Effects of Exercise Training on Heart Rate Variability in Healthy Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This meta-analysis was conducted to investigate the effects of exercise training on heart rate variability (HRV) parameters associated with the autonomic nervous system (ANS) activity. Randomized controlled trials (RCTs) involving healthy adults (aged ≥ 18 years) were included. We searched PubMed, Scopus, Web of Science, and EBSCO databases to identify relevant studies. A random-effects meta-analysis was performed using the standardized mean difference (SMD) and 95% confidence interval (CI). Sixteen RCTs with a total of 623 participants were selected for the final analysis. The analysis showed that exercise training improved the standard deviation of normal-to-normal intervals (SDNN) (SMD: 0.58 (0.16, 1.00); p = 0.007), the root mean square of successive differences in heart period series (RMSSD) (SMD: 0.84 (0.36, 1.31); p = 0.0005), and the absolute power of high-frequency band (HF) (SMD: 0.89 (0.27, 1.51); p = 0.005) parameters compared to the control group. Analysis of the moderator variables showed that the effect of exercise on HRV indices may be influenced by sex, age, and type of exercise used, specifically in HF band, absolute power of low-frequency band (LF), and LF/HF ratio parameters. Despite the limited number of existing RCTs related to the subject, the results suggest that exercise training enhances HRV parameters associated with vagal-related activity (RMSSD and HF) and both sympathetic and parasympathetic activities (SDNN). This study overcomes the lack of meta-analyses on the effects of exercise training on autonomic modulation among healthy adults and may bridge the gap in understanding the potential physiological underpinnings of the acknowledged positive health benefits of exercise.

Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

Heart rate variability as a predictor of intraoperative autonomic nervous system homeostasis.

The aim of the proof-of-concept study is to investigate the level of concordance between the heart rate variability (HRV), the EEG-based Narcotrend Index as a surrogate marker for the depth of hypnosis, and the minimal alveolar concentration (MAC) of the inhalation anesthetic sevoflurane across the entire course of a surgical procedure. This non-blinded cross-sectional study recorded intraoperative HRV, Narcotrend Index, and MAC in 31 male patients during radical prostatectomy using the Da-Vinci robotic-assisted surgical system at Mannheim University Medical Center. The degree of concordance was calculated using repeated measures correlation with the R package (rmcorr) and presented using the rmcorr coefficient (rrm). The Narcotrend Index correlates significantly across all measures with the time-dependent parameter of HRV, the standard deviation of the means of RR intervals (SDNN) (rrm = 0.2; p < 0.001), the frequency-dependent parameters low frequency (LF) (rrm = 0.09; p = 0.04) and the low frequency/high frequency ratio (LF/HF ratio) (rrm = 0.11; p = 0.002). MAC correlated significantly negatively with the time-dependent parameter of heart rate variability, SDNN (rrm = -0.28; p < 0.001), the frequency-dependent parameter LF (rrm = -0.06; p < 0.001) and the LF/HF ratio (rrm = -0.18; p < 0.001) and the Narcotrend Index (rrm = -0.49; p < 0.001) across all measures. HRV mirrors the trend of the Narcotrend Index used to monitor depth of hypnosis and the inhibitory influence of the anesthetic sevoflurane on the autonomic nervous system. Therefore, HRV can provide essential information about the homeostasis of the autonomic nervous system during general anesthesia. DRKS00024696, March 9th, 2021.

Long-Term POTS Outcomes Survey: Diagnosis, Therapy, and Clinical Outcomes.

BACKGROUND: Limited data exist on long-term outcomes in individuals with postural orthostatic tachycardia syndrome (POTS). We designed an electronic questionnaire assessing various aspects of outcomes among patients diagnosed and treated in a single-center pediatric POTS clinical program. METHODS AND RESULTS: The LT-POTS (Long Term POTS Outcomes Survey) included questions about quality of life, symptoms, therapies, education, employment, and social impact of disease. Patients age≤18 years at POTS diagnosis who were managed in the Children's Hospital of Philadelphia POTS Program were included. A total of 227 patients with POTS responded with sufficient data for interpretation. The mean age of respondents was 21.8±3.5 years. The median age of symptom onset was 13 (interquartile range 11-14) years, with mean 9.6±3.4 years symptom duration. Multiple cardiovascular, neurologic, and gastrointestinal symptoms were reported. Symptom prevalence and severity were worse for female patients, with 99% of patients reporting ongoing symptoms. Quality of life showed moderate function and limitation, with more severe limitations in energy/fatigue and general health. Nearly three quarters of patients had diagnostic delays, and over half were told that their symptoms were "in their head." Multiple medications were used and were felt to be effective, whereas fewer nonpharmacologic interventions demonstrated efficacy. Nearly 90% of patients required continued nonpharmacologic therapy to control symptoms. CONCLUSIONS: POTS is a chronic disorder leading to significant disability with a range of multisystem problems. Although symptoms can be modifiable, it rarely spontaneously resolves. Improved understanding of POTS presentation and therapeutic approaches may inform provider education, improve diagnostic success, and help patients self-advocate for appropriate medical management approaches.

