Cardiovascular Autonomic Dysfunction Research Articles

Nrf2-Keap1 in Cardiovascular Disease: Which is the Cart and Which the Horse?

High levels of oxidant stress in the form of reactive oxidant species (ROS) are prevalent in the circulation and tissues in various types of cardiovascular disease including heart failure, hypertension, peripheral arterial disease, and stroke. Here we review the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an important and widespread antioxidant and anti-inflammatory transcription factor that may contribute to the pathogenesis and maintenance of cardiovascular diseases. We review studies showing that downregulation of Nrf2 exacerbates heart failure, hypertension and autonomic function. Finally, we discuss the potential for using Nrf2 modulation as a therapeutic strategy for cardiovascular diseases and autonomic dysfunction.

Tunable Q-factor wavelet transform based identification of diabetic patients using ECG signals

Diabetes is a chronic health condition that is characterized by increased levels of glucose (sugar) in the blood. It can have harmful effects on different parts of the body, such as the retina of the eyes, skin, nervous system, kidneys, and heart. Diabetes affects the structure of electrocardiogram (ECG) impulses by causing cardiovascular autonomic dysfunction. Multi-resolution analysis of the input ECG signal is utilized in this paper to develop a machine learning-based system for the automated detection of diabetic patients. In the first step, the input ECG signal is decomposed into sub-bands utilizing the tunable Q-factor wavelet transform (TQWT) technique. In the second step, four entropy-based characteristics are evaluated from each SB and elected using the K-W test method. To develop an automatic diabetes detection system, selected features are given as input with 10-fold validation to a SVM classifier using various kernel functions. The 3 rd sub-band of TQWT with the Coarse Gaussian kernel function kernel of the SVM classifier yields a classification accuracy of 91.5%. In the same dataset, the comparative analysis demonstrates that the proposed method outperforms other existing methods.

The Degree of Cardiovascular Autonomic Dysfunction is not Different in GBA-Related and Idiopathic Parkinson's Disease Patients: A Case-Control Instrumental Evaluation.

Increased prevalence of cardiovascular autonomic failure might play a key role on Parkinson's disease (PD) progression of glucocerebrosidase gene (GBA)-mutated patients, determining a malignant phenotype of disease in these patients. To objectively characterize, for the first time, the cardiovascular autonomic profile of GBA-mutated patients compared to idiopathic PD patients by means of cardiovascular reflex tests (CRTs). This is a case-control (1 : 2) study on PD patients belonging to well-characterized prospective cohorts. For each PD patient carrying GBA variants, two idiopathic PD patients, matched for sex and disease duration at CRTs, were selected. Patients recruited in these cohorts underwent a complete clinical and instrumental evaluation including specific autonomic questionnaires, CRTs and extensive genetic analysis. A total of 23 GBA-PD patients (19 males, disease duration 7.7 years) were included and matched with 46 non-mutated PD controls. GBA-mutated patients were younger than controls (59.9±8.1 vs. 64.3±7.2 years, p = 0.0257) and showed a more severe phenotype. Despite GBA-mutated patients reported more frequently symptoms suggestive of orthostatic hypotension (OH) than non-mutated patients (39.1% vs 6.5%, p = 0.001), the degree of cardiovascular autonomic dysfunction, when instrumentally assessed, did not differ between the two groups, showing the same prevalence of neurogenic OH, delayed OH and cardiovascular reflex impairment (pathological Valsalva maneuver). GBA-PD patients did not show different instrumental cardiovascular autonomic pattern than non-mutated PD. Our findings suggested that symptoms suggestive of OH should be promptly investigated by clinicians to confirm their nature and improve patient care and management.

