Qin Q, Liu J, Fan W
… +5 more, Zhang X, Lu J, Guo X, Lei Z, Wang J
Clin Auton Res
· 2025 Jun · PMID 40216631
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BACKGROUND: The aim of our study was to investigate the changes in brain functional activity in heart transplant patients and to explore the relationship between abnormal spontaneous brain activity and cognitive function...BACKGROUND: The aim of our study was to investigate the changes in brain functional activity in heart transplant patients and to explore the relationship between abnormal spontaneous brain activity and cognitive function through amplitude of low-frequency fluctuations (ALFF). METHODS: Sixty-eight heart transplant patients and 56 healthy controls were assessed by the Montreal Cognitive Assessment (MoCA) scale and the Mini-Mental Status Examination (MMSE) scale, and resting-state functional magnetic resonance scans were performed. Cortical analysis was applied to calculate the ALFF, and two-sample t test was used to detect differences of mean ALFF in the brain region between the two groups. In addition, the correlations between abnormal functional activity brain regions, cognitive functions, and clinical indicators were analyzed. RESULTS: Heart transplant patients had significantly lower MoCA scores and MMSE scores compared to healthy subjects. ALFF were found to be decreased in the right cerebellum anterior lobe, left parahippocampal gyrus, left temporal lobe, left parietal lobe, and right postcentral gyrus, and increased in the right superior frontal gyrus and left middle frontal gyrus. In addition, ALFF in right superior frontal gyrus was positively correlated with MoCA score (r = 0.397, P < 0.05), MMSE score (r = 0.356, P < 0.05), stroke volume (SV, r = 0.412, P < 0.05), and left ventricular ejection fraction (LVEF, r = 0.614, P < 0.05) in heart transplant patients. CONCLUSIONS: Cognitive function is impaired in heart transplant patients. The brain activity was altered in heart transplant recipients compared to healthy controls. ALFF changes in these brain regions may be associated with altered hemodynamics after transplantation, leading to impaired cognitive function. These findings help us to understand the neural mechanisms of cognitive changes in heart transplant recipients and provide a basis for developing interventions and rehabilitation strategies.
Clin Auton Res
· 2025 Aug · PMID 40131648
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PURPOSE: Central autonomic dysfunction is common in acute stroke and is associated with cardiovascular complications and increased mortality. The aim of this review is to present novel diagnostic and therapeutic approach...PURPOSE: Central autonomic dysfunction is common in acute stroke and is associated with cardiovascular complications and increased mortality. The aim of this review is to present novel diagnostic and therapeutic approaches to the management of this disorder and the latest data on its impact on the clinical outcome after stroke. METHODS: We performed a narrative review of recent literature, with a particular focus on articles related to underlying pathophysiological mechanisms of cardiac autonomic dysregulation, the role of cardiac autonomic dysregulation in the activation of neuroinflammatory response and the development of cardiovascular, respiratory and metabolic complications in patients with ischemic and hemorrhagic stroke. RESULTS: The assessment of central autonomic dysfunction by non-invasive diagnostic techniques, including heart rate variability and baroreflex sensitivity, has gained wide practical application in recent years, and they may have a predictive role for evaluating disease prognosis. The emerging evidence derived from recent trials demonstrates that the presence of autonomic imbalance may lead to increased mortality and have an adverse effect on post-stroke rehabilitation. CONCLUSION: The early detection and treatment of central autonomic system dysfunction may lead to improved survival of patients with stroke. Among the available therapeutic approaches, neuromodulatory techniques and pharmacological interventions are promising strategies which may be implemented as part of standard acute stroke care to improve patient recovery. Future studies are warranted to address the long-term effects of potential therapeutic agents on the modulation of cardiovascular autonomic function in stroke survivors.
