (14.0 ± 6.8 bpm vs. 1.8 ± 8.4 bpm, respectively; p<0.001). Single-shot PVI with PFA was associated with less autonomic modulation compared with CBA at ECVS testing. This is likely the result of cardiac tissue selectivity, with minimal effect on the autonomic nervous system. The clinical impact of reduced parasympathetic denervation of PFA on AF outcome is yet to be elucidated.

PO-02-089 EMPIRIC VEIN OF MARSHALL ETHANOL INFUSION IN PATIENTS UNDERGOING REPEAT CATHETER ABLATION WITH DURABLY ISOLATED PULMONARY VEINS

The procedural strategy for patients with recurrent atrial fibrillation (AF) despite isolated pulmonary veins is unknown. Ablative strategies beyond pulmonary vein isolation (PVI) have not consistently shown benefit. Vein of Marshall (VoM) ethanol ablation has a proven benefit in patients with persistent AF undergoing index procedure, however its role in patients with durably isolated pulmonary veins is unknown. To evaluate the benefit of empiric VoM ethanol ablation in addition to posterior wall isolation (PWI) during the repeat procedure in patients with durable pulmonary vein isolation from index procedure. Twenty-three patients (age 67.1 +/- 7.4, 74% males) who received empiric VoM ethanol infusion in addition to PWI (study group) were matched for age, gender, EF and LA size with thirty-four historic patients receiving empiric PWI alone (control group). All patients in the study group underwent endocardial ablation on the mitral isthmus to complete a lateral mitral isthmus line. Additional ablation was based on program and trigger stimulation. Primary outcome was freedom from AF or AT after a blanking period of 3 months using either qualification of symptoms, routine office EKG, wearable or implantable monitor or device (pacemaker or defibrillator). Significant baseline characteristic differences between study vs control group included BMI (35.07 +/- 8.98 vs. 30.85 +/- 5.65, p = 0.033) and incidence of persistent AF (83% vs. 55%, p=0.029). The 1 year AF-free survival for the study and control groups were 20 (86.96%) and 21 (61.76%) patients respectively (p=0.038). Cox proportional hazard regression analysis showed significant reduction in AF or AT recurrence in the study group (HR 0.26, 95% CI 0.074-0.919, p=0.037). Among patients undergoing repeat catheter ablation for recurrent AF with durably isolated pulmonary veins, addition of VoM ethanol infusion increased the likelihood of remaining free from AF or AT at 12 months. The mechanism for increased long-term procedural success with VoM ethanol infusion is unclear. It may be due to ablation of non-pulmonary vein triggers originating from the ligament of Marshall, left atrial parasympathetic denervation, or transmural block across the lateral mitral isthmus with ablation of epicardial connections.

Alteration of myoepithelial cells during botulinum toxin typeA-inhibited salivary secretion.

Intraglandular injection of botulinum toxin type A (BoNT/A) effectively treats sialorrhea. Myoepithelial cells (MECs) are essential for salivary secretion. The role of MECs in BoNT/A-inhibited salivary secretion, and its underlying mechanisms remain unknown. BoNT/A was injected into rat submandibular glands (SMGs). At 1, 2, 4, 8, and 12 weeks postinjection, salivary flow rate of SMGs was measured. Electron microscopy, immunohistochemistry, immunofluorescence, and Western blot analysis were used to detect morphological and functional changes in MECs and chemical denervation in SMGs. BoNT/A temporarily decreased salivary secretion in rat SMGs and this inhibitory effect lasted 4 weeks. During the inhibitory period, MECs atrophied and expressed reduced α-smooth muscle actin (α-SMA), vimentin, and phosphorylated myosin light chain 2 (p-MLC2), suggesting that BoNT/A attenuated MEC contractility. Furthermore, BoNT/A cleaved synaptosome-associated protein 25 (SNAP-25) and decreased the expression and activity of acetylcholinesterase (AChE), indicating that BoNT/A-induced chemical parasympathetic denervation of SMGs by cleaving SNAP-25. BoNT/A temporarily caused MEC atrophy and decreased MEC contractility in rat SMGs, which contributed to reversible inhibition of salivary secretion. The underlying mechanisms involved temporary parasympathetic denervation caused by SNAP-25 cleavage. These findings provide new insights into the mechanisms of BoNT/A-inhibited salivary secretion.

