Cardiac Denervation Research Articles

Partial Cardiac Denervation to Prevent Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting: The pCAD-POAF Randomized Clinical Trial.

Efficient approaches to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) are still needed. To investigate whether partial cardiac denervation, achieved by cutting off the ligament of Marshall (LOM) and resecting the fat pad along the Waterston groove, can reduce the risk of POAF following CABG. This single-center, randomized clinical trial enrolled adult patients scheduled for isolated CABG in China. Enrollment was from August 15, 2022, to December 13, 2023; follow-up visits were 30 days after discharge. Participants were randomized into the intervention group (CABG plus partial cardiac denervation) and the control group (CABG only) in a 1:1 pattern. All participants were continuously monitored for the incidence of POAF until day 6 after the operation. The primary end point was the incidence of POAF in 6 days, defined as a supraventricular arrhythmia lasting for more than 30 seconds. The trial enrolled 430 patients (79 [18.4%] female; mean [SD] age, 61.9 [7.8] years). Compared with the control group, the 6-day incidence of POAF was significantly lower in the intervention group (18.1% vs 31.6%; P = .001; risk ratio, 0.57 [95% CI, 0.41-0.81]). To further support these results, a sensitivity analysis performed with Kaplan-Meier survival curves also showed a significant reduction in the occurrence of POAF in the intervention group (hazard ratio, 0.53 [95% CI, 0.36-0.79]; P = .002). Safety assessments showed no difference between the 2 groups, while postoperative medical cost was reduced in the intervention group. This randomized clinical trial found that partial cardiac denervation was an effective procedure to reduce the occurrence of POAF after isolated CABG without additional postoperative complications. These results suggest that partial cardiac denervation may be a good option for cardiac surgeons to consider for preventing POAF after CABG. ClinicalTrials.gov Identifier: NCT05009914.

Diabetic Charcot neuroarthropathy: A threat to both limb and life.

Diabetic Charcot neuroarthropathy (DCN), first described in 1936, occurs in less than 1% of diabetic patients, but in those diabetic subjects with distal symmetrical polyneuropathy, the overall incidence increases to 30% and the risk is even greater in those with type 1 diabetes. Factors that precipitate DCN are trauma, ischaemia due to arterio-venous shunting, increased osteoclastic activity and inflammation. DCN usually presents with a painless swollen foot and/or ankle which is 'hot to the touch'. These clinical findings are soon followed by characteristic magnetic resonance imaging (MRI) abnormalities and later X-ray changes. The joints that are most typically involved in chronological order are the tarsometatarsals followed by the naviculocuniform, sub-tarsal, talonavicular and metatarsal and tarsophalangeal. The cornerstone of therapy is prolonged (3-12 months) offloading with immobilization. Bisphosphonates may possibly accelerate recovery, whereas other unproven possible therapies include rhPTH, 1-34, calcitonin and methylprednisolone, which are not only ineffective but in some cases may also prolong the time to healing. Denosumab is potentially an efficacious, if unproven, therapy to accelerate healing. The risk of amputation is high and increases in the presence of a foot ulcer. DCN is associated with manifestations of autonomic neuropathy, including cardiac denervation, so that the risks of a cardiac event and heart failure are increased with DCN. Mortality is also increased with DCN, especially in the presence of a foot ulcer. To avoid the recurrence of DCN and especially to lower the risk of the recurrence of a foot ulcer recurrence reconstructive, surgery may be needed.

Exercise as a modality to improve heart transplantation-related functional impairments: An article review.

