Sleep apnea in heart failure increases heart rate variability and sympathetic dominance

AIMS: Sleep disordered breathing (SDB) is common in heart failure and ventilation is known to influence heart rate. Our aims were to assess the influence of SDB on heart rate variability (HRV) and to determine whether central sleep apnea (CSA) and obstructive sleep apnea (OSA) produced different patterns of HRV. METHODS AND RESULTS: Overnight polysomnography was performed in 21 patients with heart failure and SDB. Two 10-minute segments each of SDB and stable breathing from each patient were visually identified and ECG signal exported for HRV analysis. SDB increased total power (TP) with very low frequency (VLF) power accounting for the greatest increase (1.89+/-0.54 vs 2.96+/-0.46 ms2, P <0.001); LF/HF ratio increased during SDB (1.2+/-1.0 vs 2.7+/-2.1, P <0.001). Compared to OSA, CSA was associated with lower absolute LF (2.10+/-0.47 vs 2.52+/-0.55 ms2, P = 0.049) and HF power (1.69+/-0.41 vs 2.34+/-0.58 ms2, P = 0.004), increased VLF% (78.9%+/-13.4% vs 60.9%+/-19.2%, P = 0.008), decreased HF% (6.9%+/-7.8% vs 16.0%+/-11.7%, P = 0.046) with a trend to higher LF/HF ratio. CONCLUSIONS: SDB increases HRV in the setting of increased sympathetic dominance. HRV in CSA and OSA have unique HRV patterns which are likely to reflect the different pathophysiological mechanisms involved.     

Changes in resting heart rate variability across the menstrual cycle

Heart rate variability (HRV) is a noninvasive indicator of autonomic control. This study examines HRV changes across a normal menstrual cycle and proposes a novel piecewise function controlling for the effects of breathing on HRV spectral parameters. A resting ECG was collected from 13 women at five points in their menstrual cycle. Both heart rate and breathing rate increased across the cycle (p < .01) while time‐domain variability decreased (p = .04). Use of the piecewise function for breathing rate in HRV spectral analysis was confirmed by a substantial increase in model goodness‐of‐fit. HRV spectral parameters, controlled for breathing with the piecewise function, confirm that the decrease in variability is likely due to a parasympathetic withdrawal, since high frequency HRV decreases (p = .02).     

Inclusion of a rest period in diaphragmatic breathing increases high frequency heart rate variability: Implications for behavioral therapy

Heart rate variability (HRV) is associated with positive physiological and psychological effects. HRV is affected by breathing parameters, yet debate remains regarding the best breathing interventions for strengthening HRV. The objective of the current study was to test whether the inclusion of a postexhalation rest period was effective at increasing HRV, while controlling for breathing rate. A within‐subject crossover design was used with 40 participants who were assigned randomly to a breathing pattern including a postexhalation rest period or a breathing pattern that omitted the postexhalation rest period. Participants completed training on each breathing pattern, practiced for 6 min, and sat quietly during a 5‐min washout period between practices. Participants were given instructions for diaphragmatic breathing at a pace of six breaths/minute with or without a postexhalation rest period. Recordings of heart rate, breathing rate, HF‐HRV, RMSSD, LF‐HRV, and SDNN were collected before and during each of the breathing trials. HRV indices were derived from Lead 1 ECG recordings. Pairwise contrasts showed that inclusion of a postexhalation rest period significantly decreased heart rate (p < .001) and increased HF‐HRV (p < .05). No differences were found for breathing rates (p > .05), RMSSD (p > .05), and SDNN (p > .05). Results indicated that omission of the postexhalation rest period resulted in higher LF‐HRV (p < .05). A postexhalation rest period improves HF‐HRV, commonly associated with self‐regulatory control, yet the importance of a postexhalation rest period requires further exploration.     

Cross-correlation of EEG frequency bands and heart rate variability for sleep apnoea classification

Sleep apnoea is a sleep breathing disorder which causes changes in cardiac and neuronal activity and discontinuities in sleep pattern when observed via electrocardiogram (ECG) and electroencephalogram (EEG). Using both statistical analysis and Gaussian discriminative modelling approaches, this paper presents a pilot study of assessing the cross-correlation between EEG frequency bands and heart rate variability (HRV) in normal and sleep apnoea clinical patients. For the study we used EEG (delta, theta, alpha, sigma and beta) and HRV (LF_nu, HF_nu and LF/HF) features from the spectral analysis. The statistical analysis in different sleep stages highlighted that in sleep apnoea patients, the EEG delta, sigma and beta bands exhibited a strong correlation with HRV features. Then the correlation between EEG frequency bands and HRV features were examined for sleep apnoea classification using univariate and multivariate Gaussian models (UGs and MGs). The MG outperformed the UG in the classification. When EEG and HRV features were combined and modelled with MG, we achieved 64% correct classification accuracy, which is 2 or 8% improvement with respect to using only EEG or ECG features. When delta and acceleration coefficients of the EEG features were incorporated, then the overall accuracy improved to 71%.     

