Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure.

PURPOSE: Acute decompensated heart failure (ADHF) is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown whether neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level tragus stimulation on inflammation and oxidative stress in ADHF. METHODS: Nineteen patients with ejection fraction < 40% were randomized to neuromodulation 4 h twice daily (6-10 a.m. and 6-10 p.m.) (n = 8) or sham stimulation (n = 11) during hospital admission. All patients received standard-of-care treatment. Blood samples were collected at admission and discharge. Serum cytokines were assayed using standard immunosorbent techniques. Reactive oxygen species inducibility from cultured coronary endothelial cells exposed to patient sera was determined using a dihydrodichlorofluorescein probe test (expressed as fluorescein units). RESULTS: Compared to sham stimulation, neuromodulation was associated with a significant reduction of circulating serum interleukin-6 levels (-78% vs. -9%; p = 0.012). Similarly, neuromodulation led to a reduction of endothelial cell oxidative stress in the neuromodulation group (1363 units to 978 units, p = 0.003) compared to sham stimulation (1146 units to 1083 units, p = 0.094). No significant differences in heart rate, blood pressure, or renal function were noted between the two groups. CONCLUSION: In this proof-of-concept pilot study, in acute decompensated heart failure, neuromodulation was feasible and safe and was associated with a reduction in systemic inflammation and attenuation of coronary endothelial cellular oxidative stress. CLINICAL TRIAL REGISTRATION: NCT02898181.

Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure.

Purpose: Acute decompensated heart failure is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown if neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level Tragus stimulation on inflammation and oxidative stress in ADHF. Methods: 19 patients with ejection fraction < 40% were randomized to neuromodulation- 4 hours twice daily (6 AM-10 AM and 6 PM-10 PM) (n = 8) or sham stimulation (n = 11) during hospital admission. All patients received standard-of-care treatment. Blood samples were collected at admission and discharge. Serum cytokines were assayed using standard immunosorbent techniques. Reactive oxygen species inducibility from cultured coronary endothelial cells exposed to patient sera was determined using dihydrodichlorofluorescein probe test (expressed as fluorescein units). Results: Compared to sham stimulation, neuromodulation was associated with a significant reduction of circulating serum Interleukin-6 levels (-78% vs -9%; p = 0.012). Similarly, neuromodulation led to reduction of endothelial cell oxidative stress, in the neuromodulation group (1363 units to 978 units, p = 0.003) compared to sham stimulation (1146 units to 1083 units, p = 0.094). No significant difference in heart rate, blood pressure or renal function were noted between the two groups. Conclusion: In this proof-of-concept pilot study, in acute systolic heart failure, neuromodulation was feasible and safe and was associated with a reduction in systemic inflammation and attenuation of cellular oxidative stress. Clinical trial: NCT02898181.

Protein kinase A: A potential marker of sympathovagal imbalance in heart failure.

Mitigation of cardiac autonomic dysregulation by neuromodulation technologies is emerging as a new therapeutic modality of heart failure (HF). This recent progress has necessitated the identification of a biomarker for the quantification of sympathovagal balance, the potential target of 'neuromodulation' strategies. The currently available autonomic nervous system assessment parameters do not truly reflect the sympathovagal balance of the ventricle. Protein kinase A (PKA) is an intracellular enzyme that plays a major role in the pathophysiology of functional and structural ventricular remodeling in HF. Interestingly, sympathetic and parasympathetic activations exert reciprocal influence on the activity of PKA. The current review attempts to evaluate the potential concept and feasibility of using in vitro assessment of PKA activity as a marker of sympathovagal balance in HF.

Altered Heart Rate Variability During Rest in Schizophrenia: A State Marker.

