Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course.

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.

Autoimmunity to neuronal nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in many and diverse cell types, participating in various functions of cells, tissues and systems. In this review, we focus on the autoimmunity against neuronal nAChRs, the specific autoantibodies and their mechanisms of pathological action in selected autoimmune diseases. We summarize the current relevant knowledge from human diseases as well as from experimental models of autoimmune neurological disorders related to antibodies against neuronal nAChR subunits. Despite the well-studied high immunogenicity of the muscle nAChRs where autoantibodies are the main pathogen of myasthenia gravis, autoimmunity to neuronal nAChRs seems infrequent, except for the autoantibodies to the ganglionic receptor, the α3 subunit containing nAChR (α3-nAChR), which are detected and are likely pathogenic in Autoimmune Autonomic Ganglionopathy (AAG). We describe the detection, presence and function of these antibodies and especially the recent development of a cell-based assay (CBA) which, contrary to until recently available assays, is highly specific for AAG. Rare reports of autoantibodies to the other neuronal nAChR subtypes include a few cases of antibodies to α7 and/or α4ß2 nAChRs in Rasmussen encephalitis, schizophrenia, autoimmune meningoencephalomyelitis, and in some myasthenia gravis patients with concurrent CNS symptoms. Neuronal-type nAChRs are also present in several non-excitable tissues, however the presence and possible role of antibodies against them needs further verification. It is likely that the future development of more sensitive and disease-specific assays would reveal that neuronal nAChR autoantibodies are much more frequent and may explain the mechanisms of some seronegative autoimmune diseases.

Multicentre external validation of the Canadian Syncope Risk Score to predict adverse events and comparison with clinical judgement.

BACKGROUND: The Canadian Syncope Risk Score (CSRS) has been proposed for syncope risk stratification in the emergency department (ED). The aim of this study is to perform an external multicenter validation of the CSRS and to compare it with clinical judgement. METHODS: Using patients previously included in the SyMoNE database, we enrolled subjects older than 18 years who presented reporting syncope at the ED. For each patient, we estimated the CSRS and recorded the physician judgement on the patients' risk of adverse events. We performed a 30-day follow-up. RESULTS: From 1 September 2015 to 28 February 2017, we enrolled 345 patients; the median age was 71 years (IQR 51-81), 174 (50%) were men and 29% were hospitalised. Serious adverse events occurred in 43 (12%) of the patients within 30 days. The area under the curve of the CSRS and clinical judgement was 0.75 (95% CI 0.68 to 0.81) and 0.68 (95% CI 0.61 to 0.74), respectively. The risk of adverse events of patients at low risk according to the CSRS and clinical judgement was 6.7% and 2%, with a sensitivity of 70% (95% CI 54% to 83%) and 95% (95% CI 84% to 99%), respectively. CONCLUSION: This study represents the first validation analysis of CSRS outside Canada. The overall predictive accuracy of the CSRS is similar to the clinical judgement. However, patients at low risk according to clinical judgement had a lower incidence of adverse events as compared with patients at low risk according to the CSRS. Further studies showing that the adoption of the CSRS improve patients' outcomes is warranted before its widespread implementation.

Machine Learning and Syncope Management in the ED: The Future Is Coming.

In recent years, machine learning (ML) has been promisingly applied in many fields of clinical medicine, both for diagnosis and prognosis prediction. Aims of this narrative review were to summarize the basic concepts of ML applied to clinical medicine and explore its main applications in the emergency department (ED) setting, with a particular focus on syncope management. Through an extensive literature search in PubMed and Embase, we found increasing evidence suggesting that the use of ML algorithms can improve ED triage, diagnosis, and risk stratification of many diseases. However, the lacks of external validation and reliable diagnostic standards currently limit their implementation in clinical practice. Syncope represents a challenging problem for the emergency physician both because its diagnosis is not supported by specific tests and the available prognostic tools proved to be inefficient. ML algorithms have the potential to overcome these limitations and, in the future, they could support the clinician in managing syncope patients more efficiently. However, at present only few studies have addressed this issue, albeit with encouraging results.