Autism spectrum disorder in young patients with congenital central hypoventilation syndrome: role of the autonomic nervous system dysfunction.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by alveolar hypoventilation and autonomic nervous system (ANS) dysfunction requiring long-term ventilation. CCHS could constitute a risk factor of autism spectrum disorder (ASD) due to birth injury related to respiratory failure, which remains to be determined. ANS dysfunction has also been described in ASD and there are indications for altered contribution of ANS-central nervous system interaction in processing of social information; thus, CCHS could be a risk factor for ASD based on pathophysiological background also. Our study aimed to determine the prevalence of ASD among CCHS patients, identify risk factors, and explore the relationship between the ANS, evaluated by heart rate variability indices, and adaptative functioning. RESULTS: Our retrospective study, based on the analysis of records of a French national center of patients with CCHS under 20 years of age, determined that the prevalence of ASD (diagnosed by a psychiatrist, following the criteria of DSM-4 or DSM-5) was 6/69 patients, 8.7% (95% confidence interval: 3.3-18.0%). In a case (CCHS with ASD, n = 6) - control (CCHS without ASD, n = 12) study with matching on sex, longer neonatal hospitalization stay and glycemic dysfunction were associated with ASD. Adaptative functioning was assessed using Vineland Adaptative behavioral scales (VABS) and heart rate variability indices (including daytime RMSSD as an index of parasympathetic modulation) were obtained from ECG Holter performed the same day. In 19 young subjects with CCHS who had both ECG Holter and VABS, significant positive correlations were observed between RMSSD and three of four sub-domains of the VABS (communication: R = 0.50, p = 0.028; daily living skills: R = 0.60, p = 0.006; socialization: R = 0.52, p = 0.021). CONCLUSION: Our study suggests a high prevalence of ASD in patients with CCHS. Glycemic dysfunction and longer initial hospitalization stays were associated with ASD development. A defect in parasympathetic modulation was associated with worse adaptative functioning.

The effect of total sleep deprivation on autonomic nervous system and cortisol responses to acute stressors in healthy individuals: A systematic review.

OBJECTIVE: To synthesise the literature examining the autonomic nervous system (ANS) and cortisol responses to an acute stressor following total sleep deprivation (TSD) in healthy adult subjects. METHODS: We conducted a systematic review (CRD42022293857) following the latest PRISMA statement. We searched Medline (via Ovid), Embase (via Ovid), PsycINFO (via Ovid), CINAHL complete and Scopus databases, without year restriction, using search terms related to "sleep deprivation", "stress", "autonomic nervous system" and "cortisol". Two independent team members used pre-defined inclusion/exclusion criteria to assess eligibility and extract data. We used RoB 2 to assess the risk of bias in randomised controlled trials, and ROBINS-I for non-randomised studies. RESULTS: Sixteen studies, with 581 participants (mean age = 29 ± 12 years), were eligible for inclusion in the descriptive syntheses. Half of the studies (n = 8) were conducted in the United States of America. The most commonly used study designs were randomised crossover studies (n = 7) and randomised controlled trials (n = 5). Most studies used a single night of TSD (n = 13) which was followed by a psychological (n = 6), physical (n = 5) or psychological and physical (n = 5) acute stressor event. Heart rate (n = 8), cortisol (n = 7) and blood pressure (n =6) were the most reported outcomes, while only a single study used forearm vascular conductance and forearm blood flow. Ten studies found that TSD changed, at least, one marker of ANS or cortisol response. TSD compared with a sleep control condition increased cortisol level (n=1), systolic blood pressure (n=3), diastolic blood pressure (n=2), mean arterial pressure (n=1), and electrodermal activity (n=1) after acute stress. Also, compared with a sleep control, TSD blunted cortisol (n=2), heart rate (n=1) and systolic blood pressure (n=2) responses after acute stress. However, TSD did not change ANS or cortisol responses to acute stressors in 73 % of the total reported outcomes. Furthermore, 10 RCT studies (62.5 %) were assigned as "some concerns" and two RCT studies (12.5 %) were attributed "high" risk of bias. Additionally, one non-randomised trial was classified as "moderate" and three non-randomised trials as "serious" risk of bias. CONCLUSION: The markers of ANS and cortisol responses to acute stress after TSD in healthy individuals reveal a scarcity of consistent evidence. The included studies present enough evidence that TSD induces either blunted or exaggerated ANS or cortisol responses to laboratory stresses supporting the "bidirectional multi-system reactivity hypothesis.". It appears that a comprehensive understanding of this phenomenon still lacks robust evidence, and further research is needed to clarify these relationships.