Effect of spraying air freshener on particulate and volatile organic compounds in vehicles

People in these days spend approximately 6 % of their time in a means of transport. Air fresheners are frequently used in vehicles to mask odors; however, they can cause adverse health effects such as cardiovascular disease, systemic inflammation and autonomic dysfunction. This study aimed to identify the effects of air fresheners on the concentrations of particulate and volatile organic compounds (VOCs) in different vehicle cabins. Scanning mobility and optical particle sizers were used for the particle measurements. VOCs (e.g., BTEX and d-limonene) were collected using a Tenax TA. The products were sprayed for less than a minute. The study assessed three spray products (all trigger types), vehicle size (small, medium, and large), cabin temperature (10 °C, 20 °C, and 25 °C), and in-vehicle ventilation mode (all-off, recirculation, and external inflow modes). The particle concentration increased rapidly during the 1-min spraying of the products. The proportion of nanoparticles in the front seat (67.2 % ± 2.2 %) was 11.1 % ± 2.2 % lower than that in the rear seat (75.6 % ± 2.1 %). The spray product and vehicle size did not significantly affect the particle or VOC concentrations. With an increase in the temperature of the front seat, the proportion of nanoparticles increased by 25.3 % ± 3.2 %. Moreover, the maximum total VOC concentrations (front seat: 364.3 μg/m3; back seat: 241.3 μg/m3) were observed at 20 °C. Under in-vehicle ventilation, recirculation effectively reduced the overall particle concentration within the cabin; however, the generated VOCs circulated. The external inflow proved effective in cabin air purification by reducing the total VOC concentration to 56.0–57.2 % compared with other ventilation modes. These findings provide substantial insight into the persistence of particles and the dynamics of their dispersion, thereby enabling informed decision-making for particle-related risk management.

Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease.

An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD. To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications. We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX). 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001). A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.

Similar Patterns of Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue and Post-COVID-19 Syndromes.

There is a considerable overlap between the clinical presentation of post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many of their common symptoms can be linked to dysregulation of the autonomic nervous system (dysautonomia). This study aimed to objectively assess autonomic function in a general group of patients with PCC and in a group of patients with ME/CFS whose disease was not related to COVID-19. We hypothesize that the similarity in the chronic symptoms of patients with PCC and ME/CFS extends to objective autonomic nervous system abnormalities. Synchronous recordings of an electrocardiogram and continuous dynamics of blood pressure in the digital artery using the Penaz method were obtained using the spiroarteriocardiorhythmography method in 34 patients diagnosed with ME/CFS, in whom the onset of the disease was not associated with COVID-19, 29 patients meeting the PCC definition and 32 healthy controls. Heart rate variability (HRV) and systolic and diastolic blood pressure variability (BPV) were assessed at rest and in tests with fixed respiratory rates. Indicators of baroreflex regulation (baroreflex effectiveness index and baroreflex sensitivity) were additionally determined at rest. The total power and power of low-frequency and high-frequency of RR interval variability at rest as well as baroreflex sensitivity were significantly lower both in PCC and ME/CFS patients compared to healthy controls. Several diagnostic prediction models for ME/CFS were developed based on HRV parameters. During slow breathing, the HRV parameters returned to normal in PCC but not in ME/CFS patients. The correlation analysis revealed a close relationship of HRV, BPV parameters and baroreflex sensitivity with fatigue, but not with HADS depressive/anxiety symptoms in the ME/CFS and PCC patients. A similar pattern of HRV and baroreflex failure with signs of a pathological acceleration of age-dependent dysautonomia was identified in the ME/CFS and PCC patients. The clinical, diagnostic and therapeutic implications of these findings are discussed, in light of previously described relationships between inflammation, vascular pathology, atherosclerotic cardiovascular disease and autonomic dysfunction.

Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden.

Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.

