Sympathetic Denervation Research Articles

Renal sympathetic denervation ameliorates the activated inflammatory response through JAK-STAT pathway in a chronic obstructive sleep apnea animal model

ObjectivesObstructive sleep apnea (OSA) is known to increase the risk of cardiovascular disease and inflammation plays a significant role in this process. Renal denervation (RDN) is a novel approach aimed at reducing sympathetic nervous system activity. The role of RDN in the inflammatory response to chronic OSA (COSA) is currently unclear. The main objective was to study inflammatory mechanisms in the rabbit heart with COSA and the effects of RDN. MethodsEighteen rabbits were randomized into three groups: sham control, COSA, and COSA-RDN. COSA and COSA-RDN groups received liquid silicone injections, while the sham control group received normal saline. We performed combined surgical and chemical RDN through bilateral retroperitoneal flank incisions in the COSA-RDN group after silicone injections. The inflammatory mechanisms were assessed through immunoblotting, real-time PCR, and ELISA after the experiment. ResultsH&E staining showed immune cell infiltration in COSA, which decreased after RDN treatment. The level of α7nAChR was significantly reduced in COSA compared to the sham control but was restored to a similar level in the COSA-RDN group. Furthermore, the expressions of p-JAK2 and p-STAT3 were significantly reduced in COSA but showed an up-regulation following RDN treatment. Similarly, levels of the inflammatory markers IL-6, IL-1β and TNF-α were markedly increased in COSA but decreased after RDN therapy. We observed NF-κB activation in the COSA rabbit model, which decreased after RDN treatment, as evidenced by decreased NF-κB expression. ConclusionsOur study suggests that RDN treatment may prevent COSA-associated heart inflammation via the JAK2-STAT3 signaling pathway.

Proof of concept for monoclonal antibody therapy in a cellular model of acquired long QT syndrome type 3.

Long QT syndrome (LQTS) type 3 although less common than the first two forms, differs in that arrhythmic events are less likely triggered by adrenergic stimuli and are more often lethal. Effective pharmacological treatment is challenged by interindividual differences, mutation dependence, and adverse effects, translating into an increased use of invasive measures (implantable cardioverter-defibrillator, sympathetic denervation) in patients with LQTS type 3. Previous studies have demonstrated the therapeutic potential of polyclonal KCNQ1 antibody for LQTS type 2. Here, we sought to identify a monoclonal KCNQ1 antibody that preserves the electrophysiological properties of the polyclonal form. Using hybridoma technology, murine monoclonal antibodies were generated, and patch clamp studies were performed for functional characterization. We identified a monoclonal KCNQ1 antibody able to normalize cardiac action potential duration and to suppress arrhythmias in a pharmacological model of LQTS type 3 using human-induced pluripotent stem cell-derived cardiomyocytes.NEW & NOTEWORTHY Long QT syndrome is a leading cause of sudden cardiac death in the young. Recent research has highlighted KCNQ1 antibody therapy as a new treatment modality for long QT syndrome type 2. Here, we developed a monoclonal KCNQ1 antibody that similarly restores cardiac repolarization. Moreover, the identified monoclonal KCNQ1 antibody suppresses arrhythmias in a cellular model of long QT syndrome type 3, holding promise as a first-in-class antiarrhythmic immunotherapy.

Correlation of olfactory function factors with cardiac sympathetic denervation in Parkinson's disease.

