Editorial: engineering approaches to study cardiovascular physiology: modeling, estimation, and signal processing

Many patients with severe obstructive sleep apnea (OSA) do not complain of excessive daytime sleepiness (EDS), possibly due to increased sympathetic nervous activity (SNA) and accompanying heightened alertness. We hypothesized that in patients with OSA, those without subjective EDS (Epworth Sleepiness Scale, ESS score < 11) would have higher very low frequency (VLF) heart rate variability (HRV) during sleep, reflecting greater sympathetic heart rate modulation than patients with an ESS score ≥ 11. Patients with severe OSA (AHI ≥ 30: 26 with and 65 without heart failure) were divided into those with and without EDS. Heart rate (HR) signals were acquired in stage 2 sleep during periods of recurrent apneas and hypopneas and submitted to coarse graining spectral analysis, which extracts harmonic, neurally mediated contributions to HRV from total spectral power. Because the apnea-hyperpnea cycle entrains muscle SNA at VLF (0 to 0.04 Hz), VLF power was our principal between-group comparison. Subjects without EDS had higher harmonic VLF power (944 ± 839 vs 447 ± 461 msec(2), p = 0.003) than those with EDS, irrespective of the presence or absence of heart failure (1218 ± 944 vs 426 ± 299 msec(2), p = 0.043, and 1029 ± 873 vs 503 ± 533 msec(2), p = 0.003, respectively). ESS scores correlated inversely with VLF power in all (r = -0.294, p = 0.005) and in heart failure subjects (r = -0.468, p = 0.016). Patients with severe OSA but without EDS have higher VLF-HRV than those with EDS. This finding suggests that patients with severe OSA but without EDS have greater sympathetic modulation of HRV than those with EDS that may reflect elevated adrenergically mediated alertness. Taranto Montemurro L; Floras JS; Picton P; Kasai T; Alshaer H; Gabriel JM; Bradley TD. Relationship of heart rate variability to sleepiness in patients with obstructive sleep apnea with and without heart failure.

Introduction Parkinsonian syndromes of different nature feature autonomic nervous system dysfunction (ANSd) which may herald or follow motor symptoms (MS) in Parkinson disease (PD), but anticipate by years and progress more rapidly in multiple system atrophy (MSA). Abnormal Heart Rate Variability (HRV) has been reported in both PD and MSA. Purpose This study aimed to evaluating if HRV analysis (HRVa) could contribute to differentiate PD from MSA and to guide early and more appropriate treatment and prognostic assessment. Methods 66 consecutive parkinsonian patients (pts) (48 males, 18 females) (mean age 63.8±10 y) were enrolled between 2010 and 2020. Initial clinical diagnosis was MSA (19), PD (20), PD with autonomic impairment (PD-AI) (10), Lewy body disease (2), supranuclear palsy (3), undefined Parkinsonism (UP) (12). The severity of MS was quantified with UPDRS and Hoehn/Yahr scales. HRV was analyzed with linear (TD and FD) and non-linear (NL) methods (Kubios Premium 3.4.1), during daily activity and NREM sleep (2-minutes intervals) and during REM sleep (1-minute Interval). 44/66 underwent also ASN functional evaluation with the Ewing protocol. Data of 52 age-matched healthy subjects (HS) were used for comparison. For statistical analysis, SPSS software (version 21) was used. Discriminant Analysis (DA) was applied to identify the more relevant parameters differentiating PD from MSA and classifying “undefined” cases. Prolonged follow-up (f-up) provided clinical diagnostic certainty, as goldstandard for validation of HRVa classification accuracy. Results UPDRS and Hoehn/Yahr scores were higher in MSA than in PD (p&amp;lt;0.0001). Along 10-years of f-up, 16/66 pts died (56,2% MSA), 5/66 had new diagnostic definition, and 15/66 were lost to f-up. Most of HRV parameters of 34 pts with certain diagnosis (17 MSA and 17 PD) whose f-up was completed, were significantly different from those of HS. VLFpower and recurrence plot parameters calculated during active wakefulness were different (p&amp;lt;0.05) between MSA and PD, and correctly classified them with 88,2% predictive accuracy (PA) at DA, according to the formula: F1 = (vlfpw%ar* − 0,087) + (rprec* − 0,319) + (rpshen*10.81) + (−20,53) Comparative classification accuracy of HRVa, Ewing score, UPDRS and Hoehn/Yahr scales is shown in Table 1. Attempting prognostic risk assessment by applying F1 to HRV data of pts with PD-AI and of pts with UP, those classified as MSA according to F1 showed the worst clinical outcome during the f-up. Conclusions This study confirms that a higher degree of prevailing sympathetic ASNd in MSA compared to PD can be identified by a combination of Linear and NL HRV parameters, and correctly differentiate with high (88,2%) predictive accuracy all pts with certain diagnosis verified during prolonged f-up. Moreover, HRVa might be useful for earlier prognostic stratification of pts with parkinsonian symptoms of uncertain nature and to improve clinical and pharmacological management. Funding Acknowledgement Type of funding sources: None.