Syncope Time Frames for Adverse Events after Emergency Department Presentation: An Individual Patient Data Meta-Analysis.

Background and Objectives: Knowledge of the incidence and time frames of the adverse events of patients presenting syncope at the ED is essential for developing effective management strategies. The aim of the present study was to perform a meta-analysis of the incidence and time frames of adverse events of syncope patients. Materials and Methods: We combined individual patients' data from prospective observational studies including adult patients who presented syncope at the ED. We assessed the pooled rate of adverse events at 24 h, 72 h, 7-10 days, 1 month and 1 year after ED evaluation. Results: We included nine studies that enrolled 12,269 patients. The mean age varied between 53 and 73 years, with 42% to 57% females. The pooled rate of adverse events was 5.1% (95% CI 3.4% to 7.7%) at 24 h, 7.0% (95% CI 4.9% to 9.9%) at 72 h, 8.4% (95% CI 6.2% to 11.3%) at 7-10 days, 10.3% (95% CI 7.8% to 13.3%) at 1 month and 21.3% (95% CI 15.8% to 28.0%) at 1 year. The pooled death rate was 0.2% (95% CI 0.1% to 0.5%) at 24 h, 0.3% (95% CI 0.1% to 0.7%) at 72 h, 0.5% (95% CI 0.3% to 0.9%) at 7-10 days, 1% (95% CI 0.6% to 1.7%) at 1 month and 5.9% (95% CI 4.5% to 7.7%) at 1 year. The most common adverse event was arrhythmia, for which its rate was 3.1% (95% CI 2.0% to 4.9%) at 24 h, 4.8% (95% CI 3.5% to 6.7%) at 72 h, 5.8% (95% CI 4.2% to 7.9%) at 7-10 days, 6.9% (95% CI 5.3% to 9.1%) at 1 month and 9.9% (95% CI 5.5% to 17) at 1 year. Ventricular arrhythmia was rare. Conclusions: The risk of death or life-threatening adverse event is rare in patients presenting syncope at the ED. The most common adverse events are brady and supraventricular arrhythmias, which occur during the first 3 days. Prolonged ECG monitoring in the ED in a short stay unit with ECG monitoring facilities may, therefore, be beneficial.

Are Strategies Favoring Pattern Matching a Viable Way to Improve Complexity Estimation Based on Sample Entropy?

It has been suggested that a viable strategy to improve complexity estimation based on the assessment of pattern similarity is to increase the pattern matching rate without enlarging the series length. We tested this hypothesis over short simulations of nonlinear deterministic and linear stochastic dynamics affected by various noise amounts. Several transformations featuring a different ability to increase the pattern matching rate were tested and compared to the usual strategy adopted in sample entropy (SampEn) computation. The approaches were applied to evaluate the complexity of short-term cardiac and vascular controls from the beat-to-beat variability of heart period (HP) and systolic arterial pressure (SAP) in 12 Parkinson disease patients and 12 age- and gender-matched healthy subjects at supine resting and during head-up tilt. Over simulations, the strategies estimated a larger complexity over nonlinear deterministic signals and a greater regularity over linear stochastic series or deterministic dynamics importantly contaminated by noise. Over short HP and SAP series the techniques did not produce any practical advantage, with an unvaried ability to discriminate groups and experimental conditions compared to the traditional SampEn. Procedures designed to artificially increase the number of matches are of no methodological and practical value when applied to assess complexity indexes.

Diagnostic accuracy of ICD-9 code 780.2 for the identification of patients with syncope in the emergency department.

