Regular heartbeat dynamics are associated with cardiac health

The human heartbeat series is more variable and, hence, more complex in healthy subjects than in congestive heart failure (CHF) patients. However, little is known about the complexity of the heart rate variations on a beat-to-beat basis. We present an analysis based on symbolic dynamics that focuses on the dynamic features of such beat-to-beat variations on a small time scale. The sequence of acceleration and deceleration of eight successive heartbeats is represented by a binary sequence consisting of ones and zeros. The regularity of such binary patterns is quantified using approximate entropy (ApEn). Holter electrocardiograms from 30 healthy subjects, 15 patients with CHF, and their surrogate data were analyzed with respect to the regularity of such binary sequences. The results are compared with spectral analysis and ApEn of heart rate variability. Counterintuitively, healthy subjects show a large amount of regular beat-to-beat patterns in addition to a considerable amount of irregular patterns. CHF patients show a predominance of one regular beat-to-beat pattern (alternation of acceleration and deceleration), as well as some irregular patterns similar to the patterns observed in the surrogate data. In healthy subjects, regular beat-to-beat patterns reflect the physiological adaptation to different activities, i.e., sympathetic modulation, whereas irregular patterns may arise from parasympathetic modulation. The patterns observed in CHF patients indicate a largely reduced influence of the autonomic nervous system. In conclusion, analysis of short beat-to-beat patterns with respect to regularity leads to a considerable increase of information compared with spectral analysis or ApEn of heart-rate variations.     

Aging and the complexity of cardiovascular dynamics.

Biomedical signals often vary in a complex and irregular manner. Analysis of variability in such signals generally does not address directly their complexity, and so may miss potentially useful information. We analyze the complexity of heart rate and beat-to-beat blood pressure using two methods motivated by nonlinear dynamics (chaos theory). A comparison of a group of healthy elderly subjects with healthy young adults indicates that the complexity of cardiovascular dynamics is reduced with aging. This suggests that complexity of variability may be a useful physiological marker.     

A New Approach to Detect Congestive Heart Failure Using Short-Term Heart Rate Variability Measures

Heart rate variability (HRV) analysis has quantified the functioning of the autonomic regulation of the heart and heart''s ability to respond. However, majority of studies on HRV report several differences between patients with congestive heart failure (CHF) and healthy subjects, such as time-domain, frequency domain and nonlinear HRV measures. In the paper, we mainly presented a new approach to detect congestive heart failure (CHF) based on combination support vector machine (SVM) and three nonstandard heart rate variability (HRV) measures (e.g. SUM_TD, SUM_FD and SUM_IE). The CHF classification model was presented by using SVM classifier with the combination SUM_TD and SUM_FD. In the analysis performed, we found that the CHF classification algorithm could obtain the best performance with the CHF classification accuracy, sensitivity and specificity of 100%, 100%, 100%, respectively.     

Fractal dimension in health and heart failure.

BACKGROUND: Non-linear analysis of heart rate variability (HRV) can give additional information about autonomic control of the heart rate. This study applied the fractal dimension (FD) in a congestive heart failure (CHF) population. METHODS: FD and HRV were evaluated in a healthy population (n=21) and an end-stage heart failure population (n=21) using 1-h segments during the day and night from Holter recordings. RESULTS: CHF patients presented a loss of circadian variation in both FD and conventional time- and frequency-domain HRV indices. FD was higher in the CHF population both during the day and night. In the CHF population the correlation between FD and high-frequency power of HRV was lost. CONCLUSION: Day-night variations of heart rate fluctuations are lost in heart failure. Changes in FD reflecting physiological and pathophysiological changes were observed.     

