Autonomic Function In Patients Research Articles

The prevalence and clinical features of syncope in patients with concealed Brugada Syndrome

Abstract Background Brugada Syndrome (BS) is an inherited rhythm-disorder with risk of sudden-cardiac-death defined by a specific ST-segment elevation pattern in precordial ECG-leads either spontaneous or provoked by Na-channel-blocker-drug-provocation-test with Ajmaline. Scarce data denote that the prevalence of non-arrhythmic syncope is high in BS and leads to diagnostic confusions. Head-up tilt test (HUT) is a diagnostic tool used to assess autonomic function in patients with suspicious syncopal events. Purpose Our aim was to elucidate the frequency of non-arrhythmic syncope in BS patients, compare it with non-BS population with suspicious syncope and reveal possible clinical relations. Methods Adult patients with an history of Ajmaline-induced BS and patients evaluated for suspicious syncope with non-arrhyhtmic-features without BS less than 55-years-old were prospectively and consecutively evaluated with resting and higher-inter-costal-space-ECGs (HICS-ECGs), cardiac-examination and routine HUT in our center. After the exclusion of subjects with resuscitated-sudden cardiac-death/documented-malignant-dysrhythmia, any cardiac-disease, anti-arrhythmic-use, bundle-branch-blocks, pre-excitations and ventricular hypertrophies; 52 BS(+) subjects ([mean±SD] age, 33,6±14, [range]18-55 years) (male n [%overall]:33 [63.2%]) and 35 age-sex matched BS(-)subjects ([mean±SD] age, 34,1±13, [range]18-55 years) were enrolled in the study. All ECGs and HUT test results were interpreted manually by two experienced cardiologists for BS and Brugada-type-ECG-patterns (BTEPs). Results The clinical characteristics of patients with and without BS and statistical findings are presented in Table-1. BS(+) patients were slimmer, revealing more BTEPs by baseline HICS-ECGs. Baseline heart-rates were lower, PR-intervals and P-wave-duration were significantly higher in BS(+) patients. HUT-positivity of BS(+) patients were significantly higher [(39% (n: 20 [male n: 13]) vs 19% (n: 7 [male n: 4]) (p= 0,01)] revealing significantly more mixed-syncope and orthostatic hypotension response in BS(+) subjects. No cardioinhibitory response was revealed. Conclusions Non arrhtymic syncope is found to be highly prevalent in middle-aged-subjects and especially males with BS (+) without an apparent cardiac-disorder. Knowing this considerably important clinical aspect might effect risk stratification algorithms and might prevent unnecessary high-risk interventions and device decisions. Non-invasive indices regarding the delayed conduction features in ECG characteristics of BS(+) patients and a higher vagal state might be proposed as one of the probable mechanisms revealing the higher prevalence of non-arrhythmic-syncope in BS.Table-1

Circadian changes of autonomic function in patients with zoster-associated pain: A heart rate variability analysis.

To investigate the circadian changes of the autonomic function in patients with zoster-associated pain (ZAP). A total of 37 patients with ZAP from April 2022 to October 2022 were enrolled as the observation group, and 37 normal volunteers at the same time were selected as the control group. All participants were required to wear a 24-h Holter, which was used to compare the heart rate variability (HRV) between the two groups. HRV analysis involved time- and frequency-domain parameters. There was no statistically significant difference in general information between two groups. Patients with ZAP had an increased mean heart rate and decreased the standard deviation of normal-to-normal (SDNN) R-R interval, the root mean square of the differences (RMSSD) in successive RR interval, low frequency (LF), and high frequency (HF) compared with control groups in all periods (p<.05). The ratio of LF/HF between two groups had no significant difference (p=.245). SDNN had no significant difference between day and night in the control group (p>.05), whereas SDNN of ZAP patients in night period was reduced than that in day period (p<.001). The level of RMSSD during the day was lower than those at night in the control group (p<.05), whereas no significant difference of RMSSD between two periods was observed in patients with ZAP (p>.05). The results of this study indicated that ZAP contributes to the decline of autonomic nervous system (ANS) function, especially parasympathetic components. The patients with ZAP lost parasympathetic advantage and had a worse ANS during the night.

Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes.

Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement. BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance. The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.

