The Impact on Autonomic Nervous System Activity during and Following Exercise in Adults: A Meta-Regression Study and Trial Sequential Analysis.

Background and Objectives: Exercise enhances cardiovascular health through various mechanisms, including the modulation of autonomic nervous system activity. This study aimed to systematically examine the impact of exercise on heart rate variability (HRV) in adults during and within one hour after exercise (WHAE). Materials and Methods: A comprehensive literature review was conducted using the MEDLINE, Embase, Cochrane Library, Scopus, and PubMed databases to identify published studies that reported the impact of exercise on autonomic nervous system activity in adults. The studies measured the absolute power of the low-frequency band (0.04-0.15 Hz) to the absolute power of the high-frequency band (0.015-0.4 Hz) (LF/HF ratio) to assess sympathetic activity and the root mean square of successive differences between normal heartbeats (RMSSD) to assess parasympathetic activity. Results: A total of 3329 studies were screened for relevance, and finally, 10 articles that utilized methods for measuring autonomic nervous system activity, such as the LF/HF ratio and RMSSD, covering 292 adult patients, were included for meta-analysis. In the current meta-analysis, we observed a significant decrease in parasympathetic activity during and after exercise, as indicated by RMSSD, compared to pre-exercise levels (mean difference [MD] = -4.96, 95% confidence interval [CI]: -8.00 to -1.91, p = 0.003). However, sympathetic activity after exercise, represented by the LF/HF ratio, showed a borderline significant increase compared to pre-exercise levels (MD = 1.06, 95% CI: -0.01 to 2.12, p = 0.052). The meta-regression model found that factors associated with RMSSD included mean age, male gender, and duration post-exercise. Additionally, the factor associated with the LF/HF ratio was the healthy condition of participants. The trial sequential analysis provided robust evidence of a decrease in RMSSD and an increase in the LF/HF ratio during and WHAE. Conclusions: Given the limitations of the current study, the findings suggest that a significant decrease in parasympathetic activity and a borderline significant increase in sympathetic activity in adults during and WHAE, as confirmed by trial sequential analysis. Meta-regression analysis indicated that parasympathetic activity was negatively associated with participant age and male gender, but positively associated with duration post-exercise. Additionally, increased sympathetic activity was linked to the healthy conditions of participants. This study suggests that exercise might differentially affect autonomic balance in individuals with chronic conditions compared to healthy individuals. This highlights the potential need for tailored exercise interventions to improve autonomic function across different populations.

Obstructive sleep apnea syndrome and autonomic dysfunction in Duchenne muscular dystrophy.

PURPOSE: Cardiac and respiratory involvement constitutes serious complications of Duchenne muscular dystrophy (DMD). We hypothesized that obstructive sleep apnea syndrome (OSAS) may play a role in cardiac autonomic dysfunction in DMD. We sought to assess the presence of cardiac autonomic function in patients with DMD by analyzing heart rate variability (HRV) during polysomnography (PSG). METHODS: In a prospective study, all participants had whole-night PSG recorded and scored according to American Academy of Sleep Medicine guidelines. HRV analysis was performed on electrocardiography recordings from PSG recordings. RESULTS: Twelve consecutive males with DMD (mean age 9.0 ± 3.1 years, mean BMI 20.6 ± 4.8 kg/m2) and eight age-matched healthy males were enrolled. On clinical evaluation, 58% of patients with DMD had at least one symptom related to OSAS, such as snoring, witnessed apnea, or restless sleep. None of the controls had OSAS-related complaints. By PSG none of the controls had OSAS, while 42% of patients with DMD had OSAS (p = 0.004). Average R-R duration and mean percentage of successive R-R intervals > 50 ms values were significantly lower in patients with DMD than those in controls (p < 0.006). In patients with DMD and OSAS, LF/HF (low/high-frequency) ratio was significantly increased in NREM sleep compared with those in controls (p = 0.005). Higher apnea-hypopnea index and lower oxygen saturation showed significant correlations with higher LF power and LF/HF ratio (p < 0.001). CONCLUSION: Cardiac autonomic dysfunction is present in DMD, being more pronounced in the presence of OSAS.

Measurement of Cancer-Related Fatigue Based on Heart Rate Variability: Observational Study.