Chaotic Signatures of Heart Rate Variability and Its Power Spectrum in Health,Aging and Heart Failure

A paradox regarding the classic power spectral analysis of heart rate variability (HRV) is whether the characteristic high- (HF) and low-frequency (LF) spectral peaks represent stochastic or chaotic phenomena. Resolution of this fundamental issue is key to unraveling the mechanisms of HRV, which is critical to its proper use as a noninvasive marker for cardiac mortality risk assessment and stratification in congestive heart failure (CHF) and other cardiac dysfunctions. However, conventional techniques of nonlinear time series analysis generally lack sufficient sensitivity, specificity and robustness to discriminate chaos from random noise, much less quantify the chaos level. Here, we apply a ‘litmus test’ for heartbeat chaos based on a novel noise titration assay which affords a robust, specific, time-resolved and quantitative measure of the relative chaos level. Noise titration of running short-segment Holter tachograms from healthy subjects revealed circadian-dependent (or sleep/wake-dependent) heartbeat chaos that was linked to the HF component (respiratory sinus arrhythmia). The relative ‘HF chaos’ levels were similar in young and elderly subjects despite proportional age-related decreases in HF and LF power. In contrast, the near-regular heartbeat in CHF patients was primarily nonchaotic except punctuated by undetected ectopic beats and other abnormal beats, causing transient chaos. Such profound circadian-, age- and CHF-dependent changes in the chaotic and spectral characteristics of HRV were accompanied by little changes in approximate entropy, a measure of signal irregularity. The salient chaotic signatures of HRV in these subject groups reveal distinct autonomic, cardiac, respiratory and circadian/sleep-wake mechanisms that distinguish health and aging from CHF.     

Ventilatory and arousal patterns during sleep in normal young and elderly subjects

Since elderly subjects have lower chemosensitivity, we postulated that ventilation might be more state dependent in the elderly. To address this we investigated the changes in ventilation, measured by respiratory inductive plethysmography, with sleep in 12 healthy young (19-29 yr) and 13 elderly (greater than 65 yr) subjects. Ventilation was measured in representative periods in each sleep state. These data showed that there is no difference between the elderly and the young either in mean ventilation or in the variability of ventilation awake or in the different states of sleep. In both groups ventilation was variable in stage 1-2 sleep and least variable in stage 3-4 sleep. The variability in stage 1-2 sleep was due to periodic breathing (cycle time approximately 45 s) in both age groups. Although within a sleep state no differences were observed, over the night of study the elderly behaved differently from the young. Apneas occurred more frequently in the elderly, and 5 of 13 elderly met the criteria for sleep apnea syndrome compared with 1 of 12 young subjects. Apneas tended to occur predominantly in stage 1-2 sleep and seem to be an exaggeration of the periodicity that is typical of this state. Four of the elderly with apnea remained in this stage of sleep throughout the night of study. The apneic episodes usually terminated with an electroencephalogram arousal that occurred prior to or simultaneously with the onset of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of respiratory sinus arrhythmia in patients with mild heart failure

The high-frequency (HF) component of the heart rate variability (HRV) is regarded as an index of cardiac vagal responsiveness. However, when vagal tone is decreased, nonneural mechanisms could account for a significant proportion of the HF component. To test this hypothesis, we examined the HRV spectral power in 20 patients with mild chronic heart failure (CHF) and 11 controls before and during ganglion blockade with trimethaphan camsylate (3-6 mg/min iv). A small HF component was still present during ganglion blockade, and its amplitude did not differ between CHF patients and controls. The average contribution of nonneural oscillations to the HF component was 15% (range 1-77%) in patients with CHF and 3% (range 0. 7-30%) in healthy controls (P < 0.005). During controlled breathing at 0.16 Hz, however, it decreased to 1% (range 0.2-13%) in healthy controls and 5% (range 1-44%) in CHF patients. Our results indicate that the HF component can significantly overestimate cardiac vagal responsiveness in patients with mild CHF. This bias is improved by controlled breathing, since this maneuver increases the vagal contribution to HF without affecting its nonneural component.     

The pressor response to involuntary isometric exercise of young and elderly human muscle with reference to muscle contractile characteristics

Changes in heart rate (f _c) and blood pressure (BP) were observed in eight healthy young men aged [mean (SD)] 20(l) years and ten healthy elderly men aged 65 (5) years, during electrically evoked contractions of the ankle plantar flexors and elbow flexors which were sustained for 2 min. There was no significant difference in the f _c response to evoked contraction of the ankle plantar flexors or elbow flexors between young and elderly subjects. During contraction of the elbow flexors, elderly subjects produced an unexpectedly large rise in systolic BP which was significantly greater than that of the young subjects. The exaggerated response seen in the elderly group may be due to a more rigid arterial tree which is thought to occur with advancing age. Electrically evoked contraction of the slower contracting elderly ankle plantar flexors resulted in a significantly diminished diastolic BP response when compared with that of the young subjects. In contrast, during electrically evoked contraction of the elbow flexors, which showed a similar twitch time course in young and elderly subjects, the diastolic BP response was not significantly different between groups. This may reflect differences in the peripheral reflex input to the pressor response in elderly arm and leg muscles which, in turn, may be influenced by relative fast twitch fibre area.     