The effect of motor imagery and action observation on autonomic functions in patients with chronic stroke

ABSTRACT Objectives This study aimed to investigate the effects of motor imagery (MI), action observation (AO), and action execution (AE) interventions on the autonomic nervous system (ANS) in individuals with chronic stroke. Methods This was a single-center, randomized, case-control study. Thirty-six patients were randomly assigned to MI (n = 10), AO (n = 15), and the AE group (n = 11). Heart rate (HR)-based measurements (HR, heart rate variability (HRV)) and blood pressure were evaluated before the practice of each group. In the MI group, participants were instructed to imagine themselves walking at their own comfortable pace for 5 minutes. Meanwhile, in the AO group, participants were shown a video of a person walking for 5 minutes. Finally, in the AE group, participants were instructed to actually walk for 5 minutes. Then, all measurements were taken again. Results A statistically significant difference was found in HR and mean RR interval within the AE group (p < 0.05). There was a statistically significant difference in the Root Mean Square of Successive Differences Between Normal Heartbeats (RMSSD) (ms) within the AO group (p < 0.05). There was a significant difference in HR and mean RR intervals (ms) between groups (p < 0.05). According to post-hoc analyses, HR was statistically significantly higher in the AE group compared to the other groups, and the mean RR interval was statistically significantly lower (p < 0.05). Conclusions In conclusion, in patients with chronic stroke, AE and AO may affect ANS by increasing sympathetic activation. It is recommended for future studies to evaluate whether patients actually engage in imagery during the MI task.

Effect of "365 Breathing Technique" on Intraocular Pressure and Autonomic Functions in Patients With Glaucoma: A Randomized Controlled Trial.

Patients with primary open angle glaucoma were advised to follow the "365 breathing technique" for 6 weeks in addition to their pharmacological glaucoma treatment. It helped to reduce intraocular pressure (IOP), stress biomarker-cortisol, and improve autonomic dysfunction. To study the effect of the "365 breathing technique" on IOP, autonomic functions, and stress biomarkers in patients with primary open angle glaucoma. In this randomized, controlled, interventional trial, after randomization, 40 patients in the intervention group followed "365 breathing" (three times a day, breathing rate: 6 cycles/min for 5 min) in addition to their pharmacological glaucoma treatment and 40 patients in the control group continued only with their pharmacological glaucoma treatment. IOP, serum cortisol, heart rate variability (HRV), and heart rate response to deep breathing test (DBT) were recorded at preintervention and 6 weeks postintervention. The mean IOP, serum cortisol, parameters of the HRV test, and DBT were comparable between the two groups at baseline. At the 6-week follow-up, in the intervention group, mean IOP was significantly lower (16.09 ± 2.24 vs 18.38 ± 1.58 mm Hg, P = 0.03) and serum cortisol were significantly lower (13.20 ± 3.11 vs 14.95 ± 2.60 mcg/dL, P = 0.038) compared with the control group. In the HRV test, time domain analysis showed a significant difference in the root mean square of the successive difference between RR interval values between both groups at 6 weeks ( P = 0.015) pointing towards higher postintervention parasympathetic activation in the intervention group. In frequency domain analysis (HRV test), the ratio of the low-frequency component to the high-frequency component was significantly lower in the intervention group at 6 weeks (1.65 vs 1.79, P = 0.019) indicating a shift in sympathovagal balance towards greater vagal modulation.There was a significant increase in delta heart rate ( P = 0.019) and expiratory:inspiratory ratio ( P = 0.011) in the intervention group at 6 weeks when compared with baseline values, indicating improved parasympathetic reactivity to DBT. "365 breathing" technique can reduce IOP and serum cortisol, and improve autonomic dysfunction in patients with glaucoma.

Relationship between dust allergen sensitization and cardiac autonomic function in patients with chronic obstructive pulmonary disease.