Hyposmia is a common nonmotor symptom of Parkinson's disease (PD) and reportedly associated with dysautonomia in PD. The smell identification test for measuring olfactory function consists of multiple items to discriminate specific scents. In the present study, factor analysis of the smell identification test was performed, and the correlation of extracted factors with cardiac sympathetic denervation (CSD) in patients with PD was investigated. The present study included 183 early PD patients who underwent the Cross-Cultural Smell Identification Test (CC-SIT) and 123I-meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy. Factor analysis of 12 items on the CC-SIT was performed using the computed correlation matrix for the binary items, and five smell factors were extracted. Multiple linear regression was performed to determine the correlation of olfactory function with late heart-to-mediastinum (H/M) ratio of 123I-MIBG uptake. The mean CC-SIT score was 6.1 ± 2.6, and 133 patients (72.7%) had CSD. The CC-SIT score and five smell factors were not associated with dopamine transporter uptake or cognitive functions. However, the CC-SIT score significantly correlated with age (P < 0.001) and late H/M ratio (P < 0.001). Factors 1 and 5 showed an increasing trend with larger H/M ratio, although it was not statistically significant (β = 0.203, P = 0.085 and β = 0.230, P = 0.085, respectively). Factor 5 significantly correlated with the H/M ratio in PD patients with CSD (β = 0.676, P = 0.036). The results showed olfactory dysfunction to be selectively associated with cardiac sympathetic burden in PD. The correlation of certain factors with CSD indicates the possibility of selective hyposmia in PD patients.

β-adrenergic signaling triggers enteric glial reactivity and acute enteric gliosis during surgery

BackgroundEnteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common complication after abdominal surgery. Enteric gliosis of the intestinal muscularis externa (ME) has been identified as part of POI development. However, the glia-restricted responses and activation mechanisms are poorly understood. The sympathetic nervous system becomes rapidly activated by abdominal surgery. It modulates intestinal immunity, innervates all intestinal layers, and directly interfaces with enteric glia. We hypothesized that sympathetic innervation controls enteric glia reactivity in response to surgical trauma.MethodsSox10iCreERT2/Rpl22HA/+ mice were subjected to a mouse model of laparotomy or intestinal manipulation to induce POI. Histological, protein, and transcriptomic analyses were performed to analyze glia-specific responses. Interactions between the sympathetic nervous system and enteric glia were studied in mice chemically depleted of TH+ sympathetic neurons and glial-restricted Sox10iCreERT2/JellyOPfl/+/Rpl22HA/+ mice, allowing optogenetic stimulation of β-adrenergic downstream signaling and glial-specific transcriptome analyses. A laparotomy model was used to study the effect of sympathetic signaling on enteric glia in the absence of intestinal manipulation. Mechanistic studies included adrenergic receptor expression profiling in vivo and in vitro and adrenergic agonism treatments of primary enteric glial cell cultures to elucidate the role of sympathetic signaling in acute enteric gliosis and POI.ResultsWith ~ 4000 differentially expressed genes, the most substantial enteric glia response occurs early after intestinal manipulation. During POI, enteric glia switch into a reactive state and continuously shape their microenvironment by releasing inflammatory and migratory factors. Sympathetic denervation reduced the inflammatory response of enteric glia in the early postoperative phase. Optogenetic and pharmacological stimulation of β-adrenergic downstream signaling triggered enteric glial reactivity. Finally, distinct adrenergic agonists revealed β-1/2 adrenoceptors as the molecular targets of sympathetic–driven enteric glial reactivity.ConclusionsEnteric glia act as early responders during post-traumatic intestinal injury and inflammation. Intact sympathetic innervation and active β-adrenergic receptor signaling in enteric glia is a trigger of the immediate glial postoperative inflammatory response. With immune-activating cues originating from the sympathetic nervous system as early as the initial surgical incision, adrenergic signaling in enteric glia presents a promising target for preventing POI development.

Bilateral Cardiac Sympathetic Denervation for Refractory Multifocal Premature Ventricular Contractions in Patients With Nonischemic Cardiomyopathy