BACKGROUND: Autonomic nervous system (ANS) imbalance has been reported in a number of psychiatric disorders such as depression, schizophrenia, panic disorder, etc. Autonomic dysfunction in schizophrenia has been associated with the symptoms and manifestation of psychosis. Heart rate variability (HRV) as a tool has been widely used to assess ANS activity and the effect of disease on the sympathovagal balance. Therefore, in the present study, HRV derived from electrocardiogram (ECG) lead II at rest was investigated in order to understand the changes in frequency domain measures in patients with schizophrenia and their first-degree relatives compared to healthy controls. METHODS: Twenty-five patients with schizophrenia, 24 first-degree relatives of patients, and 24 healthy controls (Diagnostic and Statistical Manual of Mental Disorders (DSM)-5; 18-45 years) were included in the study. HRV of the subjects was measured after five minutes of rest. ECG lead II was recorded for five minutes and HRV was analysed in the frequency domain: low frequency (LF), high frequency (HF), total power, and LF/HF ratio. HRV parameters and heart rate were statistically analysed for group comparisons using general linear model multivariate analysis. RESULTS: Patients had significantly higher minimum heart rate and lower HF (normalized units (nu)) compared to their first-degree relatives. A trend was observed in HF (nu) with the lowest in patients followed by healthy controls and first-degree relatives and LF/HF ratio was the highest in patients followed by healthy controls and first-degree relatives, although not statistically significant. No significant difference was found between first-degree relatives and healthy controls. CONCLUSION: The alteration of HRV in schizophrenia could be attributed to reduction in vagal tone and sympathetic dominance, which in turn could serve as state markers of schizophrenia.

Altered Cardiac Autonomic Regulation in Individuals with Myasthenia Gravis-A Systematic Review and Meta-Analysis.

The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and healthy controls (HCs). Two reviewers searched four electronic databases, namely PubMed, Web of Science, EMBASE, and SCOPUS, from database inception to 7 July 2023 for studies investigating cardiovascular autonomic parameters in MG vs. HCs. A random-effects meta-analysis was performed to compute Hedges' g ± 95% confidence intervals (CI). Out of a total of 2200 records, 8 observational studies with a sample size of 301 patients with MG and 454 HCs were included in the systematic review. Meta-analysis revealed lower values of expiration/inspiration ratio (g = -0.45, I2 = 74.7), baroreflex sensitivity (g = -0.56, 95%CI -0.80, -0.33; I2 = 0.3), percentage of adjacent NN intervals differing by more than 50 ms (g = -1.2, I2 = 82.8), square root of the mean of squared differences between successive beat intervals (g = -1.94, I2 = 95.1), mean of the standard deviations of all NN intervals (g = -0.83, 95%CI -1.37, -0.28; I2 = 55.5), and high frequency of HRV during tilt (g = -0.75, 95%CI -0.11, -0.39; I2 = 0). MG patients vs. HCs had higher systolic blood pressure (g = 0.39; I2 = 56.1), sympathovagal balance at rest/during tilt (LF/HF-RRIsupine, g = 0.44; I2 = 0; LF/HF-RRItilt, g = 0.86; I2 = 0; LF/HFtilt, g = 0.40; I2 = 0). As a group, MG patients have altered cardiac autonomic function, including decreased parasympathetic function, lower baroreflex sensitivity, and higher sympathovagal balance at rest and during orthostatic challenges.

Brain Connectivity Correlates of Breathing and Cardiac Irregularities in SUDEP: A Resting-State fMRI Study.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of premature mortality among people with epilepsy. Evidence from witnessed and monitored SUDEP cases indicate seizure-induced cardiovascular and respiratory failures; yet, the underlying mechanisms remain obscure. SUDEP occurs often during the night and early morning hours, suggesting that sleep or circadian rhythm-induced changes in physiology contribute to the fatal event. Resting-state fMRI studies have found altered functional connectivity between brain structures involved in cardiorespiratory regulation in later SUDEP cases and in individuals at high-risk of SUDEP. However, those connectivity findings have not been related to changes in cardiovascular or respiratory patterns. Here, we compared fMRI patterns of brain connectivity associated with regular and irregular cardiorespiratory rhythms in SUDEP cases with those of living epilepsy patients of varying SUDEP risk, and healthy controls. We analysed resting-state fMRI data from 98 patients with epilepsy (9 who subsequently succumbed to SUDEP, 43 categorized as low SUDEP risk (no tonic-clonic seizures (TCS) in the year preceding the fMRI scan), and 46 as high SUDEP risk (>3 TCS in the year preceding the scan)) and 25 healthy controls. The global signal amplitude (GSA), defined as the moving standard deviation of the fMRI global signal, was used to identify periods with regular ('low state') and irregular ('high state') cardiorespiratory rhythms. Correlation maps were derived from seeds in twelve regions with a key role in autonomic or respiratory regulation, for the low and high states. Following principal component analysis, component weights were compared between the groups. We found widespread alterations in connectivity of precuneus/posterior cingulate cortex in epilepsy compared to controls, in the low state (regular cardiorespiratory activity). In the low state, and to a lesser degree in the high state, reduced anterior insula connectivity (mainly with anterior and posterior cingulate cortex) in epilepsy appeared, relative to healthy controls. For SUDEP cases, the insula connectivity differences were inversely related to the interval between the fMRI scan and death. The findings suggest that anterior insula connectivity measures may provide a biomarker of SUDEP risk. The neural correlates of autonomic brain structures associated with different cardiorespiratory rhythms may shed light on the mechanisms underlying terminal apnea observed in SUDEP.

