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AIMS: The autonomic nervous system includes parasympathetic and sympathetic components that monitor and regulate most of the bodily functions and play a central role in the physiology and homeostasis of the human body. Heart rate variability is a non-invasive tool for quantification of rhythmic fluctuations in heart rate that reflects the function of the autonomic nervous system. The study aims to describe the heart rate variability distribution in the general population, stratified in sex and age groups, which is currently insufficiently described.METHODS: A cross-sectional population-based study recruited participants in 10 municipalities in the western part of the greater Copenhagen area in Denmark, including 6891 men and women aged 18-72 years (participation rate was 29.5%). Short-term heart rate variability measures were obtained and related to age and gender.RESULTS: Both time and frequency domain measures showed a huge variation in the different sex and age groups. Women had a higher median heart rate than men, and the association with age was U-shaped. Measures indicating a predominance of the parasympathetic component in relation to the sympathetic component were more frequent in women and younger age groups.CONCLUSIONS: Both sex and age influence the heart rate variability in this adult Danish population. Therefore, our age- and sex-related reference values of heart rate variability in the time and frequency domain should be used in further epidemiological and clinical research.

Cecilie Bagi Nordsten,1,&ast; Christopher Rue Molbech,1,2,&ast; Jesper Mehlsen,3 Torben Lykke Sørensen1,2 1Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark; 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 3Unit of Surgical Pathophysiology, University of Copenhagen, Rigshospitalet, Denmark&ast;These authors contributed equally to this workCorrespondence: Torben Lykke Sørensen, Department of Ophthalmology, Zealand University Hospital, Vestermarksvej 23, Roskilde, 4000, Denmark, Email tlso@regionsjaelland.dkPurpose: Patients with central serous chorioretinopathy (CSC) have previously been shown to have a lower heart rate variability (HRV), implying a lower vagal tone. Vagal tone alters mineralocorticoids, which in turn affect the thickness of the choroid. Since increased choroidal thickness is characteristic of CSC, we wanted to investigate its correlation with HRV.Patients and Methods: In this case–control study, 21 acute CSC patients and 31 healthy controls were included. Diagnosis was confirmed by optical coherence tomography (OCT) and retinal examination. HRV was evaluated following accepted standards. Outcome measures were chosen beforehand as follows: Standard deviation of N–N intervals (SDNN), root mean square of successive differences (RMSDD), low frequency/high frequency ratio (LF/HF ratio), and standard deviation ratio from commonly used Poincare plot (SD2/SD1 ratio). Choroidal thickness was measured using OCT directly under the foveola.Results: Patients and healthy controls did not differ in health and medical characteristics in addition to CSC disease. Choroidal thickness was greatest in patients with CSC (mean±SD: 342± 80 μm) compared to controls (235± 60 μm, p< 0.0001). A correlation was observed between LF/HF ratio and choroidal thickness in patients with CSC (Pearson correlation 0.63, p=0.02), where the CSC group had a lower LF/HF ratio (Median 2.39 ms2, IQR: 1.

Introduction: Autonomic dysfunction is prevalent in ischemic stroke patients and associated with a worse clinical outcome. We aimed to evaluate autonomic dysfunction over time and the tolerability of the head-up tilt table test in an acute stroke setting to optimize patient care. Patients and method: In a prospective observational cohort study, patients were consecutively recruited from an acute stroke unit. The patients underwent heart rate and blood pressure analysis during the Valsalva maneuver, deep breathing, active standing, and head-up tilt table test if active standing was tolerated. In addition, heart rate variability and catecholamines were measured. All tests were performed within seven days after index ischemic stroke and repeated at six months follow-up. Results: The cohort was comprised of 91 acute stroke patients, mean (SD) age 66 (11) years, median (IQR) initial National Institute of Health Stroke Scale 2 (1–4) and modified Ranking Scale 2 (1–3). The head-up tilt table test revealed 7 patients (10%) with orthostatic hypotension. The examination was terminated before it was completed in 15%, but none developed neurological symptoms. In the acute state the prevalence of autonomic dysfunction varied between 10–100% depending on the test. No changes were found in presence and severity of autonomic dysfunction over time. Conclusion: In this cohort study of patients with mild stroke, autonomic dysfunction was highly prevalent and persisted six months after index stroke. Head-up tilt table test may be used in patients who tolerate active standing. Autonomic dysfunction should be recognized and handled in the early phase after stroke.