Selective Modulation of the Cardiac Autonomic Nervous System: A New Therapeutic Strategy for Cardioinhibitory Vasovagal Syncope

Vasovagal syncope (VVS) is the most common type of syncope. The overall prognosis of VVS is usually benign, although the quality of life can be affected when syncope is recurrent and refractory to conventional therapy. Multiple treatment options exist for patients with recurrent VVS, although the effect is modest. In this focused review, we briefly discussed the plausible pathophysiological mechanisms of VVS. We used three case examples to update the current state of cardioneuroablation (CNA) in patients with recurrent cardioinhibitory response as a potential therapeutic option. This article includes review of studies and reports on CNA summarizing the principles of this therapeutic approach; various ways of mapping to localize the parasympathetic ganglionic plexi for ablation; description of technique of extra-cardiac vagal stimulation to confirm parasympathetic denervation of the heart as well as the end points and outcomes of the reported studies. Moreover, we reviewed the pros, cons, gaps, and future directions of this potential therapeutic option in treating patients with VVS.

Parasympathetic-macrophages-ductal epithelial cells axis promotes female rat submandibular gland regeneration after excretory duct ligation/deligation

ObjectiveSubmandibular gland (SMG) regeneration depends on parasympathetic signals that modulate this process primarily by promoting ductal epithelial cell proliferation. The purpose of this study was to elucidate the mechanism underlying of parasympathetic regulation on salivary gland regeneration. Materials and methodsWe performed duct ligation/deligation with or without chorda lingual innervation in female Sprague-Dawley rats. Clodronate liposomes were administered retroductally and intravenously into the SMG to deplete macrophages. The proliferative ability and cell cycle-related genes of SMG were assessed using western blotting, quantitative real-time PCR, and immunohistochemical staining. ResultsParasympathetic stimulation boosted Interleukin-6 (IL-6) release by macrophage via muscarinic signalling. This process was suppressed by denervation, muscarinic blockade, or SMG macrophage depletion. SMG IL-6 release led to signal transducer and activator of transcription 3 (STAT3) phosphorylation in ductal epithelial cells to promote proliferation and regeneration by upregulating the expression of cell cycle-related genes. SMG parasympathetic denervation and macrophage depletion suppressed cell cycle-related genes upregulation and ductal cells proliferation. ConclusionsThese data indicated that the parasympathetic-macrophage-ductal epithelial cells axis promote SMG regeneration after duct ligation and deligation.

Importance of bilateral vagus nerve stimulation for effective atrioventricular node denervation during cardioneuroablation

Abstract Background The progression of parasympathetic denervation of the atrioventricular node (AVN) during cardioneuroablation (CNA) can be evaluated by extracardiac vagal stimulation (ECVS). The right vagus nerve is usually used for stimulation (R-ECVS) because the right jugular vein is easily accessible. However, the AVN node is predominantly under the control of the left vagus nerve. Purpose To highlight the importance of left vagus stimulation (L-ECVS) for effective AVN denervation. Methods Both R-ECVS and L-ECVS (frequency: 50 Hz; pulse width: 0.05 ms; output 1 V / 1 kg; max. 70 V, duration 5 s) was attempted in 80 patients (age: 41±12 years, 45% men) undergoing CNA with stepwise strategy consisting of ablation of right anterior ganglionated plexus (RAGP) followed by ablation of posteromedial left ganglionated plexus (PMLGP). The study objective was the AVN response to L-ECVS (evaluated as the max. R-R interval during stimulation train) at the point when AVN non-reactivity to R-ECVS was achieved. Results A total of 59 patients were suitable for the analysis. Of the remaining 21 patients, left (n=14) or right (n=2) jugular veins were not accessible, AVN non-reactivity to L-ECVS was achieved before non-reactivity to R-ECVS (n=4), or AVN denervation was not achieved at all (n=1). At baseline, the AVN response was identical for R-ECVS (max. R-R median: 6.9 s, interquartile range [IQR]: 5.7–8.2 s) and L-ECVS (median: 7.1 s, IQR: 6.0–8.3 s), P=0.44. AVN non-reactivity to R-ECVS was present already at baseline (n=2); was achieved after ablation of RAGP (n=14), after ablation PMLGP (n=38), or after extensive ablation (n=5). At the point of AVN non-reactivity to R-ECVS, the response of AVN to L-ECVS was as follows: none (n=25), 2: 1 AV block (n=13) or complete AV block (n=21). The corresponding median of max. R-R interval was: 1.2 s, IQR: 0.6–4.8 s distributed as shown in Figure 1. Conclusions In 34/59 (58%) patients, significant AVN response to L-ECVS persists after reaching AVN non-reactivity to R-ECVS. Stimulation of both vagal nerves tightens the procedural endpoint and may increase the clinical efficacy of CNA, especially in patients with dominant AVN disorder. Funding Acknowledgement Type of funding sources: None.