Time-domain heart rate dynamics in the prognosis of progressive atherosclerosis

Background and aimThe regular uptake of a high-fat diet (HFD) with changing lifestyle causes atherosclerosis leading to cardiovascular diseases and autonomic dysfunction. Therefore, the current study aimed to investigate the correlation of autonomic activity to lipid and atherosclerosis markers. Further, the study proposes a support vector machine (SVM) based model in the prediction of atherosclerosis severity. Methods and resultsThe Lead-II electrocardiogram and blood markers were measured from both the control and the experiment subjects each week for nine consecutive weeks. The time-domain heart rate variability (HRV) parameters were derived, and the significance level was tested using a one-way Analysis of Variance. The correlation analysis was performed to determine the relation between autonomic parameters and lipid and atherosclerosis markers. The statistically significant time-domain values were used as features of the SVM. The observed results demonstrated the reduced time domain HRV parameters with the increase in lipid and atherosclerosis index markers with the progressive atherosclerosis severity. The correlation analysis revealed a negative association between time-domain HRV parameters with lipid and atherosclerosis parameters. The percentage accuracy increases from 86.58% to 98.71% with the increase in atherosclerosis severity with regular consumption of HFD. ConclusionsAtherosclerosis causes autonomic dysfunction with reduced HRV. The negative correlation between autonomic parameters and lipid profile and atherosclerosis indexes marker revealed the potential role of vagal activity in the prognosis of atherosclerosis progression. The support vector machine presented a respectable accuracy in the prediction of atherosclerosis severity from the control group.

Cardioprotective effect of Extract Ethanol Ocimum basilicum on Rat Induced Cisplatin

Cisplatin is a potent chemotherapy drug that is associated with several side effects such as myelotoxicity, gastrointestinal toxicity, ototoxicity neurotoxicity, cardiotoxicity, and nephrotoxicity2-5. Cardiotoxic manifestations of cisplatin chemotherapy have been described: heart failure, angina, acute myocardial infarction, thromboembolic events, autonomic cardiovascular dysfunction, both hypertension and hypotension, myocarditis, pericarditis, and severe congestive cardiomyopathy. Oxidative stress that occurs when antioxidant defenses are inadequate can damage lipids, proteins, carbohydrates, and DNA. (Ocimum bacilicum) which belongs to the Lamiaceae family as a rich source of phytochemical compounds that can show countless pharmacological effects. This study aims to determine the cardioprotective activity of extract ethanol of Ociumum bacilicium on rats induced cisplatin. The result show that ethanol extract of Ocimum bacilicum has antioxidant activity. The cardioprotective activity of ethanol extract of Ocimum bacilicum by reducing the level of CK-MB and LDH as cardiac biomarker. Extract dose 300mg/kg BB reduce the level of CK-MB into 1200,427±15,924ng/mL meanwhile the level of LDH into 7,345±0,064 ng/mL. Briefly, it can be concluded that Ociumum bacilicium has cardioprotective effect.

Reduced resting beat-to-beat blood pressure variability in females with relapsing-remitting multiple sclerosis

BackgroundRelapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease of the central nervous system and cardiovascular autonomic dysfunction has been well documented in this population. The sympathetic nervous system contributes to beat-to-beat blood pressure regulation primarily by baroreflex control of the peripheral vasculature which may be impaired in females with RRMS. Even at rest, attenuated sympathetic control of vasomotor tone may result in large and frequent blood pressure excursions (i.e., greater blood pressure variability). Therefore, the primary purpose of this investigation was to test the following hypotheses; (1) females with RRMS have augmented beat-to-beat blood pressure variability compared to healthy controls and (2) reduced sympathetic baroreflex sensitivity in females with RRMS is related to augmented blood pressure variability. MethodsElectrocardiogram and beat-to-beat blood pressure were continuously recorded during 8–10 min of supine rest in 26 females with clinically definite RRMS and 24 sex-, age- and BMI- matched healthy controls. Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (MS, n = 15; CON, n = 14). Traditional statistical measurements of dispersions were used to index beat-to-beat blood pressure variability. Spontaneous sympathetic baroreflex sensitivity was quantified by sorting diastolic blood pressures into 3 mmHg bins and calculating MSNA burst incidence within each bin. Weighted linear regression was then used to account for the number of cardiac cycles in each bin and calculate slopes. Spontaneous cardiac baroreflex sensitivity was determined using the sequence method. ResultsGroups had similar resting mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), MSNA burst frequency and MSNA burst incidence (All P > 0.05). The standard deviation and interquartile range of MAP, SBP and DBP were less in females with RRMS compared to healthy controls (All P < 0.05). There were no between groups differences in sympathetic baroreflex sensitivity or cardiac baroreflex sensitivity (Both P > 0.05) and baroreflex sensitivity measures were not related to any indices of blood pressure variability (Both P > 0.05). ConclusionThese data suggest that females with RRMS have reduced beat-to-beat blood pressure variability. However, this does not appear to be related to changes in sympathetic or cardiac baroreflex sensitivity.