Li Z, Fan J, Gong Z
… +4 more, Tang J, Yang Y, Liu M, Zhang M
Clin Auton Res
· 2025 Jun · PMID 40056296
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PURPOSE: The aim of this study was to investigate the relationship between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis (ALS). METHODS: The heart activi...PURPOSE: The aim of this study was to investigate the relationship between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis (ALS). METHODS: The heart activity of 65 patients with ALS (28 with normal cognition [ALS-CN]; 37 with impaired cognition [ALS-CI]) and 38 healthy controls (HCs) was measured by 24-h Holter monitoring. Heart rate (HR) measures and heart rate variability (HRV) parameters were compared between the three study groups and, additionally, correlated with five Edinburgh Cognitive and Behavioral ALS Screen (ECAS) domains in the ALS subgroups. Age, gender, and educational level were adjusted. Factors associated with cognitive status were assessed using logistic regression. Survival predictors in patients with ALS were analyzed using the Kaplan-Meier estimator and Cox regression. RESULTS: Compared to the HCs, patients with ALS-CI exhibited lower RRI (R-R-interval; P = 0.017), SDNN (standard deviation of all normal RR intervals; P = 0.013), SDNN Index (P = 0.044), and VLF power (very low-frequency power; P = 0.012). Total power was reduced in the ALS-CI group compared to the HCs (P = 0.036) and ALS-CN group (P = 0.048). In patients with ALS-CN, language negatively correlated with mean HR (P = 0.001) and positively with the RRI (P = 0.003), SDNN (P = 0.001), SDANN (standard deviation of the average NN intervals; P = 0.005), total power (P = 0.006), VLF power (P = 0.011), and low-frequency power (P = 0.026). Visuospatial function correlated positively with the SDNN Index (P = 0.041). In patients with ALS-CI, executive function (P = 0.015) and ECAS total score (P = 0.009) negatively correlated with the RMSSD (square root of mean sum-of-squares of differences between adjacent NN intervals), while visuospatial function correlated positively with normalized LF value (LFnu; P = 0.049). No associations were observed between the other cognitive domains and any of the 14 HRV/HR measures in patients with either ALS-CI or ALS-CN. SDNN ≤ 100 ms was linked to cognitive impairment (P = 0.039) and also showed a borderline association (P = 0.066) with poorer survival, while cognitive impairment (P = 0.010) was significantly linked to worse outcomes. CONCLUSIONS: Patients with ALS with cognitive impairment demonstrated reduced cardiac autonomic modulations and altered cognitive autonomic associations. Cognitive impairment was linked to reduced survival, with baseline SDNN ≤ 100 ms identified as a potential marker.
Clin Auton Res
· 2025 Jun · PMID 40056295
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PURPOSE: To revisit the pharmacology and real-world use of carbidopa in the management of autonomic disorders. METHODS: To identify articles suitable for this review, a search of the PubMed database was conducted in Janu...PURPOSE: To revisit the pharmacology and real-world use of carbidopa in the management of autonomic disorders. METHODS: To identify articles suitable for this review, a search of the PubMed database was conducted in January 2025 using the keywords "Carbidopa," "MK-486," and "L-alpha-methyldopa hydrazine." RESULTS: The pharmacotherapeutic role of carbidopa extends beyond the management of Parkinson's disease. Our literature search revealed the use of carbidopa in three primary autonomic diseases to treat either nausea or symptoms of sympathetic hyperactivity: (1) familial dysautonomia, (2) hyperadrenergic postural orthostatic tachycardia syndrome (POTS), and (3) afferent baroreflex failure (familial or acquired). Even at a dose as high as 600 mg/day, carbidopa was not associated with bothersome side effects in some of the clinical trials on familial dysautonomia. Pre-clinical evidence also suggests in vitro and in vivo inhibition of T-cell activation by carbidopa and a potential therapeutic use in cytokine release syndrome. CONCLUSION: Current evidence, although limited, suggests that carbidopa has a favorable safety profile. While large, well-designed studies are warranted, observations from case series and small studies suggest that carbidopa could have utility in treating nausea in familial dysautonomia and symptoms of sympathetic hyperactivity in hyperadrenergic postural orthostatic tachycardia syndrome (POTS) and afferent baroreflex failure.