BACKGROUND: Cancer-related fatigue is a serious side effect of cancer, and its treatment can disrupt the quality of life of patients. Clinically, the standard method for assessing cancer-related fatigue relies on subjective experience retrieved from patient self-reports, such as the Brief Fatigue Inventory (BFI). However, most patients do not self-report their fatigue levels. OBJECTIVE: In this study, we aim to develop an objective cancer-related fatigue assessment method to track and monitor fatigue in patients with cancer. METHODS: In total, 12 patients with lung cancer who were undergoing chemotherapy or targeted therapy were enrolled. We developed frequency-domain parameters of heart rate variability (HRV) and BFI based on a wearable-based HRV measurement system. All patients completed the BFI-Taiwan version questionnaire and wore the device for 7 consecutive days to record HRV parameters such as low frequency (LF), high frequency (HF), and LF-HF ratio (LF-HF). Statistical analysis was used to map the correlation between subjective fatigue and objective data. RESULTS: A moderate positive correlation was observed between the average LF-HF ratio and BFI in the sleep phase (ρ=0.86). The mapped BFI score derived by the BFI mapping method could approximate the BFI from the patient self-report. The mean absolute error rate between the subjective and objective BFI scores was 3%. CONCLUSIONS: LF-HF is highly correlated with the cancer-related fatigue experienced by patients with lung cancer undergoing chemotherapy or targeted therapy. Beyond revealing fatigue levels objectively, continuous HRV recordings through the photoplethysmography watch device and the defined parameters (LF-HF) can define the active phase and sleep phase in patients with lung cancer who undergo chemotherapy or targeted chemotherapy, allowing a deduction of their sleep patterns.

Nocturnal autonomic nervous system activity and morning proinflammatory cytokines in young adult African Americans.

Compromised sleep and increased sympathetic nervous system (SNS) activity are implicated in the pathogenesis of, and disparities in, cardiovascular disease. Parasympathetic dominance during sleep may be important for cardiovascular health. Sleep and autonomic balance influence immune activity, which impacts atherogenesis. We evaluated relationships between autonomic balance during sleep and morning levels of the immune activating cytokines, C-reactive protein (CRP) and interleukin (IL)-6. Ninety-four (59 female) young adult African Americans without medical conditions and substance use disorders spent 2 consecutive nights in a clinical research unit for sleep recordings and blood drawing on awakening. Cardiac tracings from the second sleep recording were analysed for heart rate variability (HRV). Body mass index was the only non-HRV measure correlated with cytokine levels. Indicators of SNS activity for the presleep, and first non-rapid eye movement (REM) and REM sleep periods were correlated independently with morning IL-6 levels. Altered autonomic balance during sleep may be a modifiable factor that influences immune activation.

Arrhythmia risk assessment using heart rate variability parameters in patients with frequent ventricular ectopic beats without structural heart disease.

BACKGROUND: Ventricular ectopic beats (VEBs) are usually considered a benign condition that can be managed with conservative measures. Heart rate variability (HRV), which is one of the most important methods for assessing autonomic activity, is a noninvasive, quantitative method of analyzing autonomic effects on the heart. We aimed to investigate the risk of arrhythmia in patients with VEBs and without cardiovascular disease by using HRV parameters. METHODS: Patients with frequent VEBs (more than 30 times in 1 hour, according to the Lown classification) were identified. Identified patients were evaluated by 24-hour ECG recording. Our study included 43 patients with frequent VEBs and 43 controls. RESULTS: General characteristics of the study population were similar. The LF (low frequency)/HF (high frequency) ratio was significantly higher in the frequent VEBs group than in the control group (P < 0.001). The rate of paroxysmal atrial fibrillation (PAF) was higher in the frequent VEB group than in the control group (P = 0.003). The number of VEBs was correlated with LF/HF ratio and PAF (r = 0.339, P = 0.001 and r = 0.294, P = 0.006, respectively). CONCLUSIONS: Our study showed that the sympathetic nervous system is dominant in young patients with VEBs and without significant comorbidities. There is a higher risk of atrial fibrillation in patients with VEBs and they should be monitored closely for atrial fibrillation.

Iris color and day-night changes in the sympathovagal ratio.

