Assessment of cardiac autonomic function: from bench to bedside.

Heart rate (HR) variability (HRV) during ambulatory recordings may be affected by individual differences in daily physical activity (PA). However, the influence of various levels of PA on different measures of HRV is not exactly known. We examined the association between simultaneously measured HRV and objective PA data obtained with an accelerometer during waking hours among 45 healthy adults. Bouts of PA were identified from minute-by-minute accelerometer data as metabolic equivalent (METs) values and calculated as mean METs for 30 min. HRV was analyzed concurrently. Within-individual correlation analyses and sign tests were performed to study the relationships between various HRV indexes and PA. The mean PA time was 15:44 +/- 1:01 h, and the mean MET was 1.91 +/- 0.14. HR and sample entropy, but not the other measures of HRV, had a significant relationship with PA, as shown by both correlation analyses (r = 0.64, P = 0.021, and r = -0.55, P = 0.022, respectively) and sign tests (P < 0.0001 for both). Beat-to-beat R-R interval fluctuation expressed as SD1 also demonstrated a significant relation to PA according to the sign test (P = 0.037) and a trend of association according to the correlation analysis (r = -0.40, P = 0.129). The complexity measure of HRV, in addition to average HR and the short-term index of HRV (SD1), is significantly influenced by the level of PA during ambulatory conditions. Long-term HRV indexes remained relatively stable at various activity levels, making them the most robust indexes for the assessment of cardiac autonomic function during free-running ambulatory conditions.

Background Atrial fibrillation (AF) is the commonest abnormal heart rhythm with significant related morbidity and mortality. There is increasing evidence that abnormalities of the cardiac autonomic nervous system (ANS) are involved in the pathogenesis of AF. Exploring the ANS is possible through heart rate variability (HRV) evaluation. Purpose To investigate whether HRV is more abnormal in patients with permanent AF compared to paroxysmal AF. Design In a cross-sectional comparison, we studied two patient groups: permanent AF (n=30) and paroxysmal AF (n=31). Time-domain, frequency-domain and non-linear measures of HRV were determined using eMotion Faros ECG sensor. Participant's breathing was controlled with a metronome set at 12 breaths per minute. Data was analysed using SPSS software. Results Time-domain and non-linear indices of HRV were significant higher in permanent AF group compared to paroxysmal AF (table 1). Permanent AF was the only independent predictor of HRV on multivariable analysis in this cohort of patients (p=0.006) Conclusions First study investigating autonomic function in patients with permanent AF and paroxysmal AF. HRV indices were significantly higher in permanent AF compared to paroxysmal AF which may suggest pronounced cardiac autonomic influence in the pathophysiology of permanent AF. Funding Acknowledgement Type of funding sources: None.

Heart rate variability (HRV) is a useful and powerful non-invasive tool for quantitative assessment of cardiac autonomic function. Recent studies have shown that low heart rate variability is an indication of increased risk for cardiac diseases and sudden cardiac death. Yoga has been associated with improved cardio-respiratory performance. Thirty male regular yoga practitioners doing yoga for more than 3 years, age between 25-45 years (yoga group) and 30 male non-yoga practitioners, age-matched (control group) were included. A computerized Niviqure ECG system with HRV software was used for heart rate variability recording. Our results show that frequency-domain parameters like LF power, LF n.u, and LF/HF ratio were significantly lower in yoga group compared to control group. Time-domain parameters like mean RR, NN50, pNN50 were significantly higher in yoga group compared to control group. We conclude that the yoga increases heart rate variability by optimizing the autonomic functions, which is a good indicator of cardiac autonomic activity during rest.

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study

Autonomic dysfunction frequently occurs in the context of Parkinson disease (PD) and may precede onset of motor symptoms. Limited data exist on the prospective association of heart rate variability (HRV), a marker of autonomic function, with PD risk. We included 12,162 participants of the Atherosclerosis Risk in Communities study, a community-based cohort, without a diagnosis of PD at baseline (1987-1989) and with available HRV data (mean age = 54 years, 57% women). A 2-minute electrocardiogram was used to measure HRV. Incident PD was identified through 2008 from multiple sources, and adjudicated. Multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by quartiles of HRV measurements. During a mean follow-up of 18 years, we identified 78 incident PD cases. Lower values of the root mean square of successive differences in normal-to-normal R-R intervals (rMSSD) and standard deviation of normal-to-normal R-R intervals (SDNN), markers of parasympathetic activity and total variability, respectively, were associated with higher PD risk during follow-up. In multivariate models, the HR (95% CI) of PD in the bottom quartiles of rMSSD and SDNN compared to the top quartiles were 2.1 (1.0-4.3) and 2.9 (1.4-6.1), respectively. Other measures of cardiac autonomic function, including mean R-R interval and frequency-domain measurements, were not associated with PD risk. In this prospective cohort, decreased HRV was associated with an increased risk of PD. Assessment of cardiac autonomic function may help identify individuals at risk for PD.