Coon EA, Badihian N, McCarter SJ
… +6 more, Sletten DM, Berini SE, Benarroch EE, Sandroni P, Low PA, Singer W
Clin Auton Res
· 2025 Jun · PMID 40053259
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PURPOSE: Identifying features of patients who remain pure autonomic failure has implications on disease definition and offers insights into synucleinopathy progression. We sought to determine symptom timeline and autonom...PURPOSE: Identifying features of patients who remain pure autonomic failure has implications on disease definition and offers insights into synucleinopathy progression. We sought to determine symptom timeline and autonomic features in patients who retain the pure autonomic failure phenotype with prolonged follow-up. METHODS: We reviewed all patients diagnosed with pure autonomic failure from 2001 to 2011 evaluated at Mayo Clinic, Rochester, with autonomic reflex screen and over 1 year of in-person follow-up. Clinical evaluations and patient telephone calls were used to assess timeline of symptoms. RESULTS: Of 202 patients, 133 remained pure autonomic failure with median follow-up time of 9.05 years (interquartile range (IQR) 4.2-13.1). Additional autonomic symptoms included constipation (N = 60; 45%), bladder symptoms (N = 78; 59%), which were severe in 50 patients (37.6%) with incontinence or requiring catheterization, sexual dysfunction (N = 53; 40%) and thermoregulatory dysfunction (N = 51; 38%). Assessment of dream enactment behavior was completed in 86 patients and endorsed in 45 patients (52%). Median time to dream enactment behavior onset from orthostatic hypotension was 7.00 years (1.55-13.50). Other autonomic symptoms tended to occur near orthostatic hypotension. Autonomic testing showed moderate to severe autonomic failure with median composite autonomic score of 6 (IQR 4-8; N = 133) and median percentage anhidrosis of 51% (IQR 3-93%; N = 105). CONCLUSIONS: Patients with pure autonomic failure typically have symptom onset near development of orthostatic hypotension while dream enactment behavior may occur later. Our findings underscore that not all patients with pure autonomic failure will develop motor or cognitive symptoms, even with prolonged follow-up.
Clin Auton Res
· 2025 Jun · PMID 40032720
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AIM: Individuals with spinal cord injury (SCI) have an increased prevalence of orthostatic hypotension (OH). Diagnosis of OH is made with active standing or tilt table testing, with limited the use in individuals with SC...AIM: Individuals with spinal cord injury (SCI) have an increased prevalence of orthostatic hypotension (OH). Diagnosis of OH is made with active standing or tilt table testing, with limited the use in individuals with SCI. METHODS: An alternative approach to assess OH is the sit-up test, which involves passive repositioning from the supine to the seated position. The purpose of this study was to document the reliability and validity of the sit-up test, and determine whether the level or severity of injury related to orthostatic blood pressure (BP) responses in a large, diverse group of individuals with SCI. RESULTS: A total of 166 participants-119 individuals with SCI and 47 uninjured control-completed two sit-up tests, and 36 individuals who completed the sit-up tests also underwent a head-up tilt test. Change in BP from sit-up test 1 to sit-up test 2 was not significantly different for either systolic BP or diastolic BP. Neither level nor severity of injury contributed to the reliability assessments, which showed disappointing results with generally low interclass correlation coefficients (ICC), with values ranging from 0 to 0.63, and large standard error of measurements (SEM), ranging from 5.2 to 13.7 mmHg. Comparison between BP responses to the sit-up test and the head-up tilt showed good sensitivity and specificity, with positive predictive values > 75%. CONCLUSION: Prevalent BP instability likely contributed to the poor reliability of the sit-up test, but the test is easy to perform with a high likelihood ratio for the valid assessment of OH in individuals with SCI. CLINICAL TRIAL REGISTRATION: NCT01758692.
