Skin Sympathetic Nerve Activity Research Articles

Skin sympathetic nerve activity as a biomarker for outcomes in spontaneous intracerebral hemorrhage.

A rapid and accurate forecast for the early prognosis of ICH patients is challenging. This study investigated whether heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) could prognosticate poor neurological outcomes in ICH patients. Between November 2020 and November 2021, we studied 92 spontaneous ICH patients in the First Affiliated Hospital of Nanjing Medical University. Glasgow Outcome Scale (GOS) score at 2 weeks after the ICH was used to categorize patients into good and poor outcome groups. The modified Rankin Scale (mRS) assessed patients' ability to live independently for 1 year. We utilized a portable high-frequency electrocardiogram (ECG) recording system to record the HRV and SKNA information in ICH patients and control participants. 77 patients were eligible for the prediction of neurological outcome and were allocated into the good (n = 22) or poor (n = 55) outcome groups based on the GOS grade. In univariate logistic regression analysis, significant variables that could differentiate the outcomes were age, hypertension, tracheal intubation, Glasgow Coma Scale (GCS) score, existing intraventricular hemorrhage, white blood cells, neutrophil, lnVLF, lnTP, and aSKNA. Variables in the best fit multivariable logistic regression model were age, hypertension, GCS score, neutrophils, and aSKNA. The GCS score was the only independent risk factor for poor outcomes. At 30 days and 1 year of follow-up, patients with lower aSKNA had poor outcomes. ICH patients had reduced aSKNA, which could be a prognostic indicator. A lower aSKNA suggested a worse prognosis. The present data indicate that ECG signals could be helpful for prognosticating ICH patients.

Evaluation of autonomic nervous system activity in intradialytic hypotension using entropy and skin sympathetic nerve activity.

The function of the autonomic nervous system (ANS) is crucial in the development of intradialytic hypotension (IDH). This study introduced the entropy of heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) to provide a complementary nonlinear and dynamic perspective for evaluating ANS function concerning IDH. 93 patients undergoing hemodialysis (HD) were enrolled, and the baseline data, electrocardiogram (ECG), and SKNA were collected. The patients were separated into the IDH and nonIDH groups based on the thresholds, which were characterized as reductions in systolic blood pressure (SBP) of at least 20 mm Hg or mean arterial pressure (MAP) of at least 10 mm Hg. We developed a logistic regression model for IDH after analyzing the changes in the time domain, frequency domain, the entropy of HRV, and SKNA indices during HD. After 4-h HD, the detected results for heart rate, the ratio of low frequency and high frequency (LF/HF), and average SKNA (aSKNA) all increased in both groups. Nine out of the ten HRV indices and aSKNA in the nonIDH group were higher than those in the IDH group at most moments. aSKNA was positively correlated with heart rate (p = 0.0001) and LF/HF (p = 0.0005) in the nonIDH group, while the correlation disappeared in the IDH group, which indicated a worse ANS response in IDH patients. The logistic regression model exhibited the results of initial SBP [odds ratio (OR) 1.076; p = 0.001], and the difference between the last and first segments (DLF) of heart rate [OR 1.101; p =0.012] and LF/HF [OR 0.209; p =0.034], as well as the extreme value of the difference between other segments and the first segments (EOF) of aSKNA [OR 2.908; p =0.017], which were independent indicators for IDH. The new nonlinear and dynamic assessment perspectives provided by the entropy of HRV and SKNA help to distinguish differences in ANS patterns between IDH patients and nonIDH patients and have the potential to be used in clinical monitoring for HD patients.