An Examination of the Relationship Between Resting Heart Rate Variability and Heart Rate Reactivity to a Mental Arithmetic Stressor

Resting heart rate variability can be an index of sympathetic or parasympathetic dominance, according to the frequency of the variability studied. Sympathetic dominance of this system has been linked to increased risk of cardiovascular disease (CVD). Similarly, rapid and dramatic increases in heart rate reactivity to a stressor task have also been suggested as indicating increased risk of CVD via atherogenesis. Although both of these variables have been related to the development of cardiovascular disease, and both may be related to increased sympathetic activity or parasympathetic withdrawal, most research studies have tended to focus on either variable independently of the other. In order to investigate whether these two indices of stressor reactivity were related in relatively young and healthy subjects, resting heart rate variability data were collected from 80 volunteers for 20 minutes. In addition, heart rate reactivity data were collected during a 2-minute mental arithmetic stressor, which has been previously shown to induce significant increases in heart rate. After classifying subjects according to whether their heart rate variability data were above or below the mean for their gender, heart rate reactivity data were examined via MANOVA to detect significant differences between subject groups. Females showed significant effects, and males showed nonsignificant trends, but these two sets of data were in different directions, suggesting that gender may be a confounding factor in the relationship between heart rate reactivity and heart rate variability.     

Modeling baroreflex regulation of heart rate during orthostatic stress

During orthostatic stress, arterial and cardiopulmonary baroreflexes play a key role in maintaining arterial pressure by regulating heart rate. This study presents a mathematical model that can predict the dynamics of heart rate regulation in response to postural change from sitting to standing. The model uses blood pressure measured in the finger as an input to model heart rate dynamics in response to changes in baroreceptor nerve firing rate, sympathetic and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations of norepinephrine and acetylcholine. We formulate an inverse least squares problem for parameter estimation and successfully demonstrate that our mathematical model can accurately predict heart rate dynamics observed in data obtained from healthy young, healthy elderly, and hypertensive elderly subjects. One of our key findings indicates that, to successfully validate our model against clinical data, it is necessary to include the vestibulo-sympathetic reflex. Furthermore, our model reveals that the transfer between the nerve firing and blood pressure is nonlinear and follows a hysteresis curve. In healthy young people, the hysteresis loop is wide, whereas, in healthy and hypertensive elderly people, the hysteresis loop shifts to higher blood pressure values, and its area is diminished. Finally, for hypertensive elderly people, the hysteresis loop is generally not closed, indicating that, during postural change from sitting to standing, baroreflex modulation does not return to steady state during the first minute of standing.     

Fractal scale-invariant and nonlinear properties of cardiac dynamics remain stable with advanced age: a new mechanistic picture of cardiac control in healthy elderly