Clin Auton Res
· 2025 Jun · PMID 40000578
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PURPOSE: Recent studies have reported blunted increases in blood pressure (BP) during static handgrip (SHG) in patients with heart failure with preserved ejection fraction (HFpEF), which may be attributed to abnormal sym...PURPOSE: Recent studies have reported blunted increases in blood pressure (BP) during static handgrip (SHG) in patients with heart failure with preserved ejection fraction (HFpEF), which may be attributed to abnormal sympathetic reactivity during exercise and/or impaired muscle metaboreflex function. However, it is unknown whether the sympathetic neural response to SHG and isolated muscle metaboreflex activation via post-exercise circulatory occlusion (PECO) are attenuated in HFpEF. METHODS: Thirty-nine patients with HFpEF and 24 age-matched non-HFpEF controls were studied in the supine position. BP, heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured during SHG at 40% of maximal voluntary contraction until fatigue followed by 2-min PECO. RESULTS: Resting mean arterial pressure (MAP) was lower and peak increase (Δ) in MAP was smaller in patients with HFpEF than in controls during SHG (Δ23 ± 15 [standard deviation] vs. Δ34 ± 15 mmHg; P = 0.007) and PECO (Δ15 ± 11 vs. Δ19 ± 9 mmHg; P = 0.047). HR was greater in patients at rest but did not differ between the two groups at peak SHG. Patients had higher resting MSNA burst frequency than controls (37 ± 14 vs. 27 ± 13 bursts/min; P = 0.031); however, burst incidence was not different between the groups (P = 0.226). There were no differences in MSNA responses to SHG (Δ19 ± 15 vs. Δ18 ± 10 bursts/min at peak; P = 0.841) or PECO (Δ3 ± 12 vs. Δ5 ± 7 bursts/min; P = 0.495) between groups. CONCLUSION: The patients with HFpEF maintained sympathetic reactivity but had an attenuated pressor response during fatiguing SHG. Additionally, muscle metaboreflex activation of vasomotor sympathetic outflow appeared to be minimal in both groups, with no significant difference between patients and controls.
Clin Auton Res
· 2025 Apr · PMID 39969691
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PURPOSE: This review aims to summarize the complex nature of the trigeminocardiac reflex into a brief overview, focusing on its mechanism, anatomy, classification, manifestations, and treatment approaches. METHOD: By exa...PURPOSE: This review aims to summarize the complex nature of the trigeminocardiac reflex into a brief overview, focusing on its mechanism, anatomy, classification, manifestations, and treatment approaches. METHOD: By examining the latest clinical studies and anatomical insights, we outline the neural pathways of trigeminocardiac reflex, identify subtypes on the basis of stimulation points, and describe the physiological responses it elicits. RESULTS: Trigeminocardiac reflex is a brainstem reflex characterized by symptoms, such as bradycardia, hypotension, hypertension, apnea, and gastric hypermotility. It has been reported in surgical procedures involving stimulation of sensory branches of the trigeminal nerve. Trigeminocardiac reflex management typically involves prophylactic measures to prevent intraoperative cardiovascular complications. CONCLUSION: A comprehensive understanding of trigeminocardiac reflex mechanisms and subtypes is essential to anticipate and mitigate its effects during procedures that may trigger this reflex. This knowledge ensures patient well-being and optimizes surgical outcomes, highlighting the importance of continued research in this area.