Skin sympathetic nerve activity and nocturnal blood pressure nondipping in patients with postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is associated with abnormal blood pressure (BP) regulation and increased prevalence of nocturnal nondipping. We hypothesized that nocturnal nondipping of BP is associated with elevated skin sympathetic nerve activity (SKNA) in POTS. We used an ambulatory monitor to record SKNA and electrocardiogram from 79 participants with POTS (36 ± 11 years, 72 women), including 67 with simultaneous 24-h ambulatory BP monitoring. Nocturnal nondipping of BP was present in 19 of 67 (28%) participants. The nondipping group had a higher average SKNA (aSKNA) from midnight of day 1 to 0100 h on day 2 than the dipping group ( P = 0.016, P = 0.030, respectively). The differences (Δ) of aSKNA and mean BP between daytime and night-time were more significant in the dipping group compared with the nondipping group (ΔaSKNA 0.160 ± 0.103 vs. 0.095 ± 0.099 μV, P = 0.021, and Δmean BP 15.0 ± 5.2 vs. 4.9 ± 4.2 mmHg, P < 0.001, respectively). There were positive correlations between ΔaSKNA and standing norepinephrine (NE) (r = 0.421, P = 0.013) and the differences between standing and supine NE levels ( r = 0.411, P = 0.016). There were 53 (79%) patients with SBP less than 90 mmHg and 61 patients (91%) with DBP less than 60 mmHg. These hypotensive episodes were associated with aSKNA of 0.936 ± 0.081 and 0.936 ± 0.080 μV, respectively, which were both significantly lower than the nonhypotensive aSKNA (1.034 ± 0.087 μV, P < 0.001 for both) in the same patient. POTS patients with nocturnal nondipping have elevated nocturnal sympathetic tone and blunted reduction of SKNA between day and night. Hypotensive episodes were associated with reduced aSKNA.

The role of the dorsolateral prefrontal cortex in control of skin sympathetic nerve activity in humans.

The dorsolateral prefrontal cortex (dlPFC) is primarily involved in higher order executive functions, with there being evidence of lateralization. Brain imaging studies have revealed its link to the generation of skin sympathetic nerve activity (SSNA), which is elevated in states of emotional arousal or anxiety. However, no studies have directly explored dlPFC influences on SSNA. Transcranial alternating current stimulation (-2 to 2mA, 0.08Hz, 100cycles) was applied between the left or right dlPFC and nasion via surface electrodes. Spontaneous bursts of SSNA were recorded from the common peroneal nerve via a tungsten microelectrode in 21 healthy participants. The modulation index was calculated for each stimulation paradigm by constructing cross-correlation histograms between SSNA and the sinusoidal stimulus. Stimulation of the dlPFC caused significant modulation of SSNA, but there was no significant difference in the median modulation index across sides. Stimulation also caused cyclic modulation of skin blood flow and sweat release. We have shown for the first time that stimulation of the dlPFC causes modulation of SSNA, also reflected in the effector-organ responses. This supports a role for the dlPFC in the control of SSNA, which likely contributes to the ability of emotions to bring about cutaneous vasoconstriction and sweat release.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder.

Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder

Skin sympathetic nerve activity as a potential biomarker for overactive bladder

Alterations of sympathetic dynamics after atrial fibrillation ablation by analysis sympathetic nerve activity provide prognostic value for recurrence and mechanistic insights into ablation.

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Success is associated with autonomic function modulation; however, the relationship between the changes after ablation is not fully understood. We aimed to investigate the effect of ablation on autonomic modulation by skin sympathetic nerve activity (SKNA) using conventional electrocardiogram (ECG) electrodes and to predict the treatment success. We enrolled 79 patients. We recorded neuECG for 10 min at 10 kHz before and after ablation. The NeuECG was bandpass-filtered (500-1,000 Hz) and integrated at intervals of 100 ms (iSKNA). iSKNA was averaged over different time windows (1-, 5-,10-s; aSKNAs), and burst analyses were derived from aSKNAs to quantify the dynamics of sympathetic activities. AF recurrence after 3 months was defined as the study endpoint. Sixteen patients experienced AF recurrence after the ablation. For burst analysis of 1-s aSKNA, the recurrence group had a higher bursting frequency than the non-recurrence group (0.074 ± 0.055 vs. 0.109 ± 0.067; p < 0.05) before ablation. The differences between pre- and post-ablation of firing duration longer than 2 s were more in the non-recurrence group (2.75 ± 6.41 vs. -1.41 ± 5.14; p < 0.05), while no significant changes were observed in the percentage of duration longer than 10 s using 5-s aSKNA. In addition, decreases in differences in firing frequency and percentage of both overall firing duration and longer firing duration (> 2 s) between pre- and post-ablation were independently associated with AF recurrence and more area under receiver operating characteristics (ROC) curve in combination with CHADS2 score (0.833). We demonstrated the applicability of neuECG for determining sympathetic modulation during AF ablation. Decreasing sympathetic activity is the key to successful ablation.