Characterization of autonomic states by complex sympathetic and parasympathetic dynamics.

Assessment of heartbeat dynamics provides a promising framework for non-invasive monitoring of cardiovascular and autonomic states. Nevertheless, the non-specificity of such measurements among clinical populations and healthy conditions associated with different autonomic states severely limits their applicability and exploitation in naturalistic conditions. This limitation arises especially when pathological or postural change-related sympathetic hyperactivity is compared to autonomic changes across age and experimental conditions. In this frame, we investigate the intrinsic irregularity and complexity of cardiac sympathetic and vagal activity series in different populations, which are associated with different cardiac autonomic dynamics. Sample entropy, fuzzy entropy, and distribution entropy are calculated on the recently proposed sympathetic and parasympathetic activity indices (SAI and PAI) series, which are derived from publicly available heartbeat series of congestive heart failure patients, elderly and young subjects watching a movie in the supine position, and healthy subjects undergoing slow postural changes. Results show statistically significant differences between pathological/old subjects and young subjects in the resting state and during slow tilt, with interesting trends in SAI- and PAI-related entropy values. Moreover, while CHF patients and healthy subjects in upright position show the higher cardiac sympathetic activity, elderly and young subjects in resting state showed higher vagal activity. We conclude that quantification of intrinsic cardiac complexity from sympathetic and vagal dynamics may provide new physiology insights and improve on the non-specificity of heartbeat-derived biomarkers.

Automated analysis of finger blood pressure recordings provides insight in determinants of baroreflex sensitivity and heart rate variability-the HELIUS study.

Sympathovagal balance is important in the pathogenesis of hypertension and independently associated with mortality. We evaluated the value of automated analysis of cross-correlation baroreflex sensitivity (xBRS) and heart rate variability (HRV) and its relationship with clinical covariates in 13,326 participants from the multi-ethnic HELIUS study. Finger blood pressure (BP) was continuously recorded, from which xBRS, standard deviation of normal-to-normal intervals (SDNN), and squared root of mean squared successive difference between normal-to-normal intervals (RMSDD) were determined. A subset of 3356 recordings > 300 s was used to derive the minimally required duration by comparing shortened to complete recordings, defined as intraclass correlation (ICC) > 0.90. For xBRS and SDNN, 120 s and 180 s were required (ICC 0.93); for RMSDD, 60 s (ICC 0.94) was sufficient. We included 10,252 participants (median age 46 years, 54% women) with a recording > 180 s for the regression. xBRS, SDNN, and RMSDD decreased linearly up to 50 years of age. For xBRS, there was a signification interaction with sex, with for every 10 years a decrease of 4.3 ms/mmHg (95%CI 4.0-4.6) for men and 5.9 ms/mmHg (95%CI 5.6-6.1) for women. Using splines, we observed sex-dependent nonlinearities in the relation with BP, waist-to-hip-ratio, and body mass index. Future studies can help unravel the dynamics of these relations and assess their predictive value. Panel 1 depicts automatic analysis and filtering of finger BP recordings, panel 2 depicts computation of xBRS from interpolated beat to beat data of systolic BP and interbeat interval, and (IBI) SDNN and RMSDD are computed directly from the filtered IBI dataset. Panel 3 depicts the results of large-scale analysis and relation of xBRS with age, sex, blood pressure and body mass index.