Carricarte Naranjo C, Marras C, Visanji NP
… +9 more, Cornforth DJ, Sanchez-Rodriguez L, Schüle B, Goldman SM, Estévez M, Stein PK, Jelinek HF, Lang AE, Machado A
Clin Auton Res
· 2025 Jun · PMID 39969690
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PURPOSE: Increased beat-to-beat heart rate variability (HRV) is a feature of patients with Parkinson's disease (PD) who carry the G2019S mutation in the LRRK2 gene (LRRK2-PD). Since LRRK2 mutations have incomplete penetr...PURPOSE: Increased beat-to-beat heart rate variability (HRV) is a feature of patients with Parkinson's disease (PD) who carry the G2019S mutation in the LRRK2 gene (LRRK2-PD). Since LRRK2 mutations have incomplete penetrance, HRV changes preceding PD conversion would likely be observed only in a subset of LRRK2 non-manifesting carriers (NMC). We aimed to assess HRV in a subgroup of NMC with distinctive characteristics of LRRK2-PD, identified through clustering analysis. METHODS: HRV measures derived from 300 normal heartbeat intervals extracted from the electrocardiograms of 25 NMC, 32 related non-carriers (RNC), 27 unrelated healthy controls, and 14 patients with LRRK2-PD were analyzed. Clinical symptoms were evaluated using questionnaires and scales, and three NMC subgroups were identified using a k-means cluster analysis on the basis of the deceleration capacity of heart rate (DC) and Rényi entropy. Standard and advanced HRV measures were compared using multiple regression analysis, controlling for age, sex, and mean heart rate. RESULTS: Beat-to-beat HRV markers were significantly increased in a subgroup of seven NMC (NMC2, 28%) compared with RNC and controls. Increased irregularity and DC were also verified in the NMC2 compared with controls, and were typical traits in both the NMC2 and RNC. Overall, the HRV profile of NMC2 was comparable to that of patients with LRRK2-PD. NMC2 further exhibited greater motor and non-motor traits than the other NMC, RNC, and controls. CONCLUSIONS: Our results confirmed that HRV characteristics of LRRK2-PD are also found in a subset of NMC displaying clinical traits of LRRK2-PD. Further research is needed to clarify whether higher HRV represents a LRRK2-PD prodromal manifestation.
Qu H, Qu J, Chang X
… +11 more, Williams N, Mentch F, Snyder J, Lemma M, Nguyen K, Behr M, March M, Connolly J, Glessner J, Boris JR, Hakonarson H
Clin Auton Res
· 2025 Jun · PMID 39964606
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BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with serious health consequences, while its etiology remains largely elusive. OBJECTIVE: The purpose of this study was to investigate the...BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with serious health consequences, while its etiology remains largely elusive. OBJECTIVE: The purpose of this study was to investigate the genetic landscape of POTS using genomic approaches in a unique pediatric cohort. METHODS: We conducted a combined genome wide genotyping and whole exome sequencing (WES) study to systemically examine the molecular mechanisms of POTS pathogenesis. The patients were genotyped as two independent cohorts: a family cohort of 100 complete families and a case-control cohort of 207 unrelated European cases and 4063 ethnicity-matched control subjects. The WES component consisted of a subset of the genotyped subjects, including 87 unrelated European cases and 2719 unrelated European control subjects. RESULTS: The heterogeneous phenotype of POTS made achieving genome-wide significance improbable. Instead, 5670 SNPs with nominal significance (P < 0.05) were identified in both the family and case-control cohorts, with effects in the same direction. We conducted an over-representation analysis (ORA) by considering all genes that showed nominal significance. The ORA identified gene sets linked to cell-cell junction, early estrogen response, and substance-related disorders with statistical significance. Moreover, WES revealed 55 genes with genome-wide significance through rare variant burden analysis, harboring 92 variants classified as pathogenic or likely pathogenic by ClinVar. CONCLUSIONS: This study showcases the complex interplay between common and rare genetic variants in POTS development, marking a pioneering step forward in deciphering its complex etiologies. The insights from this research enrich our understanding of POTS, offering new avenues for precise treatment strategies and highlighting areas for further research.