PURPOSE: Syncope is a common condition that affects individuals of all ages and is responsible for 1-3% of all emergency department (ED) visits. Prospective studies on syncope are often limited by the exiguous number of subjects enrolled. A possible alternative approach would be to use of hospital discharge diagnoses from administrative databases to identify syncope subjects in epidemiological observational studies. We assessed the accuracy of the International Classification of Diseases, Ninth Revision (ICD-9) code 780.2 "syncope and collapse" to identify patients with syncope. METHODS: Patients in two teaching hospitals in Milan, Italy with a triage assessment for ED access that was possibly related to syncope were recruited in this study. We considered the index test to be the attribution of the ICD-9 code 780.2 at ED discharge and the reference standard to be the diagnosis of syncope by the ED physician. RESULTS: The sensitivity, specificity, positive and negative predictive values of the ICD-9 code 780.2 to identify patients with syncope were 0.63 (95% confidence interval [CI] 0.58-0.67), 0.98 (95% CI 0.98-0.99), 0.83 (95% CI 0.79-0.87) and 0.95 (95% CI 0.94-0.95), respectively. CONCLUSIONS: The moderate sensitivity of ICD-9 code 780.2 should be considered when the code is used to identify patients with syncope through administrative databases.

Neural networks as a tool to predict syncope risk in the Emergency Department.

AIMS: There is no universally accepted tool for the risk stratification of syncope patients in the Emergency Department. The aim of this study was to investigate the short-term predictive accuracy of an artificial neural network (ANN) in stratifying the risk in this patient group. METHODS AND RESULTS: We analysed individual level data from three prospective studies, with a cumulative sample size of 1844 subjects. Each dataset was reanalysed to reduce the heterogeneity among studies defining abnormal electrocardiogram (ECG) and serious outcomes according to a previous consensus. Ten variables from patient history, ECG, and the circumstances of syncope were used to train and test the neural network. Given the exploratory nature of this work, we adopted two approaches to train and validate the tool. One approach used 4/5 of the data for the training set and 1/5 for the validation set, and the other approach used 9/10 for the training set and 1/10 for the validation set. The sensitivity, specificity, and area under the receiver operating characteristic curve of ANNs in identifying short-term adverse events after syncope were 95% [95% confidence interval (CI) 80-98%], 67% (95% CI 62-72%), 0.69 with the 1/5 approach and 100% (95% CI 84-100%), 79% (95% CI 72-85%), 0.78 with the 1/10 approach. CONCLUSION: The results of our study suggest that ANNs are effective in predicting the short-term risk of patients with syncope. Prospective studies are needed in order to compare ANNs' predictive capability with existing rules and clinical judgment.

Implantable loop recorder versus conventional diagnostic workup for unexplained recurrent syncope.

BACKGROUND: The most recent syncope guideline recommends that implantable loop recorders (ILRs) are implanted in the early phase of evaluation of people with recurrent syncope of uncertain origin in the absence of high-risk criteria, and in high-risk patients after a negative evaluation. Observational and case-control studies have shown that loop recorders lead to earlier diagnosis and reduce the rate of unexplained syncopes, justifying their use in clinical practice. However, only randomised clinical trials with an emphasis on a primary outcome of specific ILR-guided diagnosis and therapy, rather than simply electrocardiogram (ECG) diagnosis, might change clinical practice. OBJECTIVES: To assess the incidence of mortality, quality of life, adverse events and costs of ILRs versus conventional diagnostic workup in people with unexplained syncope. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE, EMBASE, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal in April 2015. No language restriction was applied. SELECTION CRITERIA: We included all randomised controlled trials of adult participants (i.e. ≥ 18 years old) with a diagnosis of unexplained syncope comparing ILR with standard diagnostic workup. DATA COLLECTION AND ANALYSIS: Two independent review authors screened titles and abstracts of all potential studies we identified as a result of the literature search, extracted study characteristics and outcome data from included studies and assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We contacted authors of trials for missing data. We analysed dichotomous data (all-cause mortality and aetiologic diagnosis) as risk ratios (RR) with 95% confidence intervals (CI). We used the Chi(2) test to assess statistical heterogeneity (with P < 0.1) and the I² statistic to measure heterogeneity among the trials. We created a 'Summary of findings' table using the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes. MAIN RESULTS: We included four trials involving a total of 579 participants. With the limitation that only two studies reported data on mortality and none of them had considered death as a primary endpoint, the meta-analysis showed no evidence of a difference in the risk of long-term mortality between participants who received ILR and those who were managed conventionally at follow-up (RR 0.97, 95% CI 0.41 to 2.30; participants = 255; studies = 2; very low quality evidence) with no evidence of heterogeneity. No data on short term mortality were available. Two studies reported data on adverse events after ILR implant. Due to the lack of data on adverse events in one of the studies' arms, a formal meta-analysis was not performed for this outcome.Data from two trials seemed to show no difference in quality of life, although this finding was not supported by a formal analysis due to the differences in both the scores used and the way the data were reported. Data from two studies seemed to show a trend towards a reduction in syncope relapses after diagnosis in participants implanted with ILR. Cost analyses from two studies showed higher overall mean costs in the ILR group, if the costs incurred by the ILR implant were counted. The mean cost per diagnosis and the mean cost per arrhythmic diagnosis were lower for participants randomised to ILR implant.Participants who underwent ILR implantation experienced higher rates of diagnosis (RR (in favour of ILR) 0.61, 95% CI 0.54 to 0.68; participants = 579; studies = 4; moderate quality evidence), as compared to participants in the standard assessment group, with no evidence of heterogeneity. AUTHORS' CONCLUSIONS: Our systematic review shows that there is no evidence that an ILR-based diagnostic strategy reduces long-term mortality as compared to a standard diagnostic assessment (very low quality evidence). No data were available for short-term all-cause mortality. Moderate quality evidence shows that an ILR-based diagnostic strategy increases the rate of aetiologic diagnosis as compared to a standard diagnostic pathway. No conclusive data were available on the other end-points analysed.Further trials evaluating the effect of ILRs in the diagnostic strategy of people with recurrent unexplained syncope are warranted. Future research should focus on the assessment of the ability of ILRs to change clinically relevant outcomes, such as quality of life, syncope relapse and costs.