Cardiac autonomic function predicts cardiovascular disease risk. The aim of this study was to investigate the relationship between sensitization to dust allergens and cardiac autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD), and to provide new ideas for the prevention of cardiovascular complications in these patients. Immunoassays for sensitization to cats/dogs, cockroaches and dust mites were performed in 840 patients with COPD. Indicators of heart rate variability in these patients were used to assess cardiac autonomic function, including standard deviation of normal-to-normal intervals (SDNN), root-mean square of successive differences between normal-to-normal intervals (RMSSD), low-frequency power (LF), high-frequency power (HF), and LF/HF ratios, which were obtained based on ambulatory electrocardiographic monitoring data. The relationship between sensitization to these dust allergens and heart rate variability was explored using multivariate logistic regression. The multivariate analyses showed that sensitization to total allergens was associated with reduced levels of SDNN, RMSSD, LF and HF and with increased levels of the LF/HF ratio in the patients with COPD (p < .05). Dust allergen sensitization may be associated with cardiac autonomic dysfunction in patients with COPD. Whether desensitization can prevent cardiovascular complications in these patients should be further explored.

Effect of mandibular advancement splint therapy on cardiac autonomic function in obstructive sleep apnoea.

This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI). In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56±11 years, BMI 29.8±5.3 kg/m2, and treatment duration was 4.0±3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, - 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, - 0.4 ± 1.5, p = 0.01; LF, - 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (β(SE) = - 2.21 (0.01), t = - 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment. The study findings suggestthat successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability.

Autonomic function in sporadic and familial ALS type 8

ObjectiveTo characterize and compare autonomic function in patients with sporadic (sALS) and familial ALS type 8 (fALS8). MethodsWe selected 11 patients with sALS (7 men), 14 with fALS8 (8 men) and 26 controls (15 men). All groups were gender and age-matched. For each subject, Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT) was applied and data from heart rate variability, Quantitative Sudomotor Axon Reflex Test (QSART) and skin sympathetic response (SSR) were collected. These data were compared across groups using nonparametric tests. P-values < 0.05 were considered significant. ResultsSCOPA-AUT revealed predominant clinical complaints in thermoregulatory, pupillomotor and sexual domains in fALS8 relative to sALS as well as controls. Neurophysiological tests demonstrated significant differences in Valsalva ratio, Expiratory:Inspiratory index and RR minimum values in both ALS groups relative to controls. Sudomotor dysfunction was also observed in sALS and fALS8 groups, as shown by reduced medial forearm and foot QSART volumes and absence of SSR in lower limbs. ConclusionsDysautonomia – cardiac and sudomotor - is part of the phenotype in sALS and fALS8. The profile of autonomic symptoms, however, is different in each group. SignificancePatients with fALS8 and sALS have autonomic dysfunction involving both sympathetic and parasympathetic divisions.

A three-month physical training program improves cardiovascular autonomic function in patients with metabolic syndrome with and without diabetes - a pilot study.

Vascular complications and neuropathy may develop in the presence of metabolic syndrome. The aim of our study was to measure the cardiovascular autonomic function following physical training in patients with metabolic syndrome with and without diabetes. 56 patients with metabolic syndrome (32 men/24 women, 40 non-diabetic patients (NDMetS)/16 diabetic patients (DMetS) [mean ± SD]: age: 50.35 ± 8.03 vs. 56.8 ± 9.30 years, p=0.023; baseline BMI: 32.2 ± 7.03 vs. 32.8 ± 5.94 kg/m2, p=0.739) were involved in our study. All tests and measurements were carried out before and following a 3-month physical training period. Autonomic function was assessed by means of five standard cardiovascular reflex tests. ECG repolarization parameters, including short-term QT variability and stress-ECG were also measured. In the whole population, Valsalva-ratio (VR) and the autonomic score (AS) improved following training (VR: 1.49 ± 0.24 vs. 1.64 ± 0.34, p=0.001; AS: 2.05 ± 1.73 vs. 1.41 ± 1.36, p=0.015) accompanied by the significant decrease of the systolic (150.3 ± 16.12 vs. 134.1 ± 16.67 mmHg, p<0.001) and diastolic (90.64 ± 12.8 vs. 82.79 ± 11.1 mmHg, p<0.001) blood pressure. An improvement in VR was detected in NDMetS patients following training (1.51 ± 0.24 vs. 1.67 ± 0.31, p= 0.002). No significant changes could be detected in autonomic tests' results in the DMetS patient group following training. The applied exercise training program did not lead to significant changes in ECG repolarization. The stress-ECG test in the whole study population yielded a significant increase in the test duration (12.9 ± 3.76 vs. 15.1 ± 2.96min, p<0.001) and in the test load (10.5 ± 2.78 vs. 11.6 ± 2.39 MET, p<0.001). The load capability improved significantly in both subgroups: 11.1 ± 2.04 vs. 12.1 ± 1.82, (p<0.001) and 9.0 ± 3.64 vs. 10.4 ± 3.05, (p=0.033) in subpopulations of NDMetS and DMetS, respectively. The DMetS patients achieved a significantly lower MET score at baseline (p=0.039) and following training (p=0.044) in comparison to the NDMetS patients. The three-month exercise program improved the Valsalva-ratio and the AN score in the MetS patients, that is potentially protective against cardiovascular events. The training had some beneficial effect on blood pressure and the results of the stress-ECG tests in both groups. The absence of significant change in the reflex tests in DMetS group reflects an impaired adaptation compared to the NDMestS group.