AIDP BEFORE AND AFTER COVID-19 IN ALGERIA: SHORT COHORT STUDY

Acute inflammatory demyelinating polyradiculoneuropathy is an immune-mediated polyneuropathy (AIDP) that manifests in the form of an acute, ascending, areflexic, progressive and symmetrical paralysis. The primary infection usually from the respiratory or gastrointestinal tract and can be bacterial or viral, and during the pandemic SARS -COV2 and COVID-19 vaccine may also lead to it Life-threatening complications can occur as a result of Acute inflammatory demyelinating polyradiculoneuropathy Syndrome, such as: Severe Autonomic Cardiovascular Dysfunction and respiratory distress. We will report cases who were admitted to the ICU at Lamine Debaghine hospital between 2018 and 2023 presenting major complications and their evolution under ICU ward assistance. CATEGORY: Resuscitation and Anesthesia, Emergency Medicine KEYWORDS: Acute inflammatory demyelinating polyradiculoneuropathy syndrome, dysautonomia, ICU, AIDP, Guillain-Barre.

Individual tailored physical training in patients with postural orthostatic tachycardia syndrome after COVID-19 - a feasibility study

Abstract Background A significant proportion of patients with COVID-19 have developed persistent symptoms, described as post-acute COVID-19 syndrome (PACS ). A specific PACS variant is the postural orthostatic tachycardia syndrome (POTS). POTS is a cardiovascular autonomic dysfunction characterized by an excessive increase in heart rate in standing, deconditioning and low quality of life. Studies that have evaluated the effect and feasibility of individual tailored physical training in POTS associated with COVID-19 are sparse. Purpose To evaluate the effects and feasibility of individualized exercise on physical and psychological function in patients with POTS after COVID-19. Method Patients with POTS + PACS were enrolled between Dec 2021 and Dec 2022. The intervention consisted of individually tailored training, including endurance and muscle-strengthening exercises with a gradual progression of time, dose and position. The training was based on the study subject's heart rate and/or self-estimated exertion using BORG RPE. The intervention lasted 12 weeks. Progression of the exercise was halted if the study subject described increased symptoms &amp;gt;24h after the last exercise session. Measurements were carried out at baseline and after intervention: 6-minute walking test (6MWT), Active Standing Test (AST) and self-assessment of symptoms through forms; Malmö POTS scale (MaPS), Vanderbilt Orthostaic Symptom Score (VOSS), Fatigue Severity Scale (FSS) health-related quality of life (EQ-5D-5L), anxiety (GAD) and depression (PHQ-9). Physical activity and time in different positions (lying, sitting, standing and walking) were measured using accelerometers (ActivPAL). Recruitment rate, compliance and adverse events was registered as feasibility. Results A total of 24 patients were enrolled and 23 patients completed the intervention (19 women; mean age, 40.9 years (SD 10.7). No severe adverse events occurred however some of the patients described symptoms as post exertion malaise (PEM). After the intervention, patients demonstrated improvement in physical (6MWT, p&amp;lt;0.005) and psychological functions (PHQ-9, p&amp;lt;0.001), less symptoms related to POTS (MaPS p&amp;lt;0.01, VOSS p&amp;lt;0.02, FSS p&amp;lt;0.045) and improved HrQoL (EQ-5D p&amp;lt;0.001) (Table 1). The primary outcome, time spent in upright position increased by 1.5h/day i.e. by 49% (Figure 1). Conclusion In patients with COVID-19-related POTS, an individually tailored training seem to contribute to increased time in upright position, reduction of POTS-specific symptoms and improved functions. The intervention seems to be feasible in terms of recruitment, compliance and safety. Further studies are needed to verify these results and compare disease progression with and without intervention.Table 1Figure 1