BackgroundBilateral cardiac sympathetic denervation (BCSD) for refractory life-threatening ventricular arrhythmias is a neuromodulatory intervention targeting sympathetically driven focal or re-entrant ventricular arrhythmias. ObjectivesThis study sought to provide a more complete and successful option for intervention in patients in whom premature ventricular contraction (PVC) ablation is not feasible or has been unsuccessful. MethodsA total of 43 patients with >5% PVC burden and concomitant nonischemic cardiomyopathy (NICM) who previously failed medical and ablation therapies were referred for BCSD. All patients underwent bilateral video-assisted thoracoscopic surgical approach with T1-T4 sympathectomy. Primary effectiveness endpoints were postprocedural PVC burden resolution, improvement in left ventricular ejection fraction (LVEF), and cessation of antiarrhythmic drugs (AADs). Safety endpoints included peri- and postprocedural complications. Outcomes were assessed over a 1-year follow-up period. ResultsAmong the 43 patients who underwent BCSD, the mean age was 52.3 ± 14.7 years, 69.8% of whom were male patients. Presenting mean LVEF was 38.7% ± 7.8%, and PVC burden was 23.7% ± 9.9%. There were significant reductions in PVC burden postprocedurally (1.3% ± 1.1% post-BCSD, compared with 23.7% ± 9.9% pre-BCSD, P < 0.001) and improvements in LVEF (46.3% ± 9.5% post-BCSD, compared with 38.7% ± 7.8% pre-BCSD, P < 0.001). The rate of ICD therapies decreased from 81.4% (n = 35) to 11.6% (n = 5) (P < 0.001), leading to a significant reduction in use of AADs (100.0% to 11.6%, P < 0.001) and improvement in mean NYHA functional class (2.5 ± 0.5 to 1.4 ± 0.2, P < 0.001). Major intraoperative complications were seen in 4.7% of patients (hemothorax and chylothorax). Of the patients, 81.4% (n = 35) experienced no mortality or major complications over a 1-year follow-up period, with the remaining still within their first year postprocedure. ConclusionsBCSD is effective for the management of refractory PVCs and ventricular tachycardia who have failed previous ablation therapy.

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.

Abstract 18210: Renal Denervation in Management of Heart Failure: A Systematic Review and Meta-Analysis

Introduction: Renal denervation (RDN) is a novel intervention targeting sympathetic nerves along the renal artery. Ablation of this neurohormonal pathway alters the pathophysiology of heart failure (HF) and can lead to improvements in clinical outcomes. We conducted a systematic review and meta-analysis to review the outcome of heart failure patients undergoing RDN. Methods: We performed a comprehensive search on PubMed, Cochrane, and Embase from inceptions through June 2023 using the string “(“renal denervation” OR “renal sympathetic denervation “) AND (“heart failure” OR “congestive heart failure”)”. Exclusion criteria include non-human trials, studies without a baseline and control, and studies without outcomes of interest. We collected the number of patients with HF and the resulting outcomes. Outcomes of interest include left ventricular ejection fraction (LVEF), six minute walk distance (SMWD), NT- proBNP, and systolic and diastolic pressures. The random-effects model was used to calculate the odds ratios (OR), mean differences (MD), and confidence intervals (CI). A p value &lt;0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. Results: Nine randomized control trials involving a total of 513 patients were included in our analysis. We found a significant difference when comparing the RDN group to the control groups for LVEF (MD 1.39, 95% CI [0.03,2.75]), SMWD (MD 200.13 m, 95% CI [187.32,212.95]), NT-proBNP (MD -397.16 pg/ml, 95% CI [-438.90, -355.42]), SBP (MD -3.69 mmHg, 95% CI [-7.24, -0.14]) within 12 months. Interestingly, difference in DBP was insignificant (MD -1.13 mmHg, 95% CI [-3.33,1.07]). Our RDN group had a significant decrease in hospital admissions (OR 0.83, 95% CI [0.25,2.77]) for HF exacerbation within 12 month following denervation. When comparing RND to baseline, we found a significant difference in LVEF (MD 1.90, 95% CI [0.64,3.16]) and SMWD (MD 106.56 m, 95% CI [88.72,124.40]). Conclusions: Our analysis demonstrates RDN results in a significant difference in LVEF, SMWD, NT-proBNP, and SBP in patients with HF when compared to control and baseline. However, further research is needed with larger samples to establish the safety and effectiveness of RDN as a viable therapy in HF.