Minimal Objective Autonomic Dysfunction in Long-COVID (S43.004)

<h3>Objective:</h3> Our aim was to characterize autonomic symptoms, severity and objective measures of autonomic function in patients with post-COVID syndrome. <h3>Background:</h3> Many patients report persistent symptoms that continue beyond the acute phase of COVID-19 (SARS-CoV-2) infection, variably called “long-COVID”, “post-COVID”, or “long-haul COVID”. Common symptoms include fatigue, orthostatic intolerance, cognitive impairment, and syncope, similar to the symptom profile of POTS. Although highly prevalent (affects 33–87% of hospitalized and 37% of non-hospitalized COVID patients), the pathophysiology of long-COVID is still not well understood. It is speculated that long-COVID patients have POTS or some other immune-mediated dysautonomia. <h3>Design/Methods:</h3> Retrospective analysis approved by UT Southwestern IRB. We identified 50 patients from our large COVID Recover clinic who were referred to the UT Southwestern autonomic laboratory for testing. Prior to testing, all patients were evaluated with supine and standing orthostatic vitals and completed symptom questionnaires. <h3>Results:</h3> Of 50 long-COVID patients who underwent standard autonomic testing, 24 patients had normal testing, 6 met heart rate criteria for POTS (by tilt table), 1 had severe diffuse autonomic failure with neurogenic orthostatic hypotension, 3 had mild length-dependent sudomotor impairment, 8 had mildly abnormal testing attributable to medication effects, 10 had mild non-specific autonomic impairment. The median CASS score was 0 (mean 1.0, range 0–8). The mean COMPASS-31 score was 43.4 (n= 43 patients), indicating severe symptoms. This score was similar in severity to previously studied POTS cohort (COMPASS 31 46.01, n= 205). <h3>Conclusions:</h3> Although these long-COVID patients had severe symptoms, majority of patients had normal autonomic function tests or non-specific mild abnormalities (86%). Only 12% had testing consistent with POTS, 20% had mild non-specific autonomic dysfunction, and 2% had significant autonomic failure. This is the largest cohort to date of autonomic testing in patients with long-COVID. Long-COVID symptoms are usually not associated with POTS or other clear evidence of autonomic dysfunction. <b>Disclosure:</b> The institution of Dr. Bryarly has received research support from Theravance. Dr. Cabrera has nothing to disclose. Dr. Barshikar has received publishing royalties from a publication relating to health care. Dr. Vernino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Vernino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Vernino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Vernino has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alterity. Dr. Vernino has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LabCorp. Dr. Vernino has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Vernino has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Autonomic Neuroscience (Elsevier). The institution of Dr. Vernino has received research support from Grifols. The institution of Dr. Vernino has received research support from Dysautonomia International. The institution of Dr. Vernino has received research support from BioHaven. The institution of Dr. Vernino has received research support from Takeda. Dr. Vernino has received personal compensation in the range of $10,000-$49,999 for serving as a Content Expert Consultant with Office of Inspector General for Medicare.