18F]FEOBV positron emission tomography may not be a suitable method to measure parasympathetic denervation in patients with Parkinson's disease

IntroductionThe peripheral autonomic nervous system may be involved years before onset of motor symptoms in some patients with Parkinson's disease (PD). Specific imaging techniques to quantify the cholinergic nervous system in peripheral organs are an unmet need. We tested the hypothesis that patients with PD display decreased [18F]FEOBV uptake in peripheral organs – a sign of parasympathetic denervation. MethodsWe included 15 PD patients and 15 age- and sex matched healthy controls for a 70 min whole-body dynamic positron emission tomography (PET) acquisition. Compartmental modelling was used for tracer kinetic analyses of adrenal gland, pancreas, myocardium, spleen, renal cortex, muscle and colon. Standard uptake values (SUV) at 60–70 min post injection were also extracted for these organs. Additionally, SUVs were also determined in the total colon, prostate, parotid and submandibular glands. ResultsWe found no statistically significant difference of [18F]FEOBV binding parameters in any organs between patients with PD and healthy controls, although trends were observed. The pancreas SUV showed a 14% reduction in patients (P = 0.021, not statistically significant after multiple comparison correction). We observed a trend towards lower SUVs in the pancreas, colon, adrenal gland, and myocardium of PD patients with versus without probable REM sleep behavior disorder. Conclusion[18F]FEOBV PET may not be a sensitive marker for parasympathetic degeneration in patients with PD.

Don't Break My Heart: A Case Report of Takotsubo Syndrome in a Transplanted Heart

Cardiogenic shock after heart transplant, could be due to acute rejection, cardiac allograft vasculopathy, or myocarditis. Stress cardiomyopathy (CM) in a denervated transplanted heart is unusual. A 56-year-old man with a history of ischemic heart disease and a seizure disorder underwent orthotropic heart transplant. He had breakthrough seizures posttransplant while on levetiracetam (Keppra) and was admitted for status epilepticus. A transthoracic echocardiogram (TTE) was done for hypotension (BP 90/60). TTE showed a severely reduced left ventricular ejection fraction (LVEF) of 15%, hyperkinetic base, and apical ballooning that are consistent with stress CM. Electrocardiogram with T wave inversion in precordial leads. Troponin was elevated to 1.77. The patient had cardiogenic shock and needed an intra-aortic balloon pump and multiple pressors. He was treated for status epilepticus and the LVEF completely recovered in 1 week. The patient had a normal TTE, coronary angiography, and biopsy with no rejection 8 days before admission. Stress CM was the diagnosis of exclusion, confirmed with a complete recovery of the LVEF. There are only 5 case reports of stress CM after heart transplant, with most presenting 9 to 10 years afterwards. We describe an unusual case of cardiogenic shock from stress CM triggered by status epilepticus in a denervated heart only 1 year posttransplant. The mechanism is elusive, and some hypotheses suggest exaggerated sensitivity to a plasma catecholamine surge from parasympathetic denervation. In a denervated heart, autonomic re-innervation can be seen as early as 1 year posttransplant.

462-P: Improvement of Cardiovascular Autonomic Neuropathy after Metabolic Bariatric Surgery in Korean Subjects with Obesity

Object: Cardiovascular autonomic neuropathy (CAN) is one of chronic vascular complications of diabetes, and obesity is a major risk factor for CAN. Metabolic bariatric surgery (MBS) dramatically improved both diabetes and obesity. In this study we investigated the influence of MBS on CAN in Korean subjects with obesity. Method: We recruited patients who underwent bariatric surgery from October 20to February 2021 prospectively. CAN was evaluated before and 6 months after surgery by Ewing method including change in heart rate (HR) and blood pressure (BP) according to deep breathing, Valsalva maneuver, and postural change by AFT-800 (MEDICORE, Gyeonggi-do, Republic of Korea) . Standard deviation of NN interval (SDNN) , root mean square of successive RR interval difference (RMSSD) , total power, and very low, low, and high frequency were compared before and after surgery. Result: A total of 22 patients were evaluated. Patients' mean age was 42.1 ± 9.1 years, and 8 patients (36.4%) were male, and the mean follow-up duration was 189.0 days. Among them, 15 (68.2%) subjects had diabetes, and none had cardiovascular disease. The resting HR before surgery was 79.2 ± 13.7 bpm, and it decreased significantly to 67.4 ± 8.2 bpm after surgery (P&amp;lt;0.001) . Changes in HR and BP according to Valsalva maneuver, posture change, and handgrip were not significantly different before and after surgery. However, SDNN significantly increased from 25.3 [13.7-41.8] ms to 35.2 [22.6-40.4] ms (P=0.046) , and RMSSD also tended to increase. In addition, the high frequency significantly increased from 36.1 [16.8-180.3] ms2 to 117.8 [34.6-357.7] ms2 (P=0.042) after surgery. Conclusion: MBS significantly improved indicators of parasympathetic denervation, an early manifestation of CAN. Disclosure H.Jang: None. S.Moon: None. J.Moon: None. Y.Park: None. S.Choi: None. H.Jang: None. T.Oh: None.