Abstract 12824: Quantitative Autonomic Testing ‘Early’ and ‘Late’ After Recovery From Acute COVID-19 Illness

Background: Cardiovascular (CV) autonomic dysfunction (AD) is a known potential complication following acute COVID-19 illness and may contribute to persistent symptoms, such as fatigue and postural intolerance. However, the quantitative assessment of CV AD after an acute COVID-19 infection is largely unexplored. Objective: Compare CV autonomic testing in patients presenting ‘early’ and ‘late’ after an acute COVID-19 illness. Methods: CV autonomic testing was undertaken in symptomatic patients presenting ‘early’ (0-10 months) and ‘late’ (11-20 months) after an acute COVID-19 illness. Findings were compared to autonomic testing results in healthy control subjects. Measures included i) heart rate (HR) and blood pressure (BP) responses during active standing (AS), ii) time to BP nadir and recovery during AS, iii) Valsalva ratio (VR), and iv) respiratory sinus arrhythmia (RSA). Unpaired student t-test was used to compare findings (mean ± SD) in post-COVID patients to controls. A p-value of &lt;0.05 was statistically significant. Results: Control (n=82, mean 33 years, 87% female), ‘early’ (n= 37, mean 38 years, 89% female) and ‘late’(n=18, mean 43 years, 72% female) groups were similar in age and sex. Compared to controls, VR was abnormally low in both the ‘early’ and ‘late’ groups (‘early’ 1.5 and ‘late’ 1.4 vs. controls 1.7, both p&lt;0.03) ( Table ). Other autonomic measures did not differ significantly from controls. However, compared to the ’early’ group, the ‘late’ group exhibited a trend toward more marked AD ( Figure ). Conclusion: Patients presenting ‘early’ and ‘late’ after an acute COVID-19 illness exhibit similar severity of autonomic disturbance. Potentially, the ‘late’ group experienced more severe COVID illness leading to delayed referral for troublesome AD symptoms. Nonetheless, our findings suggest that abnormal CV AD findings may persist without apparent improvement for lengthy periods (up to 20 months in this study) after acute COVID-19 infection.

3 The Relationship Between Depression, Anxiety, and Autonomic Dysfunction in de novo Parkinson’s Disease Patients Over Time