Assessment of Cardiovascular Autonomic Function in Patients with Headache in A Tertiary Care Centre: A Prospective Study

Assessment of Cardiovascular Autonomic Function in Patients with Headache in A Tertiary Care Centre: A Prospective Study

Autonomic Functions in Patients with Allergic Rhinitis: A Cross-sectional Observational Study

Introduction: Even after decades of the development of lowcost and effective antibiotics, puerperal infections remain an important cause of preventable maternal morbidity and mortality. Aim: The aim of the present study was to determine the risk factors, morbidity, and mortality associated with puerperal infections. Materials and Methods: A retrospective study was conducted from March 2021 to October 2021, at the Obstetrics and Gynaecology Department of Gandhi Hospital in Telangana, India. The study included all women who delivered in this hospital and were referred within 42 days after delivery with fever and any of the following symptoms: pain abdomen, malodorous lochia, abdominal distention, subinvolution of the uterus, pelvic abscess, peritonitis, any system/organ failure, or shock. Various risk factors such as age, parity, socioeconomic status (according to the modified Kuppuswamy scale), BMI, rupture of membranes, mode of delivery, and comorbidities associated with puerperal infection were assessed. Complications following puerperal infection were also studied. Data analysis was performed using SPSS version 23.0, and the results were presented in frequency and percentages of categorical variables. Results: During the study period, there were 161 cases of puerperal infection. The majority of cases were between the age group of 26-30 years, constituting 72 (44.7%) cases. Among them, 86 (53.4%) cases were multiparous, 50 (31%) cases were primiparous, 10 (6.2%) cases were second gravida, and 15 (9.3%) cases were third gravida. Lower middle-class women accounted for 67 (41.6%) cases, and 85 (52.7%) cases were in the overweight range. Prolonged premature rupture of membranes for more than 24 hours was observed in 78 (48.4%) cases. Caesarean section was the mode of delivery for 90 (56%) cases of puerperal infection cases. The most commonly associated comorbidities were anaemia in 63 (39.1%) cases, severe preeclampsia in 47 (29.1%) cases, abruption in 31 (19.2%) cases, and diabetes in 20 (12.4%) cases. Prolonged hospital stay was observed in 144 (89.4%) cases, wound gaping in 26 (16.1%) cases, and disseminated intravascular coagulation in 24 (14.9%) cases. A total of 31 (19.2%) cases of women succumbed, mostly due to multi-organ failure. Conclusion: Early diagnosis, proper ICU facilities at all levels of healthcare, timely referral to tertiary facilities, health education, and strict aseptic measures would be crucial in tackling this menace.

Characteristics of Anal Sphincter Electromyography in Patients with Multiple System Atrophy

In this study, the characteristics of external anal sphincter electromyography (EAS-EMG) in patients with multiple system atrophy (MSA) were analyzed, and its value in the diagnosis of MSA was discussed. The data of 23 patients with MSA who underwent EAS-EMG examination between January 2019 and December 2021 were selected to analyze examination data such as the average duration of motor unit potentials (MUPs), average amplitude, satellite potentials, and the percentage of polyphasic waves, and to explore the correlation between the results of EAS-EMG and autonomic dysfunction in patients with MSA based on their data characteristics. The results of data analysis showed that the most common symptoms in 23 patients with MSA were urination and defecation disorders, sleep disorders, and unsteady walking, the most common signs were increased muscle tone, postural hypotension, and ataxia, and the most common autonomic dysfunction was rectal and bladder dysfunction, orthostatic hypotension, and sexual dysfunction. The average duration of MUPs was 11.6 (10.1-13.9) ms, the average amplitude was 885 (683-1198) μV, and the percentage of polyphasic waves was 26.2 (12.5-50.0)%. Patients with satellite potentials had longer disease duration. There were no significant differences in parameters between different types of autonomic dysfunction. The results suggested that abnormal changes in EAS-EMG may indicate an impaired autonomic function in patients with MSA, and this conclusion may not limit to patients with urination and defecation disorders.

Role of basal autonomic functions in patients with increased morning blood pressure surge.