Iris melanocytes are innervated by parasympathetic and sympathetic nerve endings. Light affects autonomic nervous system activity via the retino-hypothalamic pathway. The hypothesis that the day-to-night variations in the sympatovagal ratio (LF/HF) may differ among individuals with different brown iris patterns was tested. A total of 621 healthy adults, aged between 16 and 50, with brown eyes and not diagnosed with a disease that might affect the autonomous nerve system were included in the study. A digital camera was used to acquire iris photos. Subjects were grouped into iris color groups (2-0 bg, 1-0 bg, 1-1 db, 1-1 lb, 2-0 b, and 1-0 b). Iris photos were analyzed with Picture Color Analyzer RBG software. The Central/Peripheral (R/RGB) ratio was used for objective distinction between the groups. Using 24-h Holter ECG monitoring, the change in the sympathovagal ratio from day (between 07:00 and 23:00 h) to night (between 23:00 and 07:00 h) was determined with the formula [(Day-Night) LF/HF)/Day LF/HF]. The frequency of subjects with a decrease in the LF/HF ratio from day to night was the highest in the 1-1 db group (65.7%), followed by the 1-1 lb group (56.4%). The highest increase was in the 2-0 bg group (76.5%), followed by the 1-0 B group (68.9%) (p < 0.001). Based on the findings of this study, iris color may be a predictive factor in diseases in which the circadian change of autonomic nervous system activity is effective.

Menstrual Irregularity: A Physiological Adaptation to Cope Perceived Stress.

INTRODUCTION: Menstrual cycle characteristics are regulated hormonally and are integrated at the level of the hypothalamus. Stress can affect the hypothalamic-pituitary gonadal axis. The objective of the study was to analyse the stress levels of women and compare their autonomic tone and menstrual characteristics. METHODOLOGY: A group of 100 apparently healthy, young, female volunteers were included in this pilot cohort study. Subjects were assessed for perceived stress using the Perceived Stress Scale 14 Item (PSS-14) questionnaire, underwent a heart rate variability (HRV) test on the second, 10th, and 21st days of their menstrual cycle, and their menstrual history was recorded. The statistical analysis was done using Statistical Product and Service Solutions (SPSS, version 21.0; IBM SPSS Statistics for Windows, Armonk, NY) software. Metric data were expressed in terms of numerical value and analysed as mean ± SD. Paired Student's T-test was used to compare the HRV data of all three days of the menstrual cycle separately, and p value<0.05 was considered significant. Menstrual irregularity was complained of by 13 subjects (Group A), and the rest (87 subjects) reported regular menses (Group B). RESULT: The perceived stress scores of Group A were significantly higher than Group B (32.53±5.062 vs 28.057±7.618; p=0.044). On second day, Group A had higher median R-R interval (714.38±106 vs 656.84±73.50 ms; p=0.015) and lower average heart rate (85.85±12.07 vs 92.39±9.98 bpm; p=0.034) than Group B, suggesting parasympathetic dominance. On the 10th day, Group A had a higher standard deviation of heart rate (7.09±1.88 vs 5.97±1.71 bpm; p=0.032) and a very low-frequency band (1105.94±984.12 vs 730.49±557.41 µs2; p=0.046) than Group B, indicating parasympathetic dominance in Group A. On the 21st day, Group A had a higher standard deviation of R-R interval (58.19±20.46 vs 44.85±14.55 ms; p=0.004), root mean square standard deviation (55.71±29.84 vs 31.89±15.99 ms; p<0.001), percentage of R-R differing by 50 ms (19.20±19.58 vs 10.87±10.31%; p=0.020), total power (3,440.23±2722.29 vs 2,068.28±1,322.49 µs2; p=0.004), high-frequency band (1,247.57±1173.54 vs 539.06±HPO438.92 µs2; p<0.001), standard deviation ratio of the Poincaré plot (0.53±0.19 vs 0.39±0.16; p=0.003), normalised HF (44.0±12.9 vs 35.4±10.6; p=0.009), and a lower LF/HF ratio (1.43±0.80 vs 2.11±1.16; p=0.043) and normalised LF (53.9±14.4 vs 64.1±11.9; p=0.006) than Group B, suggesting higher parasympathetic tone of Group A than Group B. CONCLUSION: Analysing these results, it can be concluded that, in apparently healthy young women, menstrual irregularity is a physiological adaptation to combat perceived stress and maintain parasympathetic dominance.