Patients with severe traumatic brain injury (TBI) may have autonomic dysfunction, one manifestation of which is orthostatic intolerance. This potentially impairs physical rehabilitation. However, the exact mechanisms remain elusive. In 30 patients participating in a trial of early tilt training versus standard care and 15 healthy volunteers, 5-min electrocardiography was recorded in the supine position and during 70° head-up tilt. Heart rate variability was analyzed by the low- and high-frequency (LF and HF) power, the LF-HF ratio, the total power, the ratio of the standard deviation of normal-to-normal intervals (SDNN), the root mean square of successive differences (RMSSD), the detrended fluctuations, and sample entropy. In patients in the upright compared to the supine position, SDNN (p < 0.001), RMSSD (p < 0.001), and total power (p = 0.004) all decreased, while the remaining variables were unchanged; no long-term differences in heart rate variability in the supine position were found between early tilt training and standard care. In the healthy volunteers, all measures besides SDNN and total power changed significantly between supine and upright position. In patients with severe TBI compared to healthy volunteers, several measures of heart rate variability changed differentially during mobilization from the supine to the upright position.

Purpose: Early postoperative mobilization can be hindered by orthostatic intolerance (OI). Postoperative OI has multifactorial pathogenesis, possibly involving both postoperative hypovolemia and autonomic dysfunction. We aimed to investigate the effect of mild acute blood loss from blood donation simulating postoperative hypovolemia, on both autonomic function and OI, thus eliminating confounding perioperative factors such as inflammation, residual anesthesia, pain, and opioids. Methods: This prospective observational cohort study included 26 blood donors. Continuous electrocardiogram data were collected during mobilization and night sleep, both before and after blood donation. A Valsalva maneuver and a standardized mobilization procedure were performed immediately before and after blood donation, during which cardiovascular and tissue oxygenation variables were continuously measured by LiDCOrapid™ and Massimo Root™, respectively. The incidence of OI, hemodynamic responses during mobilization and Valsalva maneuver, as well as heart rate variability (HRV) responses during mobilization and sleep were compared before and 15 min after blood donation. Results: Prior to blood donation, no donors experienced OI during mobilization. After blood donation, 6/26 (23%; 95% CI, 9 to 44) donors experienced at least one OI symptom. Three out of 26 donors (12%; 95% CI, 2 to 30) terminated the mobilization procedure prematurely because of severe OI symptoms. Cardiovascular and cerebral tissue oxygenation responses were reduced in patients with severe OI. After blood loss, HRV indices of total autonomic power remained unchanged but increased sympathetic and decreased parasympathetic outflow was observed during mobilization, but also during sleep, indicating a prolonged autonomic effect of hypovolemia. Conclusion: We describe a specific hypovolemic component of postoperative OI, independent of postoperative autonomic dysfunction, inflammation, opioids, and pain. Study registration

Background: Early postoperative mobilization can be hindered by orthostatic intolerance (OI) due to failed orthostatic cardiovascular regulation. The underlying mechanisms are not fully understood and specific data after total knee arthroplasty (TKA) are lacking. Therefore, we evaluated the incidence of OI and the cardiovascular response to mobilization in fast-track TKA. Methods: This prospective observational cohort study included 45 patients scheduled for primary TKA in spinal anesthesia with a multimodal opioid-sparing analgesic regime. OI and the cardiovascular response to sitting and standing were evaluated with a standardized mobilization procedure preoperatively, and at 6 and 24 h postoperatively. Hemodynamic variables were measured non-invasively (LiDCO™ Rapid). Perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, opioid use, and pain during mobilization were recorded. Results: Eighteen (44%) and 8 (22%) patients demonstrated OI at 6 and 24 h after surgery, respectively. Four (10%) and 2 (5%) patients experienced severe OI and terminated the mobilization procedure prematurely. Dizziness was the most common OI symptom during mobilization at 6 h. OI was associated with decreased orthostatic responses in systolic, diastolic, mean arterial pressures, and heart rate (all p <.05), while severe OI patients demonstrated impaired diastolic, mean arterial pressures, heart rate, and cardiac output responses (all p <.05). No statistically significant differences in perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, pain, or opioid use were observed between orthostatic tolerant and intolerant patients. Conclusion: Early postoperative OI is common following fast-track TKA. Pathophysiologic mechanisms include impaired orthostatic cardiovascular responses. The progression to severe OI symptoms appears to be primarily due to inadequate heart rate response.