Morning blood pressure (BP) surge (MS) is associated with cardiovascular events. The autonomic nervous system plays an active role in the regulation of BP and its function can be evaluated by heart rate variability (HRV) analysis. This study aimed to evaluate autonomic nervous system functions in patients with increased MS. Patients who underwent ambulatory BP monitoring (ABPM) and 24-h rhythm Holter in our hospital during the same period between 2017 and 2022 were evaluated. HRV parameters were obtained from 24-h rhythm Holter recordings. MS values of the patients were calculated from ABPM records and patients were divided into four groups according to the MS quartiles. HRV parameters and other parameters were compared between the groups. A total of 129 patients were included in the study. The mean age of the patients was 57.2 ± 18.2 years, and 63 (48.8%) were male. HF, the square root of the mean squared differences of successive normal-to-normal intervals (rMSSD), and the proportion of adjacent RR intervals differing by >50 ms in the 24-h recording (pNN50) were statistically significant between the groups ( P = 0.039, P = 0.013, P = 0.011, respectively). In univariate regression analysis, low-frequency/high-frequency ratio was positively associated with MS and HF, SDNNi, rMSSD, and pNN50 were negatively associated ( β = 0.207, P = 0.019; β = -0.272, P = 0.002; β = -0.201, P = 0.022; β = -0.265, P = 0.002; β = -0.278, P = 0.001, respectively). Multiple linear regression analysis showed an independent association between HF, low-frequency/high-frequency ratio, rMSSD, pNN50, and MS ( β = -0.247, P = 0.005; β=0.206, P = 0.017; β = -0.209, P = 0.005; β = -0.227, P = 0.008, respectively). We found an independent association between HRV parameters associated with vagal tone and MS. The findings of our study suggest that the increased sympathetic activity detected in patients with high MS in previous studies may be due to a decrease in basal vagal tone.

Analysis of CACNA1C and KCNH2 Risk Variants on Cardiac Autonomic Function in Patients with Schizophrenia.

Cardiac autonomic dysfunction (CADF) is a major contributor to increased cardiac mortality in schizophrenia patients. The aberrant function of voltage-gated ion channels, which are widely distributed in the brain and heart, may link schizophrenia and CADF. In search of channel-encoding genes that are associated with both CADF and schizophrenia, CACNA1C and KCNH2 are promising candidates. In this study, we tested for associations between genetic findings in both genes and CADF parameters in schizophrenia patients whose heart functions were not influenced by psychopharmaceuticals. First, we searched the literature for single-nucleotide polymorphisms (SNPs) in CACNA1C and KCNH2 that showed genome-wide significant association with schizophrenia. Subsequently, we looked for such robust associations with CADF traits at these loci. A total of 5 CACNA1C SNPs and 9 KCNH2 SNPs were found and genotyped in 77 unmedicated schizophrenia patients and 144 healthy controls. Genotype-related impacts on heart rate (HR) dynamics and QT variability indices (QTvi) were analyzed separately in patients and healthy controls. We observed significantly increased QTvi in unmedicated patients with CADF-associated risk in CACNA1C rs2283274 C and schizophrenia-associated risk in rs2239061 G compared to the non-risk allele in these patients. Moreover, unmedicated patients with previously identified schizophrenia risk alleles in KCNH2 rs11763131 A, rs3807373 A, rs3800779 C, rs748693 G, and 1036145 T showed increased mean HR and QTvi as compared to non-risk alleles. We propose a potential pleiotropic role for common variation in CACNA1C and KCNH2 associated with CADF in schizophrenia patients, independent of antipsychotic medication, that predisposes them to cardiac arrhythmias and premature death.

Effect of RNAi therapeutics patisiran and vutrisiran on orthostatic hypotension due to dysautonomia in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy

Abstract Background Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a rapidly progressive, multisystem disease. Orthostatic hypotension, due to autonomic neuropathy, is a common yet hard-to-treat disease manifestation in patients with hATTR amyloidosis. Fatigue, muscle weakness, and deterioration in cardiac function further exacerbate orthostatic symptoms. Efficacy of RNAi therapeutics patisiran and vutrisiran was assessed in patients with hATTR amyloidosis with polyneuropathy across the APOLLO (NCT01960348), Global Open-Label Extension (OLE) (NCT02510261), and HELIOS-A (NCT03759379) studies, respectively. Purpose Evaluate the quantitative effect of patisiran and vutrisiran on orthostatic hypotension in patients with hATTR amyloidosis with polyneuropathy. Methods In APOLLO, patients were randomised 2:1 to patisiran 0.3 mg/kg or placebo, IV q3w. Patients who completed APOLLO (APOLLO-placebo, APOLLO-patisiran) were eligible to enrol into the ongoing Global OLE (patisiran 0.3 mg/kg IV q3w). In HELIOS-A, patients were randomised 3:1 to vutrisiran (25 mg SC q3m) or patisiran (0.3 mg/kg IV q3w; reference group). Primary endpoint for APOLLO and HELIOS-A was change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7) vs APOLLO placebo at M18 (APOLLO) and M9 (HELIOS-A). Orthostatic hypotension was evaluated using the postural blood pressure (PBP) component of mNIS+7, calculated as the mean of 2 supine readings of systolic BP [SBP, mmHg] taken 15 min apart minus the lowest SBP upon standing at 1, 3, and 5 min. A smaller reduction in observed SBP between supine and upright readings indicated an improved PBP. Results APOLLO enrolled 225 patients (placebo, n=77; patisiran, n=148), Global OLE 211 and HELIOS-A 164 (vutrisiran, n=122; patisiran, n=42). At baseline, the severity of orthostatic hypotension was similar between within-study treatment arms in APOLLO and HELIOS-A. In APOLLO, patisiran-treated patients showed PBP improvement or stabilization from baseline to M18 (mean [SD] change in SBP: baseline, −17.6 [19.4]; M18, −13.5 [16.8]) and was maintained at Global OLE 36m (−13.4 [15.6]). In contrast, placebo-treated patients in APOLLO had an increased change in PBP over 18m (baseline, −17.5 [16.5]; M18, −20.4 [16.9]); their PBP improved after patisiran initiation (Global OLE 36m, −16.6 [18.1]). In HELIOS-A, stabilization in PBP was observed in the vutrisiran arm (baseline, −11.2 [14.0], M18, −11.7 [14.6]). In the smaller patisiran arm, while the change in PBP increased, the value remained in the normal range (baseline, −11.6 [17.2]; M18, −14.2 [15.5]). Patisiran and vutrisiran have acceptable safety profiles. Conclusions PBP analyses quantify the benefits of RNAi therapeutics patisiran and vutrisiran on autonomic function in patients with hATTR amyloidosis with polyneuropathy. The increase in change in PBP to a symptomatic range without treatment indicates the importance of early intervention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Alnylam Pharmaceuticals

Short-term effectiveness of auricular vagus nerve stimulation in patients with myofascial pain syndrome

Objectives: To evaluate the effect of auricular vagus nerve stimulation (VNS) applied in addition to ischemic compression and stretching exercises on pain, trigger point (TP) sensitivity, grip strength, quality of life and autonomic functions in patients with myofascial pain syndrome (MPS). Methods: Sixty patients, who had neck pain, met the diagnostic MPS criteria of Travell and Simons were included in the study. The subjects were randomly divided into VNS group (n = 30) or control group (n = 30). Each group performed 10 sessions of TP ischemic compression and stretching exercises (5 days/week). Ten sessions of 30-minute long auricular VNS were added to the treatment in VNS group. Pain severity [Visual Analogue Scale (VAS)], TP sensitivity (algometer), grip strength (Jamar dynamometer), quality of life [Short Form-36 (SF-36)] and autonomic function [Composite Autonomic Symptom Scale-31 (Compass-31)] were evaluated before and after 10 sessions of treatment. Results: The VAS, algometer and Jamar measurements showed significant improvement in both groups. A statistically significant improvement was found in orthostatic intolerance, secretomotor and pupillomotor subscales of Compass-31 scale in the VNS group following the treatment (p &amp;lt; 0.05) while no significant difference was observed in the control group (p &amp;gt; 0.05). The control group showed significant improvement in all parameters of SF-36 scale, while the VNS group showed significant improvement in physical function, social functionality and pain parameters (p &amp;lt; 0.05). The changes in the VAS, algometer, Jamar scores and secretomotor subscale of the Compass-31 scale were statistically higher in the VNS group than in the control group (p &amp;lt; 0.001, p &amp;lt; 0.001, p = 0.001 and p = 0.011, respectively). Conclusions: It can be argued that auricular VNS increases the effectiveness of ischemic compression and stretching exercises in patients with MPS. Further and detailed studies are needed in which the effect of VNS alone or in combination with other treatments in patients with MPS is examined and the physiological mechanisms are investigated.