Abstract 16602: The PlGF-Nrp1 Interaction Promotes the Splenic Immune Response in Hypertension After Neuroimmune Activation

Introduction: We previously discovered that Placental Growth Factor (PlGF) is released in the spleen by a sympathetic discharge to elicit hypertension. Neuropilin1 (Nrp1) is one of PlGF receptors and, interestingly, is a transmembrane protein expressed on precursors of Dendritic cells (DCs). Hypothesis: Here we investigated the involvement of Nrp1 as the PlGF receptor mediating the neuroimmune activation of immune response during hypertension. Methods: We used flow cytometry and tail cuff to evaluate the involvement of PlGF-Nrp1 pathway in neuroimmune activation of splenic immune response in hypertension. Results: To define Nrp1 role in transducing PlGF effect during hypertension, we evaluate its expression by flow cytometry finding that monocyte-derived DCs (MoDCs) increased Nrp1 expression in response to AngII (12.7±1.3 vs 28.8±3 % Nrp1 Veh vs AngII; p&lt;0.01). This effect was blocked by splenic sympathetic denervation obtained by celiac ganglionectomy (CGX) (28.8±3 vs 14±1.5 % Nrp1 Sham AngII vs CGX AngII; p&lt;0.01). To test the relevance of PlGF-Nrp1 pathway in hypertension, we generated a transgenic mouse model with a selective deletion of Nrp1 in myeloid lineage utilizing the LysMcre (Nrp1 myeKO mice). By using an in vitro standard differentiation protocol of maturation of monocytes in DCs, we observed that CD86 and MHCII expression was up-regulated in MoDCs from the spleen of WT mice cultured in the standard medium plus rmPlGF (0.014±0.001 vs 0.035±0.005 CD86+ DCs/total cells count respectively, p&lt;0.05; 0.010±0.003 vs 0.030±0.003 MHCII+ DCs/total cells count respectively, p&lt;0.01). On the contrary, CD86 and MHCII were similarly expressed on MoDCs from Nrp1 myeKO mice cultured with and without rmPlGF indicating that PlGF is involved in the maturation of MoDCs through its interaction with Nrp1. To confirm the involvement of Nrp1 in blood pressure (BP) increase, we infused AngII to Nrp1 myeKO mice, finding that they were protected from hypertension as compared to WT control mice (Systolic BP 106±1 vs 126±2 mmHg respectively, p&lt;0.001). Conclusions: These data demonstrate that PlGF-Nrp1 pathway is a key mechanism that promote the immune response involved in hypertension and blocking the splenic innervation, hampered this response and BP increase.

Abstract 15291: Early Outcomes With Left Cardiac Sympathetic Denervation for Medically Refractory Idiopathic Ventricular Fibrillation

Introduction: Treatment options for patients with recurrent ventricular arrhythmias (VAs) refractory to pharmacotherapy and/or ablation are minimal. Although left cardiac sympathetic denervation (LCSD) is well established in long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT), LCSD’s role in idiopathic ventricular fibrillation (IVF) is less clear. Here, we report our single-center experience regarding the early outcomes of LCSD in patients with IVF. Hypothesis: To determine the efficacy of LCSD on reducing VAs in IVF patients refractory to conventional therapy. Methods: A retrospective analysis of the electronic health record of patients with IVF between January 2000 to April 2023 was performed. Cardiac event rates [defined as arrhythmic syncope/seizure, appropriate implantable cardioverter defibrillator (ICD) therapy, sudden cardiac arrest (SCA), or sudden cardiac death (SCD)] before and after LCSD for each patient were calculated and a Wilcoxon signed rank test was performed. Results: In total, 94 patients (41% female) were classified as IVF. Overall, 15/94 patients (16%) had LCSD due to refractory VAs (60% male; mean age at LCSD 36 ± 20 years) despite beta-blocker treatment (100%) or combined drug therapy (67%). In total, 14 patients (15%) had an electrophysiology study performed before LCSD of which 10 (67%) had VAs ablation. All patients had a structurally normal heart and genetic testing performed in 14/15 patients (93%) confirmed absence of genetic cardiomyopathies and channelopathies. SCA was the sentinel event in 10 of 15 patients (67%); 14 patients (93%) had an ICD in place. The average follow-up time after LCSD was 3 ± 4 years. The VA event rate before LCSD was 4 ± 3 events per year and was reduced to 1 ± 3 per year (p&lt;0.04) after LCSD. Patients had a median of 3.2 less events per year after LCSD (p=0.02) with 7 patients (47%) having no post-LCSD recurrences thus far while 3 (20%) patients were deemed LCSD non-responders with no reduction of event rate. Conclusions: LCSD represents a substrate-independent, anti-fibrillatory treatment option for patients with life-threatening, genetic arrhythmias. While not curative, the early outcomes of LCSD for patients with medically refractory IVF are promising.