Introduction Polycystic ovary syndrome (PCOS) is a frequently occurringendocrine condition prevalent in women of reproductive age characterized by chronic anovulation, hyperandrogenism, insulin resistance, and a low-grade inflammatory state. Patients with PCOS are more vulnerable to developing cardiac and metabolic co-morbidities. Sympathetic overactivity is also reported in PCOS patients. Objective This study aimed to assess cardiac autonomic function in PCOS by Heart Rate Variability Analysis, Ewing's Test, and Composite Autonomic Symptom Scale-31 (COMPASS-31). Methods Thirty female PCOS patients and 30 age-matched control females were enrolled in the study. Both cases and controls were subdivided into sub-groups based on body mass index (BMI) and waist-to-hip ratio (WHR). The cardiac autonomic functions were assessed by the COMPASS-31 questionnaire, Ewing's battery tests, and short-term heart rate variability analysis. Results There was no significant difference in age, BMI, and WHR of both groups. Additionally, cases had a significantly higher low frequency to high frequency (LF/HF) ratio and COMPASS-31 score andalsoreported more derangement in Ewing's battery test, indicating cardiac autonomic dysfunction in PCOS patients. Conclusion Patients with PCOS are more prone to developing cardiac and metabolic co-morbidities.Early assessment of cardiac autonomic function can prevent future complications with timely interventions. Altered autonomic function in PCOS patients can be due to hyperandrogenism and insulin resistance.

Background :Non linear measure of heart rate variability (HRV) is an emerging method to detect changes in cardiac autonomic nerve function in major depressive disorder (MDD).&#x0D; Objective: To observe the effect of music therapy on non linear measures of HRV in newly diagnosed MDD patients.&#x0D; Methods: This prospective interventional study was done in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka in 2018 on 60 newly diagnosed MDD patients aged 20-40 years, both male and female. They were further subdivided into 30 patients with only antidepressant medication (Mirtazapine) and 30 patients received music therapy with Raga kafi (Rabindrasangeet) along with the same medication for 3 months. Age, sex and BMI matched healthy control were also enrolled. HRV non linear parameters were recorded by Power Lab 8/35. For statistical analysis paired sample ‘t’ test and independent sample ‘t’ test were done.&#x0D; Result: SD1, SD2 and SD1/SD2 were found significantly lower in MDD patients compared to healthy control at baseline. After 3 months of music therapy, significant increment of these parameters occurred with trend of improvement in cardiac autonomic nerve function (CANF) in these patients.&#x0D; Conclusion: This study concluded that music therapy can improve CANF by increasing parasympathetic and reducing sympathetic activity in MDD patients.&#x0D; J Bangladesh Soc Physiol. 2019, June; 14(1): 7-13

Introduction: Type 2 diabetes mellitus (T2DM) is a heterogeneous polygenic metabolic disease condition that is caused by insulin resistance leading to hyperglycemia. Since, T2DM is genetically inherited and autonomic dysfunction is its major complications, healthy offsprings of diabetic parents are highly vulnerable to manifest dysautonomia leading to insulin resistance. Objectives: We aimed to assess cardiac autonomic function using heart rate variability (HRV) parameters in healthy offsprings having parental history of T2DM. Methodology: A comparative cross-sectional study was carried out in the laboratory of department of Physiology enrolling 30 healthy offsprings of non-diabetic parents (Group 1) and 30 healthy offsprings of diabetic parents (Group 2). Anthropometric, biochemical and cardiovascular variables were assessed using standard procedures. Time domain and frequency domain parameters of HRV spectrum were assessed using photoplethysmography principle. Results: HRV findings revealed that markers of sympathetic regulation were significantly higher and those of parasympathetic function were significantly reduced in subject group having parental history of T2DM. LF/HF ratio was significantly increased suggesting sympatho-vagal imbalance in offspring of diabetic parents even in their euglycemic state. Conclusion: Alteration of cardiovascular autonomic function is found in healthy offspring of diabetic parents, characterized by reduced vagal activity and pronounced sympathetic regulation. Assessment of cardiac autonomic function would help in timely detection of such dysautonomia and reducing the life-threatening effects on offspring having parental history of T2DM.

Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with acromegaly.

Spectral analysis of heart rate variability (HRV) is an accepted method for assessment of cardiac autonomic function and its relationship to numerous disorders and diseases. Various non-parametric methods for HRV estimation have been developed. The spectrum of counts, the instantaneous heart rate spectrum and the interval spectrum are mostly practised. Although extensive literature on their respective properties is available, there seems to be a need for a more complete comparison, eventually resulting in recommendations for applicability. The methods for HRV spectral analysis use their specific transforms of the primary R-R interval series into input signals for spectral computation. This is, in fact, the reason for obtaining different spectra. A basis for comparison is established, revealing the generic relationships of these HRV input signals. It allows for a more systematic evaluation and for further development of the considered methods. The results with simulated and real HRV data show better performance by the spectrum of counts and by a proposed instantaneous heart rate spectrum, obtained using a cubic spline interpolated input signal. The modulation depth of the primary signal can influence the accuracy of the HRV analysis methods.

After the European Food Safety Authority reviewed reports of methylmercury and heart rate variability (HRV) in 2012, the panel concluded that, although some studies of cardiac autonomy suggested an autonomic effect of methylmercury, the results were inconsistent among studies and the implications for health were unclear. In this study, we reconsider this association by adding a perspective on the physiological context. Cardiovascular rhythmicity is usually studied within different frequency domains of HRV. Three spectral components are usually detected; in humans these are centered at <0.04 Hz, 0.15 Hz (LF), and 0.3 Hz (HF). LF and HF (sympathetic and parasympathetic activities, respectively) are evaluated in terms of frequency and power. By searching PubMed, we identified 13 studies examining the effect of methylmercury exposure on HRV in human populations in the Faroe Islands, the Seychelles and other countries. Considering both reduced HRV and sympathodominant state (i.e., lower HF, higher LF, or higher LF/HF ratio) as autonomic abnormality, eight of them showed the significant association with methylmercury exposure. Five studies failed to demonstrate any significant association. In conclusion, these data suggest that increased methylmercury exposure was consistently associated with autonomic abnormality, though the influence of methylmercury on HRV (e.g., LF) might differ for prenatal and postnatal exposures. The results with HRV should be included in the risk characterization of methylmercury. The HRV parameters calculated by frequency domain analysis appear to be more sensitive to methylmercury exposure than those by time domain analysis.

Spontaneous heart rate variability (HRV), a frequency domain analysis, and induced heart rate peak (HRP) changes after passive head-up tilt, a time domain analysis, have been widely used for exploring the interactions between the autonomic nervous system and the heart [1] Decreases in both HRV and HRP have been demonstrated with increasing age as well as in autonomic failure. Autonomic reflex dysfunction is associated with an increased incidence of hypotension after induction of anaesthesia [2]. The combined analysis of both methods as well as their relations to ageing has never been reported. In order to assess the ageing effect on the autonomic modulation of heart rate (HR), the ECG recordings in 32 healthy volunteers (ages 24–71 years) were analysed. The HR was quantified in the time-domain measuring the three consecutive HRP (defined as P1, P2 and P3, see Fig. 4) induced by passive 70° head-up tilt. The HRV was quantified by means of the fast Fourier transform algorithm in both supine and upright positions, the frequency bands were ranged as medium (MF 0.04–0.15 Hz) and high (HF 0.15–0.4 Hz) frequencies. The population sample was split into two groups of 16: youngsters (<40 years, age: 32±1.4) and elderly (>40 years, age: 57±2.4). Unpaired t-test and cross-correlation were applied for statistical analysis.Fig. 4. (abstract 12).Significant differences were found between both groups (see Table 5). Significant positive cross-correlation were found between the HRP and the HRV and both parameters decreased with ageing. The amplitude of HRP showed a positive correlation with MF spectral bands of HRV, supine and upright (r=0.66 and 0.63, P<10−4 and 10−3 respectively, for n=32). These data suggest that changes in HRV as well as in HRP induced by passive tilt is at least partially controlled by a common physiological mechanism. The best variables to assess cardiovascular autonomic dysfunction in elderly patients were: 1. in the time domain analysis, the amplitude of the third peak; 2. In the frequency domain analysis, the MF band, considered as an index of cardiac sympathetic modulation.Table 5: abstract 12).The simultaneous analysis of HR on time- and frequency-domain is particularly useful in quantifying cardiovascular system ageing and could be considered as an alternative test in the assessment of autonomic failure.