Parasympathetic, but not sympathetic denervation, suppressed colorectal cancer progression

Disruption in the nerve-tumor interaction is now considered as a possible anticancer strategy for treating various cancer types, particularly colorectal cancer. However, the underlying mechanisms are not still fully understood. Therefore, the present study aimed to evaluate the effects of sympathetic and parasympathetic denervation on the inhibition of colorectal cancer progression in early and late phases and assess the involvement of nerve growth factor in denervation mediated anticancer effects. One-hundred and fifty male Wistar rats were assigned into 15 groups. Seven groups comprising the control group, 1,2-dimethylhydrazine (DMH) group, sympathetic denervation group (celiac-mesenteric ganglionectomy and guanethidine sulphate administration), parasympathetic denervation group (vagotomy and atropine administration), and combination group were used in the early-stage protocol. For the late-stage protocol, eight groups comprising the control, DMH, surgical and pharmacological sympathetic and parasympathetic denervation groups, combination group, and 5-flourouracil group were considered. After 8 weeks, sympathetic and parasympathetic denervation significantly reduced ACF numbers in rats receiving DMH. On the other hand, in the late stages, parasympathetic but not sympathetic denervation resulted in significant reductions in tumor incidence, tumor volume and weight, cell proliferation (indicated by reduced immunostaining of PCNA and ki-67), and angiogenesis (indicated by reduced immunostaining of CD31 and VEGF expression levels), and downregulated NGF, β2 adrenergic, and M3 receptors. It can be concluded that parasympathetic denervation may be of high importance in colon carcinogenesis and suggested as a possible therapeutic modality in late stages of colorectal cancer.

Effects of pulse field and radiofrequency pulmonary vein isolation on parasympathetic cardiac innervation

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): IKEM Background Pulmonary vein isolation (PVI) is an established treatment modality for patients with atrial fibrillation (AF). PVI performed by radiofrequency (RF) energy results in parasympathetic denervation of the heart by collateral ganglionic plexi ablation. Pulse field (PF) is a novel nonthermal energy source for PVI that selectively ablates atrial myocardium while preserving cardiac autonomic nerves, which may affect the outcome after PVI. Purpose The study compared the effect of PVI between RF and PF ablation on cardiac autonomic function and a short-term AF recurrence rate. The resting heart rate (HR) was evaluated as a simple index of sinus nodal parasympathetic innervation. Methods We investigated 45 patients (aged 64 ± 7 years, 4 women) who underwent PVI by novel three-dimensional electroanatomical mapping/ablation system (lattice electrode ablation system). PVI was performed by either high-energy RF (n = 21) or PF (n = 24) energy using the identical ablation catheter. Resting HR assessed by standard ECG was recorded the day before the procedure and at the 3-month visit. Arrhythmia recurrences were analysed by 24-Holter at the 3-month visit. Results All PVs were acutely isolated in all patients. The HR data are shown in the Table. The baseline HR did not differ between both groups. A significant increase in HR was observed only in the RF ablation subgroup. The between-group difference remained significant even after adjustment for age, gender, and baseline HR. There was no difference in arrhythmia recurrences at the 3-month visit between study groups. Conclusions Parasympathetic denervation effects on HR after the PF ablation are virtually absent. Comparable AF recurrence rate at 3-month visit after RF and PF ablation suggests that preservation of autonomic innervation has no impact on AF recurrence during short-term follow-up. Table RF PVI (n = 21) PF PVI (n = 24) P Baseline HR (bpm) 60.0 ± 7.1 63.8 ± 9.4 n.s. HR change - 3-month visit (bpm) 14.4 ± 6.9 0.3 ± 8.6 P &amp;lt;0.001 Arrhythmia recurrences 3/21 (14%) 2/24 (8%) n.s.