HRV Research

Heart rate variability Standards of measurement, physiological interpretation, and clinical use

Authors: Task Force of The European Society of Cardiology, The North American Society of Pacing and Electrophysiology

Abstract: The last two decades have witnessed the recognition of a significant relationship between the autonomic nervous system and cardiovascular mortality, including sudden cardiac death[1–4]. Experimental evidence for an association between a propensity for lethal arrhythmias and signs of either increased sympathetic or reduced vagal activity has encouraged the development of quantitative markers of autonomic activity. Heart rate variability (HRV) represents one of the most promising such markers. The apparently easy derivation of this measure has popularized its use. As many commercial devices now provide automated measurement of HRV, the cardiologist has been provided with a seemingly simple tool for both research and clinical studies[5]. However, the significance and meaning of the many different measures of HRV are more complex than generally appreciated and there is a potential for incorrect conclusions and for excessive or unfounded extrapolations. Recognition of these problems led the European Society of Cardiology and the North American Society of Pacing and Electrophysiology to constitute a Task Force charged with the responsibility of developing appropriate standards. The specific goals of this Task Force were to: standardize nomenclature and develop definitions of terms; specify standard methods of measurement; define physiological and pathophysiological correlates; describe currently appropriate clinical applications, and identify areas for future research. In order to achieve these goals, the members of the Task Force were drawn from the fields of mathematics, engineering, physiology, and clinical medicine. The standards and proposals offered in this text should not limit further development but, rather, should allow appropriate comparisons, promote circumspect interpretations, and lead to further progress in the field. The phenomenon that is the focus of this report is the oscillation in the interval between consecutive heart beats as well as the oscillations between consecutive instantaneous heart rates. ‘Heart Rate Variability’ has become the conventionally accepted term to describe variations of both instantaneous heart rate and RR intervals. In order to describe oscillation in consecutive cardiac cycles, other terms have been used in the literature, for example cycle length variability, heart period variability, RR variability and RR interval tachogram, and they more appropriately emphasize the fact that it is the interval between consecutive beats that is being analysed rather than the heart rate per se. However, these terms have not gained as wide acceptance as HRV, thus we will use the term HRV in this document.

Measurement of Heart Rate Variability: A Clinical Tool or a Research Toy?

Authors: Heikki V. Huikuri, Timo Ma ̈kikallio, K. E. Juhani Airaksinen, Raul Mitrani, Agustin Castellanos, Robert J. Myerburg

Abstract: The objectives of this review are to discuss the diversity of mechanisms that may explain the association between heart rate (HR) variability and mortality, to appraise the clinical applicability of traditional and new measures of HR variability and to propose future directions in this field of research. There is a large body of data demonstrating that abnormal HR variability measured over a 24-h period provides information on the risk of subsequent death in subjects with and without structural heart disease. However, the mechanisms responsible for this association are not completely established. Therefore, no specific therapy is currently available to improve the prognosis for patients with abnormal HR variability. Reduced HR variability has been most commonly associated with a risk of arrhythmic death, but recent data suggest that abnormal variability also predicts vascular causes of death, progression of coronary atherosclerosis and death due to heart failure. A consensus is also lacking on the best HR variability measure for clinical purposes. Time and frequency domain measures of HR variability have been most commonly used, but recent studies show that new analysis methods based on nonlinear dynamics may be more powerful in terms of risk stratification. Before the measurement of HR variability can be applied to clinical practice and used to direct therapy, more precise insight into the pathophysiological link between HR variability and mortality are needed. Further studies should also address the issue of which of the HR variability indexes, including the new nonlinear measures, is best for clinical purposes in various patient populations. (JAmCollCardiol1999;34:1878–83)©1999bytheAmerican College of Cardiology



Abstract: IN PREVIOUS studies it has been established that a cluster of social events requiring change in ongoing life adjustment is significantly associated with the time of illness onset. Similarly, the relationship of what has been called ‘life stress,’ ‘emotional stress,’ ‘object loss,’ etc. and illness onset has been demonstrated by other investigations. It has been adduced from these studies that this clustering of social or life events achieves etiologic significance as a necessary but not sufficient cause of illness and accounts in part for the time of onset of disease. Methodologically, the interview or questionnaire technique used in these studies has yielded only the number and types of events making up the cluster. Some estimate of the magnitude of these events is now required to bring greater precision to this area of research and to provide a quantitative basis for new epidemiological studies of diseases. This report defines a method which achieves this requisite.

Reduced Heart Rate Variability and New-Onset Hypertension

Authors: Jagmeet P. Singh, Martin G. Larson, Hisako Tsuji, Jane C. Evans, Christopher J. O’Donnell, Daniel Levy

Abstract: Heart rate variability (HRV) is a useful noninvasive tool to assess cardiac autonomic function. The purpose of this study was to (1) compare measures of HRV between hypertensive and normotensive subjects and (2) examine the role of HRV as a predictor of new-onset hypertension. The first 2 hours of ambulatory ECG recordings obtained from 931 men and 1111 women attending a routine examination at the Framingham Heart Study were processed for HRV. Three time-domain and 5 frequency-domain variables were studied: standard deviation of normal RR intervals (SDNN), percentage of differences between adjacent normal RR intervals exceeding 50 milliseconds, square root of the mean of squared differences between adjacent normal RR intervals, total power (0.01 to 0.40 Hz), high frequency power (HF, 0.15 to 0.40 Hz), low frequency power (LF, 0.04 to 0.15 Hz), very low frequency power (0.01 to 0.04 Hz), and LF/HF ratio. On cross-sectional analysis, HRV was significantly lower in hypertensive men and women. Among 633 men and 801 women who were normotensive at baseline (systolic blood pressure 140 mm Hg and diastolic blood pressure 90 mm Hg and not receiving antihypertensive treatment), 119 men and 125 women were newly hypertensive at follow-up 4 years later. After adjustment for factors associated with hypertension, multiple logistic regression analysis revealed that LF was associated with incident hypertension in men (odds ratio per SD decrement [OR], 1.38; 95% confidence interval [CI], 1.04 to 1.83) but not in women (OR, 1.12; 95% CI, 0.86 to 1.46). SDNN, HF, and LF/HF were not associated with hypertension in either sex. HRV is reduced in men and women with systemic hypertension. Among normotensive men, lower HRV was associated with greater risk for developing hypertension. These findings are consistent with the hypothesis that autonomic dysregulation is present in the early stage of hypertension.

Short-Term Heart Rate Variability—Influence of Gender and Age in Healthy Subjects

Authors: Andreas Voss,Rico Schroeder,Andreas Heitmann,Annette Peters,Siegfried Perz

Abstract: In the recent years, short-term heart rate variability (HRV) describing complex variations of beat-to-beat interval series that are mainly controlled by the autonomic nervous system (ANS) has been increasingly analyzed to assess the ANS activity in different diseases and under various conditions. In contrast to long-term HRV analysis, short-term investigations (<30 min) provide a test result almost immediately. Thus, short-term HRV analysis is suitable for ambulatory care, patient monitoring and all those applications where the result is urgently needed. In a previous study, we could show significant variations of 5-min HRV indices according to age in almost all domains (linear and nonlinear) in 1906 healthy subjects from the KORA S4 cohort. Based on the same group of subjects, general gender-related influences on HRV indices are to be determined in this study. Short-term 5-min HRV indices from linear time and frequency domain and from nonlinear methods (compression entropy, detrended fluctuation analysis, traditional and segmented Poincaré plot analysis, irreversibility analysis, symbolic dynamics, correlation and mutual information analysis) were determined from 782 females and 1124 males. First, we examined the gender differences in two age clusters (25–49 years and 50–74 years). Secondly, we investigated the gender-specific development of HRV indices in five age decade categories, namely for ages 25–34, 35–44, 45–54, 55–64 and 65–74 years. In this study, significant modifications of the indices according to gender could be obtained, especially in the frequency domain and correlation analyses. Furthermore, there were significant modifications according to age in nearly all of the domains. The gender differences disappeared within the last two age decades and the age dependencies disappeared in the last decade. To summarize gender and age influences need to be considered when performing HRV studies even if these influences only partly differ.

Twenty-Four Hour Time Domain Heart Rate Variability and Heart Rate: Relations to Age and Gender Over Nine Decades


Abstract: Objectives. This study sought to define the effects of age and gender effects on the normal range of time domain heart rate variability (HRV) over nine decades in healthy subjects. Background. Low HRV is considered an independent marker of mortality risk. However, the age-related decline in HRV may limit its predictive value, particularly in the elderly. Delineation of the range of HRV in healthy subjects over the life span is needed. Gender-related differences in HRV also need clarification. Methods. We determined, according to decade, 24-h heart rate (HR) and HRV of 260 healthy subjects (10 to 99 years old; 112 male, 148 female) by means of five standard time domain measures: standard deviation of all normal sinus RR intervals over 24 h (SDNN), standard deviation of the averaged normal sinus RR intervals for all 5-mm segments (SDANN), mean of the standard deviations of all normal sinus RR intervals for all 5-min segments (SDNN index), root-mean-square of successive normal sinus RR interval difference (rMSSD) and the percentage of successive normal sinus RR intervals >50 ms (pNN50). Results. 1) HRV decreased with aging, the pattern of change being measure dependent. HRV (SDNN and SDANN) decreased only very gradually, reaching 60% of baseline (second-decade values) by the tenth decade. With the SDNN index, HRV decreased linearly with aging, reaching 46% of baseline by the tenth decade. Using pNN50 and rMSSD, HRV decreased most rapidly, reaching 24% and 47% of baseline, respectively, by the sixth decade and then stabilized. 2) Using the SDNN index, rMSSD and pNN50, HRV of subjects >65 years old fell below published cutpoints for increased risk of mortality in 25%, 12% and 4%, respectively. 3) At age <30 years, HRV for all measures was lower in female than male subjects. Gender differences decreased at age >30 years and disappeared at age >50 years. 4) HR also declined with aging but much more slowly. HR at age <50 years was faster in female than in male subjects. Gender differences disappeared thereafter. Conclusions. 1) Using all measures, HRV of healthy subjects declines with aging, with measure-dependent patterns. 2) Using the SDNN index, rMSSD and pNN50, HRV of healthy subjects, particularly those >65 years old, may decrease to below levels associated with increased risk of mortality. 3) Gender influences HRV. Gender differences in HRV are age and measure dependent. 4) Age and gender also affect heart rate.

Resting Pulse Rate Reference Data for Children, Adolescents, and Adults: United States, 1999–2008

Authors: Yechiam Ostchega Ph.D. R.N., Kathryn S. Porter M.D. M.S., Jeffery Hughes M.P.H., Charles F. Dillon M.D. Ph.D., Tatiana Nwankwo M.S

Abstract: Objective—This report presents national reference data on resting pulse rate (RPR), for all ages of the U.S. population, from 1999–2008. Methods—During 1999–2008, 49,114 persons were examined. From this, a normative sample comprising 35,302 persons was identified as those who did not have a current medical condition or use a medication that would affect the RPR. RPR was obtained after the participant had been seated and had rested quietly for approximately 4 minutes. Results—RPR is inversely associated with age. There is a mean RPR of 129 beats per minute (standard error, or SE, 0.9) at less than age 1 year, which decreases to a mean RPR of 96 beats/min (SE 0.5) by age 5, and further decreases to 78 beats/min (SE 0.3) in early adolescence. The mean RPR in adulthood plateaus at 72 beats/min (SE 0.2) (p < 0.05 for trend). In addition, there is a significant gender difference, with the male pulse rate plateauing in early adulthood, while the female resting pulse plateaus later when middle-aged. There are two exceptions, that is, infants under age 1 year and adults aged 80 and over, when the mean RPR is statistically and significantly higher in females than in males (females under age 20 have an RPR of 90 beats/min, SE 0.3, and males under age 20 have an RPR of 86 beats/min, SE 0.3, p < 0.05; females aged 20 and over have an RPR of 74 beats/min, SE 0.2, and males aged 20 and over have an RPR of 71 beats/min, SE 0.3, p < 0.05). After controlling for age effects, non-Hispanic black males have a significantly (p < 0.001) lower mean RPR (74 beats/min) than non-Hispanic white males (77 beats/min) and Mexican-American males (76 beats/min). Among females, non-Hispanic black females (79 beats/min) and Mexican-American females (79 beats/min) had statistically and significantly (p < 0.01) lower mean RPRs compared with non-Hispanic white females (80 beats/min). Among males, the prevalence of clinically defined tachycardia (abnormally fast heart rate, RPR 100 beats/min) is 1.3% (95% CI = 1.1–1.7), and the prevalence of clinically defined bradycardia (abnormally slow heart rate, RPR < 60 beats/min) is 15.2% (95% CI = 14.1–16.4). For adult females, these prevalences are 1.9% (95% CI = 1.6–2.3) for clinical tachycardia and 6.9% (95% CI = 6.2–7.8) for clinical bradycardia. Controlling for age, males have higher odds (2.43, 95% CI = 2.09–2.83) of having bradycardia, and notably lower odds (0.71, 95% CI = 0.52–0.97) of having tachycardia than women. Conclusions—The data provides current, updated population-based percentiles of RPR, which is one of the key vital signs routinely measured in clinical practice

Low Heart Rate Variability in a 2-Minute Rhythm Strip Predicts Risk of Coronary Heart Disease and Mortality From Several Causes The ARIC Study

Authors: Jacqueline M. Dekker, PhD; Richard S. Crow, MD; Aaron R. Folsom, MD, MPH; Peter J. Hannan, MStat; Duanping Liao, MD, PhD;Cees A. Swenne, PhD; Evert G. Schouten, MD, PhD

Abstract: Background—Low heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. Methods and Results—We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. Conclusions—Low HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.

An Overview of Heart Rate variability Metrics and Norms

Authors: Fred Shaffer, J. P. Ginsberg

Abstract: Healthy biological systems exhibit complex patterns of variability that can be described by mathematical chaos. Heart rate variability (HRV) consists of changes in the time intervals between consecutive heartbeats called interbeat intervals (IBIs). A healthy heart is not a metronome. The oscillations of a healthy heart are complex and constantly changing, which allow the cardiovascular system to rapidly adjust to sudden physical and psychological challenges to homeostasis. This article briefly reviews current perspectives on the mechanisms that generate 24 h, short-term (~5 min), and ultra-short-term (<5 min) HRV, the importance of HRV, and its implications for health and performance. The authors provide an overview of widely-used HRV time-domain, frequency-domain, and non-linear metrics. Time-domain indices quantify the amount of HRV observed during monitoring periods that may range from ~2 min to 24 h. Frequency-domain values calculate the absolute or relative amount of signal energy within component bands. Non-linear measurements quantify the unpredictability and complexity of a series of IBIs. The authors survey published normative values for clinical, healthy, and optimal performance populations. They stress the importance of measurement context, including recording period length, subject age, and sex, on baseline HRV values. They caution that 24 h, short-term, and ultra-short-term normative values are not interchangeable. They encourage professionals to supplement published norms with findings from their own specialized populations. Finally, the authors provide an overview of HRV assessment strategies for clinical and optimal performance interventions.

The Social Readjustment Rating Scale

Authors: Thomas Holmes, Richard Rahe

Abstract: This Social Readjustment Rating Scale was created by Thomas Holmes & Richard Rahe, University of Washington School of Medicine, in the late 1960s to provide a standardized measure of the impact of a wide range of common stressors. Using the Scale To use the scale, simply add up the values for all of the listed life events that have occurred to you within the past year. If a particular event has happened to you more than once within the last 12 months, multiply the value by the number of occurrences. Enter your value total at the end of the list. The Scale Each life event is assigned a value in arbitrary “life changing units” chosen to reflect the relative amount of stress the event causes in the population studied. Stress is cumulative, so to estimate the total stress you are experiencing, add up the values corresponding to the events that have occurred in your life over the past year.

Effects of age and physical activity on the autonomic control of heart rate in healthy men

Authors: R C Melo, M D B Santos, E Silva, R J Quitério, M A Moreno, M S Reis, I A Verzola, L Oliveira, L E B Martins, L Gallo-Junior, A M Catai

Abstract: The effects of the aging process and an active life-style on the autonomic control of heart rate (HR) were investigated in nine young sedentary (YS, 23 +/2.4 years), 16 young active (YA, 22 +/2.1 years), 8 older sedentary (OS, 63 +/2.4 years) and 8 older active (OA, 61 +/1.1 years) healthy men. Electrocardiogram was continuously recorded for 15 min at rest and for 4 min in the deep breathing test, with a breath rate of 5 to 6 cycles/min in the supine position. Resting HR and RR intervals were analyzed by time (RMSSD index) and frequency domain methods. The power spectral components are reported in normalized units (nu) at low (LF) and high (HF) frequency, and as the LF/HF ratio. The deep breathing test was analyzed by the respiratory sinus arrhythmia indices: expiration/inspiration ratio (E/I) and inspiration-expiration difference (deltaIE). The active groups had lower HR and higher RMSSD index than the sedentary groups (life-style condition: sedentary vs active, P < 0.05). The older groups showed lower HFnu, higher LFnu and higher LF/HF ratio than the young groups (aging effect: young vs older, P < 0.05). The OS group had a lower E/I ratio (1.16) and deltaIE (9.7 bpm) than the other groups studied (YS: 1.38, 22.4 bpm; YA: 1.40, 21.3 bpm; OA: 1.38, 18.5 bpm). The interaction between aging and life-style effects had a P < 0.05. These results suggest that aging reduces HR variability. However, regular physical activity positively affects vagal activity on the heart and consequently attenuates the effects of aging in the autonomic control of HR.

Heart-rate variability: a biomarker to study the influence of nutrition on physiological and psychological health?

Authors: Hayley A Young, David Benton

Abstract: As the influence of diet on health may take place over a period of decades, there is a need for biomarkers that help to identify those aspects of nutrition that have either a positive or a negative influence. The evidence is considered that heart-rate variability (HRV) (the time differences between one beat and the next) can be used to indicate the potential health benefits of food items. Reduced HRV is associated with the development of numerous conditions for example, diabetes, cardiovascular disease, inflammation, obesity and psychiatric disorders. Although more systematic research is required, various aspects of diet have been shown to benefit HRV acutely and in the longer term. Examples include a Mediterranean diet, omega-3 fatty acids, B-vitamins, probiotics, polyphenols and weight loss. Aspects of diet that are viewed as undesirable, for example high intakes of saturated or trans-fat and high glycaemic carbohydrates, have been found to reduce HRV. It is argued that the consistent relationship between HRV, health and morbidity supports the view that HRV has the potential to become a widely used biomarker when considering the influence of diet on mental and physical health.