Heart beat fluctuations exhibit temporal structure with robust long-range correlations, fractal and nonlinear features, which have been found to break down with pathologic conditions, reflecting changes in the mechanism of neuroautonomic control. It has been hypothesized that these features change and even break down also with advanced age, suggesting fundamental alterations in cardiac control with aging. Here we test this hypothesis. We analyze heart beat interval recordings from the following two independent databases: 1) 19 healthy young (average age 25.7 yr) and 16 healthy elderly subjects (average age 73.8 yr) during 2 h under resting conditions from the Fantasia database; and 2) 29 healthy elderly subjects (average age 75.9 yr) during approximately 8 h of sleep from the sleep heart health study (SHHS) database, and the same subjects recorded 5 yr later. We quantify: 1) the average heart rate (); 2) the SD sigma(R-R) and sigma(DeltaR-R) of the heart beat intervals R-R and their increments DeltaR-R; 3) the long-range correlations in R-R as measured by the scaling exponent alpha(R-R) using the Detrended Fluctuation Analysis; 4) fractal linear and nonlinear properties as represented by the scaling exponents alpha(sgn) and alpha(mag) for the time series of the sign and magnitude of DeltaR-R; and 5) the nonlinear fractal dimension D(k) of R-R using the fractal dimension analysis. We find: 1) No significant difference in (P > 0.05); 2) a significant difference in sigma(R-R) and sigma(DeltaR-R) for the Fantasia groups (P < 10(-4)) but no significant change with age between the elderly SHHS groups (P > 0.5); and 3) no significant change in the fractal measures alpha(R-R) (P > 0.15), alpha(sgn) (P > 0.2), alpha(mag) (P > 0.3), and D(k) with age. Our findings do not support the hypothesis that fractal linear and nonlinear characteristics of heart beat dynamics break down with advanced age in healthy subjects. Although our results indeed show a reduced SD of heart beat fluctuations with advanced age, the inherent temporal fractal and nonlinear organization of these fluctuations remains stable. This indicates that the coupled cascade of nonlinear feedback loops, which are believed to underlie cardiac neuroautonomic regulation, remains intact with advanced age.     

The application of surface plethysmography for heart rate variability analysis after GSM radiofrequency exposure

The aim of the present study was to test whether the electromagnetic field emitted by standard GSM mobile phones results in changes in heart rate (HR) and heart rate variability (HRV) of 35 healthy young male and female subjects. Two parallel signals, electrocardiogram and infrared surface plethysmogram were recorded and compared to test their validity for the analysis. Plethysmographic recording is proved to be a fast and reliable method for HRV measurements. In the radiofrequency (RF) exposure study, there was no significant difference in the values of HR and HRV between the RF and the sham groups. Our preliminary study demonstrates that, in our experimental conditions, RF fields emitted by cellular phones do not cause observable effects on the regulation of heart rate of healthy, young adults.     

T cell responses are better correlates of vaccine protection in the elderly

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-gamma:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.     

Investigation of biophysical features of interaction between 0.1 Hz oscillations in heart rate variability and distal blood flow variability

We studied biophysical features of interaction between 0.1 Hz oscillations in heart rate variability (HRV) and distal blood flow (DBF) variability in healthy subjects and patients after acute myocardial infarction (MI). 125 patients after acute MI (72 male and 53 female) aged between 30 and 83 years and 33 healthy subjects (23 male and 10 female) aged between 20 and 46 years were included in the study. The duration of prospective study of MI patients was one year. We estimated the delay in coupling between 0.1 Hz oscillations in H RV and DBF variability. It is found out that in healthy subjects the delay in coupling from heart rate to DBF is less than delay in coupling from DBF to heart rate. Acute MI results mainly in disruption of coupling from heart rate to DBF. This coupling is partially restored in one year after acute MI, but the delay in coupling remains significantly smaller than in healthy subjects. The features of coupling from DBF to heart rate are restored in MI patients within three weeks after infarction. After this period the delay in this coupling in MI patients is approximately the same as it is in healthy subjects.     

Influence of external periodic stimuli on heart rate variability in healthy subjects and in coronary heart disease patients

Frequency estimates of the heart rate variability (HRV) spectrum influenced by external periodic stimuli were studied in healthy subjects and patients with coronary heart disease (CHD). Sensory stimulation by periodic eye opening at a rate of 15, 10, 8, 6, or 5 times per minute, as well as spontaneous and controlled breathing at a rate of 15, 10, 8, 6, or 5 times per minute, was used. It was found that the spectral response to external periodic oscillations was determined by a frequency-dependent phenomenon, the maximal amplitude of heart rate variations being observed in the case of external stimuli at a frequency of 0.1 Hz. A resonance frequency in the 0.1-Hz range may be suggested to exist in the cardiovascular controls. Significant differences in the HRV frequency characteristics between CHD patients and healthy subjects were shown. CHD patients had a characteristic decline in HRV responses to external oscillations; the power of these responses did not depend on the frequency of external stimuli.     