Altered Heart Rate Variability During Mobile Game Playing and Watching Self-Mobile Gaming in Individuals with Problematic Mobile Game Use: Implications for Cardiac Health.

Introduction: The surge in mobile gaming, fueled by smartphone and internet accessibility, lacks a comprehensive understanding of physiological changes during gameplay. Methods: This study, involving 93 participants (average age 21.75 years), categorized them into Problematic Mobile Gaming (PMG) and non-problematic Mobile Gaming (nPMG) groups based on Problematic Mobile Gaming Questionnaire (PMGQ) scores. The PMGQ is a 12-item scale developed in Taiwan to assess symptoms of problematic mobile gaming. The research delved into heart rate variability (HRV) alterations during real-time mobile gaming and self-gaming video viewing. Results: Results showed that the PMG group significantly presents a lower root mean square of successive differences (RMSSD), and High Frequency (lnHF) than does the nPMG group (F=4.73, p=0.03; F=10.65, p=0.002, respectively) at the baseline. In addition, the PMG group significantly displayed elevated HF and low-frequency to high-frequency (LF/HF) in the mobile-gaming (F=7.59, p=0.007; F=9.31, p=0.003) condition as well as in the watching self-gaming videos (F=9.75, p=0.002; F=9.02, p=0.003) than did the nPMG. Conclusion: The study suggests targeted interventions to mitigate autonomic arousal, offering a potential avenue to address adverse effects associated with problematic mobile gaming behavior. The PMG group displayed increased craving scores after real-time mobile gaming and watching self-gaming video excerpts, unlike the nPMG group. Elevated LF/HF ratios in frequent gaming cases heightened autonomic arousal, presenting challenges in relaxation after mobile gaming. These findings contribute to a nuanced understanding of the complex interplay between mobile gaming activities, physiological responses, and potential intervention strategies.

Physiological Profiling of Agitation in Dementia: Insights From Wearable Sensor Data.

Background and Objectives: The number of people with dementia is expected to triple to 152 million in 2050, with 90% having accompanying behavioral and psychological symptoms (BPSD). Agitation is among the most critical BPSD and can lead to decreased quality of life for people with dementia and their caregivers. This study aims to explore objective quantification of agitation in people with dementia by analyzing the relationships between physiological and movement data from wearables and observational measures of agitation. Research Design and Methods: The data presented here is from 30 people with dementia, each included for 1 week, collected following our previously published multimodal data collection protocol. This observational protocol has a cross-sectional repeated measures design, encompassing data from both wearable and fixed sensors. Generalized linear mixed models were used to quantify the relationship between data from different wearable sensor modalities and agitation, as well as motor and verbal agitation specifically. Results: Several features from wearable data are significantly associated with agitation, at least the p < .05 level (absolute ß: 0.224-0.753). Additionally, different features are informative depending on the agitation type or the patient the data were collected from. Adding context with key confounding variables (time of day, movement, and temperature) allows for a clearer interpretation of feature differences when a person with dementia is agitated. Discussion and Implications: The features shown to be significantly different, across the study population, suggest possible autonomic nervous system activation when agitated. Differences when splitting the data by agitation type point toward a need for future detection models to tailor to the primary type of agitation expressed. Finally, patient-specific differences in features indicate a need for patient- or group-level model personalization. The findings reported in this study both reinforce and add to the fundamental understanding of and can be used to drive the objective quantification of agitation.