An Overview of Heart Rate Variability Metrics and Norms

Authors: Fred Shaffer, J. P. Ginsberg

Abstract: Healthy biological systems exhibit complex patterns of variability that can be described by mathematical chaos. Heart rate variability (HRV) consists of changes in the time intervals between consecutive heartbeats called interbeat intervals (IBIs). A healthy heart is not a metronome. The oscillations of a healthy heart are complex and constantly changing, which allow the cardiovascular system to rapidly adjust to sudden physical and psychological challenges to homeostasis. This article briefly reviews current perspectives on the mechanisms that generate 24 h, short-term (~5 min), and ultra-short-term (<5 min) HRV, the importance of HRV, and its implications for health and performance. The authors provide an overview of widely-used HRV time-domain, frequency-domain, and non-linear metrics. Time-domain indices quantify the amount of HRV observed during monitoring periods that may range from ~2 min to 24 h. Frequency-domain values calculate the absolute or relative amount of signal energy within component bands. Non-linear measurements quantify the unpredictability and complexity of a series of IBIs. The authors survey published normative values for clinical, healthy, and optimal performance populations. They stress the importance of measurement context, including recording period length, subject age, and sex, on baseline HRV values. They caution that 24 h, short-term, and ultra-short-term normative values are not interchangeable. They encourage professionals to supplement published norms with findings from their own specialized populations. Finally, the authors provide an overview of HRV assessment strategies for clinical and optimal performance interventions.

Possible mechanisms of sudden cardiac death in top athletes: a basic cardiac electrophysiological point of view

Authors: András Varró, István Baczkó

Abstract: Sudden death among athletes is very rare (1:50,000–1:100,000 annually) but it is still 2–4 times more frequent than in the age-matched control population and attracts significant media attention. We propose a mechanism underlying sudden cardiac death in athletes that does not relate to myocardial ischemia but is based on repolarization abnormalities due to potassium channel downregulation and can also be best explained by the concurrent presence of several factors such as cardiac hypertrophy (athlete’s heart), and/or hypertrophic cardiomyopathy, increased sympathetic tone, genetic defects, drugs, doping agents, food, or dietary ingredients. These factors together can increase the repolarization inhomogeneity of the heart (“substrate”) and an otherwise harmless extrasystole (“trigger”) occurring with a very unfortunate timing may sometimes induce life-threatening arrhythmias. The effective and possible prevention of sudden cardiac death requires the development of novel cost effective cardiac electrophysiological screening methods. Athletes identified by these tests as individuals at higher proarrhythmic risk should then be subjected to more costly genetic tests in order to uncover possible underlying genetic causes for alterations in ionic channel structure and/or function.

Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020–March 2021

Authors: Kompaniyets L, Pennington AF, Goodman AB, Rosenblum HG, Belay B, Ko JY, et al.

Abstract: Introduction Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 illness. Methods We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions. Results Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio [aRR] = 1.30; 95% CI, 1.27–1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25–1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24–1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41–1.67) for patients with 1 condition to 3.82 (95% CI, 3.45–4.23) for patients with more than 10 conditions (compared with patients with no conditions).

Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections

Authors: Sivan Gazit MD MA12*, Roei Shlezinger BA1, Galit Perez MN MA2, Roni Lotan PhD Asaf Peretz MD Amir Ben-Tov MD Dani Cohen PhD4 Khitam Muhsen PhD, Gabriel Chodick PhD MHA, Tal Patalon MD

Abstract: Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARSCoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.

healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability

Authors: Fred Shaffer, Rollin McCraty, Christopher L. Zerr

Abstract: Heart rate variability (HRV), the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operate on different time scales to adapt to challenges and achieve optimal performance. This article briefly reviews neural regulation of the heart, and its basic anatomy, the cardiac cycle, and the sinoatrial and atrioventricular pacemakers. The cardiovascular regulation center in the medulla integrates sensory information and input from higher brain centers, and afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. This article reviews sympathetic and parasympathetic influences on the heart, and examines the interpretation of HRV and the association between reduced HRV, risk of disease and mortality, and the loss of regulatory capacity. This article also discusses the intrinsic cardiac nervous system and the heart-brain connection, through which afferent information can influence activity in the subcortical and frontocortical areas, and motor cortex. It also considers new perspectives on the putative underlying physiological mechanisms and properties of the ultra-low-frequency (ULF), very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) bands. Additionally, it reviews the most common time and frequency domain measurements as well as standardized data collection protocols. In its final section, this article integrates Porges' polyvagal theory, Thayer and colleagues' neurovisceral integration model, Lehrer et al.'s resonance frequency model, and the Institute of HeartMath's coherence model. The authors conclude that a coherent heart is not a metronome because its rhythms are characterized by both complexity and stability over longer time scales. Future research should expand understanding of how the heart and its intrinsic nervous system influence the brain.

Hypertension and physical exercise: The role of oxidative stress

Authors: Monica Korsager Larsen, Vladimir V. Matchkov

Abstract: Oxidative stress is associated with the pathogenesis of hypertension. Decreased bioavailability of nitric oxide (NO) is one of the mechanisms involved in the pathogenesis. It has been suggested that physical exercise could be a potential non-pharmacological strategy in treatment of hypertension because of its beneficial effects on oxidative stress and endothelial function. The aim of this review is to investigate the effect of oxidative stress in relation to hypertension and physical exercise, including the role of NO in the pathogenesis of hypertension. Endothelial dysfunction and decreased NO levels have been found to have the adverse effects in the correlation between oxidative stress and hypertension. Most of the previous studies found that aerobic exercise significantly decreased blood pressure and oxidative stress in hypertensive subjects, but the intense aerobic exercise can also injure endothelial cells. Isometric exercise decreases normally only systolic blood pressure. An alternative exercise, Tai chi significantly decreases blood pressure and oxidative stress in normotensive elderly, but the effect in hypertensive subjects has not yet been studied. Physical exercise and especially aerobic training can be suggested as an effective intervention in the prevention and treatment of hypertension and cardiovascular disease via reduction in oxidative stress.


Authors: Bernhard Grässler, Anita Hökelmann, Richard Halti Cabral

Abstract: Cognition is a major subject to be addressed nowadays due to the increasing number of cognitively affected people in most societies. Because of a lack of pharmaceutical therapies treating cognitive decline, its indicators should be diagnosed before it becomes prevalent. Scientific evidence indicates a relationship between cognition and the nervous system, especially its autonomic part. Heart rate variability (HRV) as an indicator of the autonomic nervous system functioning has been studied as a biological marker for the evaluation of cognitive performance. Therefore, HRV is a possible indicator of cognitive impairment. The aim was to provide a systematic literature review about the association between resting HRV and the cognitive performance. Five cognitive functions were analysed separately: executive functions, memory and learning, language abilities, visuospatial functioning, and processing speed. Furthermore, the global cognitive function evaluated with cognitive test batteries was considered as well. An electronic database search was conducted with five databases. Three search fields comprised HRV, cognitive performance, and adult subjects. The final dataset consisted of 27 articles. Significant correlations in each cognitive function were found, except for processing speed, suggesting a positive association between resting HRV and cognitive performance. Mechanisms underlying this association between cardiovascular health and cognition are discussed. For the future, HRV could be used in diagnostics as an indicator of cognitive impairment before symptoms of dementia get apparent. With a timely diagnosis, preventative tools could be initiated at an early stage of dementia.

Heart rate variability – a historical perspective

Authors: George E. Billman

Abstract: Heart rate variability (HRV), the beat-to-beat variation in either heart rate or the duration of the R–R interval – the heart period, has become a popular clinical and investigational tool. The temporal fluctuations in heart rate exhibit a marked synchrony with respiration (increasing during inspiration and decreasing during expiration – the so called respiratory sinus arrhythmia, RSA) and are widely believed to reflect changes in cardiac autonomic regulation. Although the exact contributions of the parasympathetic and the sympathetic divisions of the autonomic nervous system to this variability are controversial and remain the subject of active investigation and debate, a number of time and frequency domain techniques have been developed to provide insight into cardiac autonomic regulation in both health and disease. It is the purpose of this essay to provide an historical overview of the evolution in the concept of HRV. Briefly, pulse rate was first measured by ancient Greek physicians and scientists. However, it was not until the invention of the “Physician’s Pulse Watch” (a watch with a second hand that could be stopped) in 1707 that changes in pulse rate could be accurately assessed. The Rev. Stephen Hales (1733) was the first to note that pulse varied with respiration and in 1847 Carl Ludwig was the first to record RSA. With the measurement of the ECG (1895) and advent of digital signal processing techniques in the 1960s, investigation of HRV and its relationship to health and disease has exploded. This essay will conclude with a brief description of time domain, frequency domain, and non-linear dynamic analysis techniques (and their limitations) that are commonly used to measure HRV.

A Practical Guide to Heart Rate Variability Estimation

Authors: James C. Miller

Abstract: The objective of this essay is to provide the reader with practical guidance concerning the acquisition and reduction of heart rate variability (HRV) data in field studies. A brief introduction is followed by guidance on data acquisition using the electrocardiogram or the earlobe pulse waveform, the detection of the interbeat interval (IBI, or RR interval) and the smoothing of the series of intervals. Guidance is provided for resampling and then data reduction by frequency transform with reference to an international standard. Brief reviews are provided of of two HRV software programs: VivoSense by Vivonoetics, and HR Scanner by Biocom Technologies. A do-ityourself method for data reduction is provided.

Life Events: Perceptions and Frequencies


Abstract: Life changes have been associated with illness onset. The Social Readjustment Rating Scale (SRRS) records numerical perceptions of the meaning of life events while the Schedule of Recent Experience (SRE) records the frequency of occurrence of life events. Data on these two instruments from 19 studies done in this laboratory have been surveyed and analyzed. They reveal significant variability among groups in their perceptions of life events as well as in their reports of the frequency of occurrence. Variables indicated to be of significance in either or both of these parameters were age, marital status, sex, socioeconomic status, ethnicity, level of education, culture, and experiencing of an event. These variables impose caution on investigations that relate life changes to illness.

Autonomic Dysfunction and Risk Stratification Assessed from Heart Rate Pattern

Authors: A. Günther, O.W. Witte, D. Hoyer

Abstract: The modulation of the autonomic nervous system (ANS) under physiological and pathophysiological conditions is in focus of recent research. Many patients with cardioand cerebrovascular diseases display features of sympathovagal dysregulation. Measuring specific ANS parameters could improve risk stratification. Thus, the early diagnosis of ANS dysfunction in these patients poses a great challenge with high prognostic relevance.The most relevant methods and measures of Heart Rate Variability (HRV) analysis and HRV monitoring will be described in detail in this chapter. The grown importance of these easily obtainable heart rate patterns in stratifying the risk of patients with myocardial infarction and heart failure as well as ischemic stroke will be demonstrated based on recent clinical studies. In order to perspectively improve clinical management of these patients further large scale clinical investigations on the role of ANS dysfunction will be useful.

Fatigue and underperformance in athletes: the overtraining syndrome

Authors: R Budgett

Abstract: The overtraining syndrome affects mainly endurance athletes. It is a condition of chronic fatigue, underperformance, and an increased vulnerability to infection leading to recurrent infections. It is not yet known exactly how the stress of hard training and competition leads to the observed spectrum of symptoms. Psychological, endocrinogical, physiological, and immunological factors all play a role in the failure to recover from exercise. Careful monitoring of athletes and their response to training may help to prevent the overtraining syndrome. With a very careful exercise regimen and regeneration strategies, symptoms normally resolve in 6-12 weeks but may continue much longer or recur if athletes return to hard training too soon.

Effects of Age and Gender on Autonomic Control of Blood Pressure Dynamics

Authors: Sheila R. Barnett, Raymond J. Morin, Dan K. Kiely, Margaret Gagnon, Gohar Azhar, Eric L. Knight, Jerald C. Nelson, Lewis A. Lipsitz

Abstract: Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify ageand genderrelated alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60° head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (10.22 versus 1.23 mm Hg; P0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (P0.02). Upright plasma norepinephrine was lower in women (P0.02). Women had greater supine high-frequency R-R interval power than men (P0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (P0.01), despite higher supine (P0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness.

Heart Rate Variability as an Index of Resilience

Authors: Eric An, BSC USAF, Anne A T Nolty PhD, Stacy S Amano PhD, Albert A Rizzo PhD, J Galen Buckwalter PhD, Jared Rensberger PhD

Abstract: Introduction: Resilience is the ability to maintain or quickly return to a stable physical and psychological equilibrium despite experiencing stressful events. Flexibility of the autonomic nervous system is particularly important for adaptive stress responses and may contribute to individual differences in resilience. Power spectrum analysis of heart rate variability (HRV) allows measurement of sympathovagal balance, which helps to evaluate autonomic flexibility. The present study investigated HRV as a broad index of resilience. Materials and Methods: Twenty-four male participants from the Army National Guard Special Forces completed psychological measures known to relate to resilience and had HRV measured while undergoing stressful virtual environment scenarios. Pearson product-moment correlations were used to explore the relationships between HRV and resilience factors. All research was conducted with the oversight of the Human Subjects Review Committee of Fuller Theological Seminary. Results: Trends toward significance were reported in order to provide results that would reasonably be expected in a study of higher power. Trends between resilience factors and HRV were found only during specific stress-inducing simulations (see Tables III). Conclusion: Greater resilience to stress was associated with HRV during nonstress periods. Higher levels of resilience to traumatic events were associated with HRV during circumstances that were more stressful and emotionally distressing. Post hoc analysis revealed that specific factors including flexibility, emotional control, and spirituality were driving the relationship between general resilience and HRV following emotionally laden stressors. Less stress vulnerability was associated with HRV following intermittent brief stressors. In sum, HRV appears to represent some aspects of an individual’s overall resilience profile. Although resilience remains a complex, multidimensional construct, HRV shows promise as a global psychophysiological index of resilience. This study also offers important perspectives concerning ways to optimize both physical and psychological health.

Heart Rate Variability as a Prognostic Factor for Cancer Survival – A Systematic Review

Authors: Evelyne Kloter, Katja Barrueto, Sabine D. Klein, Felix Scholkmann, and Ursula Wolf

Abstract: An increasing cancer incidence affecting any age and social class is putting serious strain on populations and health care systems around the world. This systematic literature search aims (i) to examine the correlation of heart rate variability (HRV) and cancer patients’ prognosis, (ii) to examine the relationship of HRV and clinicopathological features, and (iii) to compare HRV between different patient groups, and between patient and control groups. We conducted a systematic literature review following the PRISMA Statement. We searched the PubMed and EMBASE databases for publications released by December 2017. The search terms were: “cancer” AND “heart rate variability” AND “human” NOT “animal” NOT “review.” A total of 19 studies were finally included in this review. Most publications were high-quality observational studies. The studies showed that higher HRV correlated positively with patients’ progression of disease and outcome. Thus, we conclude that individuals with higher HRV and advanced coping mechanisms seem to have a better prognosis in cancer progression. HRV appears to be a useful aspect to access the general health status of cancer patients.

Heart rate variability related to effort at work

Authors: Arja Uusitalo, Terhi Mets, Kaisu Martinmäki, Saija Mauno, Ulla Kinnunen, Heikki Rusko

Abstract: Changes in autonomic nervous system function have been related to work stress induced increases in cardiovascular morbidity and mortality. Our purpose was to examine whether various heart rate variability (HRV) measures and new HRV-based relaxation measures are related to self-reported chronic work stress and daily emotions. The relaxation measures are based on neural network modelling of individual baseline heart rate and HRV information. Nineteen healthy hospital workers were studied during two work days during the same work period. Daytime, work time and night time heart rate, as well as physical activity were recorded. An effort–reward imbalance (ERI) questionnaire was used to assess chronic work stress. The emotions of stress, irritation and satisfaction were assessed six times during both days. Seventeen subjects had an ERI ratio over 1, indicating imbalance between effort and reward, that is, chronic work stress. Of the daily emotions, satisfaction was the predominant emotion. The daytime relaxation percentage was higher on Day 2 than on Day 1 (4 ± 6% vs. 2 ± 3%, p < 0.05) and the night time relaxation (43 ± 30%) was significantly higher than daytime or work time relaxation on the both Days. Chronic work stress correlated with the vagal activity index of HRV. However, effort at work had many HRV correlates: the higher the work effort the lower daytime HRV and relaxation time. Emotions at work were also correlated with work time (stress and satisfaction) and night time (irritation) HRV. These results indicate that daily emotions at work and chronic work stress, especially effort, is associated with cardiac autonomic function. Neural network modelling of individual heart rate and HRV information may provide additional information in stress research in field conditions.

Assessment of Autonomic Function in Cardiovascular Disease

Authors: Marc K. Lahiri, Prince J. Kannankeril, Jeffrey J. Goldberger

Abstract: Certain abnormalities of autonomic function in the setting of structural cardiovascular disease have been associated with an adverse prognosis. Various markers of autonomic activity have received increased attention as methods for identifying patients at risk for sudden death. Both the sympathetic and the parasympathetic limbs can be characterized by tonic levels of activity, which are modulated by, and respond reflexively to, physiological changes. Heart rate provides an index of the net effects of autonomic tone on the sinus node, and carries prognostic significance. Heart rate variability, though related to heart rate, assesses modulation of autonomic control of heart rate and carries additional prognostic information, which in some cases is more powerful than heart rate alone. Heart rate recovery after exercise represents the changes in autonomic tone that occur immediately after cessation of exercise. This index has also been shown to have prognostic significance. Autonomic evaluation during exercise and recovery may be important prognostically, because these are high-risk periods for sudden death, and the autonomic changes that occur with exercise could modulate this high risk. These markers provide related, but not redundant information about different aspects of autonomic effects on the sinus node.

Autonomic Cardiac Activity in Patients with Smoking and Alcohol Addiction by Heart Rate Variability Analysis

Authors: Ramazan Yuksel, Rabia Nazik Yuksel, Tijen Sengezer, Senol Dane

Abstract: Purpose: Smoking and alcohol addictions are common and worldwide. In the present study, we aimed to investigate the effects of these addictions on cardiac rhythm using heart rate variability (HRV) analysis. Methods: Addicts (n=42 men: 22 cigarette; 20 cigarette and alcohol) and age-matched controls (n=34 men) were included in the study. All patients fulfill the criteria for dependence according to DSM-IV-TR. Electrocardiography (ECG) recordings were obtained for a total of 30 minutes. Fagerstrom Nicotine Addiction Test (FNAT) and CAGE questionnaire (Cut down, Annoy, Guilt, Eye opener) was applied to all patients. Results: Almost all HRV parameters were significantly decreased in cigarette and cigarette and alcohol addicts compared with controls (p<0.05). The mean heart rate (bpm) increased in both addict groups compared with control group, and this increase was particularly significant in cigarette and alcohol addicts. Conclusions: The cardiac autonomic balance shifted in favor of sympathetic activity by suppressing the parasympathetic activity in addicts; therefore, the present study shows that smoking and/or alcohol addiction leads to sympathetic activation and parasympathetic inhibition. Reduced vagal activity also predisposes to cardiac arrhythmias. This suggests an increased risk of cardiovascular mortality in subjects with smoking and alcohol addiction.