ABSTRACTResearch suggests that heart rate variability (HRV) is a physiological indicator of the flexibility of the autonomic nervous system and can provide an objective measure of an individual’s ability to appropriately match emotional responses to environmental demands. The present study investigated whether angry response to emotional stimuli was related to HRV, and whether manipulation of HRV using biofeedback could change the anger response in a healthy adult population. Fifty-eight participants received HRV biofeedback (n = 29) or an active control condition (n = 29). HRV measures included standard deviation of normal-to-normal intervals (SDNN), low-frequency (LF) and high-frequency (HF) power, and was recorded across three sessions: baseline, training, and anger induction. The anger induction procedure resulted in increased subjective experience of anger, as well as physiological changes. The biofeedback group had higher HRV than active controls both during the training session (SDNN and LF HRV) and during anger induction (LF HRV). HRV during anger induction was significantly associated with self-reported emotional response for participants receiving biofeedback but not for active controls. Results provide support for HRV as an index of emotion regulation, specifically anger. Further research is needed to determine whether long-term HRV biofeedback can have a lasting effect on managing anger.

Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse cardiovascular outcomes in individuals with coronary artery disease, but the mechanisms underlying this phenomenon are unknown. We examined the relationship between stress-induced autonomic dysfunction, measured by low heart rate variability (HRV) in response to stress, and MSIMI in patients with stable coronary artery disease. We hypothesized that stress-induced autonomic dysfunction is associated with higher odds of MSIMI. In 735 participants with stable coronary artery disease, we measured high- and low-frequency HRV in 5-minute intervals before and during a standardized laboratory-based speech stressor using Holter monitoring. HRV at rest and stress were categorized into low HRV (first quartile) versus high HRV (second to fourth quartiles); the low category was used as an indicator of autonomic dysfunction. Multivariable logistic regression models were used to examine the association of autonomic dysfunction with MSIMI. The mean age was 58 (SD, ±10) years, 35% were women, 44% were Black participants, and 16% developed MSIMI. Compared with high HRV during stress, low HRV during stress (both high and low frequencies) was associated with higher odds of MSIMI after adjusting for demographic and clinical factors (odds ratio for high-frequency HRV, 2.1 [95% CI, 1.3-3.3]; odds ratio for low-frequency HRV, 2.1 [95% CI, 1.3-3.3]). Low-frequency HRV at rest was also associated with MSIMI but with slightly reduced effect estimates. In individuals with coronary artery disease, mental stress-induced autonomic dysfunction may be a mechanism implicated in the causal pathway of MSIMI.

A-44 Implications of the Heart Rate Variability Power Spectrum on the Relationship between Prenatal Anxiety Exposure and Child Anxiety in 5-Year-Olds

Oligodendroglial alpha-synucleinopathy and MSA-like cardiovascular autonomic failure: Experimental evidence

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) may be difficult but is important for prognostic and therapeutic purposes. Varying degrees of autonomic failure have been described in PD and MSA, whereas its involvement in PSP remains controversial. The aim of this study was to investigate autonomic function in patients fulfilling strict clinical diagnostic criteria for the disorders above, to evaluate the diagnostic capacity of laboratory autonomic tests. The study group was consecutively recruited among patients referred to a movement disorder unit. Thirty-four patients with PD, 15 patients with PSP, and 47 patients with MSA were compared with 18 healthy age-matched controls. Autonomic tests included analysis of heart rate variability (HRV) in temporal domain, at rest and during forced respiration, as well as blood pressure (BP) changes during 75 degrees head-up tilt. HRV did not differ between groups during quiet breathing but was significantly reduced during forced respiration in MSA (P < 0.01), while PD and PSP groups did not differ from controls. Hypotensive responses during orthostatic provocation were seen in PD (P < 0.01) and MSA (P < 0.001), whereas BP remained stable in most PSP patients, not differing from the healthy control group. On an individual basis, decreased HRV and severe hypotensive responses were seen in MSA patients regardless of age and disease duration, whereas PD patients showed this combination only at high age and long duration. In PSP, only a few cases with decreased HRV and limited hypotensive responses were found. We conclude that cardiovascular reflex tests can supplement the clinical differentiation of Parkinsonian syndromes.