Catecholaminergic Polymorphic Ventricular Tachycardia and Gene Therapy: A Comprehensive Review of the Literature.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited channelopathy. In this review, we summarize the epidemiology, pathophysiology, clinical characteristics, diagnostics, genetic mutations, standard treatment, and the emergence of potential gene therapy. This inherited cardiac arrhythmia presents in a bimodal distribution with no association between sex or ethnicity. Six different CPVT genes have been identified, however, most of the cases are related to a heterozygous, gain-of-function mutation on the ryanodine receptor-2 gene (RyR2) and calsequestrin-2 gene (CASQ2) that causes delayed after-depolarization. The diagnosis is clinically based, seen in patients presenting with syncope after exercise or stress-related emotions, as well as cardiac arrest with full recovery or even sudden cardiac death. Standard treatment relies on beta-blockers, with add-on therapy, flecainide, and cardiac sympathetic denervation as second-line treatments. An implantable cardioverter-defibrillator is indicated for patients who have suffered a cardiac arrest. Potential gene therapy has emerged in the last 20 years and accelerated because of associated viral vector applicationin increasing the efficiency of prolonged cardiac gene expression.Nevertheless, human trials for gene therapy for CPVT have been limited as the population is rare, and an excessive amount of funding is required.

Catheter-Based Ultrasound Renal Denervation in Patients with Resistant Hypertension: A Systematic Review

Background: The maintenance and development of hypertension are fundamentally dependent on renal sympathetic hyperactivity. Through regulation of the renal sympathetic nerves, catheter-based renal sympathetic denervation has been demonstrated to dramatically lower blood pressure (BP) in patients with resistant hypertension (systolic blood pressure 160 mm Hg on three or more antihypertensive medicines, including a diuretic). This study assessed a catheter-based ultrasound device of the next generation intended to maximize nerve coverage using circumferential ultrasound energy. This study's objective is to describe the results of renal denervation (RDN) in patients with resistant hypertension using a catheter-based ultrasonography device to measure blood pressure and safety. A potential new non-pharmacological therapy for resistant hypertension is renal denervation. Method: PubMed, Web of Science, Science Direct, Cochrane Library, and Google Scholar were thoroughly searched for relevant material. Throughout this meticulous process, the Rayyan QRCI was used. Results: our review included 10 studies with parameters including the period of study, age range of patients, office blood pressure, ambulatory blood pressure and the used approach. Clinical studies are required to determine whether this method is effective in treating this resistant hypertension. Conclusion: In individuals with resistant hypertension, catheter-based ultrasound renal denervation significantly and persistently lowers blood pressure and has no negative effects on renal function or renal artery anatomy.

Sensory nerves, but not sympathetic nerves, promote reparative dentine formation after dentine injury via CGRP-mediated angiogenesis: An in vivo study.