The connection between heart rate variability (HRV), neurological health, and cognition: A literature review

Authors: Xianghong Arakaki, Rebecca J. Arechavala, Elizabeth H. Choy, Jayveeritz Bautista, Bishop Bliss, Cathleen Molloy, Daw-An Wu, Shinsuke Shimojo, Yang Jiang, Michael T. Kleinman, Robert A. Kloner

Abstract: The heart and brain have bi-directional influences on each other, including autonomic regulation and hemodynamic connections. Heart rate variability (HRV) measures variation in beat-to-beat intervals. New findings about disorganized sinus rhythm (erratic rhythm, quantified as heart rate fragmentation, HRF) are discussed and suggest overestimation of autonomic activities in HRV changes, especially during aging or cardiovascular events. When excluding HRF, HRV is regulated via the central autonomic network (CAN). HRV acts as a proxy of autonomic activity and is associated with executive functions, decision-making, and emotional regulation in our health and wellbeing. Abnormal changes of HRV (e.g., decreased vagal functioning) are observed in various neurological conditions including mild cognitive impairments, dementia, mild traumatic brain injury, migraine, COVID-19, stroke, epilepsy, and psychological conditions (e.g., anxiety, stress, and schizophrenia). Efforts are needed to improve the dynamic and intriguing heart-brain interactions.

Possibilities and limitations of the polar RS800 in measuring heart rate variability at rest

Authors: Martin Benka Wallén, Dan Hasson, To ̈res Theorell, Barbara Canlon, Walter Osika

Abstract: A growing trend among clinical studies is the use of heart rate monitors (HRMs) for assessment of heart rate variability (HRV). These instruments offer a convenient alternative to traditional electrocardiographs (ECGs) for recording and processing of R-R data. Reports on the validity of such systems are, however, conflicting. This study aimed to assess the validity of a commercial HRM on a large study sample, with emphasis on gender and age. Simultaneous recordings of R-R intervals were conducted with the Polar RS800 HRM and a 3-lead ECG on 341 individuals. Data editing was performed with individually designated software for each instrument. Agreement on SDNN, RMSSD, and HFand LF power was assessed with intraclass correlations (ICCs), standard errors of measurement (SEMs) and Bland and Altman plots. The HRM was not able to identify 18 observations with non-sinus beats. For men, agreement between instruments ranged from good to excellent (ICC ≥ 0.8) on all HRV measures, and SEMs were generally small. For women the results were weaker, with unacceptable agreement between instruments on SDNN. Women over 60 years did not reach a critical ICC value of 0.75 on any of the HRV measures. Bland and Altman plots demonstrated that the RS800 generally overestimated HRV, and that uncertainty increased with higher values. Since the Polar system did not identify errors satisfactorily, or return valid values of HRV for certain groups, it is concluded that, whenever possible, traditional ECGs should be used for both gathering and editing of HRV data.

Heart rate variability and suicidal behavior

Authors: Scott T. Wilson, Megan Chesin, Eric Fertuck, John Keilp, Beth Brodsky, J. John Mann, Cemile Ceren Sönmez, Christopher Benjamin-Phillips, Barbara Stanley

Abstract: Identification of biological indicators of suicide risk is important given advantages of biomarker-based models. Decreased high frequency heart rate variability (HF HRV) may be a biomarker of suicide risk. The aim of this research was to determine whether HF HRV differs between suicide attempters and nonattempters. Using the Trier Social Stress Test (TSST), we compared HF HRV between females with and without a history of suicide attempt, all with a lifetime diagnosis of a mood disorder. To investigate a potential mechanism explaining association between HF HRV and suicide, we examined the association between self-reported anger and HF HRV. Results of an Area under the Curve (AUC) analysis showed attempters had a lower cumulative HF HRV during the TSST than non-attempters. In addition, while there was no difference in self-reported anger at baseline, the increase in anger was greater in attempters, and negatively associated with HF HRV. Results suggest that suicide attempters have a reduced capacity to regulate their response to stress, and that reduced capacity to regulate anger may be a mechanism through which decreased HF HRV can lead to an increase in suicide risk. Our results have implications for the prevention of suicidal behavior in at-risk populations.

Heart Rate Variability: Measurement and Clinical Utility

Authors: Robert E. Kleiger, Phyllis K. Stein, J. Thomas Bigger, Jr.

Abstract: Heart rate responds dynamically to physiologic perturbations mediated by the autonomic nervous system via efferent vagal and sympathetic nerve impulses. Even at rest heart rate fluctuates cyclically. High frequency (HF) cyclic fluctuations are modulated by ventilation, mediated entirely by changes in vagal outflow. Slower fluctuations occur due to baroreflexes or due to thermoregulation. The greatest variation of heart rate occurs with circadian changes, particularly the difference between night and day heart rate, mediated by complex and poorly understood neurohormonal rhythms. Exercise and emotion also have profound effects on heart rate. Fluctuations in heart rate reflect autonomic modulation and have prognostic significance in pathological states. There are two common settings in which heart rate variability (HRV) is measured. First, HRV is assessed under controlled laboratory conditions with short‐term measurements before and after tilt, drugs, controlled ventilation, or other maneuvers selected to challenge the autonomic system. Secondly, HRV can be determined from 24‐hour electrocardiographic (ECG) recordings made while subjects perform their usual daily activities. Twenty‐four‐hour ECG recordings are particularly useful for risk stratification in a variety of pathological entities, but can also be useful for quantifying autonomic dysfunction. Methods for quantifying HRV are categorized as: time domain, spectral or frequency domain, geometric, and nonlinear. Baroreflex sensitivity (BRS) and heart rate turbulence can also be considered measures of HRV. A short discussion of each will follow.

Nonlinear Heart Rate Variability features for real-life stress detection. Case study: students under stress due to university examination

Authors: Paolo Melill, Marcello Bracale and Leandro Pecchia

Abstract: Background: This study investigates the variations of Heart Rate Variability (HRV) due to a real-life stressor and proposes a classifier based on nonlinear features of HRV for automatic stress detection. Methods: 42 students volunteered to participate to the study about HRV and stress. For each student, two recordings were performed: one during an on-going university examination, assumed as a real-life stressor, and one after holidays. Nonlinear analysis of HRV was performed by using Poincaré Plot, Approximate Entropy, Correlation dimension, Detrended Fluctuation Analysis, Recurrence Plot. For statistical comparison, we adopted the Wilcoxon Signed Rank test and for development of a classifier we adopted the Linear Discriminant Analysis (LDA). Results: Almost all HRV features measuring heart rate complexity were significantly decreased in the stress session. LDA generated a simple classifier based on the two Poincaré Plot parameters and Approximate Entropy, which enables stress detection with a total classification accuracy, a sensitivity and a specificity rate of 90%, 86%, and 95% respectively. Conclusions: The results of the current study suggest that nonlinear HRV analysis using short term ECG recording could be effective in automatically detecting real-life stress condition, such as a university examination.

Effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension

Authors: Changjun Li MD, Qinghua Chang MD, Jia Zhang MD, Wenshu Chai PhD

Abstract: This study is to investigate the effects of slow breathing on heart rate variability (HRV) and arterial baroreflex sensitivity in essential hypertension. We studied 60 patients with essential hypertension and 60 healthy controls. All subjects underwent controlled breathing at 8 and 16 breaths per minute. Electrocardiogram, respiratory, and blood pressure signals were recorded simultaneously. We studied effects of slow breathing on heart rate, blood pressure and respiratory peak, high-frequency (HF) power, low-frequency (LF) power, and LF/ HF ratio of HRV with traditional and corrected spectral analysis. Besides, we tested whether slow breathing was capable of modifying baroreflex sensitivity in hypertensive subjects. Slow breathing, compared with 16 breaths per minute, decreased the heart rate and blood pressure (all P<.05), and shifted respiratory peak toward left (P < .05). Compared to 16 breaths/minute, traditional spectral analysis showed increased LF power and LF/HF ratio, decreased HF power of HRV at 8 breaths per minute (P < .05). As breathing rate decreased, corrected spectral analysis showed increased HF power, decreased LF power, LF/HF ratio of HRV (P < .05). Compared to controls, resting baroreflex sensitivity decreased in hypertensive subjects. Slow breathing increased baroreflex sensitivity in hypertensive subjects (from 59.48 ± 6.39 to 78.93±5.04ms/mmHg, P<.05) and controls (from 88.49±6.01 to 112.91±7.29ms/mmHg, P<.05). Slow breathing can increase HF power and decrease LF power and LF/HF ratio in essential hypertension. Besides, slow breathing increased baroreflex sensitivity in hypertensive subjects. These demonstrate slow breathing is indeed capable of shifting sympathovagal balance toward vagal activities and increasing baroreflex sensitivity, suggesting a safe, therapeutic approach for essential hypertension.

Effects of Cardiac Autonomic Dysfunction on Mortality Risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

Authors: Rodica Pop-Busui, Gregory W. Evans, Hertzel C. Gerstein, Vivian Fonseca, Jerome L. Fleg, Byron J. Hoogwerf, Saul Genuth, Richard H. Grimm, Marshall A. Corson, Ronald Prineas

Abstract: OBJECTIVE — Intensive therapy targeting normal blood glucose increased mortality compared with standard treatment in a randomized clinical trial of 10,251 participants with type 2 diabetes at high-risk for cardiovascular disease (CVD) events. We evaluated whether the presence of cardiac autonomic neuropathy (CAN) at baseline modified the effect of intensive compared with standard glycemia treatment on mortality outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. RESEARCH DESIGN AND METHODS — CAN was assessed by measures of heart rate variability (HRV) and QT index (QTI) computed from 10-s resting electrocardiograms in 8,135 ACCORD trial participants with valid measurements (mean age 63.0 years, 40% women). Prespecified CAN definitions included a composite of the lowest quartile of HRV and highest QTI quartile in the presence or absence of peripheral neuropathy. Outcomes were all-cause and CVD mortality. Associations between CAN and mortality were evaluated by proportional hazards analysis, adjusting for treatment group allocation, CVD history, and multiple prespecified baseline covariates. RESULTS — During a mean 3.5 years follow-up, there were 329 deaths from all causes. In fully adjusted analyses, participants with baseline CAN were 1.55–2.14 times as likely to die as participants without CAN, depending on the CAN definition used (P 0.02 for all). The effect of allocation to the intensive group on all-cause and CVD mortality was similar in participants with or without CAN at baseline (Pinteraction 0.7). CONCLUSIONS — Whereas CAN was associated with increased mortality in this high-risk type 2 diabetes cohort, these analyses indicate that participants with CAN at baseline had similar mortality outcomes from intensive compared with standard glycemia treatment in the ACCORD cohort.

Assessment of physiological signs associated with COVID-19 measured using wearable devices

Authors: Aravind Natarajan, Hao-Wei Su, Conor Heneghan

Abstract: Respiration rate, heart rate, and heart rate variability are some health metrics that are easily measured by consumer devices and which can potentially provide early signs of illness. Furthermore, mobile applications which accompany wearable devices can be used to collect relevant self-reported symptoms and demographic data. This makes consumer devices a valuable tool in the fight against the COVID-19 pandemic. We considered two approaches to assessing COVID-19 a symptom-based approach, and a physiological signs based technique. Firstly, we trained a Logistic Regression classifier to predict the need for hospitalization of COVID-19 patients given the symptoms experienced, age, sex, and BMI. Secondly, we trained a neural network classifier to predict whether a person is sick on any specific day given respiration rate, heart rate, and heart rate variability data for that day and and for the four preceding days. Data on 1,181 subjects diagnosed with COVID-19 (active infection, PCR test) were collected from May 21 July 14, 2020. 11.0% of COVID-19 subjects were asymptomatic, 47.2% of subjects recovered at home by themselves, 33.2% recovered at home with the help of someone else, 8.16% of subjects required hospitalization without ventilation support, and 0.448% required ventilation. Fever was present in 54.8% of subjects. Based on self-reported symptoms alone, we obtained an AUC of 0.77 ± 0.05 for the prediction of the need for hospitalization. Based on physiological signs, we obtained an AUC of 0.77 ± 0.03 for the prediction of illness on a specific day with 4 previous days of history. Respiration rate and heart rate are typically elevated by illness, while heart rate variability is decreased. Measuring these metrics can help in early diagnosis, and in monitoring the progress of the disease.

Relative influence of age, resting heart rate and sedentary life style in short-term analysis of heart rate variability

Authors: E R Migliaro, P Contreras, S Bech, A Etxagibel, M Castro, R Ricca, K Vicente

Abstract: In order to assess the relative influence of age, resting heart rate (HR) and sedentary life style, heart rate variability (HRV) was studied in two different groups. The young group (YG) consisted of 9 sedentary subjects aged 15 to 20 years (YG-S) and of 9 nonsedentary volunteers (YG-NS) also aged 15 to 20. The elderly sedentary group (ESG) consisted of 16 sedentary subjects aged 39 to 82 years. HRV was assessed using a short-term procedure (5 min). R-R variability was calculated in the time-domain by means of the root mean square successive differences. Frequency-domain HRV was evaluated by power spectrum analysis considering high frequency and low frequency bands. In the YG the effort tolerance was ranked in a bicycle stress test. HR was similar for both groups while ESG showed a reduced HRV compared with YG. Within each group, HRV displayed a negative correlation with HR. Although YG-NS had better effort tolerance than YG-S, their HR and HRV were not significantly different. We conclude that HRV is reduced with increasing HR or age, regardless of life style. The results obtained in our short-term study agree with others of longer duration by showing that age and HR are the main determinants of HRV. Our results do not support the idea that changes in HRV are related to regular physical activity.

Heart Rate Variability: Measurement and Clinical Utility

Authors: Robert E. Kleiger, M.D.,Phyllis K. Stein, Ph.D.,J. Thomas Bigger, Jr., M.D.

Abstract: Electrocardiographic RR intervals fluctuate cyclically, modulated by ventilation, baroreflexes, and other genetic and environmental factors that are mediated through the autonomic nervous system. Short term electrocardiographic recordings (5 to 15 minutes), made under controlled conditions, e.g., lying supine or standing or tilted upright can elucidate physiologic, pharmacologic, or pathologic changes in autonomic nervous system function. Long‐term, usually 24‐hour recordings, can be used to assess autonomic nervous responses during normal daily activities in health, disease, and in response to therapeutic interventions, e.g., exercise or drugs. RR interval variability is useful for assessing risk of cardiovascular death or arrhythmic events, especially when combined with other tests, e.g., left ventricular ejection fraction or ventricular arrhythmias.

Making health habitual:the psychology of ‘habit-formation’ and general practice

Authors: Benjamin Gardner, Phillippa Lally, Jane Wardle,

Abstract: MAKING HEALTH HABITUAL The Secretary of State recently proposed that the NHS: ‘... take every opportunity to prevent poor health and promote healthy living by making the most of healthcare professionals’ contact with individual patients.’ 1 Patients trust health professionals as a source of advice on ‘lifestyle’ (that is, behaviour) change, and brief opportunistic advice can be effective.2 However, many health professionals shy away from giving advice on modifying behaviour because they find traditional behaviour change strategies time-consuming to explain and difficult for the patient to implement.2 Furthermore, even when patients successfully initiate the recommended changes, the gains are often transient3 because few of the traditional behaviour change strategies have built-in mechanisms for maintenance. Brief advice is usually based on advising patients on what to change and why (for example, reducing saturated fat intake to reduce the risk of heart attack). Psychologically, such advice is designed to engage conscious deliberative motivational processes, which Kahneman terms ‘slow’ or ‘System 2’ processes.4 However, the effects are typically short-lived because motivation and attention wane. Brief advice on how to change, engaging automatic (‘System 1’) processes, may offer a valuable alternative with potential for long-term impact. Opportunistic health behaviour advice must be easy for health professionals to give and easy for patients to implement to fit into routine health care. We propose that simple advice on how to make healthy actions into habits — externally-triggered automatic responses to frequently encountered contexts — offers a useful option in the behaviour change toolkit. Advice for creating habits is easy for clinicians to deliver and easy for patients to implement: repeat a chosen behaviour in the same context, until it becomes automatic and effortless.

Perceived Mental Stress and Reactions in Heart Rate Variability—A Pilot Study Among Employees of an Electronics Company

Authors: Reetta Orsila, Matti Virtanen, Tiina Luukkaala, Mika Tarvainen, Pasi Karjalainen, Jari Viik, Minna Savinainen, Clas-Håkan Nygård

Abstract: In this study perceived mental stress during occupational work was compared to heart rate variability (HRV) using a traditional questionnaire and a novel wristop heart rate monitor with related software. The aim was to find HRV parameters useful for mental stress detection. We found the highest correlation between perceived mental stress with the differences between the values of triangular interpolation of rythm-to-rythm (RR) interval histogram (TINN) and the root mean square of differences of successive RR intervals (RMSSD) obtained in the morning and during the workday (r = –.73 and r = –.60, respectively). The analysis shows that as the RMSSD and TINN value differences increase from night to morning, the stress decreases.

Heart Rate Variability as an Index of Regulated Emotional Responding

Authors: Bradley M. Appelhans, Linda J. Luecken

Abstract: The study of individual differences in emotional responding can provide considerable insight into interpersonal dynamics and the etiology of psychopathology. Heart rate variability (HRV) analysis is emerging as an objective measure of regulated emotional responding (generating emotional responses of appropriate timing and magnitude). This review provides a theoretical and empirical rationale for the use of HRV as an index of individual differences in regulated emotional responding. Two major theoretical frameworks that articulate the role of HRV in emotional responding are presented, and relevant empirical literature is reviewed. The case is made that HRV is an accessible research tool that can increase the understanding of emotion in social and psychopathological processes.

Comparison of three mobile devices for measuring R–R intervals and heart rate variability: Polar S810i, Suunto t6 and an ambulatory ECG system

Authors: Matthias Weippert, Mohit Kumar, SteY Kreuzfeld, Dagmar Arndt, Annika Rieger, Regina Stoll

Abstract: The first aim of this study was to compare an ambulatory five-lead ECG system with the commercially available breast belt measuring devices; Polar S810i and Suunto t6, in terms of R-R interval measures and heart rate variability (HRV) indices. The second aim was to compare different HRV spectral analysis methods. Nineteen young males (aged between 22 and 31 years, median 24 years) underwent simultaneous R-R interval recordings with the three instruments during supine and sitting rest, moderate dynamic, and moderate to vigorous static exercise of the upper and lower limb. For each subject, 17 R-R interval series of 3-min length were extracted from the whole recordings and then analyzed in frequency domain using (1) a fast Fourier transform (FFT), (2) an autoregressive model (AR), (3) a Welch periodogram (WP) and (4) a continuous wavelet transform (CWT). Intra-class correlation coefficients (ICC) and Bland-Altman limits of agreement (LoA) method served as criteria for measurement agreement. Regarding the R-R interval recordings, ICC (lower ICC 95% confidence interval >0.99) as well as LoA (maximum LoA: -15.1 to 14.3 ms for ECG vs. Polar) showed an excellent agreement between all devices. Therefore, the three instruments may be used interchangeably in recording and interpolation of R-R intervals. ICCs for HRV frequency parameters were also high, but in most cases LoA analysis revealed unacceptable discrepancies between the instruments. The agreement among the different frequency transform methods can be taken for granted when analyzing the normalized power in low and high frequency ranges; however, not when analyzing the absolute values.