Heart transplantation (HT), the treatment choice of advanced heart failure patients, is proven effective in increasing the survival and functional status of the recipients. However, compared to normal controls, functional status is lower in HT recipients. Exercise given in cardiac rehabilitation has been shown to improve exercise capacity as measured with peak oxygen uptake (VO2 peak) and muscle strength after completion of the program and cessation of exercise results in loss of exercise benefits. Several factors related to cardiac denervation and the use of immunosuppressive agents in HT recipients result in functional impairments including cardiovascular, pulmonary, exercise capacity, psychological, and quality of life (QoL) problems. High-intensity interval training (HIIT) is the most common type of exercise used in HT recipients and given as a hospital-based program. Improvement of functional impairments was found to have occurred due to primarily musculoskeletal adaptations through improvement of muscle structure and aerobic capacity and cardiovascular adaptations. In general, exercise given after transplantation improved VO2 peak significantly and improvement was better in the HIIT group compared to moderate intensity continuous training or no-exercise groups. Improvement of QoL was ascribed to improvement of exercise capacity, symptoms, pulmonary function, physical capacity improvement, anxiety, and depression.

Unraveling olfactory subtypes in Parkinson's disease and their effect on the natural history of the disease.

Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2-4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries.

Noradrenergic cardiac denervation is associated with gait velocity in Parkinson disease: a dual ligand PET study.

Preliminary data suggest that gait abnormalities in Parkinson disease (PD) may be associated with sympathetic cardiac denervation. No kinematic gait studies were performed to confirm this observation. We aimed to correlate spatiotemporal kinematic gait parameters with cardiac sympathetic denervation as determined by cardiac [11C]HED PET in PD. Retrospective database analysis of 27 PD patients with cardiac sympathetic denervation. All patients underwent spatiotemporal kinematic gait assessment (medication 'off' state), cardiac [11C]HED and dopaminergic brain [11C]DTBZ PET scans. We employed a hierarchical regression approach to examine associations between the extent of cardiac denervation, dopaminergic nigrostriatal neurodegeneration, and three gait parameters - velocity, step length and cadence. More extensive cardiac denervation was associated with slower velocity (estimate: -1.034, 95% CI [-1.65, -0.42], p = 0.002), shorter step length (estimate: -0.818, 95% CI [-1.43, -0.21], p = 0.011) and lower cadence (estimate: -0.752, 95% CI [-1.28, -0.23], p = 0.007) explaining alone 30% (Adjusted-R²: 0.297), 20% (Adjusted-R²: 0.202) and 23% (Adjusted-R²: 0.227) of the variability, respecivetly. These associations remained independent of striatal dopaminergic impairment and confounding factors such as age, Hoehn and Yahr (HY) stages, peripheral neuropathy, cognition, and autonomic symptoms. In contrast, striatal dopaminergic denervation was significantly associated with step length (estimate: 0.883, 95% CI [0.29, 1.48], p = 0.005), explaining about 24% of the variability but was dependent of HY stage. More severe cardiac noradrenergic denervation was associated with lower gait velocity, independent of striatal dopaminergic denervation and HY stage, impacting both step length and cadence. These results suggest independent contributions of the peripheral autonomic system degeneration on gait dynsfunction in PD.

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians.

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder

Abstract Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson’s disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43–87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1–3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson’s disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio < 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson’s disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson’s disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson’s disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.

Partial CArdiac Denervation to Prevent Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (pCAD-POAF): Study Protocol for a Randomized Controlled Trial

Postoperative atrial fibrillation (POAF) is commonly seen in patients undergoing coronary artery bypass grafting (CABG), increasing the risk of morbidity, mortality and hospital expenses. This study is aimed to evaluate the effect of partial cardiac denervation, which is achieved by cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove, on the prevention of POAF after CABG. Patients planned for CABG at our center will be screened for eligibility for this study. A total of 430 patients will be randomized into intervention (partial cardiac denervation) group and control group. Intraoperative high-frequency electrical stimulation and further histologic analysis will be performed among certain number of patients to confirm the existence of ganglia. All of the patients will be continuously monitored for the incidence of POAF through electrophysiologic device until the 6th day postoperatively, and required to complete a 30-day follow-up (twelve lead electrocardiogram and echocardiogram assesment) after discharge. The primary endpoint is the incidence of POAF, while the secondary endpoints are the cost-effectiveness and safety outcomes. In conclusion, this trial will evaluate whether partial cardiac denervation through cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove can reduce the incidence of POAF after CABG. If this procedure is revealed to be effective and safe, it may provide a potential therapeutic approach to prevent POAF in this group of patients.