Cardiovascular control in women with fibromyalgia syndrome: do causal methods provide nonredundant information compared with more traditional approaches?

The cardiovascular autonomic control and the baroreflex sensitivity (BRS) have been widely studied in fibromyalgia syndrome (FMS) patients through the computation of linear indices of spontaneous heart period (HP) and systolic arterial pressure (SAP) variabilities. However, there are many methodological difficulties regarding the quantification of BRS by the traditional indices especially in relation to the issue of causality. This difficulty has been directly tackled via a model-based approach describing the closed-loop HP-SAP interactions and the exogenous influences of respiration. Therefore, we aimed to assess whether the BRS assessed by the model-based causal closed-loop approach during supine and active standing in patients with FMS could provide complementary information to those obtained by traditional indices based on time and frequency domains. The findings of this study revealed that, at difference with the traditional methods to quantify BRS, the causality analysis applied to the HP, SAP, and respiratory series, through the model-based closed-loop approach, detected lower BRS in supine position, as well as a blunted response to the orthostatic stimulus in patients with FMS compared with healthy control subjects. Also, the strength of the causal relation from SAP to HP (i.e., along the cardiac baroreflex) increased during the active standing only in the control subjects. The model-based closed-loop approach proved to provide important complementary information about the cardiovascular autonomic control in patients with FMS.

Relationship between sympathetic activity and pain intensity in fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a syndrome characterised by chronic musculoskeletal pain, hyperalgesia on specific areas of tenderness (tender points) and by an autonomic nervous system dysfunction consistent with sympathetic overactivity. It is not known whether there is any relationship between the amount of cardiovascular sympathetic activity and the magnitude of pain. Our objective was to assess this potential relationship in patients with FM. METHODS: Electrocardiogram, finger blood pressure, respiration and post-ganglionic sympathetic discharge activity (muscle sympathetic nerve activity, MSNA) were continuously recorded at rest in 25 patients with primary FMS. The autonomic profile was assessed by MSNA and spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation and of sympathetic vasomotor control (LF-SAP) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variability. Cardiac baroreflex function was evaluated by the index α (αLF). Baroreceptor modulation of the sympathetic vasomotor control (sBRS) was assessed by the MSNA/diastolic pressure relationship. RESULTS: Pain intensity was linearly correlated with LFRR/HFRR (r² = 0.21; p=0.03), LFSAP (r² = 0.26; p=0.02) and MSNA (burst rate) (r² = 0.45; p=0.003). Pain intensity was inversely correlated with the αLF index (r² = 0.24; p=0.02) and the sBRS (r² = 0.28; p=0.03). Thus, the higher the sympathetic drive to the heart and vessels, the higher the magnitude of chronic pain. Also, the gains of both the cardiac and MSNA baroreceptor control were inversely related to the pain intensity. CONCLUSIONS: These findings raise the theoretical possibility that in FM patients the use of anti-adrenergic agents might lessen chronic pain intensity by reducing the underlying excessive sympathetic activity.