Dental pulp is richly innervated by nerve fibres, which are mainly involved in the sensation of pain. Aside from pain sensation, little is known regarding the role of dental innervation in reparative dentine formation. We herein generated a mouse model of experimental dentine injury to examine nerve sprouting within the odontoblast and subodontoblastic layers and investigated the potential effects of this innervation in reparative dentinogenesis. Mouse tooth cavity model (bur preparation + etching) was established, and then nerve sprouting, angiogenesis and reparative dentinogenesis were determined by histological and immunofluorescent staining at 1, 3, 7, 14 and 28 days postoperatively. We also established the mouse-denervated molar models to determine the role of sensory and sympathetic nerves in reparative dentinogenesis, respectively. Finally, we applied calcitonin gene-related peptide (CGRP) receptor antagonist to analyse the changes in angiogenesis and reparative dentinogenesis. Sequential histological results from dentine-exposed teeth revealed a significant increase in innervation directly beneath the injured area on the first day after dentine exposure, followed by vascularisation and reparative dentine production at 3 and 7 days, respectively. Intriguingly, abundant type H vessels (CD31+ Endomucin+ ) were present in the innervated area, and their formation precedes the onset of reparative dentine formation. Additionally, we found that sensory denervation led to blunted angiogenesis and impaired dentinogenesis, while sympathetic denervation did not affect dentinogenesis. Moreover, a marked increase in the density of CGRP+ nerve fibres was seen on day 3, which was reduced but remained elevated over the baseline level on day 14, whereas the density of substance P-positive nerve fibres did not change significantly. CGRP receptor antagonist-treated mice showed similar results as those with sensory denervation, including impairments in type H angiogenesis, which confirms the importance of CGRP in the formation of type H vessels. Dental pulp sensory nerves act as an essential upstream mediator to promote angiogenesis, including the formation of type H vessels, and reparative dentinogenesis. CGRP signalling governs the nerve-vessel-reparative dentine network, which is mostly produced by newly dense sensory nerve fibres within the dental pulp.

Cardiac sympathetic "morbidity" might reflect the neurobiology of early Parkinson's disease.

An appropriate extracranial biomarker that delineates endophenotypes of Parkinson's disease (PD) at an early stage and reflects the neurodegenerative process is lacking. An evaluation of myocardial sympathetic nerve terminals could be a good candidate. This study aimed to explore subtypes of PD patients that showed cardiac catecholaminergic vesicular defect and their characteristics. This study included 122 early drug-naïve PD patients who were followed for approximately 4-5years. All patients were examined with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane positron-emission tomography and 123I-meta-iodobenzylguanidine myocardial scintigraphy. Cardiac scans were reexamined two or three times. Patients were subgrouped into the sympathetic denervated group at the initial scan, those without evidence of denervated myocardium in the first and subsequent scans, and the converters whose myocardium was initially normal but became impaired in the subsequent scans. Cognition in 99 patients was initially assessed with neuropsychological tests. Any associations between cardiac denervation subtypes and presynaptic dopamine transporter densities were investigated. Cognitive status relevant to cardiac sympathetic denervation status was evaluated. This study found that cross-sectional comparisons of presynaptic monoamine transporter availability with a predefined order of cardiac denervation groups revealed parallel degeneration. A quadratic correlation between cardiac catecholamine capacity and cognition was observed. This association was interpreted to reflect the early neurobiology of PD. An observed cardiac catecholaminergic gradient was to mirror the central neurobiology of early PD.

Unlocking the Potential of Left Cardiac Sympathetic Denervation: A Scoping Review of a Promising Approach for Long QT Syndrome.

Left cardiac sympathetic denervation (LCSD) has emerged as an alternative therapy for individuals diagnosed with long QT syndrome (LQTS), a genetic disorder characterized by abnormal electrical activity in the heart and sudden cardiac death (SCD). This review examines the history and rationale behind LCSD in LQTS treatment, as well as the procedure, its efficacy, and indications along with the adverse effects that may be associated with it. LQTS presents with prolonged QT intervals on an electrocardiogram and can manifest asseizures, fainting, and SCD. Beta-blockers are the primary treatment for LQTS but some patients do not respond well to these medications or experience side effects. Additionally, implantable cardioverter-defibrillators (ICDs) are not always effective in preventing arrhythmias and can lead to complications. LCSD might offer an alternative approach by disrupting sympathetic activity in the heart. In humans, LCSD reduces the release of norepinephrine, normalizes the QT interval, and decreases the likelihood of life-threatening heart rhythms. The procedure does not impair heart rate or cardiac function due to the compensatory effects of the right cardiac sympathetic nerves. The surgical procedure for LCSD involves the removal of the lower half of the stellate ganglion and thoracic ganglia. Complete denervation is essential for optimal outcomes, while incomplete procedures are considered unacceptable. Traditional and minimally invasive approaches, such as video-assisted thoracic surgery (VATS), are available, with VATS offering shorter hospital stays and fewer complications. In conclusion, LCSD provides a viable treatment option for individuals with LQTS who do not respond well to beta-blockers or require additional protection beyond medication or ICDs. Further research and clinical experience are needed to enhance its acceptance and implementation in routine practice.