Clin Auton Res
· 2025 Jun · PMID 39907932
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OBJECTIVE: This meta-analysis evaluates the effectiveness and safety of ramicotomy versus sympathetic chain interruption (SCI) in treating primary hyperhidrosis (PH). METHODS: A comprehensive literature search was conduc...OBJECTIVE: This meta-analysis evaluates the effectiveness and safety of ramicotomy versus sympathetic chain interruption (SCI) in treating primary hyperhidrosis (PH). METHODS: A comprehensive literature search was conducted across multiple databases, including PubMed, Embase, Web of Science, Ovid, Cochrane Library, CNKI, and Wanfang, covering studies from their inception through October 2024. A total of 10 studies involving 970 patients were included, with 504 patients undergoing ramicotomy and 466 receiving SCI. RESULTS: The analysis revealed that patients undergoing ramicotomy experienced significantly lower rates of compensatory hyperhidrosis (CH) [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20-0.85, P = 0.02], severe CH (OR 0.17, 95% CI 0.06, 0.47, P < 0.001), and postoperative hand dryness (OR 0.10, 95% CI 0.01-0.72, P = 0.02), along with a higher recurrence rate (OR 4.03, 95% CI 2.38, 6.85, P < 0.001). No significant differences were observed in operative duration [mean difference (MD) = 0.19, 95% CI -18.23, 18.60, P = 0.98 > 0.05], length of hospital stay (MD = -0.08, 95% CI -0.19, 0.04, P = 0.20 > 0.05), total postoperative complications (OR 0.41, 95% CI 0.07, 2.34, P = 0.32 > 0.05), or surgical satisfaction (OR 0.93, 95% CI 0.45, 1.91, P = 0.83 > 0.05). CONCLUSIONS: While ramicotomy results in lower incidences of CH and postoperative hand dryness, its higher recurrence rate suggests that its application should be cautious to manage PH effectively.
Clin Auton Res
· 2025 Jun · PMID 39907931
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PURPOSE: Autonomic dysfunction is a common and often debilitating feature of long-COVID (LC), however, studies evaluating frequency and severity of chronic autonomic dysfunction in LC are limited. We utilized an establis...PURPOSE: Autonomic dysfunction is a common and often debilitating feature of long-COVID (LC), however, studies evaluating frequency and severity of chronic autonomic dysfunction in LC are limited. We utilized an established online cohort of participants with LC to assess duration and severity of autonomic dysfunction, impact on quality of life, risk factors of autonomic diagnoses including postural tachycardia syndrome (POTS), and efficacy of common treatments. METHODS: Our international cohort included 526 adults with LC aged 20-65 years who previously completed baseline evaluations of LC symptoms, autonomic symptom burden, and quality of life. Participants repeated survey instruments and completed new instruments assessing risk factors and symptom mitigation strategies. A subset of individuals completed a 10-min active stand test. Multivariable logistic regression identified predictors of autonomic symptom burden and incident autonomic diagnoses including POTS. RESULTS: A total of 71.9% of participants with LC had a Composite Autonomic Symptom Score-31 (COMPASS-31) score ≥ 20, suggestive of moderate-to-severe autonomic dysfunction. The median symptom duration was 36 [30-40] months, and 37.5% of participants could no longer work or had to drop out of school due to their illness. In addition, 40.5% of individuals with autonomic dysfunction were newly diagnosed with POTS, representing 33% of the total LC cohort. Female sex and joint hypermobility were associated with an increased risk of autonomic dysfunction. CONCLUSIONS: Evidence of chronic moderate-to-severe autonomic dysfunction was seen in most participants with LC in our cohort and was significantly associated with reduced quality of life and functional disability. POTS was the most common post-COVID autonomic diagnosis.