Post-ablation augmentation of skin sympathetic nerve activity predicts a poor outcome of idiopathic ventricular arrhythmias

BackgroundThe neuromodulation effect after ventricular arrhythmia (VA) ablation is unclear. The study aimed to investigate skin sympathetic nerve activity (SKNA) changes in patients receiving catheter ablations for idiopathic VA. MethodsOf 43 patients with drug-refractory symptomatic VA receiving ablation, SKNA was continuously recorded for 10 min during resting from electrocardiogram lead I configuration and bipolar electrodes on the right arm 1 day before and 1 day after ablation. ResultsTwenty-two patients with acute procedure success and no recurrence during follow-ups were classified as sustained success group (group 1). Other 21 patients were classified as failed ablation group (group 2). Baseline SKNA showed no significant difference between the two groups. Post-ablation SKNA in group 2 was significantly higher than in group 1. In patients with ablation involved right ventricular outflow tract (RVOT), the post-ablation SKNA was also significantly higher in group 2. In contrast, there was no difference in post-ablation SKNA between groups in patients receiving non-RVOT ablation. ConclusionThe neuromodulation response after RVOT ablation may correspond to the sympathetic nerve distribution at RVOT. Augmentation of sympathetic activity after VA ablation indicates an unsuccessful VA suppression, especially in patients receiving ablation of RVOT VA.

Higher pre-treatment skin sympathetic nerve activity and elevated resting heart rate after chemoradiotherapy predict worse esophageal cancer outcomes

BackgroundChemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality.MethodsThirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome.ResultsWe found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 μV) also had poor outcome.ConclusionsIncreased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality.Trial registrationThis study is registered with ClinicalTrials.gov, identifier: NCT03243448.

Skin sympathetic nerve activity and ventricular arrhythmias in acute coronary syndrome.

Acute coronary syndrome (ACS) is major cause of ventricular arrhythmias (VAs) and sudden death. neuECG is a noninvasive method to simultaneously record skin sympathetic nerve activity (SKNA) and electrocardiogram. The purpose of this study was to test the hypotheses that (1) ACS increases average SKNA (aSKNA), (2) the magnitude of aSKNA elevation is associated with VAs during ACS, and (3) there is a gender difference in aSKNA between patients without and with ACS. We prospectively studied 128 ACS and 165 control participants. The neuECG was recorded with electrodes at Lead I configuration at baseline, during mental math stress, and during recovery (5 minutes for each phase). All recordings were done in the morning. In the control group, women have higher aSKNA than do men at baseline (0.82 ± 0.25 μV vs 0.73 ± 0.20 μV; P = .009) but not during mental stress (1.21 ± 0.36 μV vs 1.16 ± 0.36 μV; P=.394), suggesting women had lower sympathetic reserve. In comparison, ACS is associated with equally elevated aSKNA in women vs men at baseline (1.14 ± 0.33 μV vs 1.04 ± 0.35 μV; P= .531), during mental stress (1.46 ± 0.32 μV vs 1.33 ± 0.37 μV; P = .113), and during recovery (1.30 ± 0.33 μV vs 1.11 ± 0.30 μV; P = .075). After adjusting for age and gender, the adjusted odds ratio for VAs including ventricular tachycardia and ventricular fibrillation is 1.23 (95% confidence interval 1.05-1.44) for each 0.1 μV aSKNA elevation. aSKNA is positively correlated with plasma norepinephrine level. ACS is associated with elevated aSKNA, and the magnitude of aSKNA elevation is associated with the occurrence of VAs. Women have higher aSKNA and lower SKNA reserve than do men among controls but not among patients with ACS.

Autonomic nervous activity analysis based on visibility graph complex networks and skin sympathetic nerve activity.