The Effects of a Complex Interactive Multimodal Intervention on Personalized Stress Management Among Health Care Workers in China: Nonrandomized Controlled Study.

BACKGROUND: Health care workers (HCWs) frequently face multiple stressors at work, particularly those working night shifts. HCWs who have experienced distress may find it difficult to adopt stress management approaches, even if they are aware of the effects of stress and coping processes. Therefore, an individualized intervention may be required to assist distressed HCWs in bridging the "knowledge-practice" gap in stress management and effectively alleviating stress symptoms. OBJECTIVE: The main objective of this research was to compare the effects of a complex interactive multimodal intervention (CIMI) to self-guided stress management interventions on stress symptoms of distressed HCWs, as measured by physiological (heart rate variability), psychological (perceived stress, mental distress, and subjective happiness), and sleep disorder (fatigue and sleepiness) indicators. METHODS: We conducted a nonrandomized, controlled study in 2 Chinese general hospitals. The participants in this study were 245 HCWs who fulfilled at least 1 of the 3 dimensions on the Depression, Anxiety, and Stress Scale. All eligible individuals were required to complete a questionnaire and wear a 24-hour Holter device to determine the physiological signs of stress as indexed by heart rate variability at both baseline and after the intervention. The CIMI group received a 12-week online intervention with 4 components-mobile stress management instruction, a web-based WeChat social network, personalized feedback, and a nurse coach, whereas the control group simply received a self-guided intervention. RESULTS: After a 12-week intervention, the Perceived Stress Scale (PSS) scores reduced significantly in the CIMI group (mean difference [MD] -5.31, 95% CI -6.26 to -4.37; P<.001) compared to the baseline levels. The changes in PSS scores before and after the intervention exhibited a significant difference between the CIMI and control groups (d=-0.64; MD -4.03, 95% CI -5.91 to -2.14; P<.001), and the effect was medium. In terms of physiological measures, both the control group (MD -9.56, 95% CI -16.9 to -2.2; P=.01) and the CIMI group (MD -8.45, 95% CI -12.68 to -4.22; P<.001) demonstrated a significant decrease in the standard deviation of normal-to-normal intervals (SDNN) within the normal clinical range; however, there were no significant differences between the 2 groups (d=0.03; MD 1.11, 95% CI -7.38 to 9.59; P=.80). CONCLUSIONS: The CIMI was an effective intervention for improving sleep disorders, as well as parts of the psychological stress measures in distressed HCWs. The findings provide objective evidence for developing a mobile stress management intervention that is adaptable and accessible to distressed HCWs, but its long-term effects should be investigated in future research. TRIAL REGISTRATION: ClinicalTrials.gov NCT05239065; https://clinicaltrials.gov/ct2/show/NCT05239065.

Autonomic Dysfunction in Amyotrophic Lateral Sclerosis - A Case-Control Study.

INTRODUCTION: This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) patients by evaluating sympathetic skin response (SSR). MATERIALS AND METHODS: The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged <60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an absent response was considered abnormal SSR. RESULTS: SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value <0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration. CONCLUSION: ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an association between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the association of abnormal SSR with disease severity, duration, and type.

How to properly evaluate cardiac vagal tone in oncology studies: a state-of-the-art review.

Heart rate variability (HRV) analysis provides an assessment of cardiac vagal tone and consequently global cardiac health as well as systemic condition. In systemic diseases such as cancer and during treatments that affect the whole body, like chemotherapy, the vagus nerve activity is low and deregulated. Some studies focus on using HRV to predict mortality in oncology. However, in cancer patients, systemic alterations substantially increase artifacts during HRV measurement, especially atrial ectopic beats. Moreover, HRV may be altered by various factors (duration and time of measurement, breathing, drugs, and other confounding factors) that alter each metric in different ways. The Standard Deviation of all Normal to Normal intervals (SDNN) is the most commonly used metric to evaluate HRV in oncology, but it does not appear to be specific to the cardiac vagal tone. Thus, cardiac vagal activity diagnosis and vital prognosis of cancer patients can be biased. Our review presents the main HRV metrics that can be currently used in oncology studies and their links with vagus nerve and cancer. We present the influence of external factors and the required duration and time of measurement. Considering all these parameters, this review proposes seven key points for an assessment of HRV and cardiac vagal tone in patients with cancer.