Autonomic dysfunction in multiple system atrophy (MSA) comprises cardinal symptoms of orthostatic hypotension (OH) and urinary incontinence. Additionally, cardiovagal and sudomotor abnormalities can be present. Previous studies compared hand skin temperature and its response to cooling in subjects with probable MSA and Parkinson's disease (PD). Significant differences were found indicating that disturbed thermoregulation belongs to MSA autonomic features and could be helpful in differentiation of MSA from PD. The objective of this study was to improve our knowledge about impaired thermoregulation of distal extremities in MSA with parkinsonian features (MSA-P) and PD and to assess the possible interrelations for the different subtypes of autonomic dysfunction in a large cohort of MSA-P, PD and control patients. The patients underwent a standard cooling-rewarming procedure, termed ice test (IT). Electroneurography, heart rate variability, sympathetic skin response and orthostatic tests were performed for the subdivision of the patients. The prevalence of pathological IT was slightly increased in MSA compared with PD and control groups. The presence of pathological IT was related with older patient's age in PD and control groups significantly (p<0.05). This relation was absent for the MSA patients, who themselves were significantly younger (p=0.001). Significant association between the presence of pathological IT and OH was determined (p<0.001). Defective thermoregulation of distal extremities seems to be more severe in the MSA patients. The dysfunction of preganglionic sympathetic neurons might be involved in impaired response to cooling for MSA. The results suggest pathophysiological affinity of impaired sympathetic neurovascular regulation between pathological IT and OH.

Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA).

S134 Spectral analysis of heart rate variability (HRV) and blood pressure variability (BPV) resulted in a characteristic power spectrum with two main regions: a low frequency peak (<0.15Hz) and a high frequency peak centered at the respiratory frequency. The shape of HRV and BPV power spectra may be markedly altered by hypovolemia, since hypovolemia modifies autonomic nervous control of the cardiovascular system. The aim of the present study was to evaluate the effects of hypovolemia on HRV and BPV simultaneously in dogs. METHODS: Seven dogs weighing 13-16kg were anesthetized with thiamylal(10mg/kg), maintained with alpha-chloralose(15mg/kg/hr) and vecuronium(0.1mg/kg/hr) and mechanically ventilated with room air at 14 breaths/min. Catheters were placed in the femoral artery for measurement of arterial blood pressure and in the left femoral artery for removing blood. Splenectomy was done. We induced hypovolemia by removing blood in graded stages (0%, 10%, 20%, 30%, 40% of the estimated blood volume; EBV). After blood pressure was stabilized in each stage, heart rate and mean blood pressure were continuously recorded for 10 min. The areas of the spectral peaks within each measurement were calculated as follows: LF (0.04-0.15 Hz) and HF (0.15-0.4 Hz). The data were analyzed using repeated measurement of ANOVA followed by Fisher PLSD test. P < 0.05 was considered statistically significant. RESULTS: HR did not change during hypovolemia while mean BP decreased significantly after 30% of EBV hemorrhage. LF of HRV significantly increased after 20% of EBV hemorrhage, but HF of HRV did not change. Both LF and HF of BPV increased significantly in proportion to cumulative withdrawal of the blood. DISCUSSION: LF of HRV and BPV during hypovolemia increased and HF of HRV did not changed, indicating the shift of the autonomic balance towards sympathetic dominant. An excellent quantitative correlation between the HF and LF of BPV and the degree of hypovolemia was shown during graded hemorrhage. Even small degree of hypovolemia was detected by changes in LFs of HRV and BPV and HF of BPV. HF of HRV was not useful to detect hypovolemia. Our study suggests that the spectral analysis of HRV and BPV during graded hemorrhage shows different characteristics in the quantitative evaluations of autonomic nervous system during hypovolemia. (Table 1)Table 1: Power spectrum of HRV and BPV during graded hemorrhage

Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h(-1) for 30 min, n = 6) or 6-hydroxydopamine (20 mg ml(-1) at 2.5 ml h(-1) for 3 h; n = 9). Data were analysed by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low-frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.

Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied. Twenty-four-hour ambulatory electrocardiogram measurements were recorded twice from 14 women with breast or ovarian carcinoma: once before paclitaxel treatment and once on the day after the second chemotherapy course. Heart rate variability (HRV) was assessed with spectral analysis. For the frequency domain analysis, HRV was assessed in the very low (0.005-0.040 hertz [Hz]), low (0.040-0.150 Hz), and high frequency (0.150-0.400 Hz) spectral components. The ratio between low frequency and high frequency HRV decreased (daytime values of 2.7% [standard deviation (SD) 1.6] vs. 1.7% [SD 0.91; P = 0.0098) after 2 courses of paclitaxel. The circadian fluctuation of HRV also decreased in all studied frequency components. The observed changes in spectral characteristics suggest that autonomic modulation of the heart rate is impaired after paclitaxel therapy. However, from these data it is not clear whether the observed changes are permanent or whether autonomic cardiac function returns to normal some time after treatment. Further studies are needed to examine whether these indices based on HRV can be used to detect those patients at risk for cardiac side effects during chemotherapy.

The aim of the study was to analyse parameters reflecting the sympathovagal control of ventricular depolarisation and repolarisation [heart rate variability (HRV) and QT interval dispersion (QTd)] in patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA), and determine whether HRV correlates with QT dispersion parameters. The study consisted of 26 consecutive patients (16 men, 10 women) with single-vessel coronary artery disease (CAD) who underwent elective coronary angioplasty. HRV analyses of all subjects were obtained with the time- and frequency-domain methods. For frequency-domain analysis, low-frequency HRV (LF), high-frequency HRV (HF) and the LF:HF ratio were measured. For time-domain analysis, standard deviations of the normal-to-normal QRS intervals (SDNN) and square roots of the mean squared differences of successive N-N intervals (rMSSD) were obtained. QT intervals were also corrected for heart rate using the Bazett's formula, and the corrected QT interval dispersion (QTcd) was then calculated. All measurements (HRV parameters and QTcd) were made before and immediately after PTCA. QTcd was significantly decreased after PTCA (52.2 +/- 3.5 vs 42 +/- 3.9 ms). SDNN (94.1 +/- 22 vs 123.9 +/- 35.2 ms), rMSSD (43.7 +/- 20.1 vs 73.4 +/- 14.5 ms) and HF (51.1 +/- 48.8 vs 64.2 +/- 28.6 ms(2)) were significantly higher after PTCA, whereas LF (142 +/- 41.5 vs 157.2 +/- 25.9 ms(2)) and the ratio of LF:HF (3.3 +/- 1.9 vs 2.1 +/- 1.2) were significantly decreased after PTCA. We observed a significant negative correlation after PTCA between QTcd and LF (r = -0.87, p = 0.01) and between QTcd and the ratio of LF:HF (r = -056, p < 0.05). Among the patients with CAD undergoing PTCA, QTcd significantly decreased after PTCA, and negatively correlated with LF, the parameter reflecting the sympathetic system.

The aim of the present study was to investigate reactions in trapezius muscle blood flow (MBF), muscle activity, heart rate variability (HRV) and systemic blood pressure (BP) to autonomic tests in subjects with chronic neck-shoulder pain and healthy controls. Changes in muscle activity and blood flow due to stress and unfavourable muscle loads are known underlying factors of work-related muscle pain. Aberration of the autonomic nervous system (ANS) is considered a possible mechanism. In the present study, participants (n=23 Pain, n=22 Control) performed autonomic tests which included a resting condition, static hand grip test (HGT) at 30% of maximal voluntary contraction, a cold pressor test (CPT) and a deep breathing test (DBT). HRV was analysed in time and frequency domains. MBF and muscle activity were recorded from the upper trapezius muscles using photoplethysmography and electromyography (EMG). The pain group showed reduced low frequency-HRV (LF) and SDNN during rest, as well as a blunted BP response and increased LF-HRV during HGT (∆systolic 22mm Hg; ∆LF(nu) 27%) compared with controls (∆systolic 27; ∆LF(nu) 6%). Locally, the pain group had attenuated trapezius MBF in response to HGT (Pain 122% Control 140%) with elevated trapezius EMG following HGT and during CPT. In conclusion, only HGT showed differences between groups in systemic BP and HRV and alterations in local trapezius MBF and EMG in the pain group. Findings support the hypothesis of ANS involvement at systemic and local levels in chronic neck-shoulder pain.

Dissociation between ACE activity and autonomic response to ACE inhibition in patients with heart failure