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

Time‐varying correlations between delta EEG power and heart rate variability in midlife women: The SWAN Sleep Study

No studies have evaluated the dynamic, time‐varying relationship between delta electroencephalographic (EEG) sleep and high frequency heart rate variability (HF‐HRV) in women. Delta EEG and HF‐HRV were measured during sleep in 197 midlife women (M_age = 52.1, SD = 2.2). Delta EEG–HF‐HRV correlations in nonrapid eye movement (NREM) sleep were modeled as whole‐night averages and as continuous functions of time. The whole‐night delta EEG–HF‐HRV correlation was positive. The strongest correlations were observed during the first NREM sleep period preceding and following peak delta power. Time‐varying correlations between delta EEG–HF‐HRV were stronger in participants with sleep‐disordered breathing and self‐reported insomnia compared to healthy controls. The dynamic interplay between sleep and autonomic activity can be modeled across the night to examine within‐ and between‐participant differences including individuals with and without sleep disorders.     

Age-related changes in cardiac autonomic control during sleep

Aging is commonly associated with decreased sleep quality and increased periodic breathing (PB) that can influence heart rate variability (HRV). Cardiac autonomic control, as inferred from HRV analysis, was determined, taking into account the sleep quality and breathing patterns. Two groups of 12 young (21.1 +/- 0.8 years) and 12 older (64.9 +/- 1.9 years) volunteers underwent electroencephalographic, cardiac, and respiratory recordings during one experimental night. Time and frequency domain indices of HRV were calculated in 5-min segments, together with electroencephalographic and respiratory power spectra. In the elderly, large R-R oscillations in the very-low frequency (VLF) range emerged, that reflected the frequency of PB observed in 18% of the sleep time. PB occurred more frequently during rapid eye movement sleep (REM) sleep and caused a significant (P < 0.02) increase in the standard deviation of normal R-R intervals (SDNN) and absolute low-frequency (LF) power. With normal respiratory patterns, SDNN, absolute VLF, LF, and high frequency (HF) power fell during each sleep stage (P < 0.01) compared with young subjects, with no significant sleep-stage dependent variations. An overall decrease (P < 0.01) in normalized HF/(LF + HF) was observed in the elderly, suggesting a predominant loss of parasympathetic activity which may be related to decreased slow-wave sleep duration. These results indicate that two distinct breathing features, implying different levels of autonomic drive to the heart, influence HRV in the elderly during sleep. The breathing pattern must be considered to correctly interpret HRV in the elderly.     

A common neural substrate for elevated PTSD symptoms and reduced pulse rate variability in combat-exposed veterans

Previous studies have identified reduced heart rate variability (HRV) in post-traumatic stress disorder (PTSD), which may temporally precede the onset of the disorder. A separate line of functional neuroimaging research in PTSD has consistently demonstrated hypoactivation of the ventromedial prefrontal cortex (vmPFC), a key aspect of a descending neuromodulatory system that exerts inhibitory control over heart rate. No research to date, however, has simultaneously investigated whether altered vmPFC activation is associated with reduced HRV and elevated PTSD symptoms in the same individuals. Here, we collected fMRI data during alternating conditions of threat of shock and safety from shock in 51 male combat-exposed veterans with either high or low levels of PTSD symptoms. Pulse rate variability (PRV)—a HRV surrogate calculated from pulse oximetry—was assessed during a subsequent resting scan. Correlational analyses tested for hypothesized relationships between reduced vmPFC activation, lower PRV, and elevated PTSD symptomatology. We found that PTSD re-experiencing symptoms were inversely associated with high-frequency (HF)-PRV, thought to primarily reflect parasympathetic control of heart rate, in veterans with elevated PTSD symptoms. Reduced vmPFC activation for the contrast of safety-threat was associated both with lower HF-PRV and elevated PTSD re-experiencing symptoms. These results tie together previous observations of reduced HRV/PRV and impaired vmPFC function in PTSD and call for further research on reciprocal brain-body relationships in understanding PTSD pathophysiology.     