Computational Intelligence Methods for the Identification of Early Cardiac Autonomic Neuropathy

Authors: David J Cornforth, Mika P Tarvainen, Herbert F Jelinek

Abstract: Visualization models can assist in understanding the complex pattern of disease, where the signs may be buried in complex data. In this work we propose a new method for visualization of data derived from Heart Rate Variability (HRV) analysis, to indicate whether a person has developed, or is developing, signs of definite Cardiac Autonomic Neuropathy (CAN). Here, the visualizations are compared with actual data recorded from people attending a diabetes clinic with and without definite CAN. Indications from the new visualization technique are compared to the results of established diagnostic measures using the Ewing battery of tests. We find the proposed method to offer useful insights into this disease, as rather than relying upon a binary yes/no decision, it offers a comprehensive picture of the complexity of this disease.

The Relationship Between Spectral Changes in Heart Rate Variability and Fatigue

Authors: Yvonne Tran, Nirupama Wijesuriya, Mika Tarvainen, Pasi Karjalainen, Ashley Craig

Abstract: Fatigue is a prevalent problem in the workplace and a common symptom of many diseases. However, its relationship with the autonomic nervous system, specifically with sympathetic arousal, needs clarification. The objective of this study was to determine the association between fatigue and heart rate variability (HRV). HRV is regarded as an indicator of the autonomic regulation activity of heart rate, specifically sympathetic and parasympathetic activity. Spectral changes in low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.15-0.4 Hz) components of HRV have been reported to be associated with distressing conditions such as hemorrhagic shock, acute myocardial infarction, elevated anxiety, and depressed mood. While HRV changes have been found in persons with chronic fatigue syndrome, its association with fatigue in healthy individuals still needs clarification. HRV was assessed in a total of 50 participants who were asked to perform a task until becoming fatigued. Low-frequency HRV activity increased, while indices of parasympathetic modulation such as RMSSD and pNN50 remained stable as participants experienced fatigue, suggesting that fatigue in healthy individuals may be associated with increased sympathetic arousal. In addition, employing multiple regression analyses, we could positively associate the change in LF/HF HRV ratio from baseline to fatigue with factors such as emotional stability, warmth and tension and negatively associate it with social boldness and self-reported levels of vigor.

Influence of Heart Rate Variability and Psychosocial Factors on Carotid Stiffness, Elasticity and Impedance at Menopause

Authors: Mauricio Sánchez-Barajas, Nicté Figueroa-Vega, Lorena Del Rocío Ibarra-Reynoso, Carmen Moreno-Frías, Juan Manuel Malacara

Abstract: Background and aims: The risk for cardiovascular diseases (CVD) increases after menopause. Heart rate variability (HRV), a measure of autonomic control, is a strong predictor of CVD. We undertook this study to test the association of ultrasound indices of early carotid atherosclerosis with HRV, symptoms, hormonal conditions, metabolic state, indicators of stress, and psychosocial factors in women at periand postmenopause, registering ambulatory R-R interval monitoring. Methods: In a cross-sectional design we studied 100 women at periand early postmenopause collecting anthropometry, symptoms, stress-related measurements, metabolic variables, cortisol, FSH and estradiol. We evaluated carotid ultrasonographic indices, and HRV was recorded for 4 h calculating time (SDNN, pNN50, rMSSD) and frequency domains (LF, HF, LF/HF) in women according to menopausal stage, estradiol levels, body mass index and waist circumference. Results: Carotid indices were similar in periand postmenopausal women. For HRV measurements, SDNN was increased at postmenopause. Women with estradiol levels <109.2 pmol/L had increased intima-media thickness (IMT), resistive index, and systolic diameter. Using multivariate analysis, we found the associations of IMT positively with non-HDL-cholesterol, resistive index positively with LF-HRV, but negatively with effort/reward imbalance, carotid β stiffness index inversely with estradiol, and arterial distensibility positively with HF-HRV and creatinine concentrations, but negatively with non-HDL-cholesterol. Conclusions: Carotid thickness was related mainly with lipid alterations. Indices of early carotid damage were related with various components of HRV as a manifestation of autonomic imbalance, indicating CVD risk. Other factors involved were time since last menses and psychological stress. Low creatinine was associated with diminished carotid distensibility. This suggests that estrogen, lifestyle, behavior and autonomic regulation participate in vascular damage.

Heart rate variability helps to distinguish the intensity of menopausal symptoms: A prospective, observational and transversal study

Authors: Patŕıcia Merly Martinelli, Isabel Cristina Esposito Sorpreso, Rodrigo Daminello Raimundo, Osvaldo de Souza Leal Junior, Juliana Zangirolami-Raimundo, Marcos Venicius Malveira de Lima, Andrés Pérez-Riera, Valdelias Xavier Pereira, Khalifa Elmushara

Abstract: Heart Rate Variability (HRV) represents cardiac autonomic behavior and have been related to menopausal symptoms, mainly vasomotor symptoms and their imbalance to cardiovascular risk. It is not clear in the literature which index represents this imbalance and what is their involvement with the menopausal state. The aim of this study was to evaluate HRV in menopausal transition and post-menopausal symptoms with different intensities. This cross-sectional study was conducted in Rio Branco, State of Acre, Brazil from October 2016 to July 2017. We used Kupperman-Blatt Menopausal Index (KMI) to measure menopausal symptoms intensity. HRV analysis was performed based on the guidelines of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. HRV is lower in the group with moderate/intense menopausal symptoms compared to mild symptoms. (RMSSD: p = 0.005, Cohen’s d = 0.53, pNN50: p = 0.0004, Cohen’s d = 0.68; HF: p = 0.024, Cohen’s d = 0.44). There was association between HRV and KMI (RMSSD: r = -1.248, p = 0.004; and pNN50: r = -0.615, p: 0.029) in inverse relation to the intensity of vasomotor symptoms in women in TM. In conclusion, HRV was able to distinguish menopausal symptoms, indicating reduced vagal control in women with more intense symptoms.

Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders

Authors: Elisabetta Pistorio, Maria Luca, Antonina Luca, Vincenzo Messina, Carmela Calandra

Abstract: Objective: To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. Methods: 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, AnxiousDepressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. Results: Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Conclusions: Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

The physiological basis and measurement of heart rate variability in humans

Authors: Adina E. Draghici, J. Andrew Taylor

Abstract: Cardiovascular variabilities were recognized over 250 years ago, but only in the past 20 years has their apparent utility come to be appreciated. Technological advancement has allowed precise measurement and quantification of short-term cardiovascular fluctuations; however, our understanding of the integrated mechanisms which underlie these oscillations is inadequate for their widespread application. Both autonomic branches, the parasympathetic and sympathetic nervous system, are key determinants of the magnitude of these spontaneous cardiovascular fluctuations. Heart rate variability can be an indicator of an individual cardiovascular condition. In this review, we will discuss the two primary rhythmic oscillations that underlie the complexity of the heart rate waveform. The first oscillation occurs over several cardiac cycles, is respiratory related, and termed respiratory sinus arrhythmia. The second oscillation occurs at an approximate 10 s cycle. Due to the closed-loop nature of the control system of cardiovascular oscillations, it is difficult to define specific relations among cardiovascular variables. In this review, we will present the feedforward and feedback mechanism that underlie both oscillations and their implication as quantitative measures of autonomic circulatory control. We will also review the various methodologies to assess them.

Quantitative Poincare Plots Analysis Contains Relevant Information Related to Heart Rate Variability Dynamics of Normal and Pathological Subjects

Authors: G D'Addio, GD Pinna, R Maestri, G Corbi, N Ferrara, F Rengo

Abstract: Poincarè plots (PPlots) analysis of RR time series allows a beat-to-beat approach to HRV, detecting patterns associated with non linear processes. Aim of this study was to assess the discriminating power of this method over fifty 24-hours Holter recordings of normal, hypertensive, post-MI, chronic heart failure and transplanted subjects. The analysis was performed by nine novel computer-generated quantitative descriptors of main 2D and 3D morphological characteristics of PPlots. A forward stepwise discriminant analysis showed that four variables, provided independent and significant contribution to the overall discrimination with a 82% total classification function's score between different pathological conditions. Although further investigations should be provided, this results clearly indicate that PPlots analysis contains relevant information related to different HRV dynamics of normal and cardiac patients.

ActiGraph and Short-term Heart Rate Variability Study Protocol

Authors: Anna Luong, BSN, Madison Goodyke, Susan L. Dunn, Tracy Baynard, Ulf Bronas

Abstract: Background: ActiGraph accelerometry is widely used in nursing research to estimate daily physical activity. Heart rate variability (HRV), a measure of autonomic modulation, can be assessed in conjunction with the ActiGraph using a Polar H7 Bluetooth heart rate monitor. There is a paucity of nursing literature to guide nurse researchers' protocol development when using the ActiGraph to assess both physical activity and short-term HRV via its Bluetooth capabilities. Objectives: The aim of this study was to describe a standardized research ActiGraph and HRV (ActiGraph HRV) protocol for an ongoing randomized controlled trial to measure physical activity and short-term HRV in patients with ischemic heart disease who report hopelessness. Methods: We outline the study protocol for the standardization of reliable and rigorous physical activity and HRV data collection using the ActiGraph wGT3X-BT and Polar H7 Bluetooth heart rate monitor, and data analysis using ActiLife and Kubios software programs. Results: Sixty-four participants enrolled in the randomized controlled trial to date, and 45 (70.3%) have completed or are actively participating in the study. Heart rate variability data have been collected on 43 of the 45 participants (96%) to date. During the first data collection time point, 42 of 44 participants (95.5%) wore the ActiGraph for a minimum of 5 valid days, followed by 28 of 31 participants (90.3%) and 25 of 26 participants (96.2%) at subsequent data collection time points. The intraclass correlation for physical activity in this study is 0.95 and 0.98 for HRV. Discussion: Revisions to the protocol were successfully implemented at the onset of the COVID-19 pandemic for data collection using social distancing. The protocol was additionally amended in response to an unanticipated problem with ActiGraph battery life using Bluetooth technology. Use of the ActiGraph HRV protocol has led to a reliable and rigorous measurement of physical activity and HRV for patients with ischemic heart disease who report hopelessness in this randomized controlled trial. Conclusion: We provide an ActiGraph HRV protocol that can be adapted as a model in the development of ActiGraph HRV protocols for future nursing research in community and home-based settings while maximizing social distancing in the current and future pandemics.

Parasympathetic Nervous System and Heart Failure

Authors: Brian Olshansky, Hani N. Sabbah, Paul J. Hauptman, Wilson S. Colucci

Abstract: A bundant evidence links sympathetic nervous system activation to outcomes of patients with heart failure (HF). In contrast, parasympathetic activation has complex cardiovascular effects that are only beginning to be recognized. In particular, the pathophysiological roles of normal and disordered parasympathetic innervation in patients with HF are not understood as comprehensively. In the present article, we review cardiovascular responses to parasympathetic activation, address the modulating factors that can affect parasympathetic function, discuss the role of the vagus nerve in ventricular dysfunction, and consider how activation of the parasympathetic nervous system may have important therapeutic implications for patients with congestive HF.

You may need the vagus nerve to understand pathophysiology and to treat diseases

Authors: Marijke De Couck, Boris Mravec, Yori Gidron

Abstract: Can different pathophysiological mechanisms and risk factors leading to various diseases be linked with altered transmission of signals by one common pathway? The present article provides evidence for the hypothesis that adequate vagal nerve activity reduces the risk of major diseases, via common basic mechanisms and interim risk factors. These diseases include cardiovascular disease, cancer, Alzheimer's disease and the metabolic syndrome. Three basic mechanisms contribute to such illnesses: local oxidative stress and DNA damage, inflammatory reactions and excessive sympathetic responses, all of which are inhibited by vagal nerve activity. Efferent vagal activity that can be non-invasively measured by HRV (heart rate variability), derived from an ECG, is inversely related to all three basic mechanisms, to various risk factors (e.g. diabetes and dyslipidaemia) and, more broadly, to the diseases as well. Finally, vagal activity is proposed to moderate the effects of risk factors on developing such illnesses. By proposing an integrative neurobiological model of major diseases, identifying people at risk for, and treating patients with, such diseases may be done more efficiently. People with low HRV may be identified and subsequently treated by vagus nerve activation to possibly prevent or treat such illnesses. This proposed disease paradigm may have important preventative and therapeutic implications, whose clinical effects need to be investigated.

Heart Rate Variability Measure in Breast Cancer Patients and Survivors: A Systematic Review

Authors: Claudia Arab, Daniel Penteado Martins Dias, Renata Thaís de Almeida Barbosa, Tatiana Dias de Carvalho, Vitor Engrácia Valenti, Tânia Brusque Crocetta, Marcelo Ferreira, Luiz Carlos de Abreu, Celso Ferreira

Abstract: Purpose In the current study, we aimed to review literature findings showing the clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in breast cancer (BC) patients and survivors. Methods We conducted a systematic review according to The PRISMA Statement in Medline, Scopus and Web of Science (_-2015) databases. The search was limited to articles in English language, published in peer-reviewed journals, and with adult age samples only (e.g., women, patients, or survivors, diagnosed with BC in any stage). We included observational studies and randomized trials. Detailed heart rate variability analysis (instruments, data collection protocol, and analysis methods) was required. Search terms included autonomic nervous system, heart rate variability, sympathetic and parasympathetic nervous system, autonomic dysfunction, vagal nervous and breast neoplasms, breast cancer and breast tumor. Results Twelve studies were included in this review. The clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in BC patients and survivors is demonstrated by association with effects of BC surgery, and treatments, and the adverse effects of surgery and treatments on survivors (e.g., cardiotoxicity, fatigue, and stress). Limitations The strength of evidence of included studies is low: small samples size and heterogeneity, presence of confounders, and observational studies design. Conclusions The heart rate variability analysis could be used as a complementary non-invasive tool for the early diagnosis and better prognosis of autonomic dysfunction, and survival in BC patients. There are many potential clinical applications of heart rate variability analysis in BC patients, and the employment of such approaches could lead to lower impairment of autonomic function in this individuals.

Vagal nerve activity predicts overall survival in metastatic pancreatic cancer, mediated by inflammation

Authors: Marijke De Couck, Raphaël Maréchal, Sofie Moorthamers, Jean-Luc Van Laethem, Yori Gidron

Abstract: Recent research findings suggest neuro-modulation of tumors. Finding new modifiable prognostic factors paves the way for additional treatments, which is crucial in advanced cancer, particularly pancreatic cancer. This study examined the relationship between vagal nerve activity, indexed by heart rate variability (HRV), and overall survival (OS) in patients (N=272) with advanced pancreatic cancer. A "historical prospective" design was employed, where vagal activity and other confounders were retroactively obtained from medical charts at diagnosis, and subsequent OS was examined. HRV was obtained from 10 sec ECGs near diagnosis. Levels of C-reactive protein (CRP) were measured as an inflammatory marker. OS and survival date were obtained from medical charts and the Belgian national registry. Patients with high HRV (>20 msec) survived on average more than double the days (133.5) than those with low HRV (64.0). In a multivariate cox regression, higher initial HRV was significantly correlated with lower risk of death, independent of confounders including age and cancer treatments. This relationship was statistically mediated (accounted for) by CRP levels. Importantly, in patients who lived up to one month from diagnosis only, HRV was unrelated to CRP, while in patients surviving longer, HRV was significantly inversely related to CRP (r=-0.20, p<0.05). These results are in line with possible vagal nerve protection in a fatal cancer, and propose that the mechanism may involve neuroimmuno-modulation. Future studies must test whether vagal nerve activation may help patients with advanced cancers.

The association between autonomic dysfunction and survival in male patients with advanced cancer: a preliminary report

Authors: Nada Fadul, Florian Strasser, J Lynn Palmer, Syed Wamique Yusuf, Ying Guo, Zhijun Li, Julio Allo, Eduardo Bruera

Abstract: Context: Autonomic nervous system dysfunction (AD) is a common syndrome in patients with advanced cancer. It is associated with decreased survival in several patient populations, including diabetes mellitus, heart failure, and neurological diseases. Based on this evidence, we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer. Objectives: The objective of this preliminary study was to test the association between AD, as measured by the standardized Ewing test and heart rate variability (HRV) measures, and survival in this patient population. Methods: We examined the relationship between survival and parameters of AD in subjects who participated in a prospective study of autonomic dysfunction and hypogonadism in male patients with advanced cancer. Eligibility criteria were defined based on the prospective study protocol. We collected demographic information, date of death (obtained from the online Social Security Death Index database), date of study entry, and Ewing and HRV scores. We defined survival as the interval between study entry and date of death. A survival analysis was used to test the association between survival (in days) and Ewing test (0-5) and measures of HRV, including time domain (standard deviation of normal to normal beat interval [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients were still alive at the time of this study and included in the survival analysis as being censored. Results: Forty-seven male patients were included in this study. Median age was 59 years (range: 20-79), and 30 out of 47 (63%) were Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of 47 (80%) of the patients. Median Ewing score was 3 (1-5), indicating moderate to severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002). There was a significant association between abnormal Ewing score and survival (P < 0.0001) and abnormal SDNN HRV and survival (P = 0.056). Conclusion: AD is associated with shorter survival in male patients with advanced cancer. Further longitudinal research in a large cohort is justified based on.

Characterization of heart rate variability and baroreflex sensitivity in sedentary individuals and male athletes

Authors: Leandro Yukio A. Kawaguchi, Aline C.P. Nascimento, Márcio S. Lima, Lúcio Frigo, Alderico Rodrigues de Paula Júnior, Carlos Júlio Tierra-Criollo, Rodrigo Alvaro Brandão Lopes-Martins

Abstract: Introduction: The capacity to vary the heart rate represents important physiologic role in the daily life. The variations of the RR intervals is dependent of biological modulators as the autonomic nervous system. Those variations constitute the heart rate variability (HRV). Methods: 10 athletes (Atl) and 10 sedentary (Sed) male individuals (20-35 age) were submitted to digital electrocardiography, in rest, before, during and after the maneuver. The values of RR were analyzed (software Matlab 6.1), in the time domain. Results: Both Sed and Atl presented mean heart rate of 73.5 bpm ± 2,5 and 51 bpm ± 2,4, respectively. Related to the RR intervals, the group of Sed presented average of 826.58 bad ± 5.3 and the group Atl, 1189.18 ± 6.9. The return time of sympathetic system after the maneuver was 72 ± 12 s (Sed) 37 ± 6 s (Atl). The return time of parasympathetic system was 80 ± 11 s (Sed) and 40 ± 8 s (Atl). The pNN50 was of 10 ± 3,3 (Sed) and 42,10 ± 6,9 (Atl). The value of RR variation above the average of the whole sign was 343 ± 40 (Sed) and 175 ± 39 (Atl). The RR variation below the average of the whole sign was 281 ± 27 (Sed) and 425 ± 26 (Atl). Conclusions: The analysis of HRV associated to the Valsalva maneuver can represent a simple, but important tool, for possible inferences on physical aptitude.