The Impact of Energy Drink Consumption on Heart Rate Variability after Exercise.

The effects of caffeine or caffeine-based energy drinks on the recovery of autonomic nervous system balance after exercise have been the subject of several studies which yielded inconclusive results. In a recent study by Porto et al., the impact of a caffeine-based energy drink on heart rate variability (HRV) before and after a moderate aerobic exercise (running on a treadmill) has been studied in a randomized, crossover trial on healthy and active young males. It was concluded that an energy drink consumed before exercise did not affect HRV indices during post-exercise recovery. However, this conclusion is somewhat inconsistent with the reported data and hence may be misleading. Here, I discuss the shortcomings of that study and point out some inaccuracies in the reported results. Considering the above, it appears that energy drink consumption may affect some HRV indices after exercise, at least those related to high frequency changes in the autonomic activity.

Resting heart rate variability as a diagnostic marker of cardiovascular dysautonomia in postural tachycardia syndrome.

OBJECTIVES: Postural orthostatic tachycardia syndrome (POTS) is a disorder of the autonomic nervous system characterised by orthostatic intolerance and orthostatic tachycardia without hypotension. Heart rate variability (HRV) is the most reliable and objective tool for assessing autonomic dysfunction severity. In the present study, we aimed to investigate HRV changes in resting supine position, predicting severity and cardiovascular risk in patients with POTS. METHODS: We compared 100 POTS patients with 160 healthy controls matched for age and gender in a case-control design. Along with clinical characterization, heart rate variability was evaluated using ambulatory 5 min ECG in lead II and expressed in frequency and time-domain measures. RESULTS: The resting heart rate of patients with POTS was significantly higher than that of healthy controls. In HRV measures, root mean square successive difference of RR intervals (RMSSD), total and high frequency (HF) powers were statistically lower with an increased low frequency (LF) to high-frequency ratio in patients with POTS compared to healthy controls. Further, stepwise logistic regression analysis showed increased basal HR and LF/HF as significant predictors of POTS and its severity. CONCLUSIONS: This is the first study on a large cohort of patients with POTS from India wherein HRV was assessed. The study showed reduced parasympathetic activity and increased sympathetic activity in patients with POTS compared to healthy controls. These findings of increased resting heart rate and LF/HF were found to be potential predictors of POTS and future cardiovascular risks, which need to be replicated in a larger and more homogenized cohort.

Non-invasive Vagus Nerve Simulation in Postural Orthostatic Tachycardia Syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a chronic debilitating condition of orthostatic intolerance, predominantly affecting young females. Other than postural tachycardia, symptoms of POTS include a spectrum of non-cardiac, systemic and neuropsychiatric features. Despite the availability of widespread pharmacological and non-pharmacological therapeutic options, the management of POTS remains challenging. Exaggerated parasympathetic withdrawal and sympathetic overdrive during postural stress are principal mechanisms of postural tachycardia in POTS. Non-invasive, transcutaneous, vagus nerve stimulation (tVNS) is known to restore sympathovagal balance and is emerging as a novel therapeutic strategy in cardiovascular conditions including arrhythmias and heart failure. Furthermore, tVNS also exerts immunomodulatory and anti-inflammatory effects. This review explores the effects of tVNS on the pathophysiology of POTS and its potential as an alternative non-pharmacological option in this condition.

Heart rate variability (HRV): Checklist for observational and experimental studies.

Ford et al. provided (via review study) an overview of the psychiatric features associated with encephalitis mediated by autoantibodies targeting neuronal cellsurface antigens and describe indicators of potential immunopathology underlying psychiatric manifestations. In this scientific context of psychiatric manifestations, studies strongly suggest that scientists include heart rate variability assessment in these patients (because this is a way to evaluate the autonomic nervous system's sympathetic and parasympathetic components). Ford's paper has significant clinical relevance and will generate new studies (experimental and observational) on psychiatric manifestations; therefore, we have six suggestions for the authors and other scientists/researchers who will use this article to perform further research using the heart rate variability assessment. Our objective is to contribute to scientific research and help to strengthen the new studies that will emerge.