Spectral analysis of heart rate variability (HRV) is a widely accepted approach for assessment of cardiac autonomic function and its relationship to numerous disorders and diseases. As a rule, the non-parametric methods for HRV spectral analysis are tested using the integral pulse frequency modulation (IPFM) model. However, published results with simulated HRV signals show differences requiring further development of the existing methods. With the aim of improving estimation accuracy, an entirely IPFM-based method for HRV analysis is investigated. According to this method, the spectra are computed by finding the least squares solution of two matrix equations that are derived using the IPFM model and involve irregular samples of a signal representing the HRV. The method is validated with various synthesised signals (in all tests, the relative errors of the power estimates at the modulating frequencies are within 3%, and the relative power of the spurious terms is less than 0.8% only) and is furthermore applied to the spectral analysis of R-R interval series obtained from diabetic children. The results, with simulated and real HRV signals, show that the developed method yields very accurate estimations of the spectral region below half the mean heart rate. Moreover, it allows the detection and assessment of certain genuine modulating components beyond the traditional frequency limit of the HRV spectra.

Background: This study assessed the responses of Blood Pressure (BP) and Heart Rate (HR) to change of posture, Sustained Handgrip (SH),deep breathing(DB) and Valsalva manoeuvre (VM) in order to determining the normal limits and pattern of Autonomic Cardiovascular Indices (ACI) among healthy young adults. Methods: Two hundred and four volunteer (98 men and 106 women) aged 18- 40 years (mean, 22.45 ± 4.86 years) participated in the study. After excluding systemic diseases by clinical evaluation, each participant performed five non-invasive cardiac autonomic function tests in series. Differences in supine and erect systolic BPs were assessed by sphygmomanometry, diastolic BP responses to SH were determined by dynamometry while HR variability in response to VM, DB and postural change were assessed by continuous electrocardiogram. Normal limits of ACI were determined at 5th and 95th percentiles. Results: The mean (normal limits) for SBP response to change of posture (mmHg); DBP response to sustained handgrip (mmHg); Valsalva ratio; heart rate response to deep breathing (beats per minute); PTI; tachycardia ratio; bradycardia ratio and RHR(beats per minute) respectively were: -4.26 ± 9.17(-19.00-11.00); 20.14 ± 17.35(0.00-54.00); 1.55 ± 0.40(1.10-2.40); 31.82 ± 10.81(13.0048.75); 1.41 ± 0.31(1.08-1.84); 0.80 ± 0.12(0.58-1.00); 1.21 ± 0.20(0.95-1.60) and 70.61 ± 12.23(53.00-93.00). During Valsalva maneouvre, Post-Strain Pause (PSP) which ranged from 1.2812.76s was observed in 14(6.86%) of the participants. PSP occurred more frequently in women (9.43%) than men (4.08%). No significant gender difference in the duration of post-strain pause (t=-1.628, p=0.105). In majority of the participants (67.6%), an elevation of SBP occurred within 2minutes of rising from supine to erect position. Immediate Post-Standing Pause (IPSP) occurred among 139 (68.14%) participants. Conclusion: Non-invasive assessment of cardiac autonomic function is feasible in Nigeria. Increase rather than decrease in systolic blood pressure response occurred more frequently upon a change from supine to erect posture. IPSP was a unique pattern of cardiac autonomic functions in study population.

It has been documented that impaired heart rate variability (HRV) is related to life threatening arrhythmias in children with surgically repaired congenital heart disease. We aimed to analyze the balance of the cardiac autonomic functions by assessing HRV in children with arterial switch operation (ASO). In this observational cohort study, HRV analysis using 24-h Holter electrocardiography recordings was examined in 22 patients (mean age: 59.5±38.7 months, 18 male, 4 female) who had undergone ASO during the newborn period and 22 healthy children (mean age: 65.1±39.4 months, 18 male, 4 female). After Kolmogorov-Smirnov testing for normality, Student t-test and Mann-Whitney U test were used when appropriate. Chi-square was used for categorical data. In 24-h HRV analysis showed that SDANN and VLF were significantly higher in patient group. Awake SDNN, rMSSD, pNN50, TP and VLF levels of patient group were significantly higher than those of control subjects. Awake LF/HF ratio in patient group was significantly higher than their counterpart in asleep group. In the patient group, awake rMSSD, pNN50, TP, LF and HF were significantly lower than their counterpart in the asleep group. Children with transposition of the great arteries (TGA) following ASO have not decreased levels of time and frequency HRV parameters in the mid-term follow-up period. All HRV parameters reflecting vagal tone were increased in the patient group. It is suggested that vagal tone is more predominant than sympathetic tone for children with ASO.