Progressive QTc prolongation and reduced heart rate variability in dementia with Lewy bodies compared to Alzheimer's disease

IntroductionAutonomic dysfunction (AuD) is a significant clinical challenge in patients with Dementia with Lewy Bodies (DLB). Manifestations of AuD such as orthostatic hypotension (OH) is associated with falls and decreased quality of life. Cardiac autonomic denervation is an early phenomenon in DLB and a potential contributor to OH. This retrospective study was undertaken to explore whether routine ECG tracings could be used to identify signs of autonomic dysfunction in DLB. Methods18 patients with DLB and 18 age-matched patients with Alzheimer's disease (AD) were included. ECGs and clinical data were analyzed retrospectively for heart rate variability (HRV) and QTc interval prolongation. ResultsDuring an average of 10 years observation time (first to last ECG recording), the QTc interval increased in the DLB group, but not in the AD group. HRV was significantly lower at end of follow-up in the DLB group than in the AD group. DLB patients with OH had greater QTc prolongation. ConclusionLongitudinal ECG analysis indicates that signs of AuD in DLB are reflected on routine ECG tracings. If confirmed in larger cohorts, this could influence risk stratification and help direct preventive measures.

Estimating motor progression trajectory pursuant to temporal dynamic status of cardiac denervation in Parkinson's disease.

Parkinson's disease (PD) is a multifaceted disease that encompasses diverse clinical phenotypes. The diversity of PD could be subtyped based on the temporal dynamic status of cardiac sympathetic innervation; (1) initially, denervated myocardium (peripheral nervous system-predominant; PNS-predominant), (2) preserved myocardium (central nervous system-predominant; CNS-predominant), and (3) preserved myocardium who developed cardiac sympathetic denervation (CSD) on the subsequent imaging (Converter; delayed cardiac denervation). This study assessed how the cardiac denervation could reflect the pathobiology. We investigated whether this phenotyping could help predict the motor progression trajectory of PD. Cardiac sympathetic innervation was evaluated using initial and sequential 123I-meta-iodobenzylguanidine myocardial scintigraphy and patients were stratified into three groups as above. Motor severity and progression were evaluated in each patient. The association between subtypes and dopaminergic nigrostriatal degeneration was analyzed. The influence of cardiac denervation on motor progression was also investigated. Among the enrolled 195 patients, 144 PD subjects were defined as PNS-predominant, 16 as Converter, and 35 as CNS-predominant. The most severe nigrostriatal degeneration was observed in the PNS-predominant group and the dopaminergic degeneration was the most asymmetric in the CNS-predominant group. Positive linear trends of nigrostriatal degeneration and its asymmetric degeneration of striatum and globus pallidus were found across the patterns of cardiac sympathetic innervation (PNS-predominant vs. Converter vs. CNS-predominant). It indicated an increasing degree of asymmetric degeneration among the groups. A longitudinal estimation of motor progression revealed distinct cardiac denervation trajectories for each subtype. These results implicated that the subtypes of CSD might indicate a predominant origin and spreading pattern of pathobiology.

Capabilities of intravascular imaging techniques in the diagnosis of cardiac allograft vasculopathy: Literature review