Background: Autonomic nerve system (ANS) plays an important role in regulating cardiovascular function and cerebrovascular function. Traditional heart rate variation (HRV) and emerging skin sympathetic nerve activity (SKNA) analyses from ultra-short-time (UST) data cannot fully reveal neural activity, thereby quantitatively reflect ANS intensity. Methods: Electrocardiogram and SKNA from sixteen patients (seven cerebral hemorrhage (CH) patients and nine control group (CO) patients) were recorded using a portable device. Ten derived HRV (mean, standard deviation and root mean square difference of sinus RR intervals (NNmean, SDNN and RMSSD), ultra-low frequency (<0.003 Hz, uLF), very low frequency ([0.003 Hz, 0.04 Hz), vLF), low frequency ([0.04 Hz, 0.15 Hz), LF) and high frequency power ([0.15 Hz, 0.4 Hz), HF), ratio of LF to HF (LF/HF), the standard deviation of instantaneous beat-to-beat R-R interval variability (SD1), and approximate entropy (ApEn)) and ten visibility graph (VG) features (diameter (Dia), average node degree (aND), average shortest-path length (aSPL), clustering coefficient (CC), average closeness centrality (aCC), transitivity (Trans), average degree centrality (aDC), link density (LD), sMetric (sM) and graph energy (GE) of the constructed complex network) were compared on 5-min and UST segments to verify their validity and robustness in discriminating CH and CO under different data lengths. Besides, their potential for quantifying ANS-Load were also investigated. Results: The validation results of HRV and VG features in discriminating CH from CO showed that VG features were more clearly distinguishable between the two groups than HRV features. For effectiveness evaluation of analyzing ANS on UST segment, the NNmean, SDNN, RMSSD, LF, HF and LF/HF in HRV features and the CC, Trans, Dia and GE of VG features remained stable in both activated and inactivated segments across all data lengths. The capability of HRV and VG features in quantifying ANS-Load were evaluated and compared under different ANS-Load, the results showed that most HRV features (SDNN, LFHF, RMSSD, vLF, LF and HF) and almost all VG features were correlated to sympathetic nerve activity intensity. Conclusions: The proposed autonomic nervous activity analysis method based on VG and SKNA offers a new insight into ANS assessment in UST segments and ANS-Load quantification.

Abstract P235: Relationship Between Skin Sympathetic Nerve Activity And Nocturnal Non-dipping Blood Pressure In Patients With Postural Orthostatic Tachycardia Syndrome

Background: Patients with postural orthostatic tachycardia syndrome (POTS) have a high incidence of nocturnal non-dipping of blood pressure (BP). Objective: To test the hypothesis that non-dipping of BP is associated with persistently elevated nocturnal skin sympathetic nerve activity (SKNA) in patients with POTS. Methods: We used Bittium Faros 180 ECG monitor to simultaneously record electrocardiogram (ECG) and SKNA, and SpaceLab OnTrak arterial BP monitor (ABPM) over 24-hr in 55 POTS patients (51 women, 36±10 years-old). The Faros signals were high pass filtered at 300 Hz to display the SKNA. The same original signals were bandpass filtered 0.05-150 Hz to display ECG. BP was measured every 30-min when awake (7 AM to 9 PM) and hourly at night (9 PM to 7 AM). Results: The overall successful ABPM measurement was 71±18%. Nocturnal dipping of BP was presented in 40 patients with an average dipping% of 15.5±4.8%. Nocturnal non-dipping of BP was present in 15 patients with an average dipping% of 3.9±3.7% (p&lt;0.001). Figure A shows hourly averaged SKNA. A mixed effect model was used to compare the log (SKNA) values of two groups of patients at all time points, with patient as a random effect. The non-dipping group had higher SKNA from midnight of day 1 to 4 am of day 2 (indicated by the red bars, p=0.0118, 0.0223, 0.0402, 0.0382, 0.0424). The difference between awake time and sleep time (determined by patients’ diary) average SKNA was 0.155±0.106 μV in dipping group and 0.076± 0.101 μV in the non-dipping group (p=0.017, Figure B ). Conclusion: Nocturnal non-dipping of BP is associated with non-dipping of SKNA in patients with POTS suggesting sympathetic nerve activity plays an important mechanistic role.