Napping and heart rate variability in elite athletes.

Sleep and autonomic nervous system (ANS) influence each other in a bidirectional fashion. Importantly, it has been proposed that sleep has a beneficial regulatory influence over cardiovascular activity, which is mostly controlled by autonomic regulation through the activity of sympathetic and parasympathetic pathways of the ANS. A well-established method to non-invasively assess cardiac autonomic activity is heart rate variability (HRV) analysis. We aimed to investigate the effect of a 40-min nap opportunity on HRV. Twelve professional basketball players randomly accomplished two conditions: 40-min nap (NAP) and control (CON). Nocturnal sleep and naps were monitored by actigraphic recording and sleep diaries. Total sleep time (TST), time in bed (TIB), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were analyzed. HRV was analyzed in 5-min segments during quiet wake before and after each condition with controlled breathing. Were analysed high (HF) and low frequency (LF) bands, the standard deviation of NN interval (SDNN), HRV index and stress index (SI). Wellness Hooper index and Epworth Sleepiness Scale (ESS) were assessed before and after both conditions. There was no significant difference in TIB, TST, SE, WASO, and VAS between NAP and CON. A significant increase in SDNN, HRV index, and LF and a significant decrease in HF, SI, ESS, and Hooper's stress and fatigue scores were observed from pre- to post-nap. In conclusion, napping reduces sleepiness, stress and fatigue, and might provide an advantage by preparing the body for a much-required sympathetic comeback following peaceful rest.

Functional neurological disorder, physical activity and exercise: What we know and what we can learn from comorbid disorders.

Functional neurological disorder (FND) is a common neurologic disorder associated with many comorbid symptoms including fatigue, pain, headache, and orthostasis. These concurrent symptoms lead patients to accumulate multiple diagnoses comorbid with FND, including fibromyalgia, chronic fatigue syndrome, postural orthostatic tachycardia syndrome, persistent post-concussive symptoms, and chronic pain. The role of physical activity and exercise has not been evaluated in FND populations, though has been studied in certain comorbid conditions. In this traditional narrative literature review, we highlight some existing literature on physical activity in FND, then look to comorbid disorders to highlight the therapeutic potential of physical activity. We then consider abnormalities in the autonomic nervous system (ANS) as a potential pathophysiological explanation for symptoms in FND and comorbid disorders and postulate how physical activity and exercise may provide benefit via autonomic regulation.

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

Analysis of breathing patterns to stabilize cardiovascular changes in physical stress environments : inspiration responds to rapid changes in blood pressure.

The thoracic nerves form a complex neural network that coordinates involuntary muscles such as breathing and the heart. Breathing has various patterns to maintain homeostasis in the human body. This study analyzes changes in the cardiovascular system and breathing patterns induced by stress caused by various mechanical movements performed in daily life and ultimately, the goal is to propose effective breathing patterns and breathing control methods to maintain cardiovascular homeostasis. The participants' age was 26.97 ± 3.93 years, height was 170.24 ± 8.61 cm, and weight was 65.69 ± 13.55 Kg, and there were 62 men and 38 women. Breathing and electrocardiogram were obtained using HiCard+, a biometric monitoring device. The measured electrocardiogram was analyzed for heartbeat interval, which indicates changes in the cardiovascular system, and standard deviation of normal to normal interval (SDNN) and root mean square of the successive differences (rMSSD), which indicate the activity of the autonomic and parasympathetic nervous systems. For respiration, time changes were analyzed as patterns by calculating inspiration and exhalation times. As a result of this study, rapid changes in blood pressure increased SDNN and rMSSD from 0.053 ± 0.06 and 0.056 ± 0.087 to 0.109 ± 0.114 and 0.125 ± 0.170 s, and induced an increase in spontaneous inspiratory time from 1.46 to 1.51 s (p < 0.05). Ultimately, we hope that the results of this study will be used as a breathing control training technique to prevent and manage rapid cardiovascular changes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00379-y.

Sleep Apnea, Autonomic Disturbances, and Blood Pressure Variability.