Objective:Autonomic dysfunction is an important non-motor symptom of Parkinson’s disease (PD), with point prevalence estimates of approximately 50-70%. Common presentations include cardiovascular dysregulation, gastrointestinal dysfunction, impaired thermoregulation, and sexual dysfunction. In the present study, we sought to examine whether autonomic symptoms would predict trajectories of change in depression and anxiety over a 5-year period in newly diagnosed individuals with PD. Given that alterations in autonomic nervous system functioning (e.g., reduced heart rate variability, lower autonomic arousal) are frequently observed in individuals who have anxiety and depression, as well as the negative influence these symptoms can have on quality of life/functioning, we predicted that greater autonomic symptoms would be related to increased mood symptoms over time.Participants and Methods:Participants included 414 individuals from the Parkinson’s Progression Markers Initiative, a prospective study of newly diagnosed and untreated individuals with PD. The PD participants (mean age=61.6+9.7, mean education=15.6+3.0, 92.5% non-Hispanic White) were followed annually for up to five years. Self-reported autonomic symptoms were measured using the Scales for Outcomes in Parkinson’s Disease-Autonomic Dysfunction (SCOPA-AUT), which consists of a total score and 6 subdomain scores (gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, sexual). Mood measures included the Geriatric Depression Scale (GDS) and State-Trait Anxiety Inventory (STAI). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III. Bootstrapped linear regressions were performed to evaluate the relationship between autonomic symptoms (subdomains) and mood using data from the last visit (year 5). For longitudinal analyses, bootstrapped multilevel modeling was used to examine a) changes in SCOPA-AUT total over time (unconditional growth model only) and b) the relationship between mood and SCOPA-AUT total score over time, controlling for age/sex and motor severity.Results:Autonomic symptoms explained 28.2% of the total variance in trait anxiety, with unique predictors of gastrointestinal (/3=.266, p&lt;.001) and thermoregulatory (ß=.202, p=.004) symptoms. For depression, autonomic symptoms explained 27.9% of the total variance, with unique predictors of gastrointestinal (ß=.225, p=.012), thermoregulatory (ß=.178, p=.013), and cardiovascular (ß=.154, p=.012) symptoms. There was a gradual linear increase in total autonomic symptoms over time (b=0.86, p&lt;.001). Greater total autonomic symptoms were associated with higher average trait anxiety (b=0.54, p&lt;.001), slightly greater increase in trait anxiety over time (b=0.04, p&lt;.05), and occasion-to-occasion fluctuations in trait anxiety (b=0.24, p&lt;.001). Similarly, increased total autonomic symptoms were associated with higher average depressive symptoms (b=0.14, p&lt;.001), minimally greater increase in depressive symptoms over time (b=0.01, p&lt;.05), and occasion-to-occasion fluctuations in depressive symptoms (b=0.08, p&lt;.001). Motor severity did not explain individual differences or trajectories of change in depression or trait anxiety.Conclusions:Autonomic symptoms, particularly gastrointestinal, cardiovascular, and thermoregulatory dysfunction, were related to increased mood symptoms in PD patients and predicted increases in depression/anxiety over time. Our findings do not distinguish between two theoretical possibilities - whether autonomic symptoms lead to depression/anxiety versus involvement of co-occurring neural systems underlying both. Regardless, our study highlights the importance of treating autonomic dysfunction in early PD, and future work should incorporate additional measures of autonomic dysfunction (e.g., physiological probes).

Unraveling Autonomic Dysfunction in GBA-Related Parkinson's Disease.

Patients with Parkinson's disease (PD) and GBA gene mutations (GBA-PD) develop nonmotor complications more frequently than noncarriers. However, an objective characterization of both cardiovascular and sudomotor autonomic dysfunction using extensive clinical and instrumental measures has never been provided so far. Survival is reduced in GBA-PD regardless of age and dementia, suggesting that other hitherto unrecognized factors are involved. To provide instrumental measures of pattern and severity of autonomic dysfunction in GBA-PD and explore their correlation with other non-motor symptoms and implications for clinical practice. In this cross-sectional study, 21 GBA-PD and 24 matched PD noncarriers underwent extensive assessment of motor and non-motor features, including neuropsychological testing. Cardiovascular autonomic function was explored through a comprehensive battery of indexes, including power spectral analysis of the R-R intervals and blood pressure short-term variability during resting state and active maneuvers. Dynamic Sweat Test was used to assess post-ganglionic sudomotor dysfunction. Despite minimal or absent clinical correlates, cardiovagal and sympathetic indexes, heart rate variability parameters and sudomotor postganglionic function were more severely impaired in GBA-PD than noncarriers (overcoming relatively preserved compensatory peripheral sympathetic function), suggesting more prominent cardiac sympatho-vagal demodulation, efferent baroreflex failure and peripheral sympathetic dysfunction in GBA-PD. Cardiovascular dysautonomia showed marginal correlations with cognitive impairment. Compared to PD noncarriers, GBA-PD display more severe instrumental autonomic abnormalities, which may be underestimated by purely clinical measures, despite their relevance on morbidity and mortality. This supports the necessity of implementing instrumental autonomic assessment in all GBA-PD, regardless of clinically overt symptoms.