Sympathovagal Balance Is a Strong Predictor of Post High-Volume Endurance Exercise Cardiac Arrhythmia.

Regular physical activity is important for cardiovascular health. However, high-volume endurance exercise has been associated with increased number of electrocardiogram (ECG) abnormalities, including disturbances in cardiac rhythm (arrhythmias) and abnormalities in ECG pattern. The aim of this study was to assess if heart rate variability (HRV) is associated with ECG abnormalities. Fifteen participants with previous cycling experience completed a 21-day high-volume endurance exercise cycle over 3,515 km. Participants wore a 5-lead Holter monitor for 24 h pre- and post-exercise, which was used to quantify ECG abnormalities and export sinus R-to-R intervals (NN) used to calculate HRV characteristics. As noise is prevalent in 24-h HRV recordings, both 24-h and heart rate collected during stable periods of time (i.e., deep sleep) were examined. Participants experienced significantly more arrhythmias post high-volume endurance exercise (median = 35) compared to pre (median = 12; p = 0.041). All 24-h and deep sleep HRV outcomes were not different pre-to-post high-volume endurance exercise (p > 0.05). Strong and significant associations with arrhythmia number post-exercise were found for total arrhythmia (total arrhythmia number pre-exercise, ρ = 0.79; age, ρ = 0.73), supraventricular arrhythmia (supraventricular arrhythmia number pre-exercise: ρ = 0.74; age: ρ = 0.66), and ventricular arrhythmia (age: ρ = 0.54). As a result, age and arrhythmia number pre-exercise were controlled for in hierarchical regression, which revealed that only deep sleep derived low frequency to high frequency (LF/HF) ratio post high-volume endurance exercise predicted post total arrhythmia number (B = 0.63, R 2Δ = 34%, p = 0.013) and supraventricular arrhythmia number (B = 0.77, R 2Δ = 69%, p < 0.001). In this study of recreationally active people, only deep sleep derived LF/HF ratio was associated with more total and supraventricular arrhythmias after high-volume endurance exercise. This finding suggests that measurement of sympathovagal balance during deep sleep might be useful to monitor arrhythmia risk after prolonged high-volume endurance exercise performance.

Effects of feeds, supplemented with humic substances and calcium carbonate, on performance, egg quality and heart rate variability in laying hens.

This study aimed to determine the effects of in-feed inclusion of humic substances (HS) and/or calcium carbonate (CaCO3) on the performance and welfare of laying hens. A total number of 144 Hy-Line Brown laying hens (55 weeks old) were randomly assigned to four treatments, T1-T4 (36 birds per treatment). T1 hens were fed on a control diet without HS or CaCO3, T2 hens were fed on the control diet + 2.00 g per bird per day CaCO3, T3 hens were fed on the control diet + 0.20% HS and T4 hens were fed on the control diet + 0.20% HS + 2.00 g/bird/day CaCO3. The experiment started after 15 days of adaptation and lasted 8 weeks. The parameters evaluated were percentage of hen-day egg production, food consumption, mortality, egg quality parameters and heart rate variability (welfare indicator). Hens in the T3 group showed a significantly lower feed intake than those in the other three groups, however, significantly higher daily egg production was recorded in groups T3 and T4 compared to T1 and T2. Eggshell quality characteristics were significantly improved by HS supplementation and eggs laid by hens in groups T1, and T4 presented paler yolk and shell color than those in the other groups. In conclusion, these results indicated that in-feed inclusion of HS had a beneficial effect on laying hens' productive performance including egg production and eggshells quality.

Altered Relationship Between Heart Rate Variability and fMRI-Based Functional Connectivity in People With Epilepsy.