Cardiac 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy in Parkinson's Disease: A Comprehensive Review.

Cardiac sympathetic denervation, as documented on 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, is relatively sensitive and specific for distinguishing Parkinson's disease (PD) from other neurodegenerative causes of parkinsonism. The present study aims to comprehensively review the literature regarding the use of cardiac MIBG in PD. MIBG is an analog to norepinephrine. They share the same uptake, storage, and release mechanisms. An abnormal result in the cardiac MIBG uptake in individuals with parkinsonism can be an additional criterion for diagnosing PD. However, a normal result of cardiac MIBG in individuals with suspicious parkinsonian syndrome does not exclude the diagnosis of PD. The findings of cardiac MIBG studies contributed to elucidating the pathophysiology of PD. We investigated the sensitivity and specificity of cardiac MIBG scintigraphy in PD. A total of 54 studies with 3114 individuals diagnosed with PD were included. The data were described as means with a Hoehn and Yahr stage of 2.5 and early and delayed registration H/M ratios of 1.70 and 1.51, respectively. The mean cutoff for the early and delayed phases were 1.89 and 1.86. The sensitivity for the early and delayed phases was 0.81 and 0.83, respectively. The specificity for the early and delayed phases were 0.86 and 0.80, respectively.

Sympathetic Denervation Abolishes Recurrent Ventricular Fibrillation and Intractable Coronary Spasm: Autonomic Dysfunction: A Shared Mechanism?

Sympathetic Denervation Abolishes Recurrent Ventricular Fibrillation and Intractable Coronary Spasm: Autonomic Dysfunction: A Shared Mechanism?

Detection of sympathetic denervation defects in Fabry disease by hybrid [11C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance

BackgroundMyocardial glycosphingolipid accumulation in patients with Fabry disease (FD) causes biochemical and structural changes. This study aimed to investigate sympathetic innervation in FD using hybrid cardiac positron emission tomography (PET)/magnetic resonance imaging (MRI). Methods and resultsPatients with different stages of Fabry disease were prospectively enrolled to undergo routine CMR at 1.5T, followed by 3T hybrid cardiac PET/MRI with [11C]meta-hydroxyephedrine ([11C]mHED). Fourteen patients with either no evidence of cardiac involvement (n = 5), evidence of left ventricular hypertrophy (LVH) (n = 3), or evidence of LVH and fibrosis via late gadolinium enhancement (LGE) (n = 6) were analyzed. Compared to patients without LVH, patients with LVH or LVH and LGE had lower median T1 relaxation times (ms) at 1.5 T (1007 vs. 889 vs. 941 ms, p = 0.003) and 3T (1290 vs. 1172 vs. 1184 p = .014). Myocardial denervation ([11C]mHED retention < 7%·min) was prevalent only in patients with fibrosis, where a total of 16 denervated segments was found in two patients. The respective area of denervation exceeded the area of LGE in both patients (24% vs. 36% and 4% vs. 32%). However, sympathetic innervation defects ([11C]mHED retention ≤ 9%·min) occurred in all study groups. Furthermore, a reduced sympathetic innervation correlated with an increased left ventricular mass (p = .034, rs = − 0.57) and a reduced global longitudinal strain (GLS) (p = 0.023, rs = − 0.6). ConclusionHybrid cardiac PET/MR with [11C]mHED revealed sympathetic innervation defects, accompanied by impaired GLS, in early stages of Fabry disease. However, denervation is only present in patients with advanced stages of FD showing fibrosis on CMR.

Decreased cholinesterase level combined with renal dysfunction and sympathetic denervation associated with increased cardiac mortality in systolic heart failure.