Variability of QT interval duration in obstructive sleep apnea: an indicator of disease severity

STUDY OBJECTIVE: To determine OSA-related changes in variability of QT interval duration and in heart rate variability (HRV), and to evaluate the relationship of these parameters to disease severity. DESIGN: Retrospective analysis of diagnostic sleep records. SETTINGS: Clinical sleep laboratory in a hospital setting. PATIENTS: Twenty patients (12 males and 8 females) without significant comorbidities who were undergoing polysomnography were studied. MEASUREMENTS AND RESULTS: Standard heart rate variability measures and QT variability (Berger algorithm) were computed over consecutive 5-minute ECG epochs throughout the night. The effect of sleep stage and the relationship between these parameters and the severity of OSA as determined by the respiratory disturbance index (RDI) were explored. Further, a linear regression model of QT variability was developed. Severity of OSA (RDI) was 49 +/- 28 (range from 17-107) events/ hr. QT variability was the only ECG measure significantly correlated with RDI (both log-transformed; r = 0.6, P = 0.006). Further, QT variability was correlated with the minimum oxygen saturation (r = -0.55, P = 0.01). Sleep stage showed a significant effect on HRV, but not on QT variability. In the regression model, RDI was the strongest predictor of QT variability (R2 increase 38%), followed by high and low frequency power of HRV (R2 increase 10% each). CONCLUSION: Obstructive sleep apnea is associated with changes in QT interval variability during sleep. The variance of beat-to-beat QT intervals correlates more strongly with the severity of OSA (as determined by RDI) than standard measures of heart rate variability, and is correlated with blood oxygenation, but not sleep stage.     

Heart rate variability during sleep in children with partial epilepsy

Alterations in autonomic control of cardiac activity in epileptic patients have been reported by several studies in the past, and both ictal and interictal modifications of heart rate regulation have been described. Alterations of autonomic control of cardiac activity can play an important role in sudden unexplained death in patients with epilepsy (SUDEP). However, the presence of specific changes in heart rate variability (HRV) during sleep, not correlated with seizures, has not been assessed in children with epilepsy; for this reason, we evaluated features of cardiac autonomic function during sleep without ictal epileptiform electroencephalogram (EEG) activity in a group of children with partial epilepsy. Eleven patients (five males and six females; mean age 11.5 years, SD: 3.65 years) affected by partial epilepsy were admitted to this study; 11 normal subjects (five males and six females; mean age 12.9 years, SD: 2.72 years) served as a control group. All subjects slept in the laboratory for two consecutive nights. The data were analyzed during the second night. Sleep was polygraphically recorded [including one electrocardiography (ECG) channel] and signals were digitally stored. A series of 5-min ECG epochs were chosen from each sleep stage, during periods without evident ictal epileptiform activity in the EEG. Electrocardiography signals were analyzed for automatic detection of R-waves and, subsequently, a series of time- and frequency-domain measures were calculated. Epileptic subjects tended to show an overall lower HRV in both time- and frequency-domain parameters, principally during rapid eye movement (REM) sleep and, to a lesser extent, during sleep stage 2. Among the different bands, this decrease was most evident for the high-frequency band (HF) absolute power. For this reason, the ratio between the low-frequency band (LF) and HF was always higher in epileptic patients than in normal controls and the difference was statistically significant during sleep stages 3 and/or 4 and REM sleep. Our results indicate that during sleep, a particular condition of basal modification in autonomic characteristics occurs (mostly during REM sleep) in partial epilepsy patients. This finding might represent an important factor contributing to the complex mechanism of SUDEP which takes place most often during sleep and supports the need of studying HRV specifically during this state in subjects with seizures.     

Effects of low ambient temperature on heart rate variability during sleep in humans

The effects of cold exposure on heart rate variability (HRV) during sleep were examined. Eight male subjects slept under three different conditions: 3°C, 50–80% relative humidity (RH) [3]; 10°C, 50% RH [10]; and 17°C 50% RH [17]. No significant differences were observed in HRV during rapid eye movement sleep (REM) and wakefulness. The ratio of the low frequency (LF) to high frequency component (HF) of HRV (LF/HF) significantly differed among the conditions during stage 2 and slow wave sleep (SWS) that decreased as the ambient temperature decreased. The normalized LF [LF/(LF + HF)] significantly decreased in 3 and 10 than in 17 during SWS. In low ambient temperature, predominant cardiac parasympathetic activity during stage 2 with no significant difference during REM and wakefulness may cause variations in HRV at transition from stage 2 to REM and wakefulness. These results may partly explain the peak in adverse cardiac events during winter.     