Effect of heart rate correction on pre- and post-exercise heart rate variability to predict risk of mortality—an experimental study on the FINCAVAS cohort

Authors: Paruthi Pradhapan, Mika P. Tarvainen, Tuomo Nieminen, Rami Lehtinen, Kjell Nikus, Terho Lehtimäki, Mika Kähönen, Jari Viik

Abstract: The non-linear inverse relationship between RR-intervals and heart rate (HR) contributes significantly to the heart rate variability (HRV) parameters and their performance in mortality prediction. To determine the level of influence HR exerts over HRV parameters’ prognostic power, we studied the predictive performance for different HR levels by applying eight correction procedures, multiplying or dividing HRV parameters by the mean RR-interval (RRavg) to the power 0.5–16. Data collected from 1288 patients in The Finnish Cardiovascular Study (FINCAVAS), who satisfied the inclusion criteria, was used for the analyses. HRV parameters (RMSSD, VLF Power and LF Power) were calculated from 2-min segment in the rest phase before exercise and 2-min recovery period immediately after peak exercise. Area under the receiver operating characteristic curve (AUC) was used to determine the predictive performance for each parameter with and without HR corrections in rest and recovery phases. The division of HRV parameters by segment’s RRavg to the power 2 (HRVDIV-2) showed the highest predictive performance under the rest phase (RMSSD: 0.67/0.66; VLF Power: 0.70/0.62; LF Power: 0.79/0.65; cardiac mortality/non-cardiac mortality) with minimum correlation to HR (r = −0.15 to 0.15). In the recovery phase, Kaplan-Meier (KM) survival analysis revealed good risk stratification capacity at HRVDIV-2 in both groups (cardiac and non-cardiac mortality). Although higher powers of correction (HRVDIV-4and HRVDIV-8) improved predictive performance during recovery, they induced an increased positive correlation to HR. Thus, we inferred that predictive capacity of HRV during rest and recovery is augmented when its dependence on HR is weakened by applying appropriate correction procedures.

Oxytocin Increases Heart Rate Variability in Humans at Rest: Implications for Social Approach-Related Motivation and Capacity for Social Engagement

Authors: Andrew H. Kemp, Daniel S. Quintana, Rebecca-Lee Kuhnert, Kristi Griffiths, Ian B. Hickie, Adam J. Guastella

Abstract: Oxytocin (OT) plays a key regulatory role in human social behaviour. While prior studies have examined the effects of OT on observable social behaviours, studies have seldom examined the effects of OT on psychophysiological markers such as heart rate variability (HRV), which provides an index of individual’s motivation for social behaviour. Furthermore, no studies have examined the impact of OT on HRV under resting conditions, which provides an index of maximal capacity for social engagement.

Racial and Ethnic Disparities in the Prevalence of Stress and Worry, Mental Health Conditions, and Increased Substance Use Among Adults During the COVID-19 Pandemic — United States, April and May 2020

Authors: Lela R. McKnight-Eily, Catherine A. Okoro, Tara W. Strine, Jorge Verlenden, NaTasha D. Hollis, Rashid Njai, Elizabeth W. Mitchell, Amy Board, Richard Puddy, Craig Thomas

Abstract: In 2019, approximately 51 million U.S. adults aged ≥18 years reported any mental illness,* and 7.7% reported a past-year substance use disorder† (1). Although reported prevalence estimates of certain mental disorders, substance use, or substance use disorders are not generally higher among racial and ethnic minority groups, persons in these groups are often less likely to receive treatment services (1). Persistent systemic social inequities and discrimination related to living conditions and work environments, which contribute to disparities in underlying medical conditions, can further compound health problems faced by members of racial and ethnic minority groups during the coronavirus disease 2019 (COVID-19) pandemic and worsen stress and associated mental health concerns (2,3). In April and May 2020, opt-in Internet panel surveys of English-speaking U.S. adults aged ≥18 years were conducted to assess the prevalence of self-reported mental health conditions and initiation of or increases in substance use to cope with stress, psychosocial stressors, and social determinants of health. Combined prevalence estimates of current depression, initiating or increasing substance use, and suicidal thoughts/ideation were 28.6%, 18.2%, and 8.4%, respectively. Hispanic/Latino (Hispanic) adults reported a higher prevalence of psychosocial stress related to not having enough food or stable housing than did adults in other racial and ethnic groups. These estimates highlight the importance of population-level and tailored interventions for mental health promotion and mental illness prevention, substance use prevention, screening and treatment services, and increased provision of resources to address social determinants of health. How Right Now (Qué Hacer Ahora) is an evidence-based and culturally appropriate communications campaign designed to promote and strengthen the emotional well-being and resiliency of populations adversely affected by COVID-19–related stress, grief, and loss (4). CDC licensed results from Porter Novelli’s PN View 360, a nationwide, weekly opt-in Internet panel survey of U.S. adults. The survey was administered by ENGINE Insights in English to U.S. adults aged ≥18 years using the Lucid platform (5); respondents who had not taken a survey in the previous 20 waves of survey administration were eligible to participate. Quota sampling was conducted by ENGINE Insights to identify respondents, and statistical weighting was used during the analysis to match proportions in the 2019 Current Population Survey; therefore, the sample was representative of the overall U.S. population by sex, age, region, race/ethnicity, and education. CDC licensed the results of the PN View 360 survey after data collection from Porter Novelli. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§ In both April and May, 502 respondents participated, for a combined total of 1,004 respondents; the survey included questions about increases in or initiation of substance use during the COVID-19 pandemic,¶ symptoms of current depression,** and suicidal thoughts/ideation,†† as well as questions about psychosocial stress (e.g., feeling isolated and alone), stigma or discrimination (from being blamed for spreading COVID-19), and social determinants of health (e.g., food instability). Combined and weighted response percentages and 95% confidence intervals (CIs) were calculated by using PROC SURVEYFREQ in SAS statistical software (version 9.4; SAS Institute). Because respondents were recruited from an opt-in panel rather than by probability sampling, other than using CIs, no inferential statistical tests were performed.§§ The overall prevalence estimates of current depression, suicidal thoughts/ideation, and initiation of or increase in substance use were 28.6%, 8.4%, and 18.2%, respectively (Table). Symptoms of current depression were reported 59% more frequently by Hispanic adults (40.3%) than by non-Hispanic White (White) persons (25.3%). Estimates of self-reported suicidal thoughts/ideation among Hispanic persons (22.9%) were four times those among non-Hispanic Black (Black) persons (5.2%) and White persons (5.3%) and approximately twice those of multiracial and non-Hispanic persons of other races/ethnicities (8.9%).¶¶ Increased or newly initiated substance use was reported among 36.9% of Hispanic respondents, compared with 14.3%–15.6% among all other respondents. Among U.S. adults overall, sources of psychosocial stress included family health (36.3%), feelings of isolation or loneliness (28.6%), worry about getting ill from COVID-19 or infecting others (25.7%), worry about the death of a loved one or persons dying (15.2%), workplace COVID-19 exposure (13.5%), and stigma or discrimination from being blamed for spreading COVID-19 (4.1%). White adults were more likely to report stress and worry about the health of family members and loved ones (39.3%) than were Black adults (24.5%). A larger percentage of multiracial and non-Hispanic adults of other races/ethnicities reported stress and worry about stigma or discrimination associated with being blamed for spreading COVID-19 (12.9%) than did White (2.4%) or Hispanic (3.7%) adults. Estimates of stress and worry about social determinants of health included possible job loss (27.1%), ability to obtain needed health care (18.4%), not having enough food (14.4%), and housing instability (11.8%). A higher percentage of Hispanic adults reported stress about not having enough food (22.7%) or stable housing (20.7%) than did White adults (11.9% and 9.2%, respectively).

Estrogen Can Modulate Menopausal Women’s Heart Rate Variability


Abstract: The aim of our study was to compare the responses of heart rate variability (HRV) with two different types of hormonal substitution therapy (HT) in post-menopausal women (crosssectional study) and to reveal an effect of HT shortly after beginning of its administration (follow-up study). To elucidate the influence of menopause and effects of different protocols of a HT on autonomic control of heart rate, we evaluated the heart rate variability (HRV) in 5 groups: premenopausal women (n=140), postmenopausal women without HT (n=360), women on HT with conjugated estrogen only (n=168), women on continuous combined estrogen-progesterone HT (n=117), and men (n=140). Frequency-domain of short-term stationary R-R intervals was performed to evaluate the total variance, low frequency power (LF; 0.04-0.15 Hz), high frequency power (HF; 0.15-0.40 Hz), portion of low frequency power (LF%) and ratio of LF to HF (LF/HF). Significantly lower portion of the LF was found in premenopausal women [46.9 (±2.7) nu] when compared to untreated postmenopausal women [54.3 (±2.9) nu] and men [55.2 (±3.0) nu]. Treatment by estrogen only was proved to decrease the LF% [40.1 (±2.1) nu] while no effect on HRV was observed in women treated with combination of estrogen and progesterone [57.2 (±3.1) nu]. Also the HF was lower in postmenopausal women [4.16 (±0.16) ms2] than in premenopausal women [4.79 (±0.22) ms2] and women treated with estrogen only [4.98 (±0.25) ms2] while in women treated with combined hormonal therapy the average value [3.99 (±0.21) ms2] did not significantly differ from that of untreated postmenopausal women. The follow-up study also proved increase of high frequency power already after two months of estrogen substitution therapy [4.86 (±0.14) ms2 vs. 4.19 (±0.15) ms2]. These results suggest that higher vagal modulation of heart rate that seems typical for younger women becomes after menopause similar to that of men. We also proved a positive shift of HRV parameters toward more beneficial values as for a cardiovascular risk in postmenopausal women treated with estrogens but not in those treated by combined estrogen – progesterone substitution therapy.

Age and Sex Differences in Heart Rate Variability and Vagal Specific Patterns – Baependi Heart Study

Authors: Glaucylara Reis Geovanini, Enio Rodrigues Vasques, Rafael de Oliveira Alvim, José Geraldo Mill, Rodrigo Varejão Andreão, Bruna Kim Vasques, Alexandre Costa Pereira, Jose Eduardo Krieger

Abstract: Background: Heart rate variability (HRV) is a noninvasive method for assessing autonomic function. Age, sex, and chronic conditions influence HRV. Objectives: Our aim was to evaluate HRV measures exploring differences by age, sex, and race in a sample from a rural area. Methods: Analytical sample (n = 1,287) included participants from the 2010 to 2016 evaluation period of the Baependi Heart Study, a family-based cohort in Brazil. Participants underwent 24-hour Holter-ECG (Holter) monitoring. To derive population reference values, we restricted our analysis to a ‘healthy’ subset (i.e. absence of medical comorbidities). A confirmatory analysis was conducted with a subgroup sample that also had HRV derived from a resting ECG 10’-protocol obtained during the same time period. Results: The ‘healthy’ subset included 543 participants. Mean age was 40 ± 14y, 41% were male, 74% self-referred as white and mean body-mass-index was 24 ± 3kg/m2. Time domain HRV measures showed significant differences by age-decade and by sex. Higher values were observed for males across almost all age-groups. Parasympathetic associated variables (rMSSD and pNN50) showed a U-shaped distribution and reversal increase above 60y. Sympathetic-parasympathetic balance variables (SDNN, SDANN) decreased linearly by age. Race differences were no significant. We compared time domain variables with complete data (Holter and resting ECG) between ‘healthy’ versus ‘unhealthy’ groups. Higher HRV values were shown for the ‘healthy’ subset compared with the ‘unhealthy’ group. Conclusion: HRV measures vary across age and sex. A U-shaped pattern and a reversal increase in parasympathetic variables may reflect an age-related autonomic dysfunction even in healthy individuals that could be used as a predictor of disease development.

Analysis of physiological signals for recognition of stress

Authors: Diane Mourenas, Mihai Zorila, Erwin Meinders

Abstract: People with limited communication capabilities, like people with a severe mental disability or dementia, are often not capable of expressing their emotions. This leaves these vulnerable people in many cases misunderstood and not always adequately helped. Better understanding of their emotions, feelings and unmet needs will strengthen the trust relation between the client and the caregiver. It will lead to better care for less costs and ultimately it will lead to increased quality of life and happiness. Mentech Innovation develops sensor technology that quantifies emotions to give these vulnerable people a voice. The aim of the study is to examine the body response to stress. Electrodermal activity (EDA) and heart rate (HR) signals were measured from thirteen participants while exposed to a stimulus of fear. This body response was recorded with the wristband Empatica E4 while the participants were exposed to a video scene with the fear predefined stimulus. The data set was used to derive a stress model based on in-depth variability analysis and deep learning algorithms to predict stress moments. The results of study clearly indicate patterns in body responses to a fear stimulus, and provides statistical and a deeplearning models to recognize and predict stress.

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

Authors: Marijke De Couck, David van Brummelen, Denis Schallier, Jacques De Grève, Yori Gidron

Abstract: Recent studies suggest that vagal nerve activity, indexed by heart rate variability (HRV), could have a prognostic role in cancer. However, most studies did not control adequately for confounders and included cardiac patients. Furthermore, the validity of this prognostic role needs to be tested in different types of cancer. The present study tested the prognostic role of HRV in prostate cancer (PC) and non-small cell lung cancer (NSCLC) patients, using a historical prospective design. HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients. Outcomes included prostate-specific antigen (PSA) at 6 and 24 months in PC, and overall survival (OS) (for the full sample) and survival time (for the deceased patients) in NSCLC. Furthermore, the possible mediating role of C-reactive protein (CRP) was tested (in NSCLC), as well as whether age and stage moderated the relationship between HRV and prognosis in both types of cancer. In the PC patients, HRV significantly inversely predicted PSA levels at 6 and 24 months, independent of confounders. Furthermore, this was particularly significant in metastatic PC patients, indicating moderation by stage. In NSCLC patients, HRV did not predict OS and survival time, but it did positively predict survival time in patients under the age of 65, independent of confounders. Additionally, CRP was not found to mediate the relationship between HRV and OS or survival time in NSCLC. The present results partly support previous studies and extend them to two additional common types of cancer, using a more rigorous control over confounders. Together with recent experimental findings, these results propose a modulatory role of vagal nerve activity in cancer. Therefore, routine measurement of HRV in estimating prognosis in cancer may be considered.

Improving Heart Rate Variability Measurements from Consumer Smartwatches with Machine Learning

Authors: Martin Maritsch, Vera Lehmann, Caterina Bérubé, Thomas Züger, Mathias Kraus Stefan Feuerriegel, Tobias Kowatsch, Felix Wortmann

Abstract: The reactions of the human body to physical exercise, psychophysiological stress and heart diseases are reflected in heart rate variability (HRV). Thus, continuous monitoring of HRV can contribute to determining and predicting issues in well-being and mental health. HRV can be measured in everyday life by consumer wearable devices such as smartwatches which are easily accessible and affordable. However, they are arguably accurate due to the stability of the sensor. We hypothesize a systematic error which is related to the wearer movement. Our evidence builds upon explanatory and predictive modeling: we find a statistically significant correlation between error in HRV measurements and the wearer movement. We show that this error can be minimized by bringing into context additional available sensor information, such as accelerometer data. This work demonstrates our research-in-progress on how neural learning can minimize the error of such smartwatch HRV measurements.

A Comparison of Nonlinear Measures for the Detection of Cardiac Autonomic Neuropathy from Heart Rate Variability

Authors: David Cornforth, Herbert F. Jelinek, Mika Tarvainen

Abstract: In this work we compare three multiscale measures for their ability to discriminate between participants having cardiac autonomic neuropathy (CAN) and aged controls. CAN is a disease that involves nerve damage leading to an abnormal control of heart rate, so one would expect disease progression to manifest in changes to heart rate variability (HRV). We applied multiscale entropy (MSE), multi fractal detrended fluctuation analysis (MFDFA), and Renyi entropy (RE) to recorded datasets of RR intervals. The latter measure provided the best separation (lowest p-value in Mann–Whitney tests) between classes of participants having CAN, early CAN or no CAN (controls). This comparison suggests the efficacy of RE as a measure for diagnosis of CAN and its progression, when compared to the other multiscale measures.

Normal values of heart rate variability at rest in a young, healthy and active Mexican population

Authors: Marina Medina Corrales, Blanca de la Cruz Torres, Alberto Garrido Esquivel, Marco Antonio Garrido Salazar, José Naranjo Orellana

Abstract: This study analyzed Heart Rate Variability in a large sample of active young subjects within a narrow age range (18 to 25), using time and frequency domain methods and a Poincaré plot. Heart rate was recorded (beat to beat) for 30 minutes at rest in 200 healthy subjects divided into 4 groups: 50 sportsmen (20.54 ± 1.52 years); 50 active men (21.22 ± 1.31 years); 50 sportswomen (20.10 ± 1.87 years) and 50 active women (20.92 ± 1.87 years). Significant differences were found for most parameters between athletes and active subjects (male and female) but not between genders. Percentile distributions were provided for all parameters (according to gender and physical activity level) to be used as references in future researches.

Predictive Value of Subacute Heart Rate Variability for Determining Outcome Following Adolescent Concussion

Authors: Colt A. Coffman, Jacob J. M. Kay, Kat M. Saba, Adam T. Harrison, Jeffrey P. Holloway, Michael F. LaFountaine, Robert Davis Moore

Abstract: Objective assessments of concussion recovery are crucial for facilitating effective clinical management. However, predictive tools for determining adolescent concussion outcomes are currently limited. Research suggests that heart rate variability (HRV) represents an indirect and objective marker of central and peripheral nervous system integration. Therefore, it may effectively identify underlying deficits and reliably predict the symptomology following concussion. Thus, the present study sought to evaluate the relationship between HRV and adolescent concussion outcomes. Furthermore, we sought to examine its predictive value for assessing outcomes. Fifty-five concussed adolescents (12–17 years old) recruited from a local sports medicine clinic were assessed during the initial subacute evaluation (within 15 days postinjury) and instructed to follow up for a post-acute evaluation. Self-reported clinical and depressive symptoms, neurobehavioral function, and cognitive performance were collected at each timepoint. Short-term HRV metrics via photoplethysmography were obtained under resting conditions and physiological stress. Regression analyses demonstrated significant associations between HRV metrics, clinical symptoms, neurobehavioral function, and cognitive performance at the subacute evaluation. Importantly, the analyses illustrated that subacute HRV metrics significantly predicted diminished post-acute neurobehavioral function and cognitive performance. These findings indicate that subacute HRV metrics may serve as a viable predictive biomarker for identifying underlying neurological dysfunction following concussion and predict late cognitive outcomes.