Sympathetic toggled sinus rate acceleration as a mechanism of sustained sinus tachycardia in chronic orthostatic intolerance syndrome

The role of sympathetic nerve activity to maintain sinus rate acceleration remains unclear. The purpose of this study was to test the hypothesis that sustained (>30 seconds) sinus rate acceleration can be associated with either a sympathetic driven or a sympathetic toggled mechanism. We used a patch monitor to record skin sympathetic nerve activity (SKNA) and electrocardiogram over 24 hours. Study 1 included chronic orthostatic intolerance (OI) (n = 18), atrial fibrillation (n = 7), and asymptomatic normal control (n = 19) groups. Study 2 included 17 participants with chronic OI not treated with ivabradine, pyridostigmine, or β-blockers. While a majority of sinus rate acceleration was driven by persistent SKNA in study 1, some episodes were toggled on and off by SKNA bursts without persistent SKNA elevation. The sympathetic toggled sinus rate acceleration episodes were found in 7 of 18 participants with chronic OI (39%), 2 of 7 participants with atrial fibrillation (29%), and 6 of 19 normal control participants (32%) (P = .847) and were faster and longer in the chronic OI group than in other groups. In study 2, there were a total of 11 episodes of sinus rate acceleration that persisted for >200 seconds. Among these episodes, 6 (35%) were toggled on and off by SKNA bursts. Sustained sinus rate acceleration (may be toggled on or off) is associated with SKNA bursts in participants with chronic OI, participants with atrial fibrillation, and normal controls. Patients with OI had more frequent and longer episodes than did other groups.

Alteration of Skin Sympathetic Nerve Activity after Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation.

Autonomic system plays a pivotal role in the pathogenesis of paroxysmal atrial fibrillation (AF). Skin sympathetic nerve activity (SKNA) is a noninvasive tool for assessing sympathetic tone. However, data on changes in SKNA after ablation are limited. Here, we retrospectively enrolled 37 patients with symptomatic drug-refractory paroxysmal AF who underwent pulmonary vein isolation (PVI) with radiofrequency ablation (RFA) or cryoablation (CBA). SKNA was measured from the chest and right arm 1 day prior to ablation, as well as 1 day and 3 months after ablation. One day after ablation, the SKNA-Arm increased from 517.1 µV (first and third quartiles, 396.0 and 728.0, respectively) to 1226.2 µV (first and third quartiles, 555.2 and 2281.0), with an increase of 179.8% (125% and 376.0%) (p < 0.001); the SKNA-Chest increased from 538.2 µV (first and third quartiles, 432.9 and 663.9) to 640.0 µV (first and third quartiles, 474.2 and 925.6), with an increase of 108.3% (95.6% and 167.9%) (p = 0.004), respectively. In those without recurrence, there was a significant increase in SKNA 1 day after ablation as compared with those before ablation. Twelve patients received SKNA measurement 3 months after ablation; both SKNA-Arm (p = 0.31) and SKNA-Chest (p = 0.27) were similar to those before ablation, respectively. Among patients with symptomatic drug-refractory paroxysmal AF receiving PVI, increased SKNA was observed 1 day after ablation and returned to the baseline 3 months after ablation. Elevation of SKNA was associated with lower early and late recurrences following ablation.

Skin sympathetic nerve activity in patients with chronic orthostatic intolerance.

Chronic orthostatic intolerance (OI) is characterizedby the development of tachycardia and other symptomswhen assuming an upright body position. The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or β-blockers. In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptomshad higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomaticin controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.

The Mechanism of Cardiac Sympathetic Activity Assessment Methods: Current Knowledge.