Profile of Cardiovascular Autonomic Dysfunctions in Breast Cancer Patients.

Background Patients on breast cancer chemotherapy frequently presentwith signs and symptoms of autonomic dysfunction. Cardiac autonomic dysfunction (CAD) is a significant cause of morbidity and mortality, affecting the quality of life with progressive advancing disease. It is associated with the short survival of breast cancer patients. Therefore, thoroughly assessing cardiovascular autonomic functions is crucial to monitor these patients' disease prognosis and chemotherapy side effects. The present study evaluated baseline heart rate variability (HRV) and Ewing's battery of cardiac autonomic reactivity testsin breast cancer patients on chemotherapy to evaluate CAD. Methodology This is a case-control study. Autonomic reactivity tests were performed in the autonomic function laboratory, Department of Physiology, All India Institute of Medical Sciences, Raipur. HRV was recorded using a lead II electrocardiogram (ECG) in two groups, namely, controls (n = 25 healthy female volunteers) and cases (n = 25 histologically proven stage I-III breast cancer patients, age 30-65 years, received three cycles of chemotherapy). Results Patients on chemotherapy had significantly lower reactivity for the time domain (all parameters) and frequency domain (absolute total power) of HRV compared to age-matched healthy controls. Autonomic reactivity showed significant loss in the patient group. Conclusions The sympathetic and parasympathetic parameters showed a significant loss of autonomic functions in the patient group compared to the healthy controls. This may be because of the chemotherapeutic drugs taken by the patients or cancer as the disease per se. As autonomic dysfunction is highly prevalent in patients with cancer and is associated with multiple symptoms, it is essential to study it in the cancer population.

Non-Pharmacological Treatment of Autonomic Dysfunction in Parkinson's Disease and Other Synucleinopathies.

Symptoms of autonomic dysfunction are prevalent and can be very debilitating, reducing the quality of life in patients with Parkinson's disease (PD) and other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Non-pharmacological therapies are key to effective management and are frequently used alone in patients with mild autonomic symptoms, or in combination with pharmacological therapies in patients with moderate and severe symptoms. This article focuses on non-pharmacological approaches. Our objective was to review the non-drug and non-surgical approaches to treating autonomic symptoms in patients with PD and other synucleinopathies, focusing on cardiovascular, gastrointestinal, and genitourinary autonomic dysfunction. Evidence supporting the effectiveness of non-pharmacological treatment for the management of neurogenic orthostatic hypotension, supine hypertension, constipation, and bladder and sexual dysfunction is available. High-quality prospective trials are scarce, yet some non-pharmacological interventions (e.g., physical counter maneuvers) can be evaluated relatively quickly on an individual basis and often seem effective. The emerging variety of clinical presentations advocates for a stepwise, individualized, and non-pharmacological approach for the management of autonomic symptoms. Often, the first step is to reduce or discontinue drugs that cause or aggravate autonomic symptoms followed by lifestyle measures. While non-pharmacological and non-surgical treatments are available and, in many cases, effective to improve symptoms of autonomic dysfunction in PD and other synucleinopathies, they are often overlooked. Large randomized trials testing and comparing non-pharmacological approaches are warranted.

Assessment of short-term effects of thoracic radiotherapy on the cardiovascular parasympathetic and sympathetic nervous systems.