Cognitive, behavioral, and autonomic correlates of mind wandering and perseverative cognition in major depression

Authors: Cristina Ottaviani, Leila Shahabi, Mika Tarvainen, Ian Cook, Michelle Abrams, David Shapiro

Abstract: Autonomic dysregulation has been hypothesized to play a role in the relationships between psychopathology and cardiovascular risk. An important transdiagnostic factor that has been associated with autonomic dysfunction is perseverative cognition (PC), mainly present in Major Depressive Disorder (MDD) in the form of rumination. As the ability to adaptively let our mind wander without ruminating is critical to mental health, this study aimed to examine the autonomic concomitants of functional vs. dysfunctional intrusive thoughts in MDD. Ambulatory heart rate (HR) and variability (HRV) of 18 MDD subjects and 18 healthy controls were recorded for 24 h. Approximately every 30 min during waking hours subjects reported their ongoing thoughts and moods using electronic diaries. Random regression models were performed. Compared to controls, MDD subjects were more often caught during episodes of PC. In both groups, PC required more effort to be inhibited and interfered more with ongoing activities compared to mind wandering (MW) (ps < 0.0001). This cognitive rigidity was mirrored by autonomic inflexibility, as PC was characterized by lower HRV (p < 0.0001) compared to MW. A worse mood was reported by MDD patients compared to controls, independently of their ongoing cognitive process. Controls, however, showed the highest mood worsening during PC compared to being on task and MW. HRV during rumination correlated with self-reported somatic symptoms on the same day and several dispositional traits. MDD subjects showed lower HRV during sleep, which correlated with hopelessness rumination. Results show that PC is associated with autonomic dysfunctions in both healthy and MDD subjects. Understanding when spontaneous thought is adaptive and when it is not may clarify its role in the etiology of mood disorders, shedding light on the still unexplained association between psychopathology, chronic stress, and risk for health.


Authors: Jesus Antonio Alvarez-Cedillo, Juan Carlos Herrera Lozada

Abstract: Stress is a protective mechanism that humans have created to react to an alertness and survive, most of the literature identifies it as an element eventual negative and such as part job wrong because was associated with the development of many diseases. In this article, we will show the positive aspects found by applying stress to some extent to increase the quality of teaching.

Deep learning with wearable based heart rate variability for prediction of mental and general health

Authors: Louise V.Coutts, David Plans, Alan W.Brown, John Collomosse

Abstract: The ubiquity and commoditisation of wearable biosensors (fitness bands) has led to a deluge of personal healthcare data, but with limited analytics typically fed back to the user. The feasibility of feeding back more complex, seemingly unrelated measures to users was investigated, by assessing whether increased levels of stress, anxiety and depression (factors known to affect cardiac function) and general health measures could be accurately predicted using heart rate variability (HRV) data from wrist wearables alone. Levels of stress, anxiety, depression and general health were evaluated from subjective questionnaires completed on a weekly or twice-weekly basis by 652 participants. These scores were then converted into binary levels (either above or below a set threshold) for each health measure and used as tags to train Deep Neural Networks (LSTMs) to classify each health measure using HRV data alone. Three data input types were investigated: time domain, frequency domain and typical HRV measures. For mental health measures, classification accuracies of up to 83% and 73% were achieved, with five and two minute HRV data streams respectively, showing improved predictive capability and potential future wearable use for tracking stress and well-being.

Heart failure as an autonomic nervous system dysfunction

Authors: Takuya Kishi (MD, PhD)

Abstract: In heart failure, it has been recognized that the sympathetic nervous system (SNS) is activated and the imbalance of the activity of the SNS and vagal activity interaction occurs. The abnormal activation of the SNS leads to further worsening of heart failure. Many previous clinical and basic studies have demonstrated that the abnormal activation of the SNS is caused by the enhancement of excitatory inputs including changes in: (1) peripheral baroreceptor and chemoreceptor reflexes; (2) chemical mediators that control sympathetic outflow; and (3) central sites that integrate sympathetic outflow. In particular, the abnormalities in central SNS regulation due to the renin angiotensin system—oxidative stress axis have recently been in focus. In the treatment of heart failure, the inhibition of the activated SNS, such as with beta-blockers and/or exercise training, is important. Furthermore, many experimental studies have demonstrated that vagal stimulation has beneficial effects on heart failure, and recently several clinical studies have also demonstrated that vagal stimulation is a possible novel therapy for heart failure. In conclusion, we must recognize that heart failure is a complex syndrome with an autonomic nervous system dysfunction, and that the autonomic imbalance with the activation of the SNS and the reduction of vagal activity should be treated.

Validity of Commonly Used Heart Rate Variability Markers of Autonomic Nervous System Function

Authors: Bianca Lee Thomas, Nicolaas Claassen Piet Becker Margaretha Viljoen

Abstract: Background: Despite strong reservations regarding the validity of a number of heart rate variability (HRV) measures, these are still being used in recent studies. Aims: We aimed to compare the reactivity of ostensible sympathetic HRV markers (low and very low frequency [LF and VLF]) to that of electrodermal activity (EDA), an exclusively sympathetic marker, in response to cognitive and orthostatic stress, investigate the possibility of LF as a vagal-mediated marker of baroreflex modulation, and compare the ability of HRV markers of parasympathetic function (root mean square of successive differences [RMSSD] and high frequency [HF]) to quantify vagal reactivity to cognitive and orthostatic stress. Results: None of the purported sympathetic HRV markers displayed a reactivity that correlated with electrodermal reactivity. LF (ms2) reactivity correlated with the reactivity of both RMSSD and HF during baroreflex modulation. RMSSD and HF indexed the reactivity of the parasympathetic nervous system under conditions of normal breathing; however, RMSSD performed better as a marker of vagal activity when the task required breathing changes. Conclusions: Neither LF (in ms2 or normalized units [nu]) nor VLF represent cardiac sympathetic modulation of the heart. LF (ms2) may reflect vagally mediated baroreflex cardiac effects. HRV linear analysis therefore appears to be restricted to the determination of vagal influences on heart rate. With regard to HRV parasympathetic markers, this study supports the suggestion that HRV frequency domain analyses, such as HF, should not be used as an index of vagal activity in study tasks where verbal responses are required, as these responses may induce respiratory changes great enough to distort HF power.

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

Authors: Wilhelm von Rosenberg, Theerasak Chanwimalueang, Tricia Adjei, Usman Jaffer, Valentin Goverdovsky, Danilo P. Mandic

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

ECG Artifacts and Poincaré Plot based Heart Rate Variability

Authors: Butta Singh, Manjit Singh

Abstract: The analysis of beat to beat fluctuations of heart rate known as heart rate variability (HRV) become a noninvasive clinical research tool to study the modulation that the autonomic nervous system exerts on the cardiovascular system. The missing RR intervals contribute a serious limitation to HRV analysis. The linear HRV measures are very sensitive to ECG artifacts. The objective of present study was to evaluate the robustness of Poincaré plot analysis in presence of missing RR intervals. Poincaré plot is a visual tool in which each RR interval is plotted as a function of previous RR interval. The Poincaré plot provides summary as well as detailed beat-to-beat information on the behavior of the heart. The study involves RR interval time-series data of 25 healthy volunteers. The ectopic free RR interval tachograms with length N=1000 were derived from Lead-II ECG recordings having a sampling frequency of 500 Hz. In each data set, consecutive RR interval data were randomly selected for removal, and the data length removed was increased from 0 to 100 RR intervals in an increment of 5 RR intervals. Two random selections of RR intervals were made to analyze the average effects of the missing data. In each case, the Poincaré plot (SD1 and SD2) based HRV parameters were calculated. Mean relative errors were found to be less than 1.8 for SD1 and SD2 even in the presence of 100 missing RR intervals. Poincaré plot parameters are found to be more robust than linear measures to missing RR intervals.

Reproducibility of heart rate variability parameters measured in healthy subjects at rest and after a postural change maneuver

Authors: E.M. Dantas, C.P. Gonçalves, A.B.T. Silva, S.L. Rodrigues, M.S. Ramos, R.V. Andreão, E.B. Pimentel, W. Lunz, J.G. Mill

Abstract: Heart rate variability (HRV) provides important information about cardiac autonomic modulation. Since it is a noninvasive and inexpensive method, HRV has been used to evaluate several parameters of cardiovascular health. However, the internal reproducibility of this method has been challenged in some studies. Our aim was to determine the intra-individual reproducibility of HRV parameters in short-term recordings obtained in supine and orthostatic positions. Electrocardiographic (ECG) recordings were obtained from 30 healthy subjects (20-49 years, 14 men) using a digital apparatus (sampling ratio = 250 Hz). ECG was recorded for 10 min in the supine position and for 10 min in the orthostatic position. The procedure was repeated 2-3 h later. Time and frequency domain analyses were performed. Frequency domain included low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands. Power spectral analysis was performed by the autoregressive method and model order was set at 16. Intra-subject agreement was assessed by linear regression analysis, test of difference in variances and limits of agreement. Most HRV measures (pNN50, RMSSD, LF, HF, and LF/HF ratio) were reproducible independent of body position. Better correlation indexes (r > 0.6) were obtained in the orthostatic position. Bland-Altman plots revealed that most values were inside the agreement limits, indicating concordance between measures. Only SDNN and NNv in the supine position were not reproducible. Our results showed reproducibility of HRV parameters when recorded in the same individual with a short time between two exams. The increased sympathetic activity occurring in the orthostatic position probably facilitates reproducibility of the HRV indexes.

Impaired heart rate variability in patients with mitral annular calcification: an observational study

Authors: Ertuğrul Kurtoğlu, Erdal Aktürk, Hasan Korkmaz, Halil Ataş, Bilal Çuğlan, Hasan Pekdemir

Abstract: Objective: The aim of the present study was to study time indices of heart rate variability (HRV) in patients with mitral annular calcification (MAC). Methods: A cross-sectional observational study was performed. Fifty patients with echocardiographic evidence of MAC and 50 ageand gender-matched control subjects without echocardiographic evidence of MAC were included. All the study participants underwent 2-dimensional echocardiographic examinations and 24-hour Holter monitoring for HRV analysis. Student-t, Mann-Whitney U and Chi-square tests were used for statistical analysis. Results: Hypertension and coronary artery disease were more common in the MAC group than in the control group. All HRV parameters including mean RR interval, SDNN, SDANN, SDNN index, pNN50 and RMSSD were reduced in the MAC group when compared with the control group (p<0.05 for all). In hypertensive subgroup, all HRV parameters except mean RR interval were diminished in patients with MAC when compared with those without MAC (p<0.05 for all). In non-hypertensive subgroup, all HRV parameters were also diminished in patients with MAC when compared with those without MAC. In the subgroup of patients with coronary artery disease, patients had lower HRV parameters except mean RR interval, pNN50 and RMSSD in comparison to those without MAC (p<0.05 for all). In the subgroup of patients without coronary artery disease, all HRV parameters were depressed in patients with MAC in comparison to those without MAC (p<0.05 for all). Conclusion: Our findings indicate that MAC was associated with reduced heart rate variability which possibly reflects decreased parasympathetic tone with a predominant activity of the sympathetic tone.

Association between cardiovascular autonomic functions and time to death in patients with terminal hepatocellular carcinoma

Authors: Jui-Kun Chiang, Malcolm Koo, Terry B J Kuo, Chin-Hua Fu

Abstract: Objective: To explore the association of cardiovascular autonomic functions with TTD in patients with terminal hepatocellular carcinoma. Methods: A prospective study was conducted with 33 patients with hepatocellular carcinoma recruited from the hospice ward of a regional hospital in Chiayi county, Taiwan. Serum creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, blood urea nitrogen (BUN), and serum albumin were measured on the admission day. Cardiovascular autonomic functions were evaluated by frequency-domain measures of heart rate variability (HRV) on admission. Results: TTD was significantly associated with total spectrum power (TP) (r=0.55, P=0.001) and high frequency (HF power) (r=0.44, P=0.010) of HRV measurement. The accuracy of within-one-week TTD prediction was 67% for TP and HF power. The accuracy of within-two-week TTD prediction was 82% for TP and 73% for HF. In addition, TTD of the patients was also significantly associated with serum creatinine (r=-0.42, P=0.015), serum albumin (r=-0.46, P=0.007), and BUN (r=-0.44, P=0.010). Conclusion: This is the first study to evaluate the association between cardiovascular autonomic functions and TTD in patients with terminal hepatocellular carcinoma. The inclusion of HRV measurement in prognostic models may improve accuracy in TTD prediction and, hence, facilitate medical decision making in hospice care.

Influence Diagram of Physiological and Environmental Factors Affecting Heart Rate Variability: An Extended Literature Overview

Authors: Julien Fatisson, Victor Oswald, François Lalonde

Abstract: Heart rate variability (HRV) corresponds to the adaptation of the heart to any stimulus. In fact, among the pathologies affecting HRV the most, there are the cardiovascular diseases and depressive disorders, which are associated with high medical cost in Western societies. Consequently, HRV is now widely used as an index of health. In order to better understand how this adaptation takes place, it is necessary to examine which factors directly influence HRV, whether they have a physiological or environmental origin. The primary objective of this research is therefore to conduct a literature review in order to get a comprehensive overview of the subject. The system of these factors affecting HRV can be divided into the following five categories: physiological and pathological factors, environmental factors, lifestyle factors, non-modifiable factors and effects. The direct interrelationships between these factors and HRV can be regrouped into an influence diagram. This diagram can therefore serve as a basis to improve daily clinical practice as well as help design even more precise research protocols.

Mathematical Algorithm for Heart Rate Variability Analysis


Abstract: Paper is destined for use in medicine, psychology and psychophysiology, in man’s selfdevelopment training, breathing technique’s training, in the field of stress resistance, health promotion, strengthening of the capacity for work; and it relates to the apparatus and methods for detection of the heart rate variability and it’s use in providing biofeedback during training sessions of organism’s vegetative balance and coherence.

Prognostic Value of Heart Rate Variability in Patients with Cancer

Authors: Ying Guo, MD, Shalini Koshy, David Hui, MD, J. Lynn Palmer, PhD, Ki Shin, Mehtap Bozkurt, MD, and Syed Wamique Yusuf, MD

Abstract: Introduction—Previous studies have shown that autonomic dysfunction is associated with shorter survival in patients with advanced cancer. We examined the association between heart rate variability (HRV), a measure of autonomic function, and survival in a large cohort of cancer patients. Methods—We retrospectively examined the records of 651 cancer patients who had undergone ambulatory electrocardiogram (ECG) monitoring for 20–24 hours. Time domain HRV (standard deviation of normal-to-normal beat interval [SDNN]) was calculated using power spectral analysis. Survival data was compared between patients with SDNN ≥70 ms (Group 1, n = 520) and SDNN <70 ms (Group 2, n = 131). Results—Two groups were similar in most variables, except group 2 patients had a significantly higher percentage of male patients (P=0.03), hematological malignancies (P=0.04), and use of non–selective serotonin reuptake inhibitor antidepressants (P=0.04). Patients in group 2 had a significantly shorter survival rate (25% patients in group 2 died by 18.7 weeks vs. 78.9 weeks in group 1; P <.0001). Multivariate analysis showed that SDNN<70 ms remained significant for survival (Hazard Ratio1.9, 95% Confidence Interval 1.4–2.5) independent of age, cancer stage and performance status. Conclusion—The presence of cancer in combination with decreased heart rate variability (SDNN<70ms) is associated with shorter survival time.

The effects of a brief relaxation program on symptom distress and heart rate variability in cancer patients

Authors: Arash Asher, J Lynn Palmer, Rajesh R Yadav, Syed W Yusuf, Benedict Konzen, Eduardo Bruera, Ying Guo

Abstract: Objectives: To determine whether a 15-minute, one-time guided relaxation program for cancer patients could improve symptom distress as measured by the Edmonton Symptom Assessment System (ESAS). In addition, we were interested in characterizing the changes of the autonomic nervous system, as demonstrated by heart rate variability (HRV) high-frequency (HF) spectral analysis, before and after this relaxation program. Design: Nonrandomized pilot study. Setting: Comprehensive cancer center. Methods: Twenty cancer patients underwent a 15-minute relaxation program. The ESAS and a 5-minute HRV recording were completed before and after the relaxation program. Main outcome measures: The differences between the pre- and post-summed ESAS score and HRV values were compared by a paired t-test. Results: The summed ESAS scores were significantly lower after the relaxation program (P<.01), with an average 31% decrease in total score. However, no differences were found in HRV HF power. There was no correlation between the change in HRV HF and change in symptom distress, as measured by ESAS. Conclusions: A brief guided relaxation program can significantly improve symptoms as measured by ESAS. More research is required to understand the effects of relaxation on HF HRV power.

Automated assessment of pulmonary patients using heart rate variability from everyday wearables

Authors: Md Juber Rahman, Ebrahim Nemati , Md Mahbubur Rahman , Viswam Nathan , Korosh Vatanparvar b Jilong Kuang

Abstract: Everyday wearables with enhanced computational capacity, good quality sensors, and machine learning/artificial intelligence enabled algorithms have the potential to play a key role not only in the fitness and wellness sector but also in the field of disease diagnostics and monitoring. The major challenges are a limited number of sensors, reliable data collection and processing, and deployment of computationally efficient algorithms. In this multi-cohort study, we have used everyday wearables such as chest band and smartwatch to investigate the heart rate variability (HRV) of 131 subjects which include 40 healthy controls, 69 asthma patients, 9 COPD patients and 13 patients with a co-morbidity of asthma and COPD. We aimed at a comprehensive investigation by exploring a total of 58 features including time domain, frequency domain, non-linear and entropy measures of HRV to identify the HRV indices that provide significant discriminatory information for classification between healthy and pulmonary patients. Feature ranking has been done by the area under the receiver operating characteristics curve. Classification of patients with the 15 top ranked features using data from the chest band heart rate sensor as well as estimated HRV parameters from smartwatch PPG signal have been investigated separately. Using the chest band data, a classification accuracy of 82.07%, precision of 83.13%, recall of 81.53% and F-1 score of 81.7% have been achieved; whereas using the smartwatch data, a classification accuracy of 80%, precision of 79.9%, recall of 80% and F-1 score of 79.94% have been achieved for the test set with an AdaBoost classifier. Heart rate variability metrics also showed significant correlation with disease severity and impact on health-related quality of life as measured by pulmonary function test, Asthma Symptoms Utility Index and COPD assessment test score respectively. The results indicate that HRV analysis using everyday wearables may be helpful in the assessment and management of asthma and COPD.

Heart rate variability is associated with emotion recognition: Direct evidence for a relationship between the autonomic nervous system and social cognition

Authors: Daniel S. Quintana, Adam J. Guastella, Tim Outhred, Ian B. Hickie, Andrew H. Kemp

Abstract: It is well established that heart rate variability (HRV) plays an important role in social communication. Polyvagal theory suggests that HRV may provide a sensitive marker of one's ability to respond and recognize social cues. The aim of the present study was to directly test this hypothesis. Resting-state HRV was collected and performance on the Reading the Mind in the Eyes Test was assessed in 65 volunteers. HRV was positively associated with performance on this emotion recognition task confirming our hypothesis and these findings were retained after controlling for a variety of confounding variables known to influence HRV — sex, BMI, smoking habits, physical activity levels, depression, anxiety, and stress. Our data suggests that increased HRV may provide a novel marker of one's ability to recognize emotions in humans. Implications for understanding the biological basis of emotion recognition, and social impairment in humans are discussed.