This review has summarized the methods currently available for cardiac sympathetic assessment in clinical or under research, with emphasis on the principles behind these methodologies. Heart rate variability (HRV) and other methods based on heart rate pattern analysis can reflect the dominance of sympathetic nerve to sinoatrial node function and indirectly show the average activity level of cardiac sympathetic nerve in a period of time. Sympathetic neurotransmitters play a key role of signal transduction after sympathetic nerve discharges. Plasma or local sympathetic neurotransmitter detection can mediately display sympathetic nerve activity. Given cardiac sympathetic nerve innervation, i.e., the distribution of stellate ganglion and its nerve fibers, stellate ganglion activity can be recorded either directly or subcutaneously, or through the surface of the skin using a neurophysiological approach. Stellate ganglion nerve activity (SGNA), subcutaneous nerve activity (SCNA), and skin sympathetic nerve activity (SKNA) can reflect immediate stellate ganglion discharge activity, i.e., cardiac sympathetic nerve activity. These cardiac sympathetic activity assessment methods are all based on the anatomy and physiology of the heart, especially the sympathetic innervation and the sympathetic regulation of the heart. Technological advances, discipline overlapping, and more understanding of the sympathetic innervation and sympathetic regulation of the heart will promote the development of cardiac sympathetic activity assessment methods.

An Artifact-Resistant Feature SKNAER for Quantifying the Burst of Skin Sympathetic Nerve Activity Signal.

Evaluation of sympathetic nerve activity (SNA) using skin sympathetic nerve activity (SKNA) signal has attracted interest in recent studies. However, signal noises may obstruct the accurate location for the burst of SKNA, leading to the quantification error of the signal. In this study, we use the Teager–Kaiser energy (TKE) operator to preprocess the SKNA signal, and then candidates of burst areas were segmented by an envelope-based method. Since the burst of SKNA can also be discriminated by the high-frequency component in QRS complexes of electrocardiogram (ECG), a strategy was designed to reject their influence. Finally, a feature of the SKNA energy ratio (SKNAER) was proposed for quantifying the SKNA. The method was verified by both sympathetic nerve stimulation and hemodialysis experiments compared with traditional heart rate variability (HRV) and a recently developed integral skin sympathetic nerve activity (iSKNA) method. The results showed that SKNAER correlated well with HRV features (r = 0.60 with the standard deviation of NN intervals, 0.67 with low frequency/high frequency, 0.47 with very low frequency) and the average of iSKNA (r = 0.67). SKNAER improved the detection accuracy for the burst of SKNA, with 98.2% for detection rate and 91.9% for precision, inducing increases of 3.7% and 29.1% compared with iSKNA (detection rate: 94.5% (p < 0.01), precision: 62.8% (p < 0.001)). The results from the hemodialysis experiment showed that SKNAER had more significant differences than aSKNA in the long-term SNA evaluation (p < 0.001 vs. p = 0.07 in the fourth period, p < 0.01 vs. p = 0.11 in the sixth period). The newly developed feature may play an important role in continuously monitoring SNA and keeping potential for further clinical tests.

Dynamics of Cardiac Autonomic Responses During Hemodialysis Measured by Heart Rate Variability and Skin Sympathetic Nerve Activity: The Impact of Interdialytic Weight Gain.

Background: Autonomic nervous regulation plays a critical role in end-stage kidney disease (ESKD) patients with cardiovascular complications. However, studies on autonomic regulation in ESKD patients are limited to heart rate variability (HRV) analysis. Skin sympathetic nerve activity (SKNA), which noninvasively reflects the sympathetic nerve activity, has not been used in ESKD patients. Methods: Seventy-six patients on maintenance hemodialysis (MHD) treatment (a 4-h HD session, three times a week) were enrolled. Utilizing a noninvasive, single-lead, high-frequency recording system, we analyzed the dynamic change in HRV parameters and SKNA during HD. The different characteristics between the subgroups divided based on interdialytic weight gain (IDWG, <3 kg or ≥3 kg) were also demonstrated. Results: After the HD, values for heart rate (75.1 ± 11.3 to 80.3 ± 12.3 bpm, p < 0.001) and LF/HF (1.92 ± 1.67 to 2.18 ± 2.17, p = 0.013) were significantly higher than baseline. In subgroup analysis, average voltage of skin sympathetic nerve activity (aSKNA) in IDWG ≥3 kg group was lower than the IDWG <3 kg group at the end of MHD (1.06 ± 0.30 vs 1.32 ± 0.61 μV, p = 0.046). Moreover, there was a linear correlation between mean heart rate (HR) and aSKNA in low IDWG patients (p < 0.001), which was not found in high IDWG patients. At the 1-year follow-up, high IDWG patients had a higher incidence of cardiovascular hospitalization (p = 0.046). Conclusions: In MHD patients, a gradual activation of sympathetic nerve activity could be measured by HRV and aSKNA. A lower aSKNA at the end of HD and a loss of HR-aSKNA correlation in overhydrated patients were observed. Extensive volume control is promising to improve the autonomic nervous function and clinical outcomes in this population.