Augmented blood pressure variability has emerged as a quantity predictive of adverse cardiovascular outcomes. Among the range of intrinsic and extrinsic factors shown to increase night-time, circadian, short-term, and long-term blood pressure variations, the presence and severity of obstructive sleep apnea have emerged as one of the most prevalent and potent. Obstructive sleep apnea alters acutely the normal nocturnal equilibrium between sympathetic and parasympathetic tone, magnifying nocturnal blood pressure oscillations, and induces sustained autonomic aftereffects with the capacity to amplify short-term and intersessional blood pressure variabilities. The object of this brief review is to synthesize the current understanding of the potential interrelations between obstructive sleep apnea, the acute and sustained autonomic disturbances that it elicits, and beat-to-beat blood pressure fluctuation during sleep, nocturnal dipping status, and day-to-day blood pressure variability and the consequences of these perturbations for cardiovascular risk.

Lifelong longitudinal assessment of the contribution of multi-fractal fluctuations to heart rate and heart rate variability in aging mice: role of the sinoatrial node and autonomic nervous system.

Aging is a major risk factor for sinoatrial node (SAN) dysfunction, which can impair heart rate (HR) control and heart rate variability (HRV). HR and HRV are determined by intrinsic SAN function and its regulation by the autonomic nervous system (ANS). The purpose of this study was to use multi-scale multi-fractal detrended fluctuation analysis (MSMFDFA; a complexity-based approach to analyze multi-fractal dynamics) to longitudinally assess changes in multi-fractal HRV properties and SAN function in ECG time series recorded repeatedly across the full adult lifespan in mice. ECGs were recorded in anesthetized mice in baseline conditions and after autonomic nervous system blockade every three months beginning at 6 months of age until the end of life. MSMFDFA was used to assess HRV and SAN function every three months between 6 and 27 months of age. Intrinsic HR (i.e. HR during ANS blockade) remained relatively stable until 15 months of age, and then progressively declined until study endpoint at 27 months of age. MSMFDFA revealed sudden and rapid changes in multi-fractal properties of the ECG RR interval time series in aging mice. In particular, multi-fractal spectrum width (MFSW, a measure of multi-fractality) was relatively stable between 6 months and 15 months of age and then progressively increased at 27 months of age. These changes in MFSW were evident in baseline conditions and during ANS blockade. Thus, intrinsic SAN function declines progressively during aging and is manifested by age-associated changes in multi-fractal HRV across the lifespan in mice, which can be accurately quantified by MSMFDFA.

Computational modeling for the quantitative assessment of cardiac autonomic response to orthostatic stress.

The Autonomic Nervous System (ANS) plays a critical role in regulating cardiac functions. Early detection of ANS dysfunctions is crucial for preventing or slowing the progression of cardiovascular diseases. Current methods for analyzing ANS activity, such as heart rate variability analysis and muscle sympathetic nerve activity recording, face challenges such as poor temporal resolution, invasiveness, and insufficient sensitivity to individual physiological variations, which limit personalized health assessments. This study aims to introduce the open-loop Mathematical Model of Autonomic Regulation of the Cardiac System under Supine-to-stand Maneuver (MMARCS) to overcome the limitations of existing ANS analysis methods. The MMARCS model is designed to offer a balance between physiological fidelity and simplicity, focusing on the ANS cardiac control subsystems' input-output curve. The MMARCS model simplifies the complex internal dynamics of ANS cardiac control by emphasizing input-output relationships and utilizing sensitivity analysis and parameter subset selection to increase model specificity and eliminate redundant parameters. This approach aims to enhance the model's capacity for personalized health assessments. The application of the MMARCS model revealed significant differences in ANS regulation between healthy (14 females and 19 males) and diabetic subjects (8 females and 6 males). Parameters indicated heightened sympathetic activity and diminished parasympathetic response in diabetic subjects compared to healthy subjects (p<0.05), and also suggested a more sensitive and potentially more reactive sympathetic response among diabetic subjects (p<0.05). The MMARCS model represents an innovative computational approach for quantifying ANS functionality, offering potential benefits for clinical measurements of cardiovascular, disease progression monitoring, and home health monitoring via wearable technology. Its balance between physiological accuracy and model simplicity makes it a promising tool for personalized health assessments.

Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients.

Objective.To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF).Approach.We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz (n= 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 (n= 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients (n= 30, age 59 ± 5 years, andn= 32, age 63 ± 7 years, respectively).Main results.In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (-1.0 ± 1.2 bpm,p< 0.001 and -0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (-0.9 ± 1.5 bpm,p< 0.01 and -0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (-1.1 ± 1.2 bpm,p< 0.01 and -0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects.Significance.Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147).