A Quantitative Systematic Review of Normal Values for Short-term Heart Rate Variability in Healthy Adults

Authors: David Nunan, Gavin R. H. Sandercock, David A. Brodie

Abstract: Heart rate variability (HRV) is a known risk factor for mortality in both healthy and patient populations. There are currently no normative data for short‐term measures of HRV. A thorough review of short‐term HRV data published since 1996 was therefore performed. Data from studies published after the 1996 Task Force report (i.e., between January 1997 and September 2008) and reporting short‐term measures of HRV obtained in normally healthy individuals were collated and factors underlying discrepant values were identified. Forty‐four studies met the pre‐set inclusion criteria involving 21,438 participants. Values for short‐term HRV measures from the literature were lower than Task Force norms. A degree of homogeneity for common measures of HRV in healthy adults was shown across studies. A number of studies demonstrate large interindividual variations (up to 260,000%), particularly for spectral measures. A number of methodological discrepancies underlined disparate values. These include a systematic failure within the literature (a) to recognize the importance of RR data recognition/editing procedures and (b) to question disparate HRV values observed in normally healthy individuals. A need for large‐scale population studies and a review of the Task Force recommendations for short‐term HRV that covers the full‐age spectrum were identified. Data presented should be used to quantify reference ranges for short‐term measures of HRV in healthy adult populations but should be undertaken with reference to methodological factors underlying disparate values. Recommendations for the measurement of HRV require updating to include current technologies.

A 6-weeks Treatment Program Improves HRV in Eating Disorder Patients

Authors: Herbert F Jelinek, Mika P. Tarvainen

Abstract: Background: Eating disorders such as anorexia nervosa present with a significant cardiovascular associated risk of sudden cardiac death. Bradycardia is a serious complication of eating disorders. Methods: Eating Disorder (ED) patients were admitted to a 6-week treatment program and assessed for of heart rate variability (HRV) at entrance to the program and at discharge from hospital. Linear heart rate variability measures were determined using Kubios software from Lead 3 ECG recordings following a 5-minute rest period. Nonparametric statistics were applied and significance set at p < 0.05. Results: No significant differences in HRV parameters were noted for the control group following the 6-week treatment program. For the ED group, mean RR interval length decreased significantly following treatment (median ± IQR; -64 ± 76; p = 0.002). Sympathovagal function was abnormal in the ED group on admission but improved following treatment, showing a decrease in RMSSD (median ± IQR; -9 ± 18; p = 0.048) and SD1 (median ± IQR; -6 ± 13; p = 0.048). Sample entropy, a, measure of heart rate complexity did not change significantly. Conclusion: At admission to hospital the ED group was more parasympathetic during rest compared to controls, but they became more sympathetic after the intervention and approached the HRV measures of the controls.

State Anxiety and Low-Frequency Heart Rate Variability in High-Level Amateur Golfers While Putting under Pressure

Authors: Yumiko Hasegawa, Katsuhiro Sumi, Akito Miura

Abstract: The present study investigated the relationship between psychophysiological state and clutch or choking performance during golf putting under pressure. Ten males and 13 females who were high-level competitive amateur golfers performed 25 putts under control and pressure conditions. State-Trait Anxiety Inventory-Y1 (STAI-Y1), heart rate variability (HRV), and putting scores were measured. Participants whose performance improved under the pressure condition compared to the control condition were defined as clutch performers and all others were defined as choking performers. Change ratios between the pressure and control conditions for each variable were calculated and compared between clutch and choking performers. There was a significant difference in the change ratio of the low frequency (LF) component of HRV such that LF HRV decreased under the pressure condition compared with the control condition only in choking performers. Thus, LF HRV may be associated with improved fine motor control, such as golf putting, under pressure circumstances.

Heart rate variability as a transdiagnostic biomarker of psychopathology

Authors: Theodore P. Beauchaine, Julian F. Thayer

Abstract: The Research Domain Criteria (RDoC), developed by the National Institute of Mental Health as a neuroscienceinformed alternative to traditional psychiatric nosology, is an explicitly dimensional system in which classification of psychopathology is derived inductively (i.e., from basic science), across multiple levels of analysis (e.g., genetic, neural, psychophysiological, and behavioral). Although RDoC is often presented as paradigmatically revolutionary, a review of the history of psychophysiology suggests that roots of RDoC thinking extend at least as far back as the mid-20th Century. In this paper, we briefly and selectively review the historical emergence of neurobiologically-informed dimensional trait models of psychopathology, and we summarize our thinking regarding high frequency heart rate variability (HF-HRV) as a transdiagnostic biomarker of self-regulation and cognitive control. When functional interactions between HF-HRV and systems of behavioral approach and avoidance are considered, diverse patterns of behavioral maladjustment can be subsumed into a single model. This model accommodates the general bifactor structure of psychopathology, and suggests that HF-HRV can be viewed as an autonomic, transdiagnostic biomarker of mental illness.

The Impact of a New Emotional Self-Management Program on Stress, Emotions, Heart Rate Variability, DHEA and Cortisol

Authors: Rollin McCraty, Bob Barrios-Choplin, Deborah Rozman, Mike Atkinson, Alan D. Watkins

Abstract: This study examined the effects on healthy adults of a new emotional self­ management program, consisting of two key techniques, “Cut-Thru” and the “Heart Lock-In.” These techniques are designed to eliminate negative thought loops and promote sustained p•Mositive emotional states. The hypotheses were that training and practice in these techniques would yield lowered levels of stress and negative emotion and cortisol, while resulting in increased positive emotion and DHEA levels over a one-month period. In addition, we hypothesized that increased coherence in heart rate variability patterns would be observed during the practice of the techniques. Forty-five healthy adults participated in the study, fifteen of whom acted as a compari­son group for ±e psychological measures. Salivary DHEA/DHEAS and cortisol levels were measured, autonomic nervous system function was assessed by heart rate variability analysis, and emotions were measured using a psychological questionnaire. Individuals in the experimental group were assessed before and four weeks after receiving training in the self-management techniques. The experimental group experienced significant increases in the positive affect scales of Caring and Vigor and significant decreases in the negative affect scales of Guilt, Hostility, Burnout, Anxiety and Stress Effects, while no significant changes were seen in the com­ parison group. There was a mean 23 percent reduction in cortisol and a 100 percent increase in DHEA/DHEAS in the experimental group. DHEA was significantly and posi­ tively related to the affective state Warmheartedness, whereas cortisol was significantly and positively related to Stress Effects. Increased coherence in heart rate variability pat­terns was measured in 80 percent of the experimental group during the use of the tech­niques. The results suggest that techniques designed to eliminate negative thought loops can have have important positive effects on stress, emotions, and key physiological systems. The implications are that relatively inexpensive interventions may dramatically and positively impact individuals' health and well-being. Thus, individuals may have greater control over their minds, bodies and health than previously suspected.

Effects of performance anxiety on effort and performance in rock climbing: A test of processing efficiency theory

Authors: Lew Hardy, Andrew Hutchinson

Abstract: Three studies examined the effort and performance of rock climbers in the context of processing efficiency theory. Anxiety was manipulated by different means in the three studies. In each study, the effort due only to the physical exertion of climbing was controlled for. Anxiety, effort, and performance were measured via self-report, an integrated heart rate measure, and belayer observation. Consistent with processing efficiency theory, the results showed that higher levels of anxiety were usually associated with higher levels of effort and commensurately higher levels of performance. However, the results also suggested that cognitive anxiety may not be the prime determinant of the effort and performance changes observed. Finally, the results suggested that other individual difference variables may play an important part in determining the extent to which individuals may be able to make use of anxiety-induced effort.

Eustress or Distress: An Empirical Study of Perceived Stress in Everyday College Life

Authors: Chun-Tung Li, Jiannong Cao, Tim M. H. Li

Abstract: Eustress is literally the ”good stress” that associated with positive feelings and health benefits. Previous studies focused on general stress, where the concept of eustress has been overlooked. This paper presents a novel approach towards stress recognition using data collected from wearable sensors, smartphones, and computers. The main goal is to determine if behavioral factors can help differentiate eustress from another kind of stress. We conducted a natural experiment to collect user smartphone and computer usage, heart rate and survey data in situ. By correlation and principle component analysis, a set of features could then be constructed. The performance was evaluated under leave-one-subject-out cross-validation, where the combined behavioral and physiological features enabled us to achieve 84.85% accuracy for general stress, 71.33% one kind of eustress as an urge for better performance, and 57.34% for eustress as a state of better mood. This work provided an encouraging result as an initial study for measuring eustress.


Perturbation in Parasympathetic Nervous System Activity Affects Temporal Structure of Poincare ́ Plot

Authors: Chandan Karmakar, Ahsan Khandoker, Marimuthu Palaniswami

Abstract: A novel descriptor (Complex Correlation Measure (CCM)) for measuring the variability in the temporal structure of Poincare ́ plot has been developed to characterize or distinguish between Poincare ́ plots with similar shapes. This study was designed to assess the changes in temporal structure of the Poincare ́ plot using CCM during atropine infusion, 700 head-up tilt and scopolamine administration. The aim of this study was to asses the changes in temporal structure of the Poincare ́ plot using CCM during atropine infusion (parasympathetic blockade) and transdermal scopolamine patch administration (enhanced parasympathetic activity) phases. The change in CCM values during these autonomic perturbation phases revealed the physiological relevance of the new descriptor. The concordant reduction and enhancement in CCM values with parasympathetic activity indicates that the temporal variability of Poincare ́ plot is modulated by the parasympathetic activity which correlates with changes in CCM values.

Analysis of Slope Based Heart Rate Asymmetry using Poincaré Plots

Authors: Chandan Karmakar, Ahsan Khandoker, Marimuthu Palaniswami

Abstract: Heart rate asymmetry (HRA) is considered as a physiological phenomenon seen in heart rates of healthy subjects. In this article, we propose a novel heart rate asymmetry index and assess the discriminative power of proposed index in comparison with conventional heart rate asymmetry indices. As an illustrative example we discriminate patients suffering from congestive heart failure (CHF) from a healthy (normal sinus rhythm (NSR) group using HRA of beat-to-beat time series. We evaluate the discriminative power of individual features (p<0.01 is considered statistically significant) and area under Receiver Operating Characteristic (ROC) curve. These comparisons show that proposed HRA index is superior feature to conventional HRA index for differentiating NSR from CHF subjects.

A robust algorithm for heart rate variability time series artefact correction using novel beat classification

Authors: Jukka A. Lipponen, Mika P. Tarvainen

Abstract: Purpose: Heart rate variability is a commonly used measurement to evaluate functioning of autonomic nervous system, psychophysiological stress, and exercise intensity and recovery. HRV measurements contain artefacts such as extra, missed or misaligned beat detections, which can produce significant distortion on HRV parameters. In this paper, a robust automatic method for artefact detection from HRV time series is proposed. Methods: The proposed detection method is based on time-varying thresholds estimated from distribution of successive RR-interval differences combined with a novel beat classification scheme. The method is validated using simulated extra, missed and misaligned beat detections as well as real artefacts such as atrial and ventricular ectopic beats. Results: The sensitivity of the algorithm to detect simulated missed/extra beats was 100%. The sensitivity to detect real atrial and ventricular ectopic beats was 96.96%, the corresponding specificity being 99.94%. The mean error in HRV parameters after correction was <2% for missed and extra beats as well as for misaligned beats generated with large displacement factors. Misaligned beats with smallest displacement factor were the most difficult to detect and resulted in largest HRV parameter errors after correction, largest errors being <8%. Conclusions: The HRV artefact correction algorithm presented in this study provided comparable specificity and better sensitivity to detect ectopic beats as compared to state-of-the-art algorithms. The proposed algorithm detects abnormal beats with high accuracy, is relatively easy to implement, and secures reliable HRV analysis by reducing the effect of possible artefacts to tolerable level.

Heart Rate Variability Analysis on Electrocardiograms, Seismocardiograms and Gyrocardiograms on Healthy Volunteers

Authors: Szymon Sieciński, Paweł S. Kostka, Ewaryst J. Tkacz

Abstract: Physiological variation of the interval between consecutive heartbeats is known as the heart rate variability (HRV). HRV analysis is traditionally performed on electrocardiograms (ECG signals) and has become a useful tool in the diagnosis of different clinical and functional conditions. The progress in the sensor technique encouraged the development of alternative methods of analyzing cardiac activity: Seismocardiography and gyrocardiography. In our study we performed HRV analysis on ECG, seismocardiograms (SCG signals) and gyrocardiograms (GCG signals) using the PhysioNet Cardiovascular Toolbox. The heartbeats in ECG were detected using the Pan–Tompkins algorithm and the heartbeats in SCG and GCG signals were detected as peaks within 100 ms from the occurrence of the ECG R waves. The results of time domain, frequency domain and nonlinear HRV analysis on ECG, SCG and GCG signals are similar and this phenomenon is confirmed by very strong linear correlation of HRV indices. The differences between HRV indices obtained on ECG and SCG and on ECG and GCG were statistically insignificant and encourage using SCG or GCG for HRV estimation. Our results of HRV analysis confirm stronger correlation of HRV indices computed on ECG and GCG signals than on ECG and SCG signals because of greater tolerance to inter-subject variability and disturbances.

Complex Correlation Measure: a novel descriptor for Poincaré plot

Authors: Chandan K Karmakar, Ahsan H Khandoker, Jayavardhana Gubbi, Marimuthu Palaniswami

Abstract: Background: Poincaré plot is one of the important techniques used for visually representing the heart rate variability. It is valuable due to its ability to display nonlinear aspects of the data sequence. However, the problem lies in capturing temporal information of the plot quantitatively. The standard descriptors used in quantifying the Poincaré plot (SD1, SD2) measure the gross variability of the time series data. Determination of advanced methods for capturing temporal properties pose a significant challenge. In this paper, we propose a novel descriptor "Complex Correlation Measure (CCM)" to quantify the temporal aspect of the Poincaré plot. In contrast to SD1 and SD2, the CCM incorporates point-to-point variation of the signal. Methods: First, we have derived expressions for CCM. Then the sensitivity of descriptors has been shown by measuring all descriptors before and after surrogation of the signal. For each case study, lag-1 Poincaré plots were constructed for three groups of subjects (Arrhythmia, Congestive Heart Failure (CHF) and those with Normal Sinus Rhythm (NSR)), and the new measure CCM was computed along with SD1 and SD2. ANOVA analysis distribution was used to define the level of significance of mean and variance of SD1, SD2 and CCM for different groups of subjects. Results: CCM is defined based on the autocorrelation at different lags of the time series, hence giving an in depth measurement of the correlation structure of the Poincaré plot. A surrogate analysis was performed, and the sensitivity of the proposed descriptor was found to be higher as compared to the standard descriptors. Two case studies were conducted for recognizing arrhythmia and congestive heart failure (CHF) subjects from those with NSR, using the Physionet database and demonstrated the usefulness of the proposed descriptors in biomedical applications. CCM was found to be a more significant (p = 6.28E-18) parameter than SD1 and SD2 in discriminating arrhythmia from NSR subjects. In case of assessing CHF subjects also against NSR, CCM was again found to be the most significant (p = 9.07E-14). Conclusion: Hence, CCM can be used as an additional Poincaré plot descriptor to detect pathology.

Higher Vagal Activity as Related to Survival in Patients with Advanced Breast Cancer: An Analysis of Autonomic Dysregulation

Authors: Janine Giese-Davis, Ph.D., Frank H. Wilhelm, Ph.D., Rie Tamagawa, Ph.D., Oxana Palesh, Ph.D., Eric Neri, B.S., C. Barr Taylor, M.D., Helena C. Kraemer, Ph.D., and David Spiegel, M.D.

Abstract: Objective—High levels of high-frequency heart-rate variability (HF-HRV), related to parasympathetic-nervous-system functioning, have been associated with longer survival in patients with myocardial infarction, acute trauma, and in patients undergoing palliative care. From animal studies linking higher vagal activity with better immune-system functioning and reduced metastases, we hypothesized that higher HF-HRV would predict longer survival in patients with metastatic or recurrent breast cancer (MRBC). Methods—Eighty-seven patients with MRBC participated in a laboratory task including a 5- minute resting-baseline ECG. HF-HRV was computed as the natural logarithm of the summed power spectral density of RR intervals (0.15--0.50 Hz). In this secondary analysis, of a study testing whether diurnal cortisol slope predicted survival, we tested the association between resting baseline HF-HRV on survival using Cox Proportional Hazards models. Results—A total of 50 patients died during a median follow-up of 7.99 years. Higher baseline HF-HRV predicted significantly longer survival, with a hazard ratio=0.75 (95% confidence interval=0.60 to 0.92; p=.006). Visceral metastasis status and baseline HR were related to both HF-HRV and survival. However, a combination of HF-HRV and HR further improved survival prediction, with a hazard ratio of 0.64 (95% CI=0.48 to 0.85; p=.002). Conclusions—Vagal activity of patients with MRBC strongly predicted their survival, extending the known predictive window of HF-HRV in cancer beyond palliative care. Vagal activity can be altered by behavioral, pharmacological, and surgical interventions and may be a promising target for extending life expectancy in patients suffering from metastasizing cancer.

RACIAL DISPARITIES IN HEALTH How Much Does Stress Really Matter?

Authors: Michelle J. Sternthal, Natalie Slopen, David R. Williams

Abstract: Despite the widespread assumption that racial differences in stress exist and that stress is a key mediator linking racial status to poor health, relatively few studies have explicitly examined this premise. We examine the distribution of stress across racial groups and the role of stress vulnerability and exposure in explaining racial differences in health in a community sample of Black, Hispanic, and White adults, employing a modeling strategy that accounts for the correlation between types of stressors and the accumulation of stressors in the prediction of health outcomes. We find significant racial differences in overall and cumulative exposure to eight stress domains. Blacks exhibit a higher prevalence and greater clustering of high stress scores than Whites. American-born Hispanics show prevalence rates and patterns of accumulation of stressors comparable to Blacks, while foreign-born Hispanics have stress profiles similar to Whites. Multiple stressors correlate with poor physical and mental health, with financial and relationship stressors exhibiting the largest and most consistent effects. Though we find no support for the stress-vulnerability hypothesis, the stress-exposure hypothesis does account for some racial health disparities. We discuss implications for future research and policy.