Background: Disruptions in central autonomic processes in people with epilepsy have been studied through evaluation of heart rate variability (HRV). Decreased HRV appears in epilepsy compared to healthy controls, suggesting a shift in autonomic balance toward sympathetic dominance; recent studies have associated HRV changes with seizure severity and outcome of interventions. However, the processes underlying these autonomic changes remain unclear. We examined the nature of these changes by assessing alterations in whole-brain functional connectivity, and relating those alterations to HRV. Methods: We examined regional brain activity and functional organization in 28 drug-resistant epilepsy patients and 16 healthy controls using resting-state functional magnetic resonance imaging (fMRI). We employed an HRV state-dependent functional connectivity (FC) framework with low and high HRV states derived from the following four cardiac-related variables: 1. RR interval, 2. root mean square of successive differences (RMSSD), 4. low-frequency HRV (0.04-0.15 Hz; LF-HRV) and high-frequency HRV (0.15-0.40 Hz; HF-HRV). The effect of group (epilepsy vs. controls), HRV state (low vs. high) and the interactions of group and state were assessed using a mixed analysis of variance (ANOVA). We assessed FC within and between 7 large-scale functional networks consisting of cortical regions and 4 subcortical networks, the amygdala, hippocampus, basal ganglia and thalamus networks. Results: Consistent with previous studies, decreased RR interval (increased heart rate) and decreased HF-HRV appeared in people with epilepsy compared to healthy controls. For both groups, fluctuations in heart rate were positively correlated with BOLD activity in bilateral thalamus and regions of the cerebellum, and negatively correlated with BOLD activity in the insula, putamen, superior temporal gyrus and inferior frontal gyrus. Connectivity strength in patients between right thalamus and ventral attention network (mainly insula) increased in the high LF-HRV state compared to low LF-HRV; the opposite trend appeared in healthy controls. A similar pattern emerged for connectivity between the thalamus and basal ganglia. Conclusion: The findings suggest that resting connectivity patterns between the thalamus and other structures underlying HRV expression are modified in people with drug-resistant epilepsy compared to healthy controls.

Sex-Specific Autonomic Responses to Acute Resistance Exercise.

Background and Objectives: Acute resistance exercise (RE) reduces vagal modulation and increases sympathovagal balance, which increases the risk for arrythmias. Few studies have examined sex differences in autonomic modulation after acute RE. The purpose of this investigation was to examine sex-specific responses to acute RE on autonomic modulation. Materials and Methods: Twenty-one resistance-trained individuals (men n = 11, women n = 10) between the ages of 19 and 25 y were analyzed for autonomic modulation in response to acute RE and a control (CON). Measures of autonomic modulation were collected at rest, 15 (R15), and 30 (R30) min following both conditions. Heart rate (HR), log transformed root mean square of successive differences (lnRMSSD), total power (lnTP), low-frequency power (lnLF), high-frequency power (lnHF), sample entropy (SampEn), and Lempel-Ziv entropy (LZEn) were measured at all time points. A three-way repeated analysis of variance (ANOVA) was used to analyze sex (men, women) across condition (RE, CON) and time (Rest, R15, R30). Results: The results are similar for all heart rate variability (HRV) variables at rest for both conditions (RE, CON). SampEn was significantly higher in men compared to women at rest for both conditions (p = 0.03), with no differences in LZEn (p > 0.05). There were no significant (p > 0.05) three-way interactions on any variables. Condition by time interactions demonstrated that both sexes increase in HR (p = 0.0001) and lnLF/HF ratio (p = 0.001), but decreases in lnRMSSD (p = 0.0001), lnTP (p < 0.0001), lnLF (p < 0.0001), lnHF (p = 0.0001), and LZEn (p = 0.009) at R15 and R30 compared to rest following acute RE and were different from CON. Condition by time interaction (p = 0.017) demonstrated that SampEn was attenuated at R15 compared to rest, and the CON, but not R30 following acute RE. Conclusion: Although SampEn is more complex at rest in men compared to women, autonomic modulation responses between sexes following acute RE appear to be similar.

The D allele of angiotensin-converting enzyme gene is associated with a worse autonomic heart control in community-based older adults.