Cancer-related fatigue classification based on heart rate variability signals from wearables.

Background: Cancer-related fatigue (CRF) is the most distressing side effect in cancer patients and affects the survival rate. However, most patients do not report their fatigue level. This study is aimed to develop an objective CRF assessment method based on heart rate variability (HRV). Methods: In this study, patients with lung cancer who received chemotherapy or target therapy were enrolled. Patients wore wearable devices with photoplethysmography that regularly recorded HRV parameters for seven consecutive days and completed the Brief Fatigue Inventory (BFI) questionnaire. The collected parameters were divided into the active and sleep phase parameters to allow tracking of fatigue variation. Statistical analysis was used to identify correlations between fatigue scores and HRV parameters. Findings: In this study, 60 patients with lung cancer were enrolled. The HRV parameters including the low-frequency/high-frequency (LF/HF) ratio and the LF/HF disorder ratio in the active phase and the sleep phase were extracted. A linear classifier with HRV-based cutoff points achieved correct classification rates of 73 and 88% for mild and moderate fatigue levels, respectively. Conclusion: Fatigue was effectively identified, and the data were effectively classified using a 24-h HRV device. This objective fatigue monitoring method may enable clinicians to effectively handle fatigue problems.

Heart Rate Variability in Unexplained Syncope Patients Versus Healthy Controls: A Comparative Study.

Background Syncope or fainting is the sudden and transient loss of consciousness. This could lead to an increase in mortality due to sudden cardiac death or comorbidity in these patients. Heart rate variability (HRV) is a noninvasive bedside procedure for assessing the cardiovascular autonomic function. There may be an abnormal alteration in the HRV parameters in syncope patients. This can be used for looking into cardiovascular autonomic changes in syncope. This would help in early diagnosis and intervention. Objective The aim of this present study was to compare the HRV parameters between unexplained syncope patients and age-matched healthy controls and to find a correlation between HRV parameters and cardiovascular parameters like pulse and mean blood pressure. Materials and methods A five-minute continuous electrocardiogram (ECG) was recorded and HRV analysis was done by ADInstruments' PowerLab (Oxford, United Kingdom) for 25 cases and 25 controls. Results The mean standard deviation of the RR interval (SDRR) in milliseconds was found to be significantly lower in the cases (21.93 ± 3.53) as compared to controls (71.27 ± 27.40). The mean value of the low-frequency to high-frequency ratio (LF/HF) was significantly higher in cases (1.43 ± 0.40) as compared to controls (0.98 ± 1.07). However, there was no significant correlation between the pulse, blood pressure, and HRV measures. Conclusion The findings suggest a sympathetic predominance in the cases of unexplained syncope as compared to the controls.

Oscillation of Sympathetic Activity in Patients with Obstructive Sleep Apnea during the First Hour of Sleep.

(1) Background: Snoring is a cardinal symptom of obstructive sleep apnea (OSA) and has been suggested to potentially increase sympathetic activity. On the other hand, sleep itself usually leads to a decrease in sympathetic activity. Heart rate variability (HRV) analysis is a non-invasive technique used to assess autonomic nervous system function. However, there is limited research on the combined impact of sleep and snoring on sympathetic activity in individuals with OSA, particularly during the first hour of sleep (non-rapid eye movement sleep). The current study aims to investigate the net effect of sleep and snoring on sympathetic activity and explore factors that might contribute to increased sympathetic activity in individuals with OSA during the first hour of sleep. (2) Methods: The participants were referred from the outpatient department for OSA diagnosis and underwent whole-night polysomnography (PSG). Electrocardiogram (EKG) data from the PSG were downloaded for HRV analysis. HRV measurements were conducted in both the time and frequency domain, including the root mean square of successive differences between normal heartbeats (RMSSD) and the ratio of the absolute power of the low-frequency (LF) band (0.04-0.15 Hz) to the absolute power of the high-frequency (HF) band (0.15-0.4 Hz) (LF/HF ratio), respectively. (3) Results: A total of 45 participants (38 men and 7 women) were included in the analysis. The RMSSD gradually increased from 0-5 min to 50-60 min (p = 0.024), while the LF/HF ratio decreased (p < 0.001) during the first hour of sleep (non-rapid eye movement sleep). The LF/HF ratios of the "S" (snoring) episodes were compared with those of the pre-S episodes. An elevated LF/HF ratio during the S episode was associated with the first snoring episode occurring more than 20 min after lying down to sleep (Odds ratio, OR = 10.9, p = 0.004) and with patients diagnosed with severe OSA (OR = 5.01, p = 0.045), as determined by logistic regression. (4) Conclusions: The study observed an increase in the value of RMSSD and a decrease in the value of the LF/HF ratio during the first hour of sleep for patients with OSA. Higher LF/HF ratios were associated with the first occurrence of snoring while lying down for more than 20 min and with patients with severe OSA.