Cardiac mortality in patients with heart failure (HF) is likely to be aggravated by malnutrition, assessed by serum cholinesterase (ChE) level, as well as by kidney dysfunction or impairment of cardiac sympathetic denervation. Their prognostic interactions, however, have not been determined. A total of 991 systolic HF patients were enrolled in our HF database following clinical evaluation including evaluation of the nutrition state and assessment of standardized heart-to-mediastinum ratio (sHMR) of iodine-123-labeled meta-iodobenzylguanidine activity. Patients were followed up for an average of 43 months with the primary endpoint of fatal cardiac events (CEs). The CE patient group had a lower level of ChE, lower estimated glomerular filtration rate (eGFR) and lower late sHMR than those in the non-CE patient group. A five-parameter model with the addition of serum ChE selected in the multivariate logistic analysis (model 2) significantly increased the AUC predicting risk of cardiac events compared with a four-parameter model without serum ChE (model 1), and net reclassification analysis also suggested that the model with the addition of serum cholinesterase significantly improved cardiac event prediction. Moreover, in overall multivariate Cox hazard analysis, serum ChE, eGFR and late sHMR were identified to be significant prognostic determinants. HF patients with two or all of the prognostic variables of serum ChE < 230 U/L, eGFR < 48.8 ml/min/1.73 m2 and late sHMR < 1.90 had significantly and incrementally increased CE rates compared to those in HF patients with none or only one of the prognostic variables. Decreases in cholinesterase level and kidney function further increase cardiac mortality risk in HF patients with impairment of cardiac sympathetic innervation.

Long term effect of renal denervation on 24 hour abpm blood pressure variability and blood pressure load parameters

The aim of the study was to evaluate the long-term effect of renal sympathetic denervation (RSD) on 24h ambulatory blood pressure measurement (ABPM) and blood pressure load (BP load) in patients with resistant hypertension. The study included 32 patients with treatment-resistant hypertension and performed successful RSD. The effect of renal denervation was significant both in terms of daytime, nighttime and 24-hour arterial pressure, with the most pronounced effect on nocturnal blood pressure. In addition to mean BP reduction we found out a significant improvement of weighted 24 h SD and BP load during follow-up. A long-term effect of the RSD, reported as a reduction in 24-hour systolic blood pressure above 10 mm Hg at month 12, was found in 22 patients (68.8%). In multivariate regression analysis, two parameters remained predictive for successful renal denervation &amp;ndash; higher nighttime systolic blood pressure (OR 0.9, 95% CI 0.8-1.005, p = 0.05) and lower pulse pressure (OR 1.13, 95% CI 1.01-1.26, p = 0.03).&amp;nbsp;

Left cardiac sympathetic denervation in children with Jervell Lange-Nielsen syndrome and drug refractory torsades - A case series.

Long QT syndrome is an inherited malignant channelopathy which leads to life-threatening arrhythmia, with multiple genotypes. Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive subtype of this disease, characterized by congenital sensorineural deafness and a high incidence of sudden cardiac death (SCD). We prospectively followed up six children who underwent left cardiac sympathetic denervation (LCSD) for JLNS in view of high-risk features despite being on maximally tolerated doses of oral propranolol. Mean age at diagnosis was 2.75±0.39 years, with a significant delay between onset of symptoms and diagnosis (mean 7.2±3.5 months). All had sensorineural hearing loss, conforming to the JLNS phenotype. Mean QTc interval was 603±93ms, with T wave alternans (TWA) seen in all cases. All were started on propranolol and subsequently subjected to LCSD, and 3 underwent AAI permanent pacemaker implantation. Over a mean follow-up of 20 months, there was a significant reduction in QTc (603±93ms to 501±33ms, p=.04), which was persistent on follow-up (525±41ms) and only two out of six had persistent T wave alternans on ECG (p<.01). None of these children had presyncope, syncope, seizures, torsades de pointes, cardiac arrest or death on follow up following LCSD. Jervell Lange-Nielsen syndrome is a subtype of LQTS with high-risk features. LCSD, an effective therapeutic option for those having symptoms despite being on propranolol, results in significant reduction of QTc interval and amelioration of symptoms.