Prior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools. A 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis. Thoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p < 0.001), and a significant increase in AC (-8.2 [-14.8, -4.9] vs. -5.8 [-10.1, -3.3], p = 0.003) and mean heart rate (79.8 ± 12.6 vs. 83.9 ± 13.6, p = 0.010). Subgroup analysis indicated similar trends in mean heart rate, DC, AC, and HRV parameters (SDNN, RMSSD, LF, HF, TP) in both the radiotherapy group and the combined treatment group post-radiotherapy. No statistically significant difference was noted in the changes observed in DC, AC, and HRV between the two groups pre- and post-radiotherapy. Thoracic radiotherapy may induce cardiovascular autonomic dysfunction by reducing parasympathetic activity and enhancing sympathetic activity. Importantly, the study found that the concurrent use of systemic therapies did not significantly amplify or contribute to the alterations in autonomic function in the short-term following thoracic radiotherapy. DC, AC and HRV are promising and feasible biomarkers for evaluating autonomic dysfunction caused by thoracic radiotherapy.

Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers.

Long COVID is characterized by persistent signs and symptoms that continue or develop for more than 4 weeks after acute COVID-19 infection. Patients with Long COVID experience a cardiovascular autonomic imbalance known as dysautonomia. However, the underlying autonomic pathophysiological mechanisms behind this remain unclear. Current hypotheses include neurotropism, cytokine storms, and inflammatory persistence. Certain immunological factors indicate autoimmune dysfunction, which can be used to identify patients at a higher risk of Long COVID. Heart rate variability can indicate autonomic imbalances in individuals suffering from Long COVID, and measurement is a non-invasive and low-cost method for assessing cardiovascular autonomic modulation. Additionally, biochemical inflammatory markers are used for diagnosing and monitoring Long COVID. These inflammatory markers can be used to improve the understanding of the mechanisms driving the inflammatory response and its effects on the sympathetic and parasympathetic pathways of the autonomic nervous system. Autonomic imbalances in patients with Long COVID may result in lower heart rate variability, impaired vagal activity, and substantial sympathovagal imbalance. New research on this subject must be encouraged to enhance the understanding of the long-term risks that cardiovascular autonomic imbalances can cause in individuals with Long COVID.

Abstract P169: Differences In Cardiovascular Autonomic Dysfunction Between Postural Tachycardia Syndrome And Long COVID-19 Postural Tachycardia Syndrome: A Prospective Cohort Study

Post-acute sequelae of COVID-19 infection or Long COVID-19 is a debilitating condition affecting 140 million US adults. Some Long COVID-19 patients develop cardiovascular autonomic dysfunction, particularly Postural Tachycardia Syndrome or POTS. It is unknown, however, if there are differences in cardiovascular autonomic reflexes, autonomic symptoms, or quality of life between these populations. We prospectively enrolled 42 patients (20 Long COVID-19 POTS and 22 POTS patients), 93% (39 of 42) females referred to the Vanderbilt Autonomic Dysfunction Clinic. These patients underwent standardized autonomic function testing, including head-up tilt (HUT), Valsalva maneuver (VM) and Sinus arrhythmia (SA). Autonomic symptoms were measured with COMPASS-31 survey, and quality of life assessment with EQ-5D. Results: Both groups were matched by age (37 ± 11.3 vs. 33 ± 9.3, p=0.393) and BMI (29 ± 7.5 vs. 30 ± 7.6, p=0.951). Supine SBP (p=0.145), DBP (p=0.258) and HR (p=0.130) were similar between groups. The increase in HR during 10-min HUT were similar between groups (Figure A), and upright HR absolute values were slightly but significantly lower in Long COVID-19 POTS than in POTS patients (100 ± 16.7 vs. 109 ± 27.5, p=0.04). Sympathetic vasoconstriction and cardiovagal function were similar between groups with no differences during VM and SA, respectively. Long COVID-19 POTS had a greater COMPASS-31 total score (80 ± 12.9 vs. 48 ± 8.8 in POTS, p=0.001), affecting all 6 domains (Figure B). EQ-5D was similar between groups (p =0.692). Conclusion: Autonomic symptoms were disproportionately higher in Long-COVID-19 POTS than in POTS, despite similar cardiovascular autonomic reflexes.