Clinical Autonomic Research最新文献

Purpose: Vasovagal syncope (VVS) involves autonomic dysregulation affecting cardiac electrical activity. The Tp-Te interval, reflecting transmural repolarization dispersion, may help predict positive head-up tilt test (HUTT) responses in patients with suspected VVS.

Methods: A total of 179 patients with suspected VVS were included in the study. A HUTT was performed in enrolled patients, which were divided into HUTT-negative and HUTT-positive groups, and the HUTT-positive group was further classified into three subgroups of "vasodepressor," "cardioinhibitory," and "mixed-type" responses to HUTT. QT interval, corrected QT (QTc) interval, and Tp-Te interval were measured by the baseline 12-lead surface electrocardiograph recorded before HUTT.

Results: The QT interval, QTc interval, and Tp-Te interval in the HUTT-positive group were higher than those in the HUTT-negative group (P < 0.001). Tp-Te was higher in the cardioinhibitory and mixed-type subgroups than in the vasodepressor subgroup (P < 0.05). Receiver operating characteristic curve analysis showed that Tp-Te higher than 88 ms was a significant predictor of positive HUTT results (71.70% sensitivity and 75.90% specificity), with a predictive value significantly higher than QT and QTc (P < 0.05), and Tp-Te higher than 95 ms predicted cardioinhibitory and mixed-type response to HUTT (75% sensitivity, and 57.10% specificity).

Conclusion: Baseline myocardial TDR is associated with VVS and susceptibility to VVS. The baseline Tp-Te interval might be used as a novel noninvasive index for differentiating cardioinhibitory, mixed-type, and vasodepressor responses to HUTT and for predicting the occurrence of cardioinhibitory responses in VVS patients.

Background: Syncope is a prevalent issue in pediatric patients. The nitroglycerin (NTG)-potentiated head-up tilt test (HUTT) is widely used in adults for diagnosing reflex syncope; however, few and contrasting data are available in pediatric populations. The aim of our study was to evaluate the positivity rate and types of responses to NTG-potentiated HUTT in pediatric patients with suspected reflex syncope.

Methods: We conducted a retrospective multicenter analysis of 307 pediatric patients (mean age: 14.4 ± 2.8 years; 57.6% female) who underwent HUTT at two syncope units in Naples, Italy. A group of 16 healthy pediatric subjects (13 ± 3.2 years; 37.5% female) with no history of syncope was used as a control. We described the HUTT overall positivity rate and responses; moreover, the positivity rate, sensitivity, and specificity were evaluated. A multivariate analysis was performed to test the association of positive response to HUTT with a set of clinical covariates.

Results: The overall HUTT positivity rate was 74.9%, ranging from 51.5% to 81.6% among pediatric patients with non-classical and classical presentation, respectively. The HUTT positivity rate among healthy control group was 18.7%; consequently the HUTT specificity was 81.3%. Younger age (OR: 0.84; p = 0.005) and female sex (OR: 2.3; p = 0.005) were independent predictors of HUTT positivity; in contrast, the non-classical presentation of syncope (OR: 0.23; p < 0.001) and situational syncope (OR: 0.2; p = 0.006) correlated negatively with HUTT positivity.

Conclusions: NTG-potentiated HUTT showed a high positivity rate, good sensitivity, and specificity in pediatric patients with suspected reflex syncope. Some patients and syncope-related features independently correlated with HUTT positivity. Cardioinhibitory response was more prevalent in pediatric patients with a non-classical presentation of reflex syncope.

Purpose: This study evaluated the effectiveness of morning versus bedtime antihypertensive medication administration in reducing ambulatory blood pressure (BP) in older adults aged ≥ 65, and to assess whether administration timing influences conversion from a non-dipper to a dipper BP profile.

Methods: Eight randomized controlled trials were identified through systematically screening of the PubMed and Web of Science databases. Risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted with Review Manager version 5.4 to compare the efficacy of morning versus bedtime administration on ambulatory BP indices.

Results: Bedtime administration resulted in significantly greater reductions in nocturnal systolic BP (mean difference [MD] - 4.52 mmHg, [lower and upper 95% confidence intervals [CI] - 7.15; - 1.90]; p = 0.0007) and diastolic BP (MD - 2.00 mmHg, [95% CI - 2.90; - 1.10]; p < 0.0001). No significant differences were observed in diurnal systolic BP (MD 1.28 mmHg, [95% CI - 0.17; 2.72]; p = 0.08), diastolic BP (MD 0.34 mmHg, [95% CI - 0.49; 1.16]; p = 0.42), 24/48-h systolic BP (MD - 0.02 mmHg, [95% CI - 1.37; 1.33]; p = 0.98), or 24/48-h diastolic BP (MD - 0.50 mmHg, [95% CI - 1.45; 0.45]; p = 0.30). Sensitivity analysis excluding the controversial data from Hermida confirmed significantly greater reductions in nocturnal systolic and diastolic BP with bedtime administration. Two of three studies reported that bedtime administration was associated with a lower proportion of non-dippers than morning treatment.

Conclusion: Bedtime antihypertensive administration improves control of nocturnal BP in older adults aged ≥ 65 and may facilitate restoration to a dipper BP profile. No significant differences were observed in diurnal or 24/48-h mean BP reductions compared with morning administration.