Cheshire WP, Tipton PW, Koga S
… +6 more, Sekiya H, Uitti RJ, Ross OA, Heckman MG, Sledge HJ, Dickson DW
Clin Auton Res
· 2025 Jun · PMID 39847196
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PURPOSE: This study examined occupational histories in multiple system atrophy to identify environmental associations of potential relevance to disease causation. METHODS: A total of 270 neuropathologically confirmed cas...PURPOSE: This study examined occupational histories in multiple system atrophy to identify environmental associations of potential relevance to disease causation. METHODS: A total of 270 neuropathologically confirmed cases of multiple system atrophy obtained from the Mayo Clinic Brain Bank for neurodegenerative disorders in Jacksonville, Florida, were included in this case-control study. Demographic and disease information was collected from medical records. Information regarding occupational history was collected retrospectively from medical records and published obituaries. Proportions of employment by occupational sector were compared with US census data. RESULTS: When comparing patients with US census data, significant differences were identified for education (15.2% versus 2.3%, P < 0.001), administration (14.8% versus 4.1%, P < 0.001), clerical (10.7% versus 5.5%, P = 0.001), petroleum industry (8.9% versus 5.6%, P = 0.024), metal industry (7.8% versus 3.0%, P < 0.001), electrical engineers and electricians (5.6% versus 0.4%, P < 0.001), civil or mechanical engineering (4.4% versus 0.2%, P < 0.001), real estate (4.4% versus 0.7%, P < 0.001), information technology (4.1% versus 1.8%, P = 0.011), woodworking (3.0% versus 0.03%, P < 0.001), writing or publishing (2.6% versus 0.3%, P < 0.001), law (2.2% versus 0.4%, P = 0.001), hairdressing (0.7% versus 0.1%, P = 0.03), and social work (0.7% versus 0.1%, P = 0.03). CONCLUSIONS: The listed occupational categories were significantly overrepresented in our series of patients with multiple system atrophy as compared with population data. We hypothesize that these occupational associations may signify environmental exposures, increasing the disease risk in genetically susceptible individuals. We cannot exclude a potential selection bias in patients willing to donate their brains to an academic center to contribute to scientific knowledge.
Hira R, Baker JR, Siddiqui T
… +8 more, Patel A, Valani FGA, Lloyd MG, Floras JS, Morillo CA, Sheldon RS, Raj SR, Canadian Long COVID Autonomic Network (CanLoCAN)
Clin Auton Res
· 2025 Apr · PMID 39841332
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PURPOSE: Long-coronavirus disease (long-COVID) is associated with initial orthostatic hypotension and postural orthostatic tachycardia syndrome. Whether altered autonomic tone underlies these abnormalities is unknown. We...PURPOSE: Long-coronavirus disease (long-COVID) is associated with initial orthostatic hypotension and postural orthostatic tachycardia syndrome. Whether altered autonomic tone underlies these abnormalities is unknown. We compared autonomic function between patients with long-COVID and healthy controls, and within patients with long-COVID with different orthostatic hemodynamic phenotypes. METHODS: Patients with long-COVID (n = 94; F = 76; 42 years [36, 53 years] with initial orthostatic hypotension: n = 40; F = 32; 49 years [39, 57 years]; postural orthostatic tachycardia syndrome: n = 29; F = 26; 39 years [33, 47 years]; or no abnormalities: n = 25; F = 18; 42 years [35, 49 years]), and healthy controls (n = 33; F = 25; 49 years [30, 62 years]) completed a 10-min active stand with beat-to-beat hemodynamics. Heart rate variability, blood pressure variability, and baroreflex sensitivity were calculated as indirect measures of cardiovascular autonomic health. Continuous data (median [95% confidence interval]) were analyzed with Mann-Whitney U tests or Kruskal-Wallis tests with Dunn's corrections. RESULTS: Patients with long-COVID had lower upright high frequency heart rate variability (p = 0.04) and low frequency blood pressure variability (p = 0.001) than controls. Patients with initial orthostatic hypotension had lower supine baroreflex sensitivity compared with patients without abnormalities (p = 0.01), and lower supine baroreflex sensitivity (p = 0.001) and high frequency heart rate variability (p = 0.03) than patients with postural orthostatic tachycardia syndrome. Patients with postural orthostatic tachycardia syndrome had lower upright high frequency heart rate variability (p < 0.001) and baroreflex sensitivity (p < 0.001) compared with patients without abnormalities and lower upright low frequency blood pressure variability (p = 0.04) compared with controls. CONCLUSIONS: Patients with long-COVID have attenuated cardiac autonomic function. Patients with initial orthostatic hypotension have lower supine baroreflex sensitivity. Patients with postural orthostatic tachycardia syndrome have lower upright vascular sympathetic and cardiac parasympathetic modulation. Long-COVID subgroups do not present with homogeneous pathophysiology, necessitating targeted treatment strategies.