Cardiac allograft vasculopathy (CAV) is a coronary heart disease (CHD), arising after an orthotopic heart transplant (OHT), and it is one of the leading causes of death in heart recipients. The probability of death is 10%. CAV can manifest as early as 1 year after OHT. Patients do not have pain syndrome that is typical for CHD due to cardiac denervation. The first clinical manifestations may be congestive heart failure, ventricular arrhythmias or even sudden cardiac death. Coronary angiography is the routine technique for CAV detection. However, it is not sensitive enough (about 44%) for CAV detection at an early stage of the disease. Today, intravascular imaging methods (intravascular ultrasound, optical coherence tomography), which allow the evaluation of the morphology of coronary artery lesions, including CAV, have become widespread. This article is devoted to the modern capabilities of intravascular imaging methods in the diagnosis of CAV. CAV is the main cause of myocardial infarction and chronic heart failure in patients after OHT. Intravascular imaging techniques allow early detection of this condition and prevention of unfavorable outcomes in a complex category of heart recipients. Given the advantages of optical coherence tomography (OCT) and disadvantages of intravascular ultrasound (IVUS), OCT appears to be a more informative method of CAV detection.

Abstract 16815: Outcomes of Cardiac Sympathetic Denervation via Cautery Ablation for Ventricular Arrhythmia: A Single Center Study

Introduction: Cardiac sympathectomy denervation (CSD) has been demonstrated to reduce ventricular arrhythmia (VA) burden and to improve arrhythmia-free survival. Early evidence for the clinical antiarrhythmic benefits for CSD was established in patients with long-QT syndrome and catecholaminergic polymorphic VT (CPVT). Its benefit has subsequently been shown to extend to other undifferentiated cardiomyopathies. Hypothesis: Literature on CSD for VA has been limited due to a small number of patients. Our retrospective study is to review patients who underwent CSD for VA at our center via cautery ablation. Methods: We identified 9 patients who underwent CSD from 4/2018 to 2/2022. Electronic medical record was reviewed for clinical history and outcomes. Results: Mean age was 52±17 and 5 patients (55.6%) were male. Seven patients (77.8%) had nonischemic cardiomyopathy (NICM) and 2 patients (22.2%) had CPVT. Mean LVEF was 43±19% and 5 patients (55.6%) had heart failure with NYHA class 3±0.7. Five patients (55.6%) underwent CSD in outpatient setting and 4 patients (44.4%) had polymorphic VT. Six patients (66.7%) had prior catheter-based VT ablation, 1 patient (11.1%) had prior ganglion block, and 4 patients (44.4%) had history of VT storm. All patients were on antiarrhythmics ranging from a beta blocker monotherapy to a combination of class Ic, class III, and a beta blocker. Seven patients (77.8%) had a defibrillator prior to CSD. All patients underwent CSD (7 with bilateral and 2 with left only) without any procedural complication. Five patients (55.6%) had recurrence of VA in 423±567 days with follow-up duration of 729±478 days. Three patients (33.3%) underwent heart transplant or LVAD and three patients (33.3%) died in 426±396 days since CSD. Overall, 3 patients (33.3%) including 2 CPVT patients and one NICM patient with normal EF were free of death, sustained VT, or advanced heart failure therapies. Conclusions: CSD via cautery ablation is safe and effective for patients with refractory VA to antiarrhythmics and/or VT ablation. Success rate appeared to be higher in patients with CPVT and normal EF. Lower rate of survival and freedom from VT or transplant/LVAD compared to published literature may reflect our sick population.