The relationship between the Renin-Angiotensin-Aldosterone System (RAAS) and modulation of the Autonomic Nervous System (ANS) is reported as complex and bidirectional. Thus, the present study aimed to compare autonomous heart control, through symbolic analysis parameters, in the older adults carrying different ACE I/D gene polymorphisms (rs4646994). Two hundred four older adults comprised the study population and were grouped according to the ACE I/D gene polymorphism: II + ID genotype and DD genotype. Successive RR intervals were recorded along 5 min and analyzed with Symbolic Analysis (SA) method. 0 V%, 1 V% and 2 V% patterns were quantified and compared between groups. A linear mixed model analysis was used to determine between-group differences in symbolic analysis parameters (0 V%, 1 V% and 2 V%), taken groups as fixed factor and sex, use of ACE inhibitors and Angiotensin II receptor type I blockers as random factors. The Bayesian analysis was carried out to check the magnitude of the evidence. The results of this study indicate that older adults carrying the DD genotype have statistically greater sympathetic modulation (0 V%) and poor sympathovagal balance (1 V%), but the Bayesian analysis indicate only an anecdotal effect. Sympathetic predominance is recognized a worrying condition, since may predisposes to cardiovascular risk.

Effects of central apneas on sympathovagal balance and hemodynamics at night: impact of underlying systolic heart failure.

BACKGROUND: Increased sympathetic drive is the key determinant of systolic heart failure progression, being associated with worse functional status, arrhythmias, and increased mortality. Central sleep apnea is highly prevalent in systolic heart failure, and its effects on sympathovagal balance (SVB) and hemodynamics might depend on relative phase duration and background pathophysiology. OBJECTIVE: This study compared the effects of central apneas in patients with and without systolic heart failure on SVB and hemodynamics during sleep. METHODS: During polysomnography, measures of SVB (heart rate and diastolic blood pressure variability) were non-invasively recorded and analyzed along with baroreceptor reflex sensitivity and hemodynamic parameters (stroke volume index, cardiac index, total peripheral resistance index). Data analysis focused on stable non-rapid eye movement N2 sleep, comparing normal breathing with central sleep apnea in subjects with and without systolic heart failure. RESULTS: Ten patients were enrolled per group. In heart failure patients, central apneas had neutral effects on SVB (all p > 0.05 for the high, low, and very low frequency components of heart rate and diastolic blood pressure variability). Patients without heart failure showed an increase in very low and low frequency components of diastolic blood pressure variability in response to central apneas (63 ± 18 vs. 39 ± 9%; p = 0.001, 43 ± 12 vs. 31 ± 15%; p = 0.002). In all patients, central apneas had neutral hemodynamic effects when analyzed over a period of 10 min, but had significant acute hemodynamic effects. CONCLUSION: Effects of central apneas on SVB during sleep depend on underlying systolic heart failure, with neutral effects in heart failure and increased sympathetic drive in idiopathic central apneas.

Effects of nasal high flow on sympathovagal balance, sleep, and sleep-related breathing in patients with precapillary pulmonary hypertension.

BACKGROUND: In precapillary pulmonary hypertension (PH), nasal high flow therapy (NHF) may favorably alter sympathovagal balance (SVB) and sleep-related breathing through washout of anatomical dead space and alleviation of obstructive sleep apnea (OSA) due to generation of positive airway pressure. OBJECTIVES: To investigate the effects of NHF on SVB, sleep, and OSA in patients with PH, and compare them with those of positive airway pressure therapy (PAP). METHODS: Twelve patients with PH (Nice class I or IV) and confirmed OSA underwent full polysomnography, and noninvasive monitoring of SVB parameters (spectral analysis of heart rate, diastolic blood pressure variability). Study nights were randomly split into four 2-h segments with no treatment, PAP, NHF 20 L/min, or NHF 50 L/min. In-depth SVB analysis was conducted on 10-min epochs during daytime and stable N2 sleep at nighttime. RESULTS: At daytime and compared with no treatment, NHF20 and NHF50 were associated with a flow-dependent increase in peripheral oxygen saturation but a shift in SVB towards increased sympathetic drive. At nighttime, NHF20 was associated with increased parasympathetic drive and improvements in sleep efficiency, but did not alter OSA severity. NHF50 was poorly tolerated. PAP therapy improved OSA but had heterogenous effects on SVB and neutral effects on sleep outcomes. Hemodynamic effects were neutral for all interventions. CONCLUSIONS: In sleeping PH patients with OSA NHF20 but not NHF50 leads to decreased sympathetic drive likely due to washout of anatomical dead space. NHF was not effective in lowering the apnea-hypopnoea index and NHF50 was poorly tolerated.