Application of Physiological Autonomic Activity Tracking GUI and Computational Algorithms for Measuring Persistent Vagal Nerve Dysfunction After Recovery from SARS‐CoV‐2 Infection

Post‐Acute Sequelae of SARS‐CoV‐2 infection (PASC) is now recognized as a constellation of symptoms such as postural hypotension, anxiety, and “brain fog” in addition to autonomic nervous system dysfunction such as tachycardia and labile hypertension. Better quantification of these conditions, specifically, autonomic nervous system dysfunction, is desired for future diagnostics, treatment modalities, and gaining a further understanding of PASC. This research has led to application of a novel autonomic activity tracking algorithm and GUI suite from previous work, see Figure 1, to study the physiological autonomic activity in six patients who had recovered from acute SARS‐CoV‐2 infection a mean of six months prior but were still experiencing symptoms. By measuring skin sympathetic nervous activity (SKNA), heart rate variability, and the cutaneous electrogastrogram (EGG), all before and after a water meal challenge, the data was fed into a custom analysis pipeline, shown in Figure 1. Each of the PASC patients were compared to a mean response of 34 healthy controls, each undergoing a 20‐minute baseline recording and another 20‐minute recording after ingestion of an 8 oz water test meal. All six patients showed significantly abnormal heart rate variability on frequency domain analysis in predominantly the low frequency (LF) and very low frequency (VLF) bands, and less so in the high frequency (HF) band, suggesting sympathetic nerve dysfunction. Three patients showed a significant decrease in SKNA while two showed a significant increase. All patients showed an abnormal cutaneous EGG. As shown in Figure 2, the temporal responses of aSKNA, VLF, LF, HF, and EGG for the PASC patients revealed that on average they were statistically different (p<0.05) from the healthy controls’ responses respectively during 98.4%, 78.4%, 86.76%, 47.9%, and 86.1% of the 40‐minute time period in testing, 20 minutes of baseline and 20 minutes after ingestion. In conclusion, we are looking at the sympathetic, parasympathetic, and enteric nervous systems synced temporally for applications with classification and further stratification of PASC based on the temporal dynamics of their autonomic nervous system mediated coordination from digestion. This shows that SARS‐CoV02 infection appears to have a significant effect on sympathetic and parasympathetic autonomic nervous system function and may be responsible for the disturbances noted in PASC. This work provides the framework and example of use for further applications in autonomic disorder physiological response exploration and furthermore can be expanded to other areas of neuromodulation.

Design and evaluation of an autonomic nerve monitoring system based on skin sympathetic nerve activity

The autonomic nervous system is closely related to cardiovascular diseases (CVDs). Simultaneous non-invasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) is a new method for autonomic nervous system real-time assessment. This study presented a portable monitoring system based on SKNA. A system-level modification by combining a commercial analog front end (AFE) chip with a low-noise first-stage amplifier was implemented to reduce the system noise floor without a high-cost customized chip. An adaptive power-line-interference (PLI) filter and outliers clipping were developed to reject the PLI and motion artifacts in the signal. The laboratory experiment and clinical experiment were conducted to verify the performance and effectiveness of the proposed system. The laboratory results show that the proposed AFE has a much lower noise floor with 0.1 μVrms than the reference systems (PowerLab system). Moreover, the correlation coefficient of the envelope of SKNA (eSKNA) is 0.83, and the correlation coefficient of the heart rate variability (HRV) index is 0.99, suggesting a good performance in signal recording. The clinical results show that the proposed system can reflect sympathetic nerve activity significantly before and after anesthesia injection (p < 0.01), indicating its better feasibility in this application scenario than HRV-based devices (p = 0.40). The system achieves a comparable performance to the reference system and satisfactory performance for the autonomic nervous system assessment in clinical application.