Abstract 12226: Aging Impairs the Neuro-Vascular Interface in the Heart

Aging is a major risk factor for impaired cardiovascular function. The aging heart is characterized by vascular dysfunction, increased hypertrophy, fibrosis and electrophysiological alterations. However, the interaction between the different age-associated changes in cardiac remodelling is poorly define. Since vessels are aligned with nerves, and this interplay is critical for tissue homeostasis, we investigated whether an impairment of the neuro-vascular interface may contribute to age-associated pathologies in the heart. We show that aging reduces sympathetic and sensory nerve fibers, which both align to arteries and arterioles. Aging induced a dysregulation of vascular-derived neuro-regulatory genes, especially the axon repellent factor Sema3A, which was augmented by 2.4±0.1-fold in old heart endothelial cells. Consistently, endothelial Sema3a overexpression reduced axon density in vivo, thus mimicking the observed aged heart phenotype. Since cellular senescence was induced at the same time point when nerve density declined (16 months of age) and senescence endothelial cells showed a higher expression of Sema3a, we hypothesized that endothelial senescence may contribute to cardiac denervation. Indeed, supernatants of senescent endothelial cells reduced neurite outgrowth in vitro in a Sema3A-dependent manner. In vivo studies further confirmed that endothelial-specific induction of senescence by overexpression of Progerin induced left ventricular denervation and induced Sema3a expression. By contrast, the pharmacological removal of senescent cells by the senolytic drugs dasatinib and quercetin rescued age-induced denervation and prevented the age-induced induction of endothelial Sema3a expression. Functional studies additionally demonstrated that endothelial senescence reduced heart rate variability, while senolytics preserved heart rate variability, restored age-associated declines in sympathetic and parasympathetic activity and reduced age-associated increase in arrhythmias. These data suggest that senescence-associated regulation of neuro-regulatory genes in endothelial cells is associated with reduced nerve density and, thereby, contributes to age-associated cardiac dysfunction.

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<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<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<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.

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.

Endothelial cell dysfunction: the culprit for cardiac denervation in aging?

Endothelial cell dysfunction: the culprit for cardiac denervation in aging?

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.

Cardiac Vagal Nerve Activity Increases During Exercise to Enhance Coronary Blood Flow.

The phrase complete vagal withdrawal is often used when discussing autonomic control of the heart during exercise. However, more recent studies have challenged this assumption. We hypothesized that cardiac vagal activity increases during exercise and maintains cardiac function via transmitters other than acetylcholine. Chronic direct recordings of cardiac vagal nerve activity, cardiac output, coronary artery blood flow, and heart rate were recorded in conscious adult sheep during whole-body treadmill exercise. Cardiac innervation of the left cardiac vagal branch was confirmed with lipophilic tracer dyes (DiO). Sheep were exercised with pharmacological blockers of acetylcholine (atropine, 250 mg), VIP (vasoactive intestinal peptide; [4Cl-D-Phe6,Leu17]VIP 25 µg), or saline control, randomized on different days. In a subset of sheep, the left cardiac vagal branch was denervated. Neural innervation from the cardiac vagal branch is seen at major cardiac ganglionic plexi, and within the fat pads associated with the coronary arteries. Directly recorded cardiac vagal nerve activity increased during exercise. Left cardiac vagal branch denervation attenuated the maximum changes in coronary artery blood flow (maximum exercise, control: 63.5±5.9 mL/min, n=8; cardiac vagal denervated: 32.7±5.6 mL/min, n=6, P=2.5×10-7), cardiac output, and heart rate during exercise. Atropine did not affect any cardiac parameters during exercise, but VIP antagonism significantly reduced coronary artery blood flow during exercise to a similar level to vagal denervation. Our study demonstrates that cardiac vagal nerve activity actually increases and is crucial for maintaining cardiac function during exercise. Furthermore, our findings show the dynamic modulation of coronary artery blood flow during exercise is mediated by VIP.

Ischemia-induced ventricular proarrhythmia and cardiovascular autonomic dysreflexia after cardioneuroablation