Neural Networks for Heart Rate Time Series Analysis

Authors: Sami Saalasti

Abstract: The dissertation introduces method and algorithm development for nonstationary, nonlinear and dynamic signals. Furthermore, the dissertation concentrates on applying neural networks for time series analysis. The presented methods are especially applicable for heart rate time series analysis. Some classical methods for time series analysis are introduced, including improvements and new aspects for existing data preprocessing and modeling procedures, e.g., time series segmentation, digital filtering, data-ranking, detrending, time-frequency and time-scale distributions. A new approach for the creation of hybrid models with a discrete decision plane and limited value range is illustrated. A time domain peak detection algorithm for signal decomposition, i.e., estimation of a signal’s instantaneous power and frequency, is presented. A concept for constructing reliability measures, and the utilization of reliability to improve model and signal quality with postprocessing are grounded. Also a new method for estimating the reliability of instantaneous frequency for time-frequency distributions is presented. Furthermore, error tolerant methods are introduced to improve the signal-to-noise ratio in the time series. Some new principles are grounded for the neural network theory. Optimization of a time-frequency plane with a neural network as an adaptive filter is introduced. The novelty of the method is the use of a neural network as an inner function inside an instantaneous frequency estimation function. This is an example of a new architecture called a transistor network that is introduced together with the general solution for its unknown parameters. Applicability of the dynamic neural networks and model selection using physiological constraints is demonstrated with a model estimating excess post-exercise oxygen consumption based on heart rate time series. Yet another application demonstrates the correlation between the training and testing error and usage of the neural network as a memory to repeat the different RR interval patterns.;sequence=1

Mathematical Algorithm for Heart Rate Variability Analysis


Abstract: Paper is destined for use in medicine, psychology and psychophysiology, in man’s self development training, breathing technique’s training, in the field of stress resistance, health promotion, strengthening of the capacity for work; and it relates to the apparatus and methods for detection of the heart rate variability and it’s use in providing biofeedback during training sessions of organism’s vegetative balance and coherence.

Effects of stress on heart rate complexity—A comparison between short-term and chronic stress

Authors: C. Schubert, M. Lambertz, R.A. Nelesen, W. Bardwell, J.-B. Choi, J.E. Dimsdale

Abstract: This study examined chronic and short-term stress effects on heart rate variability (HRV), comparing time, frequency and phase domain (complexity) measures in 50 healthy adults. The hassles frequency subscale of the combined hassles and uplifts scale (CHUS) was used to measure chronic stress. Short-term stressor reactivity was assessed with a speech task. HRV measures were determined via surface electrocardiogram (ECG). Because respiration rate decreased during the speech task (p < .001), this study assessed the influence of respiration rate changes on the effects of interest. A series of repeated-measures analyses of covariance (ANCOVA) with Bonferroni adjustment revealed that short-term stress decreased HR D2 (calculated via the pointwise correlation dimension PD2) (p < .001), but increased HR mean (p < .001), standard deviation of R–R (SDRR) intervals (p < .001), low (LF) (p < .001) and high frequency band power (HF) (p = .009). Respiratory sinus arrhythmia (RSA) and LF/HF ratio did not change under short-term stress. Partial correlation adjusting for respiration rate showed that HR D2 was associated with chronic stress (r = −.35, p = .019). Differential effects of chronic and short-term stress were observed on several HRV measures. HR D2 decreased under both stress conditions reflecting lowered functionality of the cardiac pacemaker. The results confirm the importance of complexity metrics in modern stress research on HRV.

Where to put your best foot forward: Psycho- physiological responses to walking in natural and urban environments

Authors: Christopher J Gidlow, Marc V Jones, Gemma Hurst, Daniel Masterson, David Clark- Carter, Mika P Tarvainen, Graham Smith, Mark Nieuwenhuijsen

Abstract: There is convergent evidence that natural environments allow restoration from stress. This randomised, cross-over field-based trial compared psychological and physiological responses of unstressed individuals to self-paced 30-minute walks in three pleasant environments: residential (urban), natural (green), and natural with water (blue). Changes from baseline (T1) to T2 (end of 30-minute walk), and T3 (30 minutes after leaving environment) were measured in terms of mood, cognitive function, restoration experiences, salivary cortisol, and heart rate variability (HRV). In the final sample (n=38; 65% male; mean age 40.9±17.6 years), mood and cortisol improved at T2 and T3 in all environments. Green and blue environments were associated with greater restoration experiences, and cognitive function improvements that persisted at T3. Stress reduction (mood and cortisol changes) in all environments points to the salutogenic effect of walking, but natural environments conferred additional cognitive benefits lasting at least 30 minutes after leaving the environment.

A Lunchtime Walk in Nature Enhances Restoration of Autonomic Control during Night-Time Sleep: Results from a Preliminary Study

Authors: Valerie F. Gladwell, Pekka Kuoppa, Mika P. Tarvainen, Mike Rogerson 1

Abstract: Walking within nature (Green Exercise) has been shown to immediately enhance mental well-being but less is known about the impact on physiology and longer lasting effects. Heart rate variability (HRV) gives an indication of autonomic control of the heart, in particular vagal activity, with reduced HRV identified as a risk factor for cardiovascular disease. Night-time HRV allows vagal activity to be assessed whilst minimizing confounding influences of physical and mental activity. The aim of this study was to investigate whether a lunchtime walk in nature increases night-time HRV. Participants (n = 13) attended on two occasions to walk a 1.8 km route through a built or a natural environment. Pace was similar between the two walks. HRV was measured during sleep using a RR interval sensor (eMotion sensor) and was assessed at 1–2 h after participants noted that they had fallen asleep. Markers for vagal activity were significantly greater after the walk in nature compared to the built walk. Lunchtime walks in nature-based environments may provide a greater restorative effect as shown by vagal activity than equivalent built walks. Nature walks may improve essential recovery during night-time sleep, potentially enhancing physiological health.

A Two Process Model of Sleep Regulation

Authors: A.A. Borbely

Abstract: Presents a model of sleep regulation based on experimental studies. It is proposed that 2 processes play a dominant role in sleep regulation: a sleep-dependent process (Process S) and a sleep-independent circadian process (Process C). The time course of Process S was derived from the spectral analysis of slow wave activity in the human EEG. Its level shows an exponential decline during sleep and an increase during waking. The level of Process S at sleep onset is therefore considered to be a function of prior waking time. Process C is reflected by the rhythmic variation of sleep propensity during prolonged sleep deprivation and is assumed to be controlled by a circadian oscillator. In the model, sleep propensity and the duration of sleep are determined by the combined action of the 2 processes. The model is able to stimulate the variations of sleep duration as a function of sleep onset time.

Genetic influences on heart rate variability

Authors: Simon Golosheykin, Julia D. Grant, Olga V. Novak, Andrew C. Heath, Andrey P. Anokhin

Abstract: Heart rate variability (HRV) is the variation of cardiac inter-beat intervals over time resulting largely from the interplay between the sympathetic and parasympathetic branches of the autonomic nervous system. Individual differences in HRV are associated with emotion regulation, personality, psychopathology, cardiovascular health, and mortality. Previous studies have shown significant heritability of HRV measures. Here we extend genetic research on HRV by investigating sex differences in genetic underpinnings of HRV, the degree of genetic overlap among different measurement domains of HRV, and phenotypic and genetic relationships between HRV and the resting heart rate (HR). We performed electrocardiogram (ECG) recordings in a large populationrepresentative sample of young adult twins (n = 1060 individuals) and computed HRV measures from three domains: time, frequency, and nonlinear dynamics. Genetic and environmental influences on HRV measures were estimated using linear structural equation modeling of twin data. The results showed that variability of HRV and HR measures can be accounted for by additive genetic and non-shared environmental influences (AE model), with no evidence for significant shared environmental effects. Heritability estimates ranged from 47 to 64%, with little difference across HRV measurement domains. Genetic influences did not differ between genders for most variables except the square root of the mean squared differences between successive R-R intervals (RMSSD, higher heritability in males) and the ratio of low to high frequency power (LF/HF, distinct genetic factors operating in males and females). The results indicate high phenotypic and especially genetic correlations between HRV measures from different domains, suggesting that N 90% of genetic influences are shared across measures. Finally, about 40% of genetic variance in HRV was shared with HR. In conclusion, both HR and HRV measures are highly heritable traits in the general population of young adults, with high degree of genetic overlap across different measurement domains.

Reduced Heart Rate Variability and Mortality Risk in an Elderly Cohort

Authors: HisakoTsuji,MD; FerdinandJ.Venditti,Jr,MD; EmilyS.Manders,BS;JaneC.Evans,MPH; Martin G. Larson,ScD; CharlesL.Feldman, ScD; Daniel Levy,MD

Abstract: Background: The prognostic implications of alterations in heart rate variability have not been studied in a large community-based population. Methods and results: The first 2 hours of ambulatory ECG recordings obtained on original subjects of the Framingham Heart Study attending the 18th biennial examination were reprocessed to assess heart rate variability. Subjects with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1 hour of recording time, processed time < 50% of recorded time, and those taking antiarrhythmic medications were excluded. The associations between heart rate variability measures and all-cause mortality during 4 years of follow-up were assessed. There were 736 eligible subjects with a mean age (+/SD) of 72 +/6 years. The following five frequency domain measures and three time domain measures were obtained: very-low-frequency power (0.01 to 0.04 Hz), low-frequency power (0.04 to 0.15 Hz), high-frequency power (0.15 to 0.40 Hz), total power (0.01 to 0.40 Hz), the ratio of low-frequency to high-frequency power, the standard deviation of total normal RR intervals, the percentage of differences between adjacent normal RR intervals that are > 50 milliseconds, and the square root of the mean of the squared differences between adjacent normal RR intervals. During follow-up, 74 subjects died. In separate proportional hazards regression analyses that adjusted for relevant risk factors, very-low-frequency power (P < .0001), low-frequency power (P < .0001), high-frequency power (P = .0014), total power (P < .0001), and the standard deviation of total normal RR intervals (P = .0019) were significantly associated with all-cause mortality. When all eight heart rate variability measures were assessed in a stepwise analysis that included other risk factors, low-frequency power entered the model first (P < .0001); thereafter, none of the other measures of heart rate variability significantly contributed to the prediction of all-cause mortality. A 1 SD decrement in low-frequency power (natural log transformed) was associated with 1.70 times greater hazard for all-cause mortality (95% confidence interval of 1.37 to 2.09). Conclusions: The estimation of heart rate variability by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional risk factors.

Heart rate variability and myocardial infarction: systematic literature review and metanalysis


Abstract: Background: Heart rate, measured as beat-to-beat intervals, is not constant and varies in time. This property is known as heart rate variability (HRV) and it has been investigated in several diseases, including myocardial infarction (MI). The main hypothesis is that HRV embed some physiological processes that are characteristics of regulatory systems acting on cardiovascular system. It is possible to quantify such a complex behaviour starting from RR intervals properties itself with the idea that any event affecting the cardiac regulatory system significantly will disrupt and change HRV. In this article, we first review different methodologies previously published to calculate HRV indexes. We then searched literature for studies published on HRV and MI and we derive a metanalysis where published data allow calculation of composite outcomes. Material and Methods: Articles considered eligible for metanalysis were original retrospective/prospective studies investigating HRV after myocardial infarction, reporting follow up for mortality or significant cardiac complications. Random effect model was used to assessed for homogeneity and calculate composite outcome and its 95% confidence interval (CI). Results: 21 studies were identified as eligible for subsequent analysis. Among these studies 5 large trials were eligible for metanalysis: “they included 3489 total post-MI patient with an overall mortality of 125/577 (21,7%) in patients with standard deviation of RR intervals (SDNN) less than 70 msec compared to 235/2912 (8,1%) in patients with SDNN

Cue reactivity and its relation to craving and relapse in alcohol dependence: A combined laboratory and field study

Authors: Jurriaan Witteman, Hans Post, Mika Tarvainen, Avalon de Bruijn, Elizabeth De Sousa Fernandes Perna, Johannes G. Ramaekers, Reinout W. Wiers

Abstract: The present study investigated the nature of physiological cue reactivity and craving in response to alcohol cues among alcohol-dependent patients (N = 80) who were enrolled in detoxification treatment. Further, the predictive value with regard to future drinking of both the magnitude of the physiological and craving response to alcohol cues while in treatment and the degree of alcohol-cue exposure in patients' natural environment was assessed. Physiological reactivity and craving in response to experimental exposure to alcohol and soft drink advertisements were measured during detoxification treatment using heart rate variability and subjective rating of craving. Following discharge, patients monitored exposure to alcohol advertisements for five consecutive weeks with a diary and were followed up with an assessment of relapse at 5 weeks and 3 months post-discharge. The results indicated that the presence of alcohol cues such as the portrayal of the drug and drinking behaviour induced physiological cue reactivity and craving. Additionally, cue reactivity and craving were positively correlated, and cue reactivity was larger for patients with shorter histories of alcohol dependence. Further, patients reported a substantial daily exposure to alcohol cues. The magnitude of cue reactivity and the craving response to alcohol cues at baseline and degree of exposure to alcohol cues in patients' natural environment did not predict relapse. It is concluded that the presence of alcohol cues such as portrayal of alcoholic beverages and drinking behaviour induces cue reactivity and craving in alcohol dependence through a conditioned appetitive response.

Heart Rate Variability Standards of Measurement, Physiological Interpretation, and Clinical Use

Authors: Task Force of the European Society of Cardiology, North American Society of Pacing and Electrophysiology

Abstract: The clinical relevance of HRV was first appreciated in 1965 when Hon and Lee6 noted that fetal distress was preceded by alterations in interbeat intervals before any appreciable change occurred in heart rate itself. Twenty years ago, Sayers7 and others8-10 focused attention on the existence of physiological rhythms imbedded in the beat-to-beat heart rate signal. During the 1970s, Ewing et al11 devised a number of simple bedside tests of short-term RR differences to detect autonomic neuropathy in dia­betic patients. The association of higher risk of postin­ farction mortality with reduced HRV was first shown by Wolf et al12 in 1977. In 1981, Akselrod et al13 introduced power spectral analysis of heart rate fluctuations to quan­ titatively evaluate beat-to-beat cardiovascular control. These frequency domain analyses contributed to the understanding of autonomic background of RR interval fluctuations in the heart rate record.14’15 The clinical importance of HRV became appreciated in the late 1980s, when it was confirmed that HRV was a strong and independent predictor of mortality after an acute myo­cardial infarction.16-18 With the availability of new, digi­tal, high-frequency, 24-hour, multichannel ECG rec­orders, HRV has the potential to provide additional valuable insight into physiological and pathological con­ditions and to enhance risk stratification.

Firstbeat VO2 estimation - valid or voodoo?

Authors: BJRMD

Abstract: VO2 is the rate of oxygen usage by the body during a given amount of exercise. As an analogy, think of it as the amount of O2 (air) used by your auto engine cruising along the road. The gasoline used is analogous to the carbohydrates your body is using as fuel. In either case a certain amount of oxygen (along with the fuel) is required depending on the load. Running up a mountain at the same speed as on flat land will require more O2 (and carbs), just like your automobile will require more fuel and O2 to tackle the mountain than level ground. The VO2 is simply a "gas" measurement, a volume of O2 used per minute (ml/min or ml/kg/min). The VO2 max is the greatest amount of O2 (per minute) you are able to utilize at a high work load. Going higher on the workload (more watts) is possible but at the expense of anaerobic metabolism since O2 usage is already maxed out. Calculating the true VO2 is difficult and needs elaborate gear, so many alternate formula, nomograms and other methods have been developed that do not rely upon gas exchange measurements. By using running speed or cycling power at (near) maximum heart rate and ventilation rates, it is possible to infer VO2max equivilant speed or power as well as derive an actual VO2 value in ml/kg/min. This type of calculation relies on principles of physics to some extent. For example, equate running speed to the speed of the car. If we know the speed of the vehicle, it should be possible to use multiple parameters (vehicle mass, aerodynamics, wind speed, grade and empiric correction factors) to figure the instantaneous fuel usage (or VO2). In my post of VO2 peak/max, some formulas were reviewed. However, a huge downside to this type of process is that it needs to be done at a peak or maximum effort. Over the years many groups have attempted to come up with ways to infer a VO2 peak without doing a maximal load. Firstbeat (the company Garmin uses for VO2 metrics) has developed methods to estimate VO2 max, without the max effort being done. Their rational is sound many subjects either can't physically exercise at a maximal level or it's just not part of their training program for that particular cycle. If a non gas exchange, sub maximal method was accurate in estimating VO2 peak, it would be valuable indeed.

A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health

Authors: Julian F. Thayera, Fredrik, Mats Fredrikson, John J. Sollers, Tor D. Wagere

Abstract: The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model and update it with recent results. Specifically, we performed a meta-analysis of recent neuroimaging studies on the relationship between heart rate variability and regional cerebral blood flow. We identified a number of regions, including the amygdala and ventromedial prefrontal cortex, in which significant associations across studies were found. We further propose that the default response to uncertainty is the threat response and may be related to the well known negativity bias. Heart rate variability may provide an index of how strongly ‘top–down’ appraisals, mediated by cortical-subcortical pathways, shape brainstem activity and autonomic responses in the body. If the default response to uncertainty is the threat response, as we propose here, contextual information represented in ‘appraisal’ systems may be necessary to overcome this bias during daily life. Thus, HRV may serve as a proxy for ‘vertical integration’ of the brain mechanisms that guide flexible control over behavior with peripheral physiology, and as such provides an important window into understanding stress and health.

Validity of Commonly Used Heart Rate Variability Markers of Autonomic Nervous System Function

Authors: Bianca Lee Thomas, Nicolaas Claassen, Piet Becker, Margaretha Viljoen

Abstract: Background: Despite strong reservations regarding the validity of a number of heart rate variability (HRV) measures, these are still being used in recent studies. Aims: We aimed to compare the reactivity of ostensible sympathetic HRV markers (low and very low frequency [LF and VLF]) to that of electrodermal activity (EDA), an exclusively sympathetic marker, in response to cognitive and orthostatic stress, investigate the possibility of LF as a vagal-mediated marker of baroreflex modulation, and compare the ability of HRV markers of parasympathetic function (root mean square of successive differences [RMSSD] and high frequency [HF]) to quantify vagal reactivity to cognitive and orthostatic stress. Results: None of the purported sympathetic HRV markers displayed a reactivity that correlated with electrodermal reactivity. LF (ms2) reactivity correlated with the reactivity of both RMSSD and HF during baroreflex modulation. RMSSD and HF indexed the reactivity of the parasympathetic nervous system under conditions of normal breathing; however, RMSSD performed better as a marker of vagal activity when the task required breathing changes. Conclusions: Neither LF (in ms2 or normalized units [nu]) nor VLF represent cardiac sympathetic modulation of the heart. LF (ms2) may reflect vagally mediated baroreflex cardiac effects. HRV linear analysis therefore appears to be restricted to the determination of vagal influences on heart rate. With regard to HRV parasympathetic markers, this study supports the suggestion that HRV frequency domain analyses, such as HF, should not be used as an index of vagal activity in study tasks where verbal responses are required, as these responses may induce respiratory changes great enough to distort HF power.