两种计算正常成年人短时心率变异性方法的比较研究

目的利用光电容积脉搏波法分析心率变异性,为通过心率变异性(heart rate variability,HRV)参数表征自主神经系统的变化提供新的研究方法。方法对46个健康成年受试者分别同步采集自主呼吸状态下的心电信号和光电容积脉搏波信号,利用二阶差分极大值提取心电图的RR间期,搜索脉搏波极大值提取脉搏波主波波峰间期PP,然后计算通用HRV参数SDNN、RMSSD和LF/HF,并利用回归的统计学方法结合Bland-Altman随机分析法对这两种方法获取的HRV结果进行比较。结果两种方法计算得到的心率变异性参数结果的Pearson相关系数分别为0.998、0.995和0.992,均显著相关(P0.01),Bland-Altman分布图也均在一致性区间内,说明这两种方法在计算心率变异性上具有一致性。结论利用光电容积脉搏波法分析心率变异具有可行性。     

The effect of ventilation on spectral analysis of heart rate and blood pressure variability during exercise

Heart rate variability (HRV) and systolic blood pressure variability (BPV) during incremental exercise at 50, 75, and 100% of previously determined ventilatory threshold (VT) were compared to that of resting controlled breathing (CB) in 12 healthy subjects. CB was matched with exercise-associated respiratory rate, tidal volume, and end-tidal CO(2) for all stages of exercise. Power in the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, >0.15-0.4 Hz) for HRV and BPV were calculated, using time-frequency domain analysis, from beat-to-beat ECG and non-invasive radial artery blood pressure, respectively. During CB absolute and normalized power in the LF and HF of HRV and BPV were not significantly changed from baseline to maximal breathing. Conversely, during exercise HRV, LF and HF power significantly decreased from baseline to 100% VT while BPV, LF and HF power significantly increased for the same period. These findings suggest that the increases in ventilation associated with incremental exercise do not significantly affect spectral analysis of cardiovascular autonomic modulation in healthy subjects.     

Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in rats

To explore whether depth of sleep is related to changes in autonomic control in rats, continuous power-spectral analysis of electroencephalogram (EEG) and heart rate variability (HRV) was performed in unanesthetized rats during normal daytime sleep. Quiet sleep (QS) was associated with an increase in high-frequency power of HRV (0.6-2.4 Hz, HF) but a decrease in low-frequency power (0.06-0.6 Hz) to HF ratio (LF/HF) compared with awakening. During QS, LF/HF was significantly and negatively correlated with delta power of EEG (0.5-4.0 Hz), whereas mean R-R interval and HF were not. As in humans, cardiac sympathetic regulation in rats is negatively related to the depth of sleep during QS, although vagal regulation is not. Our methodology offers a parallel way of studying the interaction between cerebral cortical and autonomic functions in rats.     

Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in humans

To explore whether depth of sleep is related to changes in autonomic control, continuous power-spectral analysis of the electroencephalogram (EEG) and heart rate variability (HRV) was performed in ten normal subjects during nocturnal sleep. Quiet sleep (QS) was associated with an increase in high-frequency power (HF) of HRV (0.15-0.4 Hz) but a decrease in low-frequency power (LF) (0.04-0.15 Hz) to HF ratio (LF/HF) compared with awakening. During QS, LF/HF was significantly and negatively correlated with delta power of EEG (0.5-4.0 Hz), whereas mean R-R interval and HF were not. We conclude that during QS, cardiac sympathetic regulation is negatively related to the depth of sleep, although vagal regulation is not. Our methodology offers a quantitative analysis to study the interaction between cerebral cortical and autonomic functions.     

Assessment of heart rate variability derived from finger-tip photoplethysmography as compared to electrocardiography

Heart rate variability (HRV) is traditionally derived from RR interval time series of electrocardiography (ECG). Photoplethysmography (PPG) also reflects the cardiac rhythm since the mechanical activity of the heart is coupled to its electrical activity. Thus, theoretically, PPG can be used for determining the interval between successive heartbeats and heart rate variability. However, the PPG wave lags behind the ECG signal by the time required for transmission of pulse wave. In this study, finger-tip PPG and standard lead II ECG were recorded for five minutes from 10 healthy subjects at rest. The results showed a high correlation (median = 0.97) between the ECG-derived RR intervals and PPG-derived peak-to-peak (PP) intervals. PP variability was accurate (0.1 ms) as compared to RR variability. The time domain, frequency domain and Poincaré plot HRV parameters computed using RR interval method and PP interval method showed no significant differences (p < 0.05). The error analysis also showed insignificant differences between the HRV indices obtained by the two methods. Bland-Altman analysis showed high degree of agreement between the two methods for all the parameters of HRV. Thus, HRV can also be reliably estimated from the PPG based PP interval method.     

Influence of intensive cycling training on heart rate variability during rest and exercise.