Motor rehabilitation as a therapeutic tool for spinal cord injury: New perspectives in immunomodulation

Traumatic spinal cord injury (SCI) is a devastating condition that significantly impacts motor, sensory and autonomic function in patients. Despite advances in therapeutic approaches, there is still no curative therapy currently available. Neuroinflammation is a persisting event of the secondary injury phase of SCI that affects functional recovery, and modulation of the inflammatory response towards a beneficial anti-inflammatory state can improve recovery in preclinical SCI models. In human SCI patients, rehabilitative exercise, or motor rehabilitation as we will refer to it from here on out, remains the cornerstone of treatment to increase functional capacity and prevent secondary health implications. Motor rehabilitation is known to have anti-inflammatory effects; however, current literature is lacking in the description of the effect of motor rehabilitation on inflammation in the context of SCI. Understanding the effect on different inflammatory markers after SCI should enable the optimization of motor rehabilitation as a therapeutic regime. This review extensively describes the effect of motor rehabilitation on selected inflammatory mediators in both preclinical and human SCI studies. Additionally, we summarize how the type, duration, and intensity of motor rehabilitation can affect the inflammatory response after SCI. In doing so, we introduce a new perspective on how motor rehabilitation can be optimized as an immunomodulatory therapy to improve patient outcome after SCI.

Investigation of the Cardiac Autonomic Functions in Patients with Essential Tremor

Introduction: Essential tremor is a neurological disorder that causes involuntary shaking. The aim of this study was to examine cardiac autonomic functions in patients diagnosed with essential tremor, as previous studies have differed in their findings regarding whether cardiac autonomic functions are affected in essential tremor patients. Patients and Methods: The study included 32 patients diagnosed with essential tremor and 26 individuals without any diseases as the control group. Consensus criteria were used for the diagnosis of essential tremor. A clinical rating scale was utilized to measure the characteristics and degree of essential tremor. Based on this scale, patients were classified as having a mild, moderate, marked, or severe disability. An exercise treadmill test was performed in both the tremor and control groups. Chronotropic index values were used to evaluate the sympathetic system, and resting heart rate index values were calculated to evaluate the parasympathetic system. Heart rate recovery values were calculated at one, two, three, four, and five minutes after the exercise treadmill test. Results: The descriptive characteristics of the tremor and control groups were similar. The Chronotropic index values were statistically different between the tremor and control groups, as they were significantly decreased in the tremor group. This was evaluated as sympathetic incompetence. The resting heart rate index values did not differ significantly between the tremor and control groups at minutes one or two, but they were significantly higher in the tremor group at minutes three, four, and five. The parasympathetic activity was found to be insufficient in the later period. Conclusion: The findings suggest that cardiac autonomic functions may be affected in patients with essential tremor.

Comprehensive evaluation of patterns of hypoglycemia unawareness (HUA) and glycemic variability (GV) in patients with fibrocalculous pancreatic diabetes (FCPD): A cross-sectional study from South India.

Hypoglycemia unawareness (HUA) in patients with FCPD is common with an unclear etiology. We evaluated the prevalence, characteristics of HUA, glycemic variability (GV), its possible association with pancreatic glucagon secretion & cardiac autonomic function in patients with FCPD. A two-week ambulatory glucose profile (AGP) and cardiac autonomic function test was done in patients with FCPD (n = 60), and categorized into UNAWARE (n = 44) and AWARE (n = 16) groups based on the Hypoglycemia Unawareness Index (HUI) score. Glycaemic variability was assessed from the AGP data using Easy GV 9.0.2 software. A subset of patients from both the groups (n = 11) underwent a mixed-meal challenge test and were compared with healthy individuals (controls; n = 11). HUA was evidenced in 73% (44/60) of patients with FCPD. Significant hypoglycemia, nocturnal hypoglycemia, duration of hypoglycemia and poor cardiac autonomic functions (p = 0.01) were prominent in the UNAWARE group. The overall GV was greater in the UNAWARE group. In the UNAWARE group, significantly reduced fasting and post prandial glucagon levels negatively correlated with HUI (r = -0.74, p < 0.05) and GV-hypoglycemia indices (p < 0.05) In contrast, significantly higher post prandial glucagon levels in the AWARE group positively correlated with post prandial hyperglycemia (r = 0.61, p < 0.05). Heterogeneity in patterns of glucagon secretion were significantly associated with HUA and GV. Reduced glucagon levels contribute to greater risks of HUA, nocturnal hypoglycemia and greater GV, while hyperglucagonemia predisposes to postprandial hyperglycemia and hypoglycemia awareness in patients with FCPD.