Heart Rate Variability as a Predictor of Mortality in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review the medical literature to determine the utility of heart rate variability in predicting mortality for moderate to severe traumatic brain injury. METHODS: A search for randomized controlled trials, nonrandomized trials, and prospective and retrospective cohort studies was carried out using PubMed, SCOPUS, Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Reference lists of included studies were also searched to identify potentially eligible studies. RESULTS: Five articles comprising 542 patients met inclusion criteria. Heart rate variability as low-frequency/high-frequency ratio (area under the curve [AUC] receiver operating characteristic [ROC]) for predicting mortality was found to be statistically significant (AUC ROC 0.810, P < 0.001) with high heterogeneity (I2 = 61.98%, P = 0.032). Meta-analysis of low-frequency/high-frequency ratio, High frequency peak, and total power were statistically significant for predicting mortality. Odd's ratio for predicting mortality for LF/HF ratio, HF peak, and TP were 16.17, 19.09, 22.59 respectively. High-frequency peak in predicting mortality showed an AUC ROC of 0.986 (P ≤ 0.001) with a low level of heterogeneity. Total power (TP) showed an AUC ROC of 0.93 (P < 0.001) in predicting mortality with a high level of heterogeneity (I2 = 83.16%, P = 0.002). Funnel plot analysis to assess the presence of publication bias for TP showed a high level of heterogeneity and asymmetry among studies. CONCLUSIONS: This meta-analysis predicted high mortality based on odds ratio for variables low-frequency/high-frequency ratio, high-frequency peak, and TP. However, the statistical analysis was weakened owing to the high level of heterogeneity in the included studies. Further research is needed to generate high-quality recommendations regarding heart rate variability as a predictor of mortality after traumatic brain injury.

Heart rate variability for treatment response between patients with major depressive disorder versus panic disorder: A 12-week follow-up study.

BACKGROUND: Heart Rate Variability (HRV) parameters have been used to evaluate the autonomic nervous system. We hypothesized that patients with major depressive disorder (MDD) and panic disorder (PD) showed different HRV profiles compared to healthy controls. We also hypothesized that we could predict the responder groups in the MDD and PD patients, using differences in HRV indices between the stress and rest phases. METHODS: 28 MDD patients and 29 PD patients were followed for 12 weeks, and we also followed 39 healthy control subjects. We measured HRV parameters at the rest, stress, and recovery phases. RESULTS: Patients with MDD and PD demonstrated lower pNN50 than controls during the stress (F = 7.49, p = 0.001), and recovery phases (F = 9.43, p = 0.0001). Patients with MDD and PD also showed higher LF/HF ratio than controls during the stress phase (F = 6.15, p = 0.002). Responders in the PD group presented a lower level of LF/HF ratio during the stress phase compared to non-responders (F = 10.14, p = 0.002), while responders in the MDD group showed a lower level of heart rate during all three phases, compared to non-responders. Additionally, we could predict treatment response in patients with MDD using ΔLF/HF ratio (OR: 1.33, 95% CI = 1.07-1.65, p = 0.011) and ΔpNN50 (OR: 1.49, 95% CI 1.09-1.77, p = 0.014). CONCLUSION: The changes of HRV parameters of pNN50 and LF/HF ratio between the stress and recovery phase may be clinical markers of predictors of treatment responsiveness in MDD and PD patients.

Resolving Ambiguities in the LF/HF Ratio: LF-HF Scatter Plots for the Categorization of Mental and Physical Stress from HRV.