Ruiz de Lazcano A, Pérez-Núñez P, Pallarès-Sastre M
… +3 more, García-Sanchoyerto M, García I, Amayra I
Clin Auton Res
· 2025 Apr · PMID 39838139
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PURPOSE: The aim of the study is to analyze and compare the cognitive profile between 59 patients with long-COVID [LC; 30 of them with and 29 without a positive coronavirus disease 2019 (COVID-19) confirmatory test] and...PURPOSE: The aim of the study is to analyze and compare the cognitive profile between 59 patients with long-COVID [LC; 30 of them with and 29 without a positive coronavirus disease 2019 (COVID-19) confirmatory test] and 31 patients with postural orthostatic tachycardia syndrome (POTS) and a matched group of 39 healthy control participants. METHODS: Participants were examined on a battery of neuropsychological tests, including verbal memory, visuospatial abilities, attention, processing speed, verbal fluency, working memory, and visual memory. Anxious-depressive symptomatology was also analyzed and then controlled for possible influence on cognitive performance. RESULTS: Patients with LC and POTS showed significantly lower performance compared with healthy peers. Differences on anxious and depressive symptoms were also found between the clinical and control groups, resulting in LC without a positive confirmatory test group exhibiting the highest rates of anxious symptoms. After controlling the effects of anxious-depressive symptomatology, the differences were eliminated for some of the cognitive variables, but additional differences were found between patients with LC and POTS after post hoc analysis. CONCLUSIONS: Findings from the present study contribute toward the reinforcement of the evidence on cognitive alterations associated with LC and POTS. Anxious-depressive symptomatology has to be considered in both clinical groups since it could be affecting cognitive performance.
Leal-Menezes R, Rodrigues-Krause J, Dos Santos GC
… +4 more, do Nascimento Queiroz J, Silva da Silva C, Umpierre D, Reischak-Oliveira A
Clin Auton Res
· 2025 Jun · PMID 39821813
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PURPOSE: The present review investigates the responses of heart rate variability indices following high-intensity interval aerobic exercise, comparing it with moderate-intensity continuous exercise in adults, with the ai...PURPOSE: The present review investigates the responses of heart rate variability indices following high-intensity interval aerobic exercise, comparing it with moderate-intensity continuous exercise in adults, with the aim of informing clinical practice. METHODS: Searches were conducted in four databases until March 2023. Eligible studies included randomized controlled trials that assessed heart rate variability indices such as the standard deviation of normal-to-normal heartbeat intervals (SDNN), the root mean square of successive differences (RMSSD), the proportion of the number of pairs of successive normal-to-normal (NN or R-R) intervals that differ by more than 50 ms (NN50) divided by the total number of NN intervals (pNN50), power in high frequency range (HF), power in low frequency range (LF), and LF/HF before and after high-intensity interval and moderate-intensity continuous aerobic exercise. The risk of bias in included studies was evaluated using the RoB 2 tool. RESULTS: A total of 16 studies were included in the systematic review, while 9 were included in the meta-analysis. Overall, the majority of included individuals were healthy and young. Our meta-analysis indicated that individuals who performed high-intensity interval exercise showed a slower recovery to baseline levels for HF (standardized mean difference, SMD -0.98 [95% CI -1.52 to -0.44], p < 0.001) and LF (SMD -0.42 [95% CI -0.81 to -0.02], p = 0.04) within the first 10 min of recovery, which did not occur after 1 h. Among the 16 included studies, 10 had some concerns related to bias risk, while 6 were classified as high risk. CONCLUSIONS: High-intensity interval aerobic exercise results in delayed recovery of HF and LF indices within the first 10 min after the session. However, our review indicates that healthy individuals restore modulation of the autonomic nervous system to baseline levels after this time interval, regardless of exercise intensity.