Syncope recurrence and mortality: a systematic review.

AIMS: Data on adverse events and death rates following syncope are heterogeneous among studies, and knowledge of syncope prognosis could help to better define the correct management of patients. METHODS AND RESULTS: We performed a systematic review of literature by searching for prospective observational studies enrolling consecutive patients presenting to the Emergency Department because of syncope. The outcomes considered were syncope recurrence and short- and long-term mortality. Morbidity and a composite of morbidity and mortality were also assessed. Pooled event rates and 95% confidence intervals (CI) were calculated for each outcome using the random effects model. Twenty-five studies (11 158 patients) were included. The incidence of syncope relapse linearly increased from 0.3% at 30 days to 22% at 2 years follow-up. One-year mortality rate varied between 5.7 and 15.5%; the pooled estimate was 8.4% (95% CI: 6.7-10.2%). The incidence of adverse events (morbidity) varied between 6.1 and 25.2% at 10 days and 2 years, respectively. The short-term (10 days) pooled incidence of the composite of morbidity and mortality was 9.1% (95% CI: 6.6-12.5%). We found a high statistical heterogeneity between studies. CONCLUSION: This meta-analysis of prospective observational studies shows that the chance of being asymptomatic linearly progressively decreased over time after the first syncope. Short-term (10-30 days) mortality after syncope was <2% and that the overall 10-day rate of the composite endpoint of death and major events was ∼9%. The knowledge of syncope prognosis could help clinicians to understand syncope patients' prognosis and researchers to design future studies.

Priorities for emergency department syncope research.

STUDY OBJECTIVES: There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research. METHODS: We recruited a multinational panel of syncope experts. A preconference survey identified research priorities, which were refined during and after the conference through an iterative review process. RESULTS: There were 31 participants from 7 countries who represented 10 clinical and methodological specialties. High-priority research recommendations were organized around a conceptual model of ED decisionmaking for syncope, and they address definition, cohort selection, risk stratification, and management. CONCLUSION: We convened a multispecialty group of syncope experts to identify the most pressing knowledge gaps and defined a high-priority research agenda to improve the care of patients with syncope in the ED.

Nitrate-potentiated head-up tilt testing (HUT) has a low diagnostic yield in patients with likely vasovagal syncope.

BACKGROUND: Vasovagal syncope (VVS) is characterized by a wide spectrum of clinical presentations, but the relationship between clinical presentation and response to head-up tilt testing (HUT) has not yet been evaluated in detail. The aim of this study was to assess the relationship between the clinical presentation of VVS and HUT and clinical outcome at long-term follow-up. METHODS: Out of 671 consecutive subjects undergoing nitroglycerin-potentiated HUT for suspected VVS, 369 patients with normal electrocardiogram and no structural heart disease were included in our study. RESULTS: A history suggestive of typical or atypical VVS was obtained in 198 and 171 patients, respectively. The positivity rate of HUT was 65% and 36% in patients with established and likely VVS, respectively (P < 0.0001). In patients with established VVS, a time interval of ≤28 days between the last syncope and HUT was the only independent predictor of a positive test. In patients with likely VVS, no variable was predictive of a positive HUT. At a mean follow-up of 43 ± 27 months, the rate of adverse events (all-cause mortality, syncope recurrence, and major diagnostic and/or therapeutic procedures) was similar in patients of both groups, independent of HUT results. CONCLUSION: In patients with likely VVS, HUT has a low-diagnostic yield and may be inadequate to establish a reliable diagnosis. Similar long-term outcomes were observed in patients with positive or negative test results, suggesting that HUT is of limited value in the management of patients with suspected neurally mediated syncope.