It is generally accepted that the activities of the autonomic nervous system (ANS), which consists of the sympathetic (SNS) and parasympathetic nervous systems (PNS), are reflected in the low- (LF) and high-frequency (HF) bands in heart rate variability (HRV)-while, not without some controversy, the ratio of the powers in those frequency bands, the so called LF-HF ratio (LF/HF), has been used to quantify the degree of sympathovagal balance. Indeed, recent studies demonstrate that, in general: (i) sympathovagal balance cannot be accurately measured via the ratio of the LF- and HF- power bands; and (ii) the correspondence between the LF/HF ratio and the psychological and physiological state of a person is not unique. Since the standard LF/HF ratio provides only a single degree of freedom for the analysis of this 2D phenomenon, we propose a joint treatment of the LF and HF powers in HRV within a two-dimensional representation framework, thus providing the required degrees of freedom. By virtue of the proposed 2D representation, the restrictive assumption of the linear dependence between the activity of the autonomic nervous system (ANS) and the LF-HF frequency band powers is demonstrated to become unnecessary. The proposed analysis framework also opens up completely new possibilities for a more comprehensive and rigorous examination of HRV in relation to physical and mental states of an individual, and makes possible the categorization of different stress states based on HRV. In addition, based on instantaneous amplitudes of Hilbert-transformed LF- and HF-bands, a novel approach to estimate the markers of stress in HRV is proposed and is shown to improve the robustness to artifacts and irregularities, critical issues in real-world recordings. The proposed approach for resolving the ambiguities in the standard LF/HF-ratio analyses is verified over a number of real-world stress-invoking scenarios.

Frequency analysis of a task-evoked pupillary response: Luminance-independent measure of mental effort.

Pupil diameter is a widely-studied cognitive load measure, which, despite its convenience for non-intrusive operator state monitoring in complex environments, is still not available for in situ measurements because of numerous methodological limitations. The most important of these limitations is the influence of pupillary light reflex. Hence, there is the need of providing a pupil-based cognitive load measure that is independent of light conditions. In this paper, we present a promising technique of pupillary signal analysis resulting in luminance-independent measure of mental effort that could be used in real-time without a priori on luminous conditions. Twenty-two participants performed a short-term memory task under different screen luminance conditions. Our results showed that the amplitude of pupillary dilation due to load on memory was luminance-dependent with higher amplitude corresponding to lower-luminance condition. Furthermore, our experimentation showed that load on memory and luminance factors express themselves differently according to frequency. Therefore, as our statistical analysis revealed, the ratio between low (0-1.6 Hz) and high frequency (1.6-4 Hz) bands (LF/HF ratio) of power spectral densities of pupillary signal is sensitive to the cognitive load but not to luminance. Our results are promising for the measurement of load on memory in ecological settings.

Comparison between Myocardial Infarction and Congestive Heart Failure Using by Heart Rate Variability Analysis of 24 hours Holter Monitoring

OBJECTIVES: Power spectrum analysis decomposes the heart rate signal into its frequency components and facilitates separation of sympathetic (low frequency) and parasympathetic (high frequency) activity. In congestive heart failure, augmented sympathetic tone and decreased parasympathetic tone were found. Autonomic nervous system was normalized 6 months after myocardial infarction. So we compared the autonomic nervous system activity by the heart rate variability in congestive heart failure and old myocardial infarction. METHODS: The protocol involved 20 healthy subjects (Group 1), 5 congestive heart failure patients not caused by myocardial infarction (Group 2), 4 congestive heart failure patients due to myocardial infarction and 11 old myocardial infarction patients without heart failure. We took 24 hour Holter monitoring by Del Mar Avionic tape recorder. All Holter tapes were analyzed with use of Model 563 Stratascan Holter Analysis System. We computed power spectra on each 256 sec segment of each hour during 24 hour recording. So, RR interval, SD of RR interval by time domain, and LF, HF, LF/HF ratio, Total PSD by frequency domain were measured. RESULTS: In congestive heart failure, nocturnal HF peak and diurnal variation of LF/HF ratio was decreased relative to healthy subjects. Nocturnal HF peak in old myocardial infarction was not visualized. All of LF, HF and Total PSD in congestive heart failure and old myocardial infarction patients relative to healthy subjects. CONCLUSION: On heart rate variability analysis using by 24 hour Holter monitoring, abnormal autonomic nervous activity was demonstrated in congestive heart failure and old myocardial infarction patients relative to healthy subjects.