Analysis of Non-stationary Data for Heart-rate Fluctuations in Terms of Drift and Diffusion Coefficients

We describe a method for analyzing the stochasticity in non-stationary data for the beat-to-beat fluctuations in the heart rates of healthy subjects, as well as those with congestive heart failure. The method analyzes the return time series of the data as a Markov process, and computes the Markov time scale, i.e., the time scale over which the data are a Markov process. We also construct an effective stochastic continuum equation for the return series. We show that the drift and diffusion coefficients, as well as the amplitude of the return time series for healthy subjects are distinct from those with CHF. Thus, the method may potentially provide a diagnostic tool for distinguishing healthy subjects from those with congestive heart failure, as it can distinguish small differences between the data for the two classes of subjects in terms of well-defined and physically-motivated quantities. PACS: 05.10.Gg 05.40.-a, 05.45.Tp, 87.19.Hh     

螺内酯联合美托洛尔缓释片治疗老年慢性心力衰竭患者的疗效 及对左室心功能的影响

目的:探究螺内酯联合美托洛尔缓释片治疗老年慢性心力衰竭(CHF)患者的临床疗效,并分析其对左室心功能的影响。方法:选择2012年2月至2015年5月期间我院收治的老年CHF患者87例,将其随机分为研究组和对照组,研究组45例,对照组42例。对照组采用常规药物治疗方式,研究组在对照组基础上采用螺内酯联合美托洛尔缓释片治疗,疗程共12周。对比两组患者的临床疗效及治疗前后的左心室功能变化。结果:研究组患者总有效率为91.11%,对照组为69.05%,组间差异有统计学意义(P0.05);治疗后研究组LVEF高于治疗前,LVEDV、LVESV低于治疗前,且改善程度明显优于对照组,差异均有统计学意义(P0.05)。结论:螺内酯联合美托洛尔缓释片能够显著改善老年CHF患者的左室重构和心脏功能,疗效显著,可在临床上推广使用。     

老年慢性心力衰竭患者肿瘤坏死因子、脑钠肽水平变化及其相关性分析

目的：探讨老年慢性心力衰竭（CHF）肿瘤坏死因子α（TNF-α）以及脑利钠肽水平的变化,并对其进行相关性分析。方法：选择老年CHF患者59例,根据心功能分级,Ⅱ级19例,Ⅲ级25例,Ⅳ级15例;另选心功能正常的老年人36例。所有入选者予以血清BNP、TNF-α测定,并采用彩色多普勒超声测定左心室舒张末内径并计算左室射血分数（LVEF）。结果：与对照组比较,CHF组心功能Ⅲ、Ⅳ级患者TNF-α水平明显升高（P〈0．05）,心功能Ⅱ、Ⅲ、Ⅳ级患者血BNP水平明显升高（P〈0．05）,并随心功能分级加重而增加。血TNF-α水平与BNP呈正相关（r=0．57,P〈0．05）。CHF患者中血清TNF-α和BNP水平与LVEF比较均呈负相关（F-0．48,r=-0．64,P〈0．05）。结论：老年CHF患者血TNF-α显著升高,并与BNP及LVEF关系密切,是反应CHF患者心功能恶化的重要预测指标。     

Interaction of 0.1-Hz oscillations in heart rate variability and distal blood flow variability

Biophysical features of 0.1-Hz oscillations of heart rate variability (HRV) and distal blood flow (DBF) variability were compared in healthy subjects and patients after acute myocardial infarction (MI). Patients with acute MI (72 men and 53 women; 125 in total) and healthy subjects (23 men and 10 women; 33 in total) aged 30?C83 and 20?C46 years, respectively, participated in the study. The patients were involved in the study for a year after acute MI. The delay in coupling 0.1-Hz oscillations of HRV and DBF variability was estimated. In healthy subjects, the delay in the heart ?? DBF coupling proved to be less than the delay in the DBF ?? heart coupling. Acute MI results mainly in disruption of the heart ?? DBF coupling, which is partially restored by the end of the first year after acute MI, though it remains lower than in healthy subjects. The DBF ?? heart coupling is rapidly restored to the level of healthy subjects within three weeks after acute MI.     

Echocardiography,Spirometry, and Systemic Acute-Phase Inflammatory Proteins in Smokers with COPD or CHF: An Observational Study

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥50 years and with ≥10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.