The Long-COVID autonomic syndrome in hospitalized patients: A one-year prospective cohort study.

Long-COVID syndrome is characterized by fatigue, orthostatic intolerance, tachycardia, pain, memory difficulties, and brain fog, which may be associated with autonomic nervous system abnormalities. We aimed to evaluate the short and long-term course of COVID-19 autonomic symptoms and quality of life (QoL) after SARS-CoV-2 infection through a one-year follow-up combined with validated questionnaires. Additionally, we aimed to identify patients with worsening autonomic symptoms at 6 and 12 months by dividing the patient cohort into two sub-groups: the Post-COVID healed Control sub-group (total score<16.4) and the Long-COVID autonomic syndrome sub-group (total score>16.4). This prospective cohort studied 112 SARS-CoV-2 positive patients discharged from Humanitas Research Hospital between January and March 2021. Autonomic symptoms and QoL were assessed using the composite autonomic symptom scale 31 (COMPASS-31) and Short Form Health Survey (SF-36) questionnaires at various time points: before SARS-CoV-2 infection (PRE), at hospital discharge (T0), and at 1 (T1), 3 (T3), 6 (T6), and 12 (T12) months of follow-up. COMPASS-31 total score, Orthostatic Intolerance and Gastrointestinal function indices, QoL, physical functioning, pain, and fatigue scores worsened at T0 compared to PRE but progressively improved at T1 and T3, reflecting the acute phase of COVID-19. Unexpectedly, these indices worsened at T6 and T12 compared to T3. Subgroup analysis revealed that 47% of patients experienced worsening autonomic symptoms at T6 and T12, indicating Long-COVID autonomic syndrome. Early rehabilitative and pharmacological therapy is recommended for patients at the T1 and T3 stages after SARS-CoV-2 infection to minimize the risk of developing long-term autonomic syndrome.

Long-COVID autonomic syndrome in working age and work ability impairment.

Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability. This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6. One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.

Favorable effects of carotid endarterectomy on baroreflex sensitivity and cardiovascular neural modulation: a 4-month follow-up.

Carotid surgery variably modifies carotid afferent innervation, thus affecting arterial baroreceptor sensitivity. Low arterial baroreflex sensitivity is a well-known independent risk factor for cardiovascular diseases. The aim of this study was to assess the 4-mo effects of carotid endarterectomy (CEA) on arterial baroreceptor sensitivity and cardiovascular autonomic profile in patients with unilateral carotid stenosis. We enrolled 20 patients (72 ± 8 yr) with unilateral >70% carotid stenosis. ECG, beat-by-beat blood pressure, and respiration were continuously recorded before and 126 ± 9 days after CEA, at rest and during a 75° head-up tilt. Both pharmacological (modified Oxford technique, BRS) and spontaneous (index α, spectral analysis) arterial baroreflex sensitivity were assessed. Cardiovascular autonomic profile was evaluated by plasma catecholamines and spectral indexes of cardiac sympathovagal modulation [low-frequency R-R interval (LFRR), low frequency-to high frequency ratio (LF/HF), high-frequency R-R interval (HFRR)] and sympathetic vasomotor control [low-frequency systolic arterial pressure (LFSAP)] obtained from heart rate and SAP variability. After CEA, both the index α and BRS were higher (P < 0.02) at rest. SAP variance decreased both at rest and during tilt (P < 0.02). Before surgery, tilt did not modify the autonomic profile compared with baseline. After CEA, tilt increased LF/HF and LFSAP and reduced HFRR compared with rest (P < 0.02). Four months after CEA was performed, arterial baroreflex sensitivity was enhanced. Accordingly, the patients' autonomic profile had shifted toward reduced cardiac and vascular sympathetic activation and enhanced cardiac vagal activity. The capability to increase cardiovascular sympathetic activation in response to orthostasis was restored. Baroreceptor sensitivity improvement might play an additional role in the more favorable outcome observed in patients after carotid surgery.