Cardioneuroablation (CNA) is an attractive treatment of vasovagal syncope. Its long-term efficacy and safety remain unknown. The purpose of this study was to develop a chronic porcine model of CNA to examine the susceptibility to ventricular tachyarrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) and cardiac autonomic function after CNA. A percutaneous CNA model was developed by ablation of left- and right-sided ganglionated plexi (n = 5), confirmed by histology. Reproducible bilateral vagal denervation was confirmed after CNA by extracardiac vagal nerve stimulation (VNS) and histology. Chronic studies included 16 pigs randomized to CNA (n= 8) and sham ablation (n = 8, Control). After 6 weeks, animals underwent hemodynamic studies, assessment of cardiac sympathetic and parasympathetic function using sympathetic chain stimulation and direct VNS, respectively, and proarrhythmic potential after left anterior descending(LAD) coronary artery ligation. After CNA, extracardiac VNS responses remained abolished for 6 weeks despite ganglia remaining in ablated ganglionated plexi. In the CNA group, direct VNS resulted in paradoxical increases in blood pressure, but not in sham-ablated animals (CNA group vs sham group: 8.36% ± 7.0% vs -4.83% ± 8.7%, respectively; P = .009). Left sympathetic chain stimulation (8 Hz) induced significant corrected QT interval prolongation in the CNA group vs the sham group (11.23% ± 4.0% vs 1.49% ± 4.0%, respectively; P < .001). VT/VF after LAD ligation was more prevalent and occurred earlier in the CNA group than in the control group (61.44 ± 73.7 seconds vs 245.11 ± 104.0 seconds, respectively; P = .002). Cardiac vagal denervation is maintained long-term after CNA in a porcine model. However, chronic CNA was associated with cardiovascular dysreflexia, diminished cardioprotective effects of cardiac vagal tone, and increased susceptibility to VT/VF in ischemia. These potential long-term negative effects of CNA suggest the need for rigorous clinical studies on CNA.

Electrocardiographic patterns of autonomic dysfunction in the diagnosis of autonomic neuropathy in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus poses a serious threat to the health of people worldwide. Despite active detection and stringent measures to control and treat diabetes, the condition leads to a variety of complications, including autonomic neuropathy, resulting in autonomic cardiac denervation associated with an increased risk of painless myocardial ischemia and sudden cardiac death. However, digital verification by finding electrocardiographic (ECG) patterns of autonomic dysfunction is possible.&#x0D; The available literature on ECG patterns of myocardial electrical instability, which reflect autonomous myocardial dysfunction, was summarized. A literature review of scientific papers on ECG diagnosis of autonomic myocardial dysfunction in patients with type 2 diabetes mellitus over the past 5 years was performed using PubMed and eLIBRARY data.&#x0D; Among different ECG patterns that reflect autonomic dysfunction, the most common is the investigation of heart rhythm variability, which is based on the mathematical analysis of respiration rate intervals. The simplest variables are used to obtain a series of statistical indicators such as SDANN, RMSSD, NN50, and pNN50. A new and understudied ECG pattern of autonomic dysfunction is heart rate turbulence (HRT), which is a short-term rhythm change that develops in response to a ventricular extrasystole. The extrasystole is followed by a short episode of sinus tachycardia lasting several cardiac cycles, which is followed by a longer episode of bradycardia. These heart rate fluctuations are based on baroreflex compensation of intracardiac hemodynamic changes. Two parameters are estimated to characterize the HRT: turbulence onset and turbulence slope. A specific marker of autonomic dysfunction is the rate of cardiac rhythm recovery after controlled exercise. A recovery rate of 12 beats per first minute was associated with an increased risk of all-cause mortality, whereas a reduction in recovery rate of 40 beats per 2 min was found to be a strong independent risk factor for all-cause mortality.&#x0D; An imbalance in the tone of sympathetic and parasympathetic systems underlies all the described indicators. Therefore, a risk-stratifying significance of autonomic dysfunction markers in a wide range of pathologies, including peptic ulcer disease, gallstone disease, hypertension, chronic heart failure, chronic obstructive pulmonary disease, bronchial asthma, thyreopathies, and anemias apart from type 2 diabetes mellitus, exists. This explains the high sensitivity of tests, while having a low positive predictive value and specificity. The ease of performing tests dictates the need for further study of the features of autonomic dysfunction markers in patients with type 2 diabetes mellitus, since these markers are associated with a high risk of painless myocardial ischemia and sudden cardiac death.&#x0D; Currently, several ECG patterns (heart rate variability, HRT, and heart rate recovery rate) reflect autonomous myocardial dysfunction. The patterns enable early detection of autonomous neuropathy in patients with type 2 diabetes mellitus, which will allow timely diagnosis and adequate therapy. However, further study is required due to their low specificity to identify the peculiarities in specific nosological forms.