Heart rate variability (HRV) is a predictor of mortality and morbidity after non-lethal cardiac ischemia, but the relation between preoperatively measured HRV and intra- and postoperative complications is sparsely studied and most recently reviewed in 2007. We, therefore, reviewed the literature regarding HRV as a predictor for intra- and postoperative complications and outcomes. We carried out a systematic review without meta-analysis. A PICO model was set up, and we searched PubMed, EMBASE, and CENTRAL. The screening was done by one author, but all authors performed detailed review of the included studies. We present data from studies on intraoperative and postoperative complications, which were too heterogeneous to warrant formal meta-analysis, and we provide a pragmatic review of HRV indices to facilitate understanding our findings. The review was registered in PROSPERO (CRD42021230641). We screened 2337 records for eligibility. 131 records went on to full-text assessment, 63 were included. In frequency analysis of HRV, low frequency to high frequency ratio could be a predictor for intraoperative hypotension in spinal anesthesia and lower total power could possibly predict intraoperative hypotension under general anesthesia. Detrended fluctuation analysis of HRV is a promising candidate for predicting postoperative atrial fibrillation. This updated review of the relation between preoperative HRV and surgical outcome suggests a clinically relevant role of HRV but calls for high quality studies due to methodological heterogeneity in the current literature. Areas for future research are suggested.

INTRODUCTION. The Composite Autonomic Symptom Score (COMPASS 31) is a validated self-assessment questionnaire quantifying the severity and distribution of autonomic symptoms across six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor functions) by scoring 31 clinically selected questions. The aim of this study was to translate into Danish and validate the Danish version of COMPASS 31. METHODS. The original (US) English version of the COMPASS 31 questionnaire was translated into Danish via forward/backward translation and validated in accordance with a protocol set forth by the Autonomic Group at the Mayo Clinic. Ten healthy controls and 20 patients with disorders associated with a variable degree of autonomic dysfunction were enrolled – all bilingual (Danish mother tongue, proficiency in English). RESULTS. A total of 20 patients (16 women, aged 48 + 17 years) and ten healthy controls (six women, aged 40 + 19 years) were included. Test-retest reliability was high with no consistent bias, and the Danish version of the COMPASS 31 significantly correlated with the English version of the COMPASS 31 in both total score and all sub-scores. Patients scored significantly higher on the COMPASS 31 questionnaire than healthy controls (34.0 (26.5-49.2) versus 2.3 (1.6-24.3) (median (interquartile ranges); p = 0.01). CONCLUSIONS. We present a Danish version of the COMPASS 31 – a validated self-reported questionnaire allowing for the quantification of autonomic dysfunction. We hope this Danish version will be implemented in both clinical practice and research settings in Denmark.

Cerebral autoregulation is a complex mechanism that serves to keep cerebral blood flow relatively constant within a wide range of cerebral perfusion pressures. The mean flow index (Mx) is one of several methods to assess dynamic cerebral autoregulation, but its reliability and validity have never been assessed systematically. The purpose of the present systematic review was to evaluate the methodology, reliability and validity of Mx. Based on 128 studies, we found inconsistency in the pre-processing of the recordings and the methods for calculation of Mx. The reliability in terms of repeatability and reproducibility ranged from poor to excellent, with optimal repeatability when comparing overlapping recordings. The discriminatory ability varied depending on the patient populations; in general, those with acute brain injury exhibited a higher Mx than healthy volunteers. The prognostic ability in terms of functional outcome and mortality ranged from chance result to moderate accuracy. Since the methodology was inconsistent between studies, resulting in varying reliability and validity estimates, the results were difficult to compare. The optimal method for deriving Mx is currently unknown.