The current study examined whether changes in heart rate variability (HRV) following intensive cycling training contribute to the mechanism of training-induced bradycardia. Thirteen healthy untrained subjects, ages 18-27 years, underwent recordings of heart rate (HR) and VO2max before and after 8 weeks of cycling, 25-60 min/day, 5 days/week at > 80% maximum HR (HRmax). Heart rate recordings were obtained during supine rest and submaximal exercise and were analysed for the following components of HRV: low frequency (LF, 0.041-0.15 Hz); high frequency (HF, 0.15-0.40 Hz); LF/HF ratio and total power (TP, 0-0.40 Hz). At posttraining, VO2max was significantly increased while HR was significantly reduced at rest and all absolute exercise work rates. Training-induced lower HR was accompanied by significantly greater HF and TP during rest as well as LF, HF, and TP during all absolute exercise work rates. Posttraining HR and the majority of HRV measures were similar to pretraining values at the same relative exercise intensity (% HRmax). These results indicated that 8 weeks of intensive cycling training increased HRV and cardiac vagal modulation during rest and absolute exercise work rates but had little effect during relative exercise work rates. Increased vagal modulation resulting from intensive exercise training may contribute to the mechanism of training-induced bradycardia.     

自主呼吸状态下光电容积脉搏波法对 健康人群心率变异性的分析

目的 分析自主呼吸状态下光电容积脉搏波法对健康人群心率变异性。方法 选取2016年10月~2018年9月我校本科生健康志愿者64名,所有志愿者均行心电图（ECG）及光电容积脉搏波法（PPG）检测,比较3 min的ECG与PPG检测HRV时的RR间期标准差（SDNN）、RR间期差值均方根值（RMSSD）、低频功率与标准化高频功率的比值（LF/HF）,并分析ECG与PPG检测的心率变异性参数的相关性与一致性。结果 64例志愿者3 min的ECG与PPG心率变异性参数比较,差异无统计学意义（P＞0.05）。经Pearson相关性分析发现,PPG检测SDNN、RMSSD、LF/HF与ECG各指标呈正相关（SDNN:r=0.999,P＜0.001;RMSSD:r=0.998,P＜0.001;LF/HF:r=0.998,P＜0.001）;经可靠性分析发现,PPG用于检测健康人群心率变异性与ECG一致性较高（ICC=0.915,95% CI:0.878~0.943,P＜0.001）。结论 健康人群自主呼吸状态下光电容积脉搏波法可用于心率变异性的检测,临床上有较好的应用价值。     

Inward-attention meditation increases parasympathetic activity: a study based on heart rate variability

Phenomenon of the heart rate variability (HRV) during various meditation techniques has been reported. However, most of these techniques emphasized the skill of slow breathing (<0.15 Hz). This paper reports our study on HRV during meditation which emphasizes inward attention. Inward attention has been an important approach for the Zen-meditation practitioners to enter into transcendental consciousness. Two groups of subjects were investigated, 10 experimental subjects with Zen-meditation experience and 10 control subjects without any meditation experience. We analyzed HRV both in time and frequency domains. The results revealed both common and different effects on HRV between inward-attention meditation and normal rest. The major difference of effects between two groups were the decrease of LF/HF ratio and LF norm as well as the increase of HF norm, which suggested the benefit of a sympathovagal balance toward parasympathetic activity. Moreover, we observed regular oscillating rhythms of the heart rate when the LF/HF ratio was small under meditation. According to previous studies, regular oscillations of heart rate signal usually appeared in the low-frequency band of HRV under slow breathing. Our findings showed that such regular oscillations could also appear in the high-frequency band of HRV but with smaller amplitude.     

Daily worry is related to low heart rate variability during waking and the subsequent nocturnal sleep period.

Stress and anxiety are risk factors for cardiovascular (CV) disease. Worry might be a mediator of their risks by prolonging their cognitive representation and concomitant CV activity. We hypothesized that daily stressors and worry, and trait anxiety and trait worry would be associated with high heart rate (HR) and low heart rate variability (HRV) during waking and the subsequent nocturnal sleep period, and that worry would mediate the effects of daily stressors. Low HRV and high HR are physiological risk factors for CV disease. Using an hourly diary, stressors, worry frequency and duration, and biobehavioral variables were measured during one day in 52 healthy subjects. During this time and the subsequent nocturnal sleep period, ambulatory ECG was measured. Stressors, worry and traits were related to higher HR and lower HRV during waking, and the effects of stressors and worry were extended into the sleeping period. Worry duration mediated the effects of stressors. The results were largely independent of biobehavioral variables including sleep quality. The results support the notion that worry, by prolonging CV activity, is a mediator of the CV risks of stress. They also imply a role for unconscious cognitive representation of stress.