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, R² = 0.4) along with increased sympathetic vascular transduction (p = 0.0008, R² = 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.

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.

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% O₂) and isocapnic hypoxia (IH, 10% O₂). During both conditions, oxygen saturation, beat-to-beat BP, MSNA, and end-tidal CO₂ (PetCO₂) were continuously monitored, with PetCO₂ 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 PetCO₂ 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.

Objective: Parkinson's disease (PD) is frequently associated with orthostatic hypotension (OH). Research on the prevalence of OH in PD and its effects on patients has produced inconsistent findings.

Methods: A systematic review and meta-analysis were conducted by searching for studies related to PD and OH in the PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate the prevalence of OH in patients with PD, along with odds ratios (OR), weighted mean differences (WMD), or standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic.

Results: The prevalence of OH in patients with PD was found to be 33.1% (95% CI 29.3-37%) in a pooled sample of 7748 subjects. Patients with PD and OH were significantly older at the time of examination (WMD 2.92 years) and had a longer disease duration (WMD 0.71 years) compared with those without OH. There was no significant difference in the distribution of sex, or in the scores of the Unified Parkinson's Disease Rating Scale (UPDRS)/the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I and II, as well as the total scores among patients with Parkinson's disease with or without OH. In addition, patients with PD and OH exhibited significantly higher UPDRS/MDS-UPDRS scores across part III section scores (SMD 0.41, 95% CI 0.23-0.59).

Conclusions: The prevalence of OH in PD is 33.1%. Patients with PD and OH are generally older at examination, have a longer disease duration, and display more severe motor symptoms compared with those without OH.

Purpose: We aimed to clarify the mechanism for presyncope, defined as the gradual onset of hypotension, starting some minutes before vasovagal syncope. Although there is a fall in cardiac output and usually vasodilatation, the control of sympathetic activity during presyncope is uncertain.

Methods: We retrospectively compared haemodynamics and muscle sympathetic nerve activity levels from positive tilt tests (without provocation) in patients with known vasovagal syncope (age 41 ± 3 years, 13 female, n = 27) to controls (age 39 ± 3 years, 8 female, n = 13). We used sequence methods to measure vascular sympathetic and cardiovagal baroreflex gain at baseline (lying supine) during tilt, presyncope and recovery.

Results: Patients were tilted for 18.1 ± 1 min, and mean arterial pressure fell to 62 ± 3 mmHg before tilt-back. At baseline and early tilt, all haemodynamic variables were similar to controls, however sympathetic baroreflex gain was increased: -2.7 ± 0.2 bursts/100 beats/mmHg versus -2.0 ± 0.3 (p = 0.03). Cardiovagal baroreflex gain was increased at baseline 11.8 ± 0.6 ms/mmHg versus 9.3 ± 0.8 (p = 0.02). During early presyncope (from 8 to 4 min before tilt-back), sympathetic baroreflex gain fell to -2.4 bursts/100 b/mmHg and thereafter to -0.5 ± 0.3 (p = 0.01) during late presyncope, before losing correlation with mean arterial pressure. In some patients, the regression coefficient reversed before correlation was lost (n = 8) but this did not result in lower levels of nerve activity. At tilt-back, nerve activity fell below baseline levels in at least 63% of patients.

Conclusion: Presyncope appeared to be initiated by a fall in sympathetic baroreflex gain despite increased levels at baseline and early tilt.

Background: The autonomic synucleinopathy multiple system atrophy (MSA) can be difficult to distinguish clinically from Parkinson disease with orthostatic hypotension (PD+OH). ¹⁸F-Dopamine positron emission tomography separates these conditions based on cardiac noradrenergic deficiency in PD+OH and not in MSA but is available only at the NIH Clinical Center. 3,4-Dihydroxyphenylglycol (DHPG) is the main neuronal metabolite of norepinephrine. This retrospective observational study examined whether DHPG levels in cerebrospinal fluid (CSF) or plasma differentiate MSA from PD+OH.

Methods: We reviewed CSF and plasma neurochemical data from all patients referred for evaluation at the NIH Clinical Center between 1995 and 2024 for chronic autonomic failure or parkinsonism. A concurrently studied comparison group included healthy volunteers or patients with orthostatic intolerance.

Results: CSF DHPG was decreased in MSA (N = 67, p < 0.0001) compared to the controls but also tended to be decreased in PD+OH (N = 31, p = 0.0776). Antecubital venous plasma DHPG was decreased in PD+OH (N = 47, p = 0.0064) but not in MSA. CSF/plasma concentration ratios of DHPG were lower in MSA than in PD+OH (p = 0.0005). Cardiac arteriovenous increments in plasma DHPG and cardiac norepinephrine spillovers were strikingly decreased in PD+OH (N = 6) and were lower than in MSA (N = 20, p < 0.0001 each). Combining cardiac arteriovenous increments in plasma DHPG with norepinephrine spillovers completely separated PD+OH from MSA.

Conclusions: CSF/plasma ratios of DHPG, cardiac arteriovenous increments in plasma DHPG, and cardiac norepinephrine spillovers separate MSA from PD+OH. On the basis of our results we propose that biomarker combinations involving DHPG in biofluids may enable a clinical laboratory distinction of MSA from PD+OH.

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.