Carnagarin R, Sesa-Ashton G, Ward NC
… +5 more, Nolde J, Joyson A, Chan J, Jose A, Schlaich MP
Clin Auton Res
· 2025 Dec · PMID 40676310
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PURPOSE: Short-chain fatty acids (SCFAs), metabolites of colonic microflora fermentation of dietary fibre, have been implicated in experimental models and clinical trials to impact blood pressure (BP) regulation. Dietary...PURPOSE: Short-chain fatty acids (SCFAs), metabolites of colonic microflora fermentation of dietary fibre, have been implicated in experimental models and clinical trials to impact blood pressure (BP) regulation. Dietary interventions increasing serum SCFA levels have been associated with reduced 24-h systolic BP in hypertensive patients. However, the underlying mechanisms remain elusive. Given the role of the gut-brain axis and clear evidence for sympathetic nervous system activation as important modulators of blood pressure, we examined the relationship between sympathetic drive and SCFA concentration in patients with resistant hypertension (RH) and healthy control subjects (HC). METHODS: A total of 21 patients with RH (68.6 ± 9.7 years, 47% male) and 28 healthy control subjects (HC) (34.6 ± 16.7 years, 75% male) were recruited to undergo microneurography for determination of muscle sympathetic nerve activity (MSNA), automated office BP (AOBP) and blood collection for serum SCFA. RESULTS: Mean systolic AOBP was 156 ± 21 mmHg and 115 ± 10 mmHg for RH and HC, respectively (p < 0.0001). Serum acetate levels were 1340 ± 115.4 umol/L for HC and 724.5 ± 116.9 umol/L for RH (p < 0.0001). Butyrate and propionate concentrations did not significantly differ between groups. MSNA burst frequency was markedly elevated in RH compared with HCs (p < 0.001), with 25.3 ± 7.4 burst/minute in HC compared with 40.24 ± 8.3 burst/minute in RH. An inverse relationship was evident between serum acetate levels and MSNA burst frequency (p = 0.0267, R = 0.4) along with increased sympathetic vascular transduction (p = 0.0008, R = 0.82) in RH. CONCLUSIONS: Our findings suggest that the beneficial effects of SCFA levels, in particular acetate, on cardiovascular regulation may at least in part be mediated by sympatho-inhibition and altered sympathetic vascular transduction.
Umehara T, Mimori M, Kokubu T
… +7 more, Ozawa M, Shiraishi T, Onda A, Matsuno H, Omoto S, Murakami H, Iguchi Y
Clin Auton Res
· 2025 Dec · PMID 40616749
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PURPOSE: Few studies have examined the association between cardiovascular autonomic failure and minor hallucinations in patients with Parkinson's disease (PD). The aim of this study was to clarify this association. METHO...PURPOSE: Few studies have examined the association between cardiovascular autonomic failure and minor hallucinations in patients with Parkinson's disease (PD). The aim of this study was to clarify this association. METHODS: The subjects were 133 patients with PD without well-structured visual hallucinations. Visual illusory responses were evaluated using the noise pareidolia test. Cardiac I-metaiodobenzylguanidine (I-MIBG) uptake and neurogenic orthostatic hypotension (nOH) and supine hypertension (nSH) on head-up tilt-table testing were examined in association with the incidence of pareidolia. RESULTS: Fifty-one (38%) patients had pareidolia. nOH (β = 0.220, p = 0.008), cognitive impairment (β = -0.228, p = 0.028), and longer symptom duration (β = 0.273, p = 0.006) were associated with an increased incidence of pareidolia independently of age, sex, motor severity, levodopa-equivalent dose, and anticholinergic and cholinesterase inhibitor use. An increased incidence of pareidolia was also associated with nSH (β = 0.214, p = 0.009), while no such association was found with cardiac I-MIBG uptake. Patients with severe nOH or nSH tended to have a higher incidence of pareidolia than those with mild nOH (p = 0.063) or nSH (p < 0.003), respectively. CONCLUSION: nOH and nSH were associated with the severity of pareidolia in early PD patients without well-structured visual hallucinations. Further studies are required to clarify whether this association is attributable to widespread central pathological changes related to cardiovascular autonomic failure, or to degeneration of the sympathetic nervous system.
Ojikutu QA, Sabino-Carvalho JL, Latham K
… +7 more, Rocha M, Mattos JD, Campos MO, Mansur DE, Vianna LC, Nóbrega ACL, Fernandes IA
Clin Auton Res
· 2025 Dec · PMID 40531379
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BACKGROUND: Hypoxia is a common feature of arterial hypertension that does not consistently elevate blood pressure (BP), but triggers exaggerated increases in muscle sympathetic nerve activity (MSNA) and may disturb symp...BACKGROUND: Hypoxia is a common feature of arterial hypertension that does not consistently elevate blood pressure (BP), but triggers exaggerated increases in muscle sympathetic nerve activity (MSNA) and may disturb sympathetic transduction and baroreflex sensitivity in hypertensive individuals. Elevated resting MSNA, enhanced sympathetic transduction, and reduced baroreflex sensitivity are all associated with increased blood pressure variability (BPV), a marker of target organ damage independent of absolute BP levels. We hypothesized that hypoxia would elicit greater BPV in hypertensive individuals compared to normotensive controls METHODS: Nine young- to middle-aged men with untreated stage 1-2 hypertension (HT) and normotensive controls (NT) were exposed to normoxia (21% O) and isocapnic hypoxia (IH, 10% O). During both conditions, oxygen saturation, beat-to-beat BP, MSNA, and end-tidal CO (PetCO) were continuously monitored, with PetCO clamped. BPV was quantified using standard deviation, coefficient of variation, and average real variability for systolic (SBP), diastolic (DBP), and mean BP (MBP). Sympathetic transduction was assessed using a time-domain signal averaging technique. Cardiac baroreflex sensitivity (cBRS) was evaluated using the sequence method, and sympathetic baroreflex sensitivity (sBRS) was calculated via MSNA-DBP regression RESULTS: IH induced comparable oxygen desaturation in both groups (NT: -25.7 ± 3.3% vs. HT: -21.2 ± 4.0%, p > 0.05). Although BP and PetCO remained unchanged, MSNA responses were significantly greater in HT (NT: +8 ± 2 vs. HT: +12 ± 2 bursts/min, p = 0.03). IH increased all indices of BPV and sympathetic transduction, while both cBRS and sBRS were similarly impaired in the two groups. CONCLUSIONS: In conclusion, IH similarly exacerbates BPV and disrupts sympathetic transduction and baroreflex function in normotensive and untreated hypertensive men, despite greater MSNA reactivity in the hypertensive group.
Prandin G, Naccarato M, Furlanis G
… +8 more, Mancinelli L, Palacino F, Vincis E, Quagliotto M, Ricci E, Cattaruzza L, Caruso P, Manganotti P
Clin Auton Res
· 2025 Dec · PMID 40493288
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BACKGROUND: Sympathetic activation, inflammation, and neuro-endocrine response after an ischemic stroke contribute to the development of the stroke heart syndrome (SHS). One marker of SHS is a troponin "rise and fall pat...BACKGROUND: Sympathetic activation, inflammation, and neuro-endocrine response after an ischemic stroke contribute to the development of the stroke heart syndrome (SHS). One marker of SHS is a troponin "rise and fall pattern" > 30%. Among the beta-blocker drugs, the β1 antagonist class has a selective effect on the heart against sympathetic neurotransmitters. The aim of this study is to evaluate the possible role of pre-stroke chronic cardioselective β1 blocker treatment (B1B) in preventing SHS. METHODS: We retrospectively analyzed data of 891 acute stroke patients admitted to the stroke unit at the University Hospital of Trieste (Italy) between 2018 and 2020. In total, 490 patients met the inclusion criteria. Clinical data, imaging characteristics and markers of cardiac injury (troponin I [TnI], N-terminal fragment of B type natriuretic peptide (NT-proBNP), and "rise and fall pattern" > 30%) and the chronic pre-stroke use of B1B were collected. We compared SHS against lack of SHS (no-SHS), subsequently examining the data through a multivariable analysis to determine possible SHS predictive factors. RESULTS: No association between chronic B1B pre-stroke use and SHS (odds ratio [OR] 1.031; 95% confidence interval [CI] 0.636-1.672; p = 0.900) has been observed. The same result has been found in a sub-analysis on patients with chronic heart failure characterized by high NT-proBNP levels (> 900 pg/mL; n = 212), in which no association between chronic pre-stroke use of B1B and SHS (OR 0.807; 95% CI 0.449-1.451; p = 0.474) was identified. CONCLUSIONS: In our single-center retrospective cohort, a pre-stroke chronic B1B treatment seems not to prevent the development of SHS, including in patients with NT-proBNP > 900 pg/mL with chronic heart failure. These results should be confirmed by future randomized controlled trials to better understand the lack of effect of beta blockers on SHS.
Szaszkiewicz J, Sheldon R, Raj S
… +1 more, Rabajoli A
Clin Auton Res
· 2025 Dec · PMID 40461610
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BACKGROUND: The SPRITELY study showed no differences in the recurrence of syncope in patients with bifascicular block (BFB) and syncope, regardless of whether patients received an empiric pacemaker (PM) or an implantable...BACKGROUND: The SPRITELY study showed no differences in the recurrence of syncope in patients with bifascicular block (BFB) and syncope, regardless of whether patients received an empiric pacemaker (PM) or an implantable cardiac monitor (ICM). Whether syncope resistant to pacing can be predicted by baseline clinical variables is unknown. OBJECTIVES: To determine whether baseline clinical characteristics predict syncope recurrence in patients with bifascicular block and a permanent pacemaker. METHODS: This was a retrospective analysis of the SPIRITELY trial, a randomized clinical trial in which patients with syncope and bifascicular block were assigned randomly to receive either a pacemaker or implantable loop recorder as an initial management strategy. In 60 patients who received a pacemaker, we tested the ability of 38 baseline clinical variables to predict a syncope recurrence. These included demographics, comorbidities, medications, and syncopal history and symptoms. Univariable and multivariate statistics were performed and a p < 0.05 was accepted as significant. RESULTS: In the 60 patients who received a pacemaker, 12 (20%) had recurrent syncope. Only the use of angiotensin receptor blockers (ARB) and a history of a composite of one or more of asystole, supraventricular tachycardia (SVT), or diabetes were univariable significant predictors of recurrent syncope (p = 0.042). In the multivariate analysis only a history of a composite of one or more of asystole, SVT, or diabetes significantly predicted syncope (p = 0.03). Neither SVT nor diabetes alone predicted syncope recurrence. CONCLUSIONS: In older patients with syncope and bifascicular heart block, only a history of one or more of asystole, SVT, or diabetes significantly predicted syncope.
Ruška P, Jerković A, Sila S
… +4 more, Močić Pavić A, Krbot Skorić M, Habek M, Hojsak I
Clin Auton Res
· 2025 Aug · PMID 40387976
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OBJECTIVES: This study aimed to investigate the subjective and objective autonomic nervous system (ANS) abnormalities in children with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) compared with hea...OBJECTIVES: This study aimed to investigate the subjective and objective autonomic nervous system (ANS) abnormalities in children with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) compared with healthy children (HC). METHODS: In total, 69 children were enrolled: 23 in the IBD, 28 in the IBS, and 18 HC group. ANS symptoms were evaluated using the Composite Autonomic Symptom Score (COMPASS-31). The severity and distribution of ANS function were quantitated using adrenergic, cardiovagal, and sudomotor indices of the Composite Autonomic Severity Scale (CASS). Health-related quality of life (HRQoL) was assessed with the Pediatric Quality of Life Inventory (PedsQL). RESULTS: Children with IBS scored highest on the COMPASS-31, followed by patients with IBD and HC (median 11.5, 6.3, and 1.7, respectively; p = 0.001). There was no significant difference between groups in CASS (p = 0.09); however, children with IBD had a higher score on the sudomotor index (p = 0.012). There was a significant difference in symptomatic autonomic dysfunction (defined as COMPASS-31 > 7.913 and CASS > 0) between children with IBS (61.5%) compared with children with IBD (42.1%) and HC (7.1%), p = 0.004. In multivariable logistic regression, the number of squats decreased the probability of special health care needs by 17.2%, and the presence of symptomatic autonomic dysfunction increased the probability by 515.4%. CONCLUSIONS: The ANS is frequently affected in children with IBD and IBS; children with IBS show greater autonomic symptom burden, while children with IBD have greater sudomotor dysfunction. HRQoL is significantly influenced by observed ANS changes in both groups.
Manabe K, D'Souza AW, Takeda R
… +5 more, Hissen SL, Washio T, Akins JD, Sanchez B, Fu Q
Clin Auton Res
· 2025 Dec · PMID 40381175
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PURPOSE: In our previous study (Manabe et al., J Appl Physiol 128:1196-1206, 1985), we demonstrated that the cerebral and cardiovascular responses induced by a pre-exercise countdown elicited peripheral vasodilation via...PURPOSE: In our previous study (Manabe et al., J Appl Physiol 128:1196-1206, 1985), we demonstrated that the cerebral and cardiovascular responses induced by a pre-exercise countdown elicited peripheral vasodilation via baroreflex-mediated sympathetic withdrawal, which is likely advantageous for rapid oxygen delivery to contracting skeletal muscles in young men. Whether this is also true in young women, who generally show different neuro-cardiovascular responses to stress compared to men, remains unknown. Thus, we examined whether biological sex would affect the neuro-cardiovascular responses to anticipation before exercise. METHODS: Young healthy women (n = 11) and men (n = 10) performed 1 min of static handgrip at 30% of maximal voluntary contraction force twice; once with a 30 sec countdown and once after being immediately signaled to begin exercise (without countdown), with the order randomized. Middle cerebral artery blood velocity (V; transcranial Doppler), heart rate (HR), cardiac index [CI; HR × stroke volume (Modelflow)/body surface area], mean arterial pressure (MAP; finger photoplethysmography), muscle sympathetic nerve activity (MSNA; microneurography), and leg vascular conductance [LVC = superficial femoral artery blood flow (ultrasound)/MAP] were measured continuously. RESULTS: During countdown, women exhibited smaller increases in CI, MAP, and LVC and a smaller decrease in MSNA than men (p < 0.05). Increases in V and HR, and the sympathetic baroreflex sensitivity did not differ between sexes (p > 0.05). CONCLUSION: Young women seem to have less baroreflex-mediated sympathetic withdrawal and peripheral vasodilatory responses to the countdown compared to young men, despite similar cerebral vascular responses. These findings may suggest women have reduced neuro-vascular responses to exercise anticipation, which could impact the ability of oxygen delivery at exercise onset.
Mehr PE, Ortiz PJ, O'Rourke KR
… +8 more, Ding T, Hackstadt AJ, Kulapatana S, Diedrich A, Claassen DO, Biaggioni I, Peltier AC, Shibao CA
Clin Auton Res
· 2025 Aug · PMID 40360851
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PURPOSE: Postprandial hypotension (PPH) defined as a decrease in systolic blood pressure of more than 20 mmHg within 2 h post meal is prevalent in patients with autonomic failure and is associated with negative cardiovas...PURPOSE: Postprandial hypotension (PPH) defined as a decrease in systolic blood pressure of more than 20 mmHg within 2 h post meal is prevalent in patients with autonomic failure and is associated with negative cardiovascular outcomes. Previous studies reported peripheral autonomic failure with less residual sympathetic tone in Parkinson disease (PD). Therefore, we hypothesized that PPH is more severe in PD than in multiple system atrophy (MSA) with central autonomic failure. METHODS: Thirteen patients with PD and 13 patients with MSA were enrolled. Autonomic function testing and neurohormonal measurements were performed to assess autonomic failure and residual sympathetic activity. Subjects were fed a standard breakfast. Systolic and diastolic blood pressure and heart rate were monitored every 5 min from 30 min before to 120 min post meal. Postprandial hemodynamic changes were summarized using area under the curve (AUC). Differences between the groups were assessed with two-sample independent t test and linear regression. RESULTS: Patients with PD (69% male, 72 ± 9 years) had a significantly lower post-meal diastolic blood pressure (P = 0.003) and heart rate AUC (P = 0.007) than patients with MSA (62% male, 62 ± 8 years). After adjusting for age and supine systolic blood pressure, PD as diagnosis still had significant estimate effect for diastolic blood pressure AUC (P = 0.019). No significant difference was found in the mean systolic blood pressure AUC, but at 30 min post meal, systolic blood pressure decrease was significantly lower in PD (P = 0.016). CONCLUSION: The PD group with peripheral autonomic failure exhibits more severe PPH than the MSA group. This highlights the need for tailored management for PPH in PD.
Mueller BR, Mehta M, Campbell M
… +8 more, Neupane N, Cedillo G, Lee G, Coyle K, Qi J, Chen Z, George MC, Robinson-Papp J
Clin Auton Res
· 2025 Aug · PMID 40347412
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PURPOSE: Pre-clinical studies have demonstrated direct influences of the autonomic nervous system (ANS) on the immune system. However, it remains unclear if ANS-immune connections delineated in these preclinical studies...PURPOSE: Pre-clinical studies have demonstrated direct influences of the autonomic nervous system (ANS) on the immune system. However, it remains unclear if ANS-immune connections delineated in these preclinical studies underlie the relationship between autonomic dysregulation and chronic inflammatory diseases in patients with human immunodeficiency virus (HIV). The aims of this study were: (1) to examine the relationship between interleukin-6 (IL-6) and the parasympathetic/vagal component of baroreflex sensitivity in people with HIV; (2) to determine whether the subtype and severity of HIV-autonomic neuropathy (AN) would predict distinct immunotypes; and (3) to compare the burden of non-acquired immunodeficiency syndrome (AIDS)-related co-morbidities between immunotypes. METHODS: A total of 79 adults with well-controlled HIV underwent a standard battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A, respectively) (Low: Mayo Clin Proc 68:748-752, 1993). Levels of immune biomarkers were measured in all participants using the Target 96 Inflammation Panel on the Olink proteomics platform, and immunotypes were identified using unbiased, non-negative matrix factorization. Mass cytometry (CyTOF) was completed on a subset of participants with and without autonomic neuropathy (N = 10). RESULTS: Reduced BRS-V predicted higher levels of IL-6 (p = 0.002). A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy characterized by deficits in sympathetic nervous system activity (adjusted odds ratio 4.7, p = 0.017). This pro-inflammatory immunotype was older with a greater burden of co-morbidities. CONCLUSION: Deficits in the parasympathetic/cardiovagal and the sympathetic nervous system are associated with inflammation and disease burden in people living with HIV. Future longitudinal research is needed to examine causality.
Clin Auton Res
· 2025 Aug · PMID 40316786
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OBJECTIVE: This study compared clinical characteristics and response to head-up tilt test (HUTT) between micturition syncope (MS) and typical vasovagal syncope (VVS). METHODS: Consecutive patients who underwent nitroglyc...OBJECTIVE: This study compared clinical characteristics and response to head-up tilt test (HUTT) between micturition syncope (MS) and typical vasovagal syncope (VVS). METHODS: Consecutive patients who underwent nitroglycerin-potentiated HUTT were retrospectively dichotomized into two groups: those with a history of MS and those with a history of VVS. The patients with MS were further subdivided into patients with MS alone and with MS and at least one episode of VVS. RESULTS: A total of 2637 patients were enrolled: 204 had MS (MS alone in 103 and MS+VVS in 101), and 216 had typical VVS. Patients with MS were older (38.6 ± 13.1 vs. 36.3 ± 18.5, p = 0003) and more likely to be male (66.2% vs. 48.1%, p < 0.001). Multivariable analysis revealed that smoking habit (odds ratio [OR] 2.16, p < 0.0001), history of traumatic syncope (OR 2.24, p = 0.0001), and drinking alcohol before syncope (OR 2.63, p < 0.0001) were independently associated with MS. HUTT was positive in 141 (69.1%) patients with MS and in 144 (66.7%) patients with VVS (p = 0.592). Patients with MS showed more mixed (46.1% vs. 28.2%, p < 0.001) and vasodepressor forms (15.2% vs. 7.9%, p = 0.013) and fewer cardioinhibitory responses than others (7.4% vs. 30.6%, p < 0.001). CONCLUSIONS: Compared with VVS, patients with MS have different clinical characteristics, and drinking alcohol was an important precipitating factor for MS. The positivity rate of HUTT is high and similar to that of VVS, although patients with MS show a higher prevalence of hypotensive responses.
Abičić A, Skorić MK, Gabelić T
… +3 more, Barun B, Habek M, Adamec I
Clin Auton Res
· 2025 Aug · PMID 40310594
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PURPOSE: The aim of this work is to determine the relationship between the cross-sectional area (CSA) of the vagus nerve and cardiovagal function in people with multiple sclerosis (pwMS) and healthy controls (HC). METHOD...PURPOSE: The aim of this work is to determine the relationship between the cross-sectional area (CSA) of the vagus nerve and cardiovagal function in people with multiple sclerosis (pwMS) and healthy controls (HC). METHODS: We enrolled 50 pwMS and 50 HC. All participants underwent an ultrasound of the vagus nerve and autonomic nervous system testing. The Croatian version of the COMPASS-31 questionnaire was used as a measure of autonomic symptom burden. Cardiovagal function was evaluated with the respiratory sinus arrhythmia (RSA), Valsalva ratio (VR), and heart rate variability. RESULTS: The mean vagus CSA in pwMS was 2.03 ± 0.49 mm on the right side and 1.72 ± 0.38 mm on the left side. The mean vagus CSA in HC was 2.08 ± 0.50 mm on the right side and 1.74 ± 0.37 mm on the left side. There was no statistically significant difference between the two groups in right (p = 0.615) or left (p = 0.866) vagus CSA. In the HC, there was a statistically significant positive correlation between the mean right CSA and both RSA (r = 0.331, p = 0.019) and VR (r = 0.327, p = 0.020). On univariable linear regression analysis in the HC group, the mean right CSA was a predictor of both RSA (B = 5.599, 95% CI 0.974-10.224, p = 0.019) and VR (B = 0.253, 95% CI 0.041-0.466, p = 0.020). These findings were not present in pwMS. CONCLUSIONS: The loss of correlation between vagus nerve CSA and parameters of parasympathetic nervous system function in pwMS corroborates the presence of cardiovagal